III. Kidney transplant from donors with hepatitis B: A challenging treatment option
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- Please summarise this article in your own words
- What is the level of evidence provided by this article?
- Will you accept living or deceased donations from HBV-positive donors?
Thank you, All
Will you consider HBV-positive donors based on level 5 evidence (this article)? Why and how?
It would have to be under careful consideration.
The potential recipients have to be counseled on the risks.
It will depend on the serostatus of the donors and antibody status of the recipient
Donors with HBV and HBeAg positive will be automatically disqualified
The best outcome will be in donors who are antiHBC positive/HBsAg neg and recipients with antiHBs titers more than 10 mIU/ml
Donors who are HBsAg positive/HBV DNA negative who donate to HBV negative recipients, the recipients will need prophylaxis. The risk of seroconversion to HBsAg is lower and the risk is reduced by using antiviral prophylaxis.
It is of utmost importance that all patients with CKD are vaccinated against hepatitis B so that these patients can develop antibodies as patients who are reach ESKD have a lower take of the vaccination
I agree Dr Bagha,
Ajay
Thank you Prof
We should exclude HBV s Ag with HBV e Ag and HBV DNA case from donation and careful allocation to appropriate recipients can be successfully performed, particularly with HBV s Ag + and HBV e Ag negative and HBV DNA negative with cover of antiviral with or without HBVIG.
This in special situation:
1- Urgent condition included patients with exhausted vascular access for hemodialysis, patients with ongoing uremia despite adequate dialysis prescription, and patients who cannot remain in the dialysis treatment.
2- Recipients with positive HBsAg.
3- Recipients who active waiting list who have waiting time longer than the median time to receive a kidney in each national society.
Consent should be taken and vaccination to achieve anti-HBs at least > 10 mIU/mL, no co viral infection and HBIG, antiviral medication should be used.
Yes Dr Saad, I like your viewpoint.
The topic needs more and more extensive studies but in certain cases I will accept this donors group although level evidence is low
▪︎ anti-HBc (+) donors with negative HBs Ag , negative HBe Ag , and undetectable DNA
▪︎ urgent recepiants whose have anti-HBs (> 10 mIU/mL) after discussion their willingness and the risks arising therefrom
▪︎ HBsAg positive recipients with no HCV coinfection nor other cause of chronic liver disease
if HBV PCR negative and HBsAg positive with anti-HBsAg antibody at least 10 can be accepted if there is unavailable donor or staying long time on dialysis and no other available option
It has been shown in a number of studies that performing a kidney transplant using organs from donors who tested positive for HBsAg may be both cost-effective and advantageous in terms of extending the pool of potential donors.
Therefore, transplantation from HBV-s Ag positive donors is taken into consideration for the following:
-Recipients who are currently on an active waiting list and who have a long waiting period.
-Patients who had exhausted their vascular access for hemodialysis were considered to be in an urgent condition.
– Recipients who tested positive for HBsAg.
-Vaccination should be administered in order to establish anti-HBs levels of at least 10 mIU/mL, there should be no co-viral infection, and HBIG and antiviral treatment should be used. Consent should be obtained before
Only in certain situations … because the evidence provided by this article is week as it is level 5
From living donor, I will not accept because of the possible risk to the donor since HBV is associated with the possibility of glomerulonephritis and PAN which can have bad impact on the kidney and according to British guidelines any patient with active HBV infection should be excluded form donation
From deceased donor I may accept if the following are met
As these criteria will put the patient at minimal risk of reactivation with either no or single antiviral agent for at least 1 year with close follows up every 3 months, except if the recipient is HBV positive at this situation I will initiate treatment before transplantation
Care full assessment and categorization should be done to assess how risky the condition is;
Conder eradication therapy for HBV infection
Careful consideration of recipient receiving induction therapy, e.g rituximab, ATG
Prophylaxis treatment of HB(+)D/(-)R
Consider anti-HBs titre in HD recipient and regiment of treatment according to protocol
Vaccination program
Evidence provided by this article is low, so we can not rely on it, but there are certain circumstances when we may accept such donors: if the recipients accept the idea, recipients with exhausted access, no compatible donor and long time on dialysis.
No, but in patients with no access to dialysis and no potential healthy donor can be considered, after discussing the issue with patient explaining the risks and benefits
after figuring out the donors viremia status, and put the treatment strategies.
must have HBV DNA testing to exclude the possibility of occult HBV infection.
British Transplantation Society Guidelines
would accept in special circumstances outlined in this article , such as HBs antigen positive recipient and urgent kidney transplantion . Each patient has to be assessed as per his merits .Would assess the donor with HBe ang and HBe antibodies, NAT , and HBV DNA assay. If the donor is featuring active infection with replicative activity would decline the donor. If the donor is only HBs antigen positive with negative HBV DNA, would accept the donation with maximum precautionary measures including the use of HBIG and prophylactic antivirals such Lamivudine and Enticavir . particularly in recipient who is vaccinated with antibody titer of more than 10 IU/ml which represent protective status. Similarly would initiate vaccination protocol for those unvaccinated . Nevertheless, KDIQO guideline recommend booster dose or revaccination for those recipients with antibody titer below 100 IU/ml.
In our local practice, we have no cadaveric transplantation program. Transplanting a kidney from a hepatitis B virus (HBV) positive donor to HBV negative recipient is prohibited. However, this article may provide an unordinary option in exceptional situations (e.g. patients with exhausted vascular access who may die secondary to dialysis withdrawal).
In kidney transplant,there are a lot of limitations in performing large size studies and RTC.In the presence of increased number of a waiting patient, clinicians should consider all options in their decision making and be alert to new published evidence that clarifies the balance of benefit versus harm; patient preference should have a substantial influencing role.
We are currently not using HBV positive donors in Pediatric Renal transplantation in entire country and in terms of center protocol, HBV positive donors are excluded for adult transplantation as well.
In terms of evidence (level 5), I shall not consider HBV positive donors as this issue has lot of ethical concerns associated with it and hence needs higher level of evidence and validation
Antiviral medication and HBIG
To prevent HBV transmission via kidney transplant organ was the use of antiviral medication (lamivudine or entecavir).and HBIG.
The optimal dose of HBIG to be used for kidney transplant recipient from donor with HBV was not clearly Known .
Risk benefit of transplantation and criteria for HBsAg donor utilization
1- Patient with urgent need to recipient KT.
2- Multiaccess failure on HD .
3- Patient with on going uraemia despite adequate dialysis prescription.
4- Patient who can not remain in dialysis treatment (HD or CAPD) due to any reason .
5- Recipient with positive HBsAg.
Can be condidered with-
Although this is not original research but rather a review with level 5 evidence, It utilized the guidelines and many original research papers. The number of patients in all research is limited by nature. So, with referral to original papers, It seems reliable and can be relied on for accepting HSag donors for recipients with anti-HBs protection. We need to immunise all CKD patients, especially before stage 5. immunization against HBV was not routine until the last 3 decades. Despite that, some CKD patients especially stage 5D, may lose their protective antibodies.
We can’t consider HBV-positive donors based on article level 5, However, according to the big gab between the number of recipients and donors
we need new resources for donation
HBV positive donor isn’t the first choice but in some cases it would be the only solution, for example
Recipients on waiting list for long time.
Persistent uremia in spite of intense dialysis
Patient without good vascular for dialysis
use of kidney organs from donors with HBV infection in the area where the national organ donation rate is less than the rate of endemic HBV infection is a better alternative than discarding the organ
In this case, we should compare the mortality and morbidity if we deny HBV pos donor
2- 8% of patients on waiting list die or get worse
But not all recipient will have sero positive after renal transplant
For the moment, we should at least well select the donor by performing a precise investigations
(HBS ag) ( anti HBS antibodies ) (HBe Ag) (anti HBe antibodies) ( anti HBc antibodies)
And if available NAT
Donor with (HBS ag ) neg may be safe for recipient especially if he has anti HBs antibodies more than 10
Donor with ( HBS ag) pos
In this case if NAT neg , the recipient even don’t need NAs if he has ( anti HBs antibodies) more than 100
If NAT pos, we should be cautious notably if Rituximab is used for induction in a recipient with (anti HBs ) neg
Because those recipients may progress do novo infection
NAs is indicated with or without HBIG
The criteria mentioned above need We need large studies (RCT) with long follow up duration to get over results belonging to graft survival and function
Yes, HBV positive donors can be taken up after detailed counselling.
The criteria should be stringent.
The best scenario would be recipient with Anti-HBs antibody >100 mIU/ml and low immunological risk (without using induction) who can be transplanted a kidney from HBsAg positive donor,but should be kept under close follow-up.
Recipient with Anti-HBs >10mIU/ml and donor HBsAg positive: If donor is HBV DNA positive, prophylaxis in form of NA with or without HBIG would be needed
Recipient with Anti-HBs <10mIU/ml and donor HBsAg positive: If donor is HBV DNA positive, the transplant should be avoided. If going ahead with transplant, prophylaxis in form of NA with or without HBIG should be offered.
I think it should be considered since there is a limited pool of donors and the recipient must be advised of the same.
close follow-up must be done and liver function tests and sees if there are any signs of positive replications.
Appropriately selecting recipients and effective post-transplantation immunoprophylaxis significantly reduce the risk of hepatitis B viral reactivation. so based on the article and guidelines it can be used.
Yes ,With shortage of donors and waiting in transplant risk . a Carefully selected donors
will be considered or at least those with hepatitis b infection with both HBIG and antiviral
cover.
if HBV PCR negative and HBsAg positive with anti-HBsAg antibody at least 10 can be accepted if there is unavailable donor or staying long time on dialysis and no other available option
I would try to consider HBV-positive donor if (though the level of evidence is low – level 5 and guidelines recommend against such donation)
Yes. even week evidence does not mean that I cannot accept HBV+ donor, as I can follow preventive measures suggested in the article, with closed follow up. Also, sometimes I need urgent transplantation for those with no access and no suitable donor
The presence of positive HBsAg in potential organ donors should not preclude the use of kidney organs. Several additional steps and experienced transplant teams are specifically required to prepare waiting list candidates who are willing to receive a kidney from such donors. Target recipients include those with exhausted vascular access for hemodialysis, patients with ongoing uremia despite adequate dialysis prescription, and patients who cannot remain in the dialysis treatment (hemodialysis or CAPD) due to any reason. The second group is the recipients with positive HBsAg. The third group is patients being registered as active waiting list who have waiting time longer than the median time to receive a kidney in each national society.
Potential recipients should be fully informed and consent must be obtained. In addition, all potential recipients should be vaccinated that aim to achieve anti-HBs at least > 10 mIU/mL. The potential recipients should not have HCV coinfection nor other cause of chronic liver disease which may worsen after kidney transplant. All recipients of HBsAg (+) donors should receive anti-viral medication, especially in the situation when the result of HBV DNA cannot be obtained before actual transplantation. HBIG may be considered for recipients with non-protective anti HBsAb level and/or in the situation of unknown HBV DNAemia of the donor. It is an ethical challenge to allocate kidneys from donors with positive HBsAg to potential recipients with anti-HBs < 10 IU/ml. In our opinion, this treatment option should be limited to recipients with urgent criteria under a careful management that includes HBIG, antiviral medication and a careful protocol.
In order to expand the pool of donation
They proposed this criteria for HBV infected donors
Level of evidence 5
1. Please summarise this article in your own words
Ø Screening test for HBV infection in organ donors
1. Screening for HBV infection usually relies on a panel of serologic tests. The test for HBsAg is widely distributed. However, it can fail to detect disease during a 35-44 d window period after inoculation or occult infection defined as detectable viral DNA in absence of HBsAg
2. In acute hepatitis B infection, immunoglobulin M (IgM) antibody to hepatitis B core antigen (IgM anti-HBc) becomes positive after 4 wk to 6 wk of exposure indicating recent infection and active viral replication
3. whereas total hepatitis B core antibody (anti-HBc) appear at the onset of symptoms and persists for life.
4. Hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) are additional tests to identify viral replicative activity as HBeAg positivity which indicates active viral replication (i.e., usually a viral load > 10000 IU/mL).
5. In contrast, anti-HBe positivity indicates the presence of the non-replication phase (i.e., a viral load < 10000 IU/mL).
6. Lastly, hepatitis B antibody (anti-HBs) is a marker of immune status due to either naturally- or vaccine-acquired immunity
Ø Risk of HBV transmission and infection after kt
The risk of donor-transmitted HBV infection is lower in kidney transplant recipients compared with liver transplant recipients with similar serologic marker positivity. Donors with HBV infections are generally categorized into two groups according to their serologic status. The first donor group is the anti-HBc positive group in which the rate of transmission appears to be negligible according to the recipient’s protective immunity status. The overall seroconversion rate was 3.24%. The second donor group is the HBsAg positive group where the HBV transmission remains a challenging problem.
In principle, the recipients who received kidneys from donors with hepatitis B should have protective anti-HBs. Several guidelines and studies have suggested that an antiHBs > 10 mIU/mL was protective.
Ø Monitoring of HBV infection after transplantation:
For kidney transplant recipients, The American Association for the Study of Liver Diseases (AASDL) suggested periodic assessment of serum ALT, HBV DNA, and HBsAg during immunosuppressive therapy. Reactivation of HBV infection was defined by detectable HBV DNAemia or positive HBsAg seroconversion. In addition, hepatitis flare was defined by rising of serum ALT more than 3 times the baseline level and > 100 U/L with evidence of hepatitis B reactivation. every 3 mo for at least 12 mo post-transplantation. Subsequent management was based on the evolution of test results over the first year
Ø The role of prophylaxis therapy:
Anti-HBs play a key role to minimize the risk of HBV transmission. Hepatitis B vaccination should be given to naïve recipients or previously immune recipients who have anti-HBs concentration below 10 mIU/mL Also, the KDIGO guideline suggested a concentration of Anti-HBs below 100 mIU/mL can be rapidly lowered down to a non-protective level and may require a booster dose at this step
Antiviral medications (nucleos(t)ide analogues) and HBIG are Another modality to prevent HBV transmission via kidney transplant organs . HBIG provides passive immunity for a high concentration of anti-HBs that are aimed to act as neutralizing antibodies to HBV
Ø Long term outcomes and survival:
· Regarding HBsAg (-) anti-HBc (+) donors, historic studies found that there were no HBsAg seroconversion and no excess risk of morbidity and graft failure
· The amount of information on KT from HBsAg (+) donors is much less than antiHBc (+) donors. However, the results of long-term outcomes being reported showed favorable outcomes when compared with donors with no markers of HBV with proper prophylaxis regimen
· result of HBsAg (+) donor to anti-HBs (> 10 mIU/mL) recipient reported a ten-year actuarial graft survival rate of 84.6% and patient survival rate of 92.8% (with no hepatitis and hepatoma) provided that the recipients received no induction therapy
Ø Risk benefit of transplantation and proposed criteria for HBsAg (+) donor utilization
with careful individual risk and benefit assessment, these organs may be utilized safely and serve as an alternative treatment to shorten waiting time rather than stay on a usual transplant waiting list. Shortened waiting time was also beneficial in improving 10-year graft survival in both living and deceased donor KTs Moreover, recipients can benefit from excellent graft survival without excess risk of liver disease as aforementioned.
What is the level of evidence provided by this article?
Level 5
Will you accept living or deceased donations from HBV-positive donors?
Living donation, no
Deceased donations, yes but after specific criteria
INTRODUCTION :
There is an organ scarcity since there are considerably more ESKD patients waiting for KT than there are available organs worldwide. Due to this significant obstacle, the waiting list pool’s patient death rate has increased, resulting in a longer waiting period .
In the Americas, the prevalence of chronic HBV infection ranges from 0.4% to 1.6%, in Europe it ranges from 1.2% to 2.6%, in Southeast Asia it ranges from 1.5% to 4.0%, in the Eastern Mediterranean it ranges from 2.6% to 4.3%, in the Western Pacific it ranges from 5.1 to 7.6%, and in Africa it ranges from 4.6% to 8.5% .
Current recommendations state that there is a growing trend toward using non-liver organs from total hepatitis B core antibody-positive [anti-HBc (+)] donors in any recipient, regardless of HBV immune status, without prophylaxis because there is such a little chance of de novo infection. However, the use of kidneys from donors who have HBsAg (+)—positive for hepatitis B surface antigen—remains debatable, and it is typically advised that such organs be rejected.
RISK OF HBV TRANSMISSION AND INFECTION AFTER KT :
Donor factors :
Compared to liver donors, the danger is reduced for kidney donors
Awareness of potential HBV reactivation in the immunocompromised host has increased as a result of the discovery of persisting HBV viral genome in the liver and peripheral blood mononuclear cells of patients with acute and chronic HBV infection after the clearance of HBsAg in the blood
When evaluating the risk of HBV transmission from the donors, significant behavioural risk factors for HBV (and other concomitant diseases like HIV and HCV) should be thoroughly evaluated.
In general, two categories are distinguished between donors who have HBV infections based on their serologic status. According to the recipient’s level of protective immunity, the first donor group—those who have tested positive for anti-HBc—seems to have a minimal incidence of infection.
The HBsAg positive group is the second donor group, and HBV transmission in this population continues to be a difficult issue[5]. There is more intriguing material available now on using kidneys from HBsAg (+) donors.
Recipient factors:
An anti-HBs > 10 mIU/mL was considered protective
Clinical signs of HBV infection are not always the result of HBV transmission
Both kidney transplants from anti-HBc (+) and HBsAg (+) donors were associated with subclinical infection that showed up as anti-HBc seroconversion in recepients
According to geography
the predominant genotype in North America is A, B in Europe, C in Asia and Australia, and D in the Middle East and Central Asia,
MONITORING OF HBV INFECTION AFTER TRANSPLANTATION :
The (AASDL) recommended routine monitoring of blood ALT, HBV DNA, and HBsAg levels when receiving immunosuppressive medication. Detectable HBV DNAemia or a positive HBsAg seroconversion were used to identify reactivation of the HBV infection. Additionally, a hepatitis flare was identified by a rise in serum ALT that was greater than three times the baseline level and greater than 100 U/L, together with signs of hepatitis B reactivation.
THE ROLE OF PROPHYLAXIS THERAPY :
Patients who have never had the hepatitis B vaccine or who have received it before and whose anti-HBs concentration is less than 10 mIU/mL should receive it.
If anti-HBs were discovered to be less than 10 mIU/mL, KDIGO proposed re-evaluating anti-HBs yearly and delivering a booster immunization.
Antiviral medications (nucleos(t)ide analogues) and HBIG :
It was discovered that HBIG and antiviral together performed better than HBIG or antiviral alone
The most widely used prophylactic drug in the world is lamivudine However, a tiny proportion of lamivudine-resistant cases of hepatitis B limited its effectiveness. Consequently, other medications with a strong genetic barrier, including entecavir, were thought to be a preferable choice
What is the level of evidence provided by this article?
V
Kidney transplant from donors with hepatitis B: A challenging treatment option
Scarcity of the donor has been apparent although the benefit of KT in comparison with remaining on dialysis. Active HBV infection was considered a contraindication to donation previously
Cases of fulminant hepatitis after transplantation from donors who were HBsAg and HBeAg positive has been reported. Chronic HBV is not uncommon and its prevalence from 1.2-2.6% in Europe and highest about 4.6-7.6% in Africa.
Donors should be screened for HBV (HBs Ag and anti-HBc Ab)
Screening Test For HBV Infection In Organ Donors
Risk Of HBV Transmission And Infection After KT
Donor factors and the role of HBV DNA
Recipient factors and the role of protective immunity
Antiviral prophylaxis includes NA and HBIG.
Use of prophylaxis depends on the donor and recipient factors.
The long-term graft and patient survival rates in donors with HBsAg positivity have shown to be favourable.
The proposed criteria for utilizing HBsAg positive donors is in 3 settings:
Level of evidence is V.
LRKT-I will accept donor with HBsAg positive recipient, treated untilHBV DNA negative and no cirrhosis.
For cadaveric donation- it depends on the KTR, and centre experiences. In Our centre -patients always refuse HepB donors.
Kidney transplantion is the best theraputic choice for ESRD patients offering better survival and quality of life compared with dialysis and being on waiting list for long time , but due to shortage of donor pool , the use of extended criteria donors including HBV infected donors has increased. HBV is endemic in many countries and non liver donation from HBV infected patients is increased but requires careful assessment of donor risk , proper recipient selection, clinical assessment, adjust IS protocol and careful monitoring post transplantion
In order to solve the global shortage of kidney donor pool , HBV infected kidneys could be considered under certain circumstances as assessing donor and recipient risk ( via serological tests , NAT and HBV DNA monitoring) of active HBV infection , immunization status of the recipient, tailor IS protocol, adequate post transplant prophylaxis and monitoring of HBV status.
Screening for HBV include
– HBs Ag : most commonly used screening test indicating recent infection,false negative results may occur at window phase
– HB e Ag + : indicate active viral infection.While Anti HB e Ab indicate low viral replication if <10000
– HBc Ab + ve Ig M : indicate active viral replications.
The most commoly used screening tests are
1) HBs Ag , Anti HBc Ab .
2) NAT : Is more sensitive than serological test
3) HBV DNA PCR
The risk of HBV transmission after kidney transplantion is lower than that’s of the liver transplant. For kidney transplantion from HBV infected donor , the recipient should have anti HBs Ab at protective level that’s> 10 m IU /ml. It should be noticed that recieving non liver graft from HBV infected donor doesn’t always result in active HBV infection in the recipient specially if the recipient was protected with anti HBs level >10 mIU/ml.
The definition of active HBV transmission in recipient is variable , depending on immune status of the recipient where active HBV infection could be diagnosed with positive seroconversion of HBs Ig M and HBc Ig M appearance and HBV DNA detection in recipient serum.Yet , estimating the rate of HBV transmission is difficult, this may be due to HBV polygenucity and variable level of anti HBs Ab required to produce immunity among different genotypes.
Monitoring of disease transmission
AASLD recommended frequent monitoring of the kidney recipients with LFT specially ALT and HBV DNA and HBs Ag , the optimal frequency of monitoring was not defined but Infectious Disease Community of Practice of the American Society of Transplantation recommended monitoring every 3 months for 12 months post transplant.
Prophylactic protocols
KDIGO recommend HBV vaccination for all kidney recipients who are not previous vaccinated or have low HBs Ab level and also booster dose of the vaccine for CKD patients with anti HBs titre <100m IU/ml for fear of immunesenscences in patients with renal impairment.
Administration
As initial 3-4 vaccine series to achieve anti HBs level >10 m IU/ml .
Booster dose of 3 more doses for patients who didn’t achieve the desirable protective level.
2- other protective strategies include using antiviral medications as nucleoside analogues and HBIG in combination , yeilding better results than septated.
Longterm out come of kidney graft transplantion from HBV infected donor
1- From donor with HBs Ig G – ve and anti HBc + ve : long term follow up revealed no increase in HBV sero conversion and patient and graft survival were comparable to HBV naive donors .While a fewer studies evaluated the outcome of grafts from HBs Ag + ve donors to HBs -ve donors , but studies including 412 donors revealed good results.
Conclusions
HBV infected grafts could be used safely for HBV negative recipient under certain conditions including assessment of donor and recipient risk for HBV reactivation , maximize the immune protective status of the donor and close monitoring of liver functions specially ALT and HBV status .
Levelof evidence : 5
In our center ,we would accept HBV positve donor only for HBV positive recipient.
Potential HBV positive donors can donate following detailed counselling; with strict criteria.
The best process would be recipient with Anti-HBs antibody >100 mI U/ml9immune) and low immunological risk, who can be transplanted a kidney from HBsAg positive donor ,but should be kept under close monitoring.
Recipient with Anti-HBs >10mIU/ml and HBsAg positive donor : If donor is HBV DNA positive, prophylaxis in form of NA with or without HBIG would be given.
Recipient with Anti-HBs <10mIU/ml and donor HBsAg positive: If donor is HBV DNA positive, transplant should be declined If going for transplant, prophylaxis in form of NA with or without HBIG should be implemented.
Due to the gab between increase in demands to kidney donors and few supplies ,expanded kidney criteria donation is more acceptble now adays.
This article discuss the beniefit and risk of getting kidneys from HBV virus donors
Screening :
The article suggest that all serologic tests for HBV (HBsAg, anti-HBc, HBeAg, antiHBe) as well as other essential infectious markers are done at the donor hospitals. In parallel, a universal NAT test for HBV (usually in combination with HIV and HCV) should be conducted at the central or regional organ allocation center and the result should come back before or at the time of organ retrieval.
Risk factors for HBV transmission :
Anti HBC positive have low risk of transmission
Anti HBC negative have high risk
HBeAg with positive DNA test have high risk
also recipent play a role in risk stratification
If they had been v accinated and the antibodies level usually more than 10 is protective .
Early monitoring of liver function and serologies after transplantation is important .
Despite resolved infection in some patients ,reinfection is not uncommon .
Prophylactic therapy with vaccination and HBIG is indicated in some patients espessialy high risk patient
Antiviral therapy maybe used in high risk patients.(positive HBE ag -positive HBV DNA ).
There are no definitive criteria for HBV donor patients ,however low risk patients maybe accepted as donors to increase donor pools with carfull monitoring .
2- What is the level of evidence provided by this article?
level 5
3- Will you accept living or deceased donations from HBV-positive donors?
Accepting for kidney donation not for liver donation in this circumstances :
1-Negative HBE AG
2Negative HBV DNA.
3-Normal liver function test
4Anti HBC antibodies more than 10
4-early monitoring of liver function test .
Introduction
The prevalence of chronic HBV infection depends on the difference of geographic areas, it is estimated by 0.4% to 1.6% in the region of the Americas, 1.2% to 2.6% in Europe, 1.5% to 4.0% in Southeast Asia, 2.6% to 4.3% in the Eastern Mediterranean, 5.1 to 7.6 % in the Western Pacific, and 4.6% to 8.5% in Africa. Prophylactic therapy as well as frequent monitoring decreased the associated risk of HBV transmission to allow expansion of donor pool especially in endemic areas.
Recently, guidelines are reconsidering accepting non-liver organs from total hepatitis B core antibody-positive [anti-HBc (+)] candidate donors to be used in any recipient regardless of HBV immune status without prophylaxis based on the negligible risk of de novo infection.
This article is concerned by evaluation of the risk of HBV transmission, liver related morbidities, and the possible outcomes of renal graft derived from HBsAg (+) donors.
Screening for HBV infection
HBsAg test despite being available, however the detection limit of it is defective in the context of 35-44 day window interval after inoculation or occult infection termed as detectable viral DNA. Serologic screening test for previous HBV exposure is mainly performed by the anti-HBc. Cases with established acute hepatitis B infection, display immunoglobulin M (IgM) antibody to hepatitis B core antigen (IgM anti-HBc) that becomes positive after 4 wk to 6 wk post exposure. It is indicative of recent infection and active viral replication, consequently total hepatitis B core antibody (anti-HBc) appear at the onset of symptoms and remains positive for lifelong.
Hepatitis B antibody (anti-HBs) is a screening marker of immune status either naturally or vaccine-acquired immunity. Hepatitis B e antigen (HBeAg) test signifies positive viral replicative activity upon exceeding a viral load of 10000 IU/mL. While anti-HBe positivity suggests the non-replication phase of a viral load less than 10000 IU/mL.
In deceased renal donation, HBs Ag and anti-HBc can be approved as cost-effective screening tools. Recent techniques were adopted to improve the sensitivity of screening tools in the form of nucleic acid testing (NAT) for HIV/HCV/HBV multiplex. It is a wise option for donor screening test as it shortens the window period to 20-22 days.
Risk of HBV transmission and infection
Donor factors and the role of HBV DNA
It is proposed that renal donation has less incidence of HBV transmission compared to hepatic donation with the same serologic marker positivity owing to the hepatotropism phenomenon of HBV receptor recognition in the liver tissues.
The identification of persistent HBV viral genome in the liver and peripheral blood mononuclear cells of patients in cases of both acute and chronic HBV infection after the clearance of HBsAg in the blood might explain the possibility of HBV reactivation in the immunocompromised host. This is primarily due to the incorporation of HBV DNA within the patient’s DNA in the form of covalently closed circular DNA and total DNA in the serum of patients with negative HBsAg.
Living HBsAg (+) donors can be possible donate to anti-HBs (+) recipients with protection who after exclusion of abnormalities of liver function, history of liver disease within the previous 28 days, and non-living in the area of mutation strain of HBV. HBeAg and anti-HBe are to be routinely checked in HBsAg (+) donors to confirm low infectivity of HBV prior to renal transplantation. The recent era after advances in the antiviral medications of HBV provided more hope for donor pool expansion. It was responsible for accomplishing a functional cure of HBV in renal transplant recipients.
The assumed protocol of therapy utilized the use of both hepatitis B immunoglobulin (HBIG) and antiviral medication as prophylaxis treatment. The results were satisfactory regarding excellent graft and patient survival without further HBV transmission.
A study conducted by Chancharoenthana et al demonstrated that renal transplants derived from HBsAg(+)/HBV DNA (-) (< 20 IU/mL) donors to 20 immune recipients (anti-HBs > 100 mIU/mL) were found to safe in addition to no HBV viremia, hepatitis or death have been encountered even in the absence of antiviral prophylaxis.
Recipient factors and the role of protective immunity
A titer of anti-HBs > 10 mIU/mL was considered to be protective to accept renal transplantation from HBV grafts. It is also concluded by previous studies that even in the presence of evidence of HBV transmission by the renal grafts no clinical manifestations of HBV infection can be encountered.
This was confirmed also by Tuncer et al and Asuman et al that no de novo HBV infection or active liver diseases were associated.
The genotype prevalence by region is A in North America, B in Europe, C in Asia and Australia, and D in the Middle East and central Asia. The advancement of HBV vaccines even it is against genotype A2, offered cross-protection against other genotypes. The accepted antibody concentration should not be less than 50 mIU/mL.
Monitoring of HBV infection after transplantation
The American Association for the Study of Liver Diseases (AASDL) recommended frequent evaluation of serum ALT, HBV DNA, and HBsAg during immunosuppressive therapy post renal transplantation every 3 months for at least 12 months. Reactivation of HBV infection was established after detection of HBV DNA viremia or HBsAg positive seroconversion.
Caution is critical after using intensive immunosuppression particularly rituximab as reactivation might occur. The possibility of HBV reactivation was the focus of Kim et al work, they studied HBV reactivation in a cohort of 499 renal transplant recipients. They observed that the rate of HBV reactivation incidence was only 2% after follow-up during 6.7 years at a median time of 2.8 years. Reactivation was evident in certain situations whereas intensification of immunosuppressive therapy was mandatory as recipients with ABO incompatibility, or those who received plasmapheresis or received acute rejection therapy, and patients who received induction therapy with rituximab.
The role of prophylaxis therapy
Vaccination and revaccination protocol
Here comes the important recognition of Hepatitis B vaccination in naïve recipients or previously immune recipients having anti-HBs concentration below 10 mIU/mL. The KDIGO guidelines even doubted this limit suggesting administration of booster dose for concentration of Anti-HBs below 100 mIU/mL, as it can be rapidly lowered down to a non-protective level after transplantation.
Difference is mainly dependent on impaired response in CKD to viral infection in patients. Insufficient response to HBV occurs by suppression of both memory T and B cells, leading to low or absent antibody titer. Thus, monitoring of anti-HBs concentration should be done on annual basis with the administration of booster dose of vaccine upon need. Higher levels of antibody concentration was evident in patients who had short duration of dialytic support as well as positive anti-HBc status prior to transplantation.
The last CDC guidelines recommended RecombivaxTM vaccine at 0, 1, and 6 months or Engerix BTM at 0, 1, 2, and 6 months, yet achieving full immunization of ESRD is still doubted. Various strategies have been adopted to improve vaccine efficacy depending on type, dose, route of administration and developing vaccines specifically derived from common genotype in the specific geographical area are being tried.
Antiviral medications (nucleotide analogues) and HBIG
HBIG allows passive immunity to take place using high concentration of anti-HBs consequently neutralizing antibodies to HBV. Combination regimen of both lines was found superior to using HBIG or NA alone. Nucleotide analogues (NAs) are antiviral medications that directly suppress HBV virus replication.
High genetic barrier NA entecavir combined with HBIG was found superior to lamivudine combined with HBIG in the prevention of recurrent HBV infection. Cases known to be HBsAg (+)/HBV DNA (+) donor according to different studies are advised to administer NA prophylaxis with or without HBIG.
Long term outcomes and survival
This study revealed that the result of HBsAg (+) donor to anti-HBs (> 10 mIU/mL) recipient had a ten-year graft survival rate of 84.6% and patient survival rate of 92.8% (with no hepatitis and hepatoma) assuming that all the recipients had no induction therapy.
Patients who developed HBV DNA viraemia are primarily linked to either lamivudine resistance or non-adherence to treatment.
The criteria for utilization of kidneys from donors with HBsAg positivity is still unclear. This study suggests to classify recipients into three groups; patients who have urgent need to get renal transplants, recipients with positive HBsAg, and the last group are those who have been on longer waiting list duration.
The recipients have to decide to accept by themselves after being fully informed. Consent must be taken besides prior vaccination to achieve anti-HBs at least > 10 mIU/mL. Careful selection of the recipients as they should not have HCV co-infection or any other cause of chronic liver disease. All recipients of HBsAg (+) donors must receive antiviral medication. HBIG is considered upon need for recipients without protective anti HBsAb level or situations of unknown HBV viremia of the donor.
Recently the AASDL recommends surveillance in cases of HBV viremia by evaluation of HBV DNA, ALT as well as staging with biopsy or elastography to identify the potential risk of advanced fibrosis or cirrhosis in order to assess the need for simultaneous liver Kidney transplantation.
Level of evidence is V.
Our centre doesn’t accept HBV donation from living donors. Deceased donation is still not feasible in our country.
Please summarize this article in your own words
This article reviewed the evidence of renal transplants from donors with HBV.
HBV markers include the following: HBsAg, Anti-HBc, HBeAg, Anti-HBe, Anti-HBs.
NAT can be used for donor screening to increase sensitivity of screening tests and it reduces the window period to 20-22 days instead of 35-44 days with HBsAg.
NAT (Nucleic acid test) is expensive, it requires a lot of technical proficiency, and it takes 8 hours as long turn around times. Currently, this test is gradually becoming accepted in national policies in several countries.
Transmission of HBV from donor to recipient in Kidney transplantation is lower than in Liver transplantation. Assessment of HBV transmission risk should include assessment of behavioral factors. Patients with HBV/HCV/HIV risk factors should be screened via HBsAg, HBV NAT then HBV DNA.
Donors with HBV are divided serologically into: Anti-HBc positive and HBsAg positive.
Anti-HBc positive donors carry a very low risk of transmission that depends on protective immunity of the recipient.
HBsAg positive donors carry high risk of transmission. They can donate to recipients with anti-HBs positive.Recipients with anti-HBs >10 mIU/ml have protective immunity according to several guidelines and studies like Tuncer et al.
Subclinical infection was noticed in renal transplant recipients from donors with both HBc positive and HBsAg positive.Most HBV vaccines were produced using HBV genotype A2.
Follow up of renal transplant recipients from HBV positive donors include the following:
1- Periodic ALT, HBV DNA, and HBsAg.
2- HBV DNAemia or positive HBsAg seroconversion indicates Reactivation.
3- Rising ALT more than 3 times of the baseline or above 100 U/L with evidence of HBV reactivation indicates Hepatitis flare.
4- Check AST, HBsAg, and HBV DNA every 3 months in the first-year post transplantation.
5- Lifelong follow up is needed for renal transplant recipients from HBV positive donors.
6- Resolved infection can be reactivated with heavy immune suppressive therapy especially Rituximab.
As per KDIGO guidelines: Vaccination for recipients or immune-suppressed patients with anti-HBs below 10 mIU/ml, they need booster dose if anti-HBs below 100 mIU/ml. anti-HBs should be monitored yearly.
Reactivation after kidney transplantation was reported in those with anti-HBs below 100 mIU/ml. Combined HB-IG and antiviral neutralizing antibodies to HBV was superior to either alone.
Organs from HBsAg positive donors can be donated safely after informed consent of the recipients who should be vaccinated to achieve anti-HBs more than 10 mIU/ml.
Recipients should not have HCV co-infection and no other cause of chronic liver disease.
Recipients should receive anti-viral medication if HBsAg + donor. HBIG is given if recipients don’t have protective anti- HBsAb.
What is the level of evidence provided by this article?
Level V
Will you accept living or deceased donations from HBV-positive donors?
this study carries level V evidence.
The decision to accept or refuse donation from HBV positive donors should be individualized. Donors with HBV positive serology can be accepted for donation. However, in our center we don’t accept donation from these donors.
Please summarize this article in your own words
Screening tests are:
Risks of HBV transmission and infection in kidney transplantation:
v kidney donors have lower risk compared to liver donors.
v Donors with anti-HBc positive have low rate of transmission appears according to the recipient’s protective immunity status.
v Living HBsAg (+) donors can be donate to anti-HBs (+) recipients who do not have any history of liver disease, abnormalities of liver function within the previous 28 days. However, before transplantation HBeAg and anti-HBe are routinely checked in HBsAg (+) donors to ensure a low infectivity rate.
v Donation from HBsAg (+)/HBV DNA (-) (< 20 IU/mL) donors to immune recipients (anti-HBs > 100 mIU/mL) was found safe and not associated with HBV viremia in some studies.
v kidneys recipients from donors with hepatitis B should have protective anti-HBs (anti-HBs > 10 mIU/mL was protective).
v HBV transmission can occur with no clinical evidence of HBV infection.
MONITORING: Post-transplant monitoring in form of Serum ALT, HBV DNA PCR and HBsAg should be done once in 3 months for 1 year, with later monitoring as per the test results. Any episode of intensive immunosuppression especially rituximab increases the risk of disease reactivation.
Prophylaxis therapy by IM vaccination (3-4 doses) for all potential recipients and those with Anti-HBs antibody < 10 mIU/ml should be done. If response is inadequate, SC route can be used. The target is to achieve anti-HBs antibody >100 mIU/ml. Anti-HBs antibody should be annually assessed, if it dropped <10 mIU/ml, patients should be revaccinated.
Antiviral prophylaxis includes nucleoside and nucleotide analogues (NA) and HBIG. Use of prophylaxis depends on the donor and recipient factors.
What is the level of evidence provided by this article?
Review article, level 5 evidence
Will you accept living or deceased donations from HBV-positive donors?
– HBsAg positive recipients
– long waiting period on the wait-list
– Urgent need of transplant eg: exhausted vascular access.
This article summarize the current evidence regarding the use kidneys from HBsAg (+) donors with an emphasis on the risk of HBV transmission, liver related morbidities, and the outcomes of KT
Screening for HBV infection usually relies on a panel of serologic tests:
· HBs Ag: it can fail to detect disease during a 35-44 d window period after inoculation or occult infection
· Anti-HBc IgM antibody : indicating recent infection and active viral replication
· Total hepatitis B core antibody: appear at the onset of symptoms and persists for life
· Hepatitis B e antigen and e antibody: active viral replication and presence of the non-replication phase respectively
· Hepatitis B antibody: marker of immune status due to either naturally- or vaccine-acquired immunity isolated anti-HBc: occur in the early window period of acute hepatitis B , with resolved HBV infection with waning of anti-HBs titer , a false positive test and an occult chronic HBV infection with low viremia and undetectable HBsAg.
In deceased kidney donation, HBs Ag and anti-HBc are the usual tests used in addition to the donor history. In the presence of risk factors, other tests can be used.
The nucleic acid test (NAT), is a form of an HIV/HCV/HBV multiplex donor screening test. it shortens the windows period , but there are concern regarding its cost effective. This test is gradually becoming accepted in national policies in several countries.
Donor derived transmission of hepatitis B virus is affected by risk factors and protective factors. Risk factors are the limitation of method of viral detection, organism virulence, the viral load and the immunosuppressive drugs. While protective factors are first the prophylaxis in form of vaccine, IG and nucleotide analogue, and second the immunity in form of anti HBV s level and recipient immunity. If the HBV antigen positive donor has positive e antigen and HBV DNA then he should be discarded. If e AG is negative , we would assess the recipient risk of infection by assessing the level of anti HBVs to define if the duration of treatment. If the HBV DNA is positive in the presence of negative e and low anti HBVs, the organs are used for selected patients.
the level of evidence is V.
in endemic areas this practice carries a high risk of transmitting the infection to the recipients.
first iwill consider other test such as HBeAg HBe and HB DNA and the recipeint if he on long list and has multiacess faulre iwill counselling recipent about the risk of transmission but if there are better option iwill try to avoid if HBsAg postive if yes iwill give antiviral plus IG and close monitring in first year
summary of Kidney transplant from donors with hepatitis B: A challenging treatment optionIntroduction
The kidney transplantation challenge is the donor shortage so the solution is to expand the donor pool by using extended donor criteria organs.
Such donors included donors with hepatitis B virus infection.
These donors with hepatitis B are allocated at low risk of acquiring a donor-transmitted hepatitis B infection, prophylactic therapy, and appropriate monitoring.
According to current guidelines, hepatitis B core Ab-positive donors be used in any recipient regardless of HBV immune status.
But donors with HBsAg are controversial. The nucleic acid test for HIV,HCV, and HBV multiplex is donor screening
Screening test for HBV infection in organ donors
Screening for hepatitis HBV infection usually relies on a panel of serological tests, however, it can fail to detect the disease during the window period after inoculation or occult infection
Risk of HBV transmission and infection after kidney transplantation
Donor factors and the role of HBV DNA.
The risk of donor-transmitted HBV infection is lower in kidney transplant recipients compared with liver transplant recipients with similar serology marker positivity;
Reactivation by immunosuppression of hepatitis B can result from persistent HBV genome in the liver and peripheral blood mononuclear cells of patients with acute and chronic HBV infection after the clearance of HBsAg
The patient who has hepatitis B should be tested for hepatitis c and HIV.
Donors with hepatitis B should be into two groups according to their serologic status.
1-donor has an anti -HBc positive group in which the rate of transmission appears to be negligible according to the recipient’s protective immunity status.
2- the donor group is HBsAg positive and HBV transmission remains a challenging problem.
Kidney transplants from living HBsAg-positive donors can be donated to anti-HBsAg-positive recipients with protection who have no liver dysfunction and not living in an area with possible mutation of strain HBV.
HBe Ag and anti-HBe should be checked before transplantation.
There is a study that showed evidence of HBV transmission by the kidney graft without any clinical manifestation of HBV infection.
Immunity to hepatitis B was crucial to prevent donor-derived infection.
In kidney transplantation recipients the study of (AASDL) suggested periodic assessment of serum ALT, HBV DNA, and HBsAg during immunosuppression therapy.
Hepatitis B flares by rising of ALT more than 3 times from the baseline and more than 100u/l
Post-transplantation monitoring :
1- Liver enzymes.
2- HBsAg.
3- HBV DNA
Every 3 months for 12 months post-transplantation:
HBV reactivation can be after rituximab.
Vaccination and revaccination protocol:
Anti -HBs play a role to minimize the risk of HBV transmission.
To prevent HBV transmission the use of antiviral medication and HBIG.
HBsAg seroconversion and no excess risk of morbidity and graft failure.
All the studies highlight the benefit of expanding the donor pool by using kidneys from donors with HBsAg positive.
Conclusion
Positive HBsAg in potential donors should not preclude the use of kidney organs
Several steps experienced by transplant teams are specific. required to prepare a waiting list of candidates who are willing to receive a kidney from such donors.
level evidence 5
Summary
Introduction
Kidney transplantation is the best treatment compared to long waiting on dialysis. In order to solve the problem of donor shortage one of the important steps is to consider the usage of donors with HBV infection however a complete approach is wanted, which includes full donor risk assessment, optimal allocation to the proper recipient-suitable immunosuppressant therapy, adjusting the prophylactic therapy, and post-transplant monitoring for reactivation. in this review article they give us an overview of the available evidence about the use of HBV positive donors. Based on the evidence from the recent guidelines there is a growing tendency of accepting non-liver organs from donors with hepatitis B core antibody-positive [anti-HBc (+)] to be utilized for any recipient irrespective of HBV immune status without prophylaxis due to the insignificant risk of de novo infection. The evidence is diverse and some centers discarded organs from donors with HBs AG positive.
For HBV screening many serological tests are needed and depend on how endemic HBV infection, overall, the DD program uses HBsAg and anti-HBc screening while in the endemic area as they even use additional serological tests like HBe AG and HBe AB biomarkers which reflect the viral replication risk. The sensitivity of such serological tests is limited by low sensitivity especially in the window period as we can miss the occult infections
What is the level of evidence provided by this article?
Narrative review level 5 of evidence
Please reflect on the guidelines provided above and on your practice.
According to the evidence from the guidelines, there is growing acceptance of HBV infection donors’ however such practice should follow the local center policy taking into consideration special circumstances related to the endemic area of HBV and the recipient’s underlying risk factors in the long waiting on dialysis
in our center we decline donors with HBs Ag +VE to HBsA-ve recipient .
The risk of HBV transmission remain a challenge. To reduce the risk of transmission a comprehensive approach is required, included assessment of donor risk, viral load, proper recipient, appropriate immunosuppression regime, post-transplant monitoring.
So the donation depends on multiple factor also viral load, antibodies formation, otherwise there is no contraindication.
To prevent transmission recipient should be vaccinated, if needed can be given IVIG.
level V.
This is a narrative review study (level V) providing data on the risk of transmission of the Hepatitis B virus and its comorbidities in kidney transplant recipients.
Screening tests such as AntiHbc and HbsAg are commonly used, the first being related to the previous contact with the virus and the second its activity at some point. New tests with greater sensitivity using nucleic acid testing (NAT) and more specific depending on the patient’s status: AntiHbs to determine immunity, HbeAg disease replication, AntiHbe post replication status. In liver transplantation, this transmission is well considered, either by hepatic tropism or by established disease where the transplant was a consequence.
Recently, new treatments and greater immunopathological knowledge help to determine the stage of the disease, how to monitor the possibility of reactivation, as well as a vaccine or drug prophylaxis. Positive antiHbs determines protection, but its quantitative value can be conflicting. For monitoring, you should measure ALT, HBV DNA, and HbsAg. Reactivation has been greater, especially in those who underwent plasmapheresis or rituximab, which is very common in patients with HLA or ABO incompatibility.
Immunization in immunosuppressed patients should be performed with a double dose and four instead of three doses. Repeat if antiHbs remains below 10. Prophylaxis with Lamivudine, Entecavir, and more recently with Tenofovir alaphenyl can be used in conjunction with specific immunoglobulin HBIG depending on the immune status of the donor and recipient.
HbeAg+ and HBV DNA+ donors should be discarded
HbeAg-HBV DNA + proceed with prophylaxis. If the receptor is AntiHbs negative, add HBIG.
HbeAg – and HBV DNA – proceed with prophylaxis, being able to do HBIG if the recipient is AntiHbs negative.
The study suggests urgent transplantation, positive HbsAg recipients, and individuals who wait for a prolonged Tx (elevated cPRA).
With the new medications available and monitoring of the recipient without the need for plasmapheresis or rituximab, I would proceed with the transplant, by talking to the recipient about the risks involved and the benefits of getting off the waiting list.
Kidney transplantation is the treatment of choice for patients with ESRD. Due to increase burden of ESRD and increased number of patients on the transplantation waiting list and shortage of organ, Utilizing of kidneys from donors with hepatitis B is one of the solution, But There is a Problem of HBV transmission that can limit this.
There is a variation in the prevelance of chronic HBV infection in the world,the highest one in Africa about 4.6 to 8.5 %.
Discarding of all kidney donors with HBV infection will affect the donor pool in endemic areas .
The best utilization is the allocation of such kidneys to transplant patients at low risk of developing a donor transmitted hepatitis B infection.
There is an increasing trend of accepting non liver organs from total hepatitis B core antibody positive donors regardless HBV immune status without prophylaxis due to negligible risk of de novo infection
But the problem is with utilizing kidneys from donors with hepatitis B surface antigen positive
Screenìng test for HBV infection in organ donors
HBs Ag and anti-HBc are screenìng tools in deceased kidney donation. In endemic areas they add anti-HBe and HBe Ag to assess high viral replication and infectivity activity.
To improve sensitivity of screening test, we can do the nucleic acid test ( NAT) as screening tool .
Donors with HBV infection are classified into
1. The first group is the anti-HBc positive in which the risk of transmission is negligible.
2. The second group is the HBs Ag positive. With increased rate of transmission. Previously the trend is to discard these organs
But now may be utilized under some circumstances with some cautions.
Recipient factors and the role protective immunity
The recipient who will receive kidney from donor with HBV should have protective anti -HBs , the guidelines suggested that the level of anti-HBs more than 10 mIU/ml.
Monitoring of HBV infection after transplantation
Assessment of liver enzymes, HBsAg and HBV DNA every 3 months for at least 12 months post transplant, subsequent Monitoring according to test results.
Vaccination
Hepatitis B vaccination should be given to naive recipient or previously immune recipient who have anti HBs concentration below 10 mIU/ ml . A booster dose can be given to patients with anti-HBs below 100 mIU/ml as this level can be lowered down to a non protective level.
Antiviral medications
To prevent HBV transmission , Antiviral medication and HBIG can be used.
Long-term outcomes and survival
Donors with HBs Ag negative and anti-HBc positive has no risk of HBs Ag seroconversion and no risk of graft failure .
In donors with HBs Ag positive , the data is insufficient, but the results of long-term outcomes was favorable compared to donors with no markers of HBV with proper prophylaxis regime
The results of HBs Ag positive donors to anti-HBs more than 10 mIU / ml recipients showed that without using induction therapy ,
The ten year graft survival and patient survival were 84.6 % and 92.8% respectively.
Level of evidence 5
In living donor , I don’t accept a donor with HBV infection
In deceased donors, I will accept after careful allocation to appropriate recipient, but due to risk of transmission, recipient should be fully informed and consent must be taken, potential recipient should be vaccinated, the potential donor should not have HCV confection nor other causes of chronic liver disease
All recipients should receive anti viral medication. Good monitoring after transplantation
Level of evidence is IV
hepatitis B viral infection in America is range from 0.4 to 1.6 %
HBsAg is used for screening for hepatitis B
In deceased donor HBsAg and anti-core is accepted as screening tools
Antiviral and immunoglobulin for prevent transmission
Shortage in living donor pool is main challenge facing the renal transplantation program world wide , using HBV donors is one of the solution especially in high endemic area such as Africa (up to 8%).
Donors with HBV infections are generally categorized into two groups according to their serologic status :
1- Donors with hepatitis B core antibody-positive are safe to donate non liver organs to negative recipient (whatever his immune state to HBV), (with minimal risk of denovo infection).
2- donors with HBsAg positive group where the HBV transmission remains a challenging problem
Summary of hepatitis B serology test
general roles must be considered :
1. All recipients must be educated,counseled well due the small risk of viral transmission
2. All recipients must be vaccinated against HBV targeting anti-HBsAb > 10 mlU/L
3.No co-infection with HCV or other causes of chronic liver disease
4. All recipients of HBsAg +ve donors anti-viral prophylaxis particularly if HBV DNA result is not available before transplantation
5. HBIG should be considered for recipients with ant-HBsAb < 10 mlU/L or in case the donors viral load is not known
6. All HBVsAg +ve recipients must be referred, treated and evaluated by hepatologist
7. A protocol for monitoring, surveillance of viral replication and liver disease must be put in pace
8. Further evaluation of HBV DNA, ALT, liver biopsy or fibroscan to define the stage of fibrosis or cirrhosis may be required to assess the need for simultaneous liver-kidney transplantation
9.HBVsAg +ve donors to recipient with anti-HBsAg < 10 mlU/L only considered in urgent cases with careful management including HBIG, antiviral drugs, and careful protocol (Ethical issues ?)
Conclusion: The use of HBV positive donors requires good allocation system and choice of appropriate donor for appropriate recipient. to provide certain recipients with better quality of life than being on waiting list (prolonged dialysis duration).
Especially, those need urgent transplant as exhausted vascular access, those with positive HBV and those with very long duration on waiting list. the patient should be counseled and choose the most appropriate for him, written consent, vaccination with protective antibody titer are crucial before transplantation
2- Will you accept living or deceased donations from HBV-positive donors?
in our transplant center we didn’t have all the facility and labs to evaluate donor with HBV so we decline these donors
thanks
summary:
Kidney transplantation is the best treatment option for patients with ESRD. It is associated with decreased mortality and improved quality of life. However, organ shortage is a major barrier and it has led to prolonged waiting time and ultimately excess mortality. So, many efforts had tried to expand the donor pool, for example; using extended donor criteria organs. Such organs can be from donors with hepatitis B virus (HBV) infection. Discarding all kidneys from donors with markers of HBV infections may substantially harm the donor pool in endemic areas. Determining the optimal use of kidneys from such donors is challenging. Allocation of such kidneys to transplant candidates at low risk of acquiring a donor-transmitted hepatitis B infection, prophylactic therapy and appropriate monitoring of the recipient to eliminate the risk of HBV transmission, all these strategies increase utilization of such donor’s kidneys.
Non-liver organs from donors with hepatitis B core antibody-positive (anti-HBc (+)) can be used to any recipients regardless of HBV immune status without prophylaxis as there is negligible risk of de novo infection according to current guidelines. However, utilizing kidneys from donors with positive HBsAg remains controversial.
Screening test for HBV infection in organ donors:
Panels of serological tests are used.
1- HBsAg test is widely used, although it can be false negative in the window period after inoculation or occult infection, which is a period at which viral DNA is detectable in the absence of HBsAg.
2- Anti-HBc indicates previous infection.
3- IgM anti-HBc antibodies indicates acute infection and an active viral replication. (4-6 wks of exposure), total anti-HBc antibodies persist for life.
4- HBe Ag if positive indicates active viral replication while anti-HBe antibodies if positive indicate the presence of non-replication phase.
5- Anti-HBs antibody is a marker of immune status due to either naturally-or vaccine-acquired immunity.
Hbs Ag and anti-HBc are generally acceptd as cost-effective screening tools in case of deceased kidney donation. In addition to other donor information about important behavioral risk to assess the risk factors to acquire infection. In endemic areas, some transplant centers add anti-HBe and HBe Ag to donor screen.
Because of long window period of the infection and lack of sensitivity to detect occult infection, these tests still have limitations.
Anti-HBc is common in clinical practice, it occurs in:
1- Early window period of acute hepatitis B.
2- Resolved HBV infection with waning of anti-HBs titer.
3- False positive anti-HBc (low prevalence area)
4- Occult chronic HBV infection with low viremia and undetected HBs Ag (poor test quality/ or mutation of HBs Ag)
Nucleic acid test (NAT) has been proposed as optional donor screening test. It shortens the window period to 20 – 22 days as compared to 35 – 44 days by conventional serologic tests. But it has limitations as well, especially the cost.
However, a look-back study demonstrated adding NAT to routine screening by serologic testing enhanced the physician’s confidence in using organ with discordant results [i.e., anti-HBc(+)/NAT(-)], and adding NAT led to a gain in overall organ utilization after policy implementation. Now the test is gradually becoming accepted in national policies in several countries.
Risk of HBV transmission and infection after KT:
Donor factors and the role of HBV DNA.
The risk of donor- transmitted HBV infection is lower in kidney transplant recipients than liver transplanted recipient. As viral genome persists in the liver and peripheral monoclonal cells.
Donor with HBV are classified into two groups according to serological status:
1- Anti-HBc positive group in which the transmission appears to be negligible. ( anti-HBc seroconversion).
2- HBsAg positive group where the HBV transmission remains a challenging problem.
KT from living HBsAg (+) donors can be donated to anti-HBs (+) recipients with protection.
HBeAg and anti-HBe should be checked routinely in HBsAg (+) donors to ensure a low infectivity rate of HBV before performing KTm because fulminant hepatitis B had been reported from donors with HBsAG (+)/HBeAg (+).
Two studies reported excellent outcomes of transplanting kidneys from HBsAg (+)/ HBV DNA (-) to recipients with anti-HBs > 10 m IU/m L.
Recipients factors and the role of protective immunity
Most guidelines and studies suggest that an anti-HBs > 10 m IU/ml was protective, although, HBV transmission may not necessarily lead to clinical evidence of HBV infection. There had been no evidence to support high anti-HBs concentration > 100 m IU/ml in protection against HBV transmission.
There was variation in the definitions of HBV transmission via transplantation of non-liver organs. In the setting of kidney transplants from HBsAg (-) donors to immune protective recipients (Anti-HBs > 10 mIU/mL), definitions of HBV transmission may include anti-HBc IgM seroconversion, HBsAg seroconversion, and HBV DNAemia.
Monitoring of HBV infection after transplantation:
Periodic assessment of serum ALT, HBV DNA, and HBsAg during immunosuppressive therapy.
Reactivation of HBV infection was defined by detectable HBV DNAemia or positive HBsAg seroconversion.
Hepatitis flare was defined by rising of serum ALT > 3 times the baseline level, and > 100 U/L with evidence of hepatitis B reactivation.
The optimal frequency of monitoring for HBV infection in a susceptible individual is still varied. The Infectious Disease Community of Practice of the American Society of Transplantation advised monitoring liver enzymes, HBsAg, and HBV DNA every 3 mo for at least 12 mo post-transplantation.
In one study; HBV reactivation was observed at the median time of 2.8 years (range 1.4-11.5). A high incidence of reactivation was observed in recipients with ABO incompatibility, who received plasmapheresis, received acute rejection therapy, and received induction therapy with rituximab.
These findings provided evidence that HBV reactivation can occur at any time after KT. As such, HBV reactivation may be the consequence of either donor derived infection or the resolved recipient infection.
THE ROLE OF PROPHYLAXIS THERAPY
Vaccination and revaccination protocol
Anti-HBs has important role in minimize the risk of HBV transmission. HB vaccination should be given to naïve recipients or previously immune recipients who have anti-HBs concentration below 10 m IU/ml.
KDIGO guideline suggested a concentration of anti-HBs below 100 m IU/ml can be rapidly lowered down to a non-protective level and may require a booster dose at this step. Anti-HBs concentration should be monitored at least yearly because they are likely to wane over time, and so, further booster dose of vaccine may be required.
CDC recommended Recombivax vaccine at 0,1, and 6 mo or Engerix B at 0, 1,2, and 6 mo. In addition, use of a vaccine specifically derived from common genotype in specific geographical area will add a layer of protection. Despite a debate, there was a suggestion to keep anti-HBs concentration > 100 m IU/ml. KDIGO suggested revaccination annually and administering re-vaccination if anti-HBs were found to be 10 m IU/ml.
Antiviral medications (nucleos(t)ide analogues) and HBIG
HBIG provides passive immunity for high concentratin of anti-HBs that are aimed to act as neutralizing antibodies to HBV. Most HBIG were used in combination with antiviral nucleos(t)ide analogs (NAs0 that aim to prevent recurrent infection of HBV after liver transplantation. combination of them are better than either alone. Optimal HBIG was not clearly known.
Lamivudine was the most used prophylaxis agent globally. But it has some resistant cases. Entecavir were considered as a better alternative. Especially for patient at risk of lamivudine resistance, such as those who received kidneys from donors previously treated with lamivudine.
Serological markers may have some impact on the choice to prescribe antiviral medications.
. Anti HBs (> 10 mIU/mL) and positive recipients can receive kidney transplants from anti-HBc (+) donors without a need for prophylaxis antiviral medications.
naïve recipients who received kidneys from anti-HBc (+) donors should receive lamivudine prophylaxis without HBIG for at least 1 year.
HBs Ag (+) donors, recipients with protective anti-HBs (> 10 m IU/ml) were considered suitable to receive the allocation of kidney grafts. And further risk should be assessed by result of the NAT test and HBV DNA measurement. If NAT was negative and HBV DNA was undetectable, preventive strategies varied from no NA prophylaxis (if no potent induction used) or prescription of NA alone without HBIG.
If HBV DNA was not measured by suitable test, NA may be prescribed to decrease risk of transmission.
In the setting of HBsAg (+)/HBV DNA (+) donor, most authors prescribed universal NA prophylaxis with or without HBIG as a prophylaxis regimen among patients with different levels of anti-HBs concentration
Especially in those receive potent induction to decrease risk of transmission. HBIG dose is not clearly known.
Use of HBsAg (+)/DNA (+) donors to recipients with naïve or anti-HBs < 10 m IU/ml was the group of the highest risk. Even with the use of prophylactic NA or HBIG or combination. Thus should be restricted only to urgent KT (as exhausted multiple vascular access, )
The use of HBsAg positive donors to recipients with HBsAg positive serology. A few studies have reported favorable outcomes of this treatment option provided that the recipients received antiviral treatment before transplantation. specially in those receive rituximab as either induction or anti-rejection therapy.
Long term outcome and survival:
1- HBsAg (-)/ Anti-HBc (+) donors, there were no HBs Ag seroconversion and no excess risk of morbidity and graft failure. So tese can be transplanted safely to patients with ESRD
2- HBsAg + donor to anti-HBs (> 10 m IU/ml) recipient reported 10 years graft survival rate of 84.6% and patient survival rate of 92.8% provided that no induction therapy.
3- Most HBV DNAemia being observed were usually observed with lamivudine resistance or non-adherence.
RISK BENEFIT OF TRANSPLANTATION AND PROPOSED CRITERIA FOR HBsAg (+) DONOR UTILIZATION:
Organs from HBsAg (+) donors are generally suggested to be discarded, however, with careful individual risk and benefit assessment, these organs may be utilized safely and so attributed to shorten the waiting time to transplantation by increasing the organs pool.
The authors describe their proposed criteria to define three groups of potential recipients:
1- Patients with urgent need to receive KT (exhausted vascular access, ongoing uremia despite adequate dialysis, and patients who cannot remain in the dialysis treatment due to any reason.
2- The recipients with positive HBsAG.
3- Patients have waiting time longer than the median time to receive a kidney in each national society.
Due to the risk of infection transmission before undergoing KT, recipients should be fully informed and consent must be obtained from each individual. And the recipient must be counseled regarding the risks and the precautions should be followed in case of accepting such donors.
CHALLENGING PERSPECTIVE
NAT for HBV is now accepted to be a useful screening test. The result of a sensitive HBV DNA test is of
prime importance in the organ allocation and the design of the prophylactic protocol. Although, the rate of HBV transmission from KT was reported to be low, regular monitoring schedule for HBV is an essential part of post-transplant care.
Conclusion:
Within this era of several newer antiviral medications, the presence of positive HBsAg in potential organ donors should not preclude the use of kidney organs. Experienced transplant teams are specially required to go on with this procedure that needs careful assessment.
Level 5
· One option to expand donor pole is to accept donor with hepatitis B
· The aim of this study is to give a summary of last evidence of use of HBsAg (+) donors kidneys
· In acute hepatitis B infection, IgM anti-HBc becomes positive after 4 wk to 6 wk of exposure indicating recent infection and active viral replication, whereas anti-HBc appear at the onset of symptoms and persists for life
· HBeAg and anti-HBe indicates active viral replication
· anti-HBs is a marker of immune status due to either naturally- or vaccine-acquired immunity
· Window period: detectable viral DNA in absence of HBsAg (35-44 d after inoculation or occult infection)
· In deceased kidney donor, HBs Ag and anti-HBc are generally accepted as cost-effective screening tools.
· Isolated anti-HBc is common and may occur in
1. the early window period of acute hepatitis B.
2. a resolved HBV infection with waning of anti-HBs titer.
3. a false positive anti-HBc. Mostly seen in area with a low prevalence of HBV infection.
4. an occult chronic HBV infection with low viremia and undetectable HBsAg.
· Patients who have strong risk factors for HBV/ HCV/HIV combination should be tested for HBsAg, HBV NAT, and then HBV DNA
· Donors with HBV infections classified according to their serologic status in to 2 groups:
1. the anti-HBc positive group (rate of transmission is negligible)
2. HBsAg positive group (HBV transmission remains a challenging problem)
· KT from living HBsAg (+) donors can be donated to
1. anti-HBs (+) recipients with protection who have normal liver function test, and no history of liver disease within the previous 28 days,
2. who are not living in the area of possible mutation strain of HBV
· HBeAg and anti-HBe should be checked in HBsAg (+) donors to ensure a low infectivity rate of HBV before performing KT
· Use of antiviral medications to treat HBV add benefit to the treatment plan to use organs from HBsAg (+) donors.
· Unlike liver transplantation, KT from HBsAg (+) donors can add a functional cure of HBV
· The recipients who received kidneys from donors with hepatitis B should have protective anti-HBs ( > 10 mIU/mL)
· In the setting of kidney transplants from HBsAg (-) donors to immune protective recipients (Anti-HBs > 10 mIU/mL), definitions of HBV transmission may include anti-HBc IgM seroconversion, HBsAg seroconversion, and HBV DNAemia
· Subclinical infection presenting with anti-HBc seroconversion was observed with kidney transplants from both anti-HBc (+) and HBsAg (+) donors
· kidney transplant recipients who have a resolved infection of HBV (positive anti-HBc) may have HBV reactivation during a course of intensive immunosuppression particularly rituximab
· A high incidence of reactivation was observed in recipients with ABO incompatibility, who received plasmapheresis, received acute rejection therapy, and received induction therapy with rituximab
THE ROLE OF PROPHYLAXIS THERAPY
Vaccination and revaccination protocol
· Hepatitis B vaccination should be given to naïve recipients or previously immune recipients who have anti-HBs concentration below 10 mIU/mL
· As an antibody concentration is likely to wane over time, monitoring of anti-HBs concentration should be done at least yearly
· A further booster dose of vaccine may be required. This can be prescribed by either a single-shot high dose (40 µg) or a total complete course with a follow-up level at 4-wk after a complete course of treatment
Antiviral medications (nucleos(t)ide analogues) and HBIG
· HBIG in combination with antiviral nucleos(t)ide analogs (NAs) is superior to HBIG or NA alone to prevent recurrent infection of HBV after liver transplantation.
· entecavir is a better alternative to lamivudine (in resistant cases) that directly suppress HBV virus replication
· Anti HBs (> 10 mIU/mL) and positive recipients can receive kidney transplants from anti-HBc (+) donors without a need for prophylaxis antiviral medications due to the negligible risk of HBV transmission
· In contrast, naïve recipients who received kidneys from anti-HBc (+) donors should receive lamivudine prophylaxis without HBIG for at least 1 year
· If donor has HBs Ag (+), recipient with protective anti-HBs (> 10 mIU/mL) is considered suitable to receive the allocation of kidney grafts
· If the result of nucleic acid for HBV was negative and HBV DNA was undetectable:
– no NA prophylaxis is needed if potent induction therapy was not given
– or prescription of NA alone without HBIG.
· If the anti-HBs is > 100 mIU/mL, one can proceed to KT without NA prophylaxis
· if HBV DNA was not measured by a method of optimum low detection limit or the result of HBV DNA cannot be obtained due to any reason, NA may be prescribed
· Use of HBsAg (+)/DNA (+) donors to recipients with naïve or anti-HBs < 10 mIU/mL was the group with the highest risk being reported
· One important use of NAs was in the setting of treatment with rituximab
LONG TERM OUTCOMES AND SURVIVAL
· Regarding HBsAg (-) anti-HBc (+) donors, there were no HBsAg seroconversion and no excess risk of morbidity and graft failure
· The outcome of HBsAg (+) donor to anti-HBs (> 10 mIU/mL) recipient reported a ten-year actuarial graft survival rate of 84.6% and patient survival rate of 92.8% (with no hepatitis and hepatoma) provided that the recipients received no induction therapy
RISK BENEFIT OF TRANSPLANTATION AND PROPOSED CRITERIA FOR HBsAg (+) DONOR UTILIZATION
· Use of kidney from HBsAg + donor, may shorten time of waiting list
· Recipient can benefit from excellent graft survival without excess risk of liver disease
· Suggested criteria to define 3 groups of potential recepients:
1. Patient with urgent need for transplantation
2. recipients with positive HBsAg
3. Long waiting time
· all potential recipients should be vaccinated with target anti-HBs at least > 10 mIU/mL
· The potential recipients should not have HCV coinfection nor other cause of chronic liver disease which may worsen after KT
· All recipients of HBsAg (+) donors should receive anti-viral medication,
· HBIG may be considered for recipients with non-protective anti HBsAb level and/or in the situation of unknown HBV DNAemia of the donor
CONCLUSION
As new antiviral drugs are available, donors with HBsAg+ , should not be precluded.
What is the level of evidence provided by this article?
Narrative review level 5
Will you accept living or deceased donations from HBV-positive donors?
If I have no other option. After counselling with the recipient and preparing him before he gets the graft, I would go for transplantation with prophylactic antiviral
Due to shortage of organs and long waiting list for kidney transplantation,one of the solutions to expand the donor pool is including donors with HBV infection as refusing kidneys from donors with HBV infections will decrease number of donors in endemic areas..
-The challenge is determining the optimal use of kidneys from such donors and best utilization to allocate these kidneys to low risk recipients. with proper prophylactic therapy and monitoring
-According to current guidelines, there is acceptance of non-liver organs from total hepatitis B core antibody-positive [anti-HBc (+)] donors to be used in any recipient regardless of HBV immune status without prophylaxis due to the negligible risk of de novo infection.
– kidneys donors with positive hepatitis B surface antigen (HBsAg) [HBsAg (+)] remains controversial, and it is generally suggested that such organs be discarded.
▪︎SCREENING TEST FOR HBV INFECTION IN ORGAN DONORS
-testing for HBsAg (but it fails to detect disease during a 35-44 d window period after inoculation or occult infection.
– test for previous HBV expodure with core antibody (anti-HBc) which appears at the onset of symptoms and persists for life.
-HBeAg positivity indicates active viral replication (i.e., usually a viral load > 10000 IU/mL).
-anti-HBe positivity indicates the presence of the non-replication phase (i.e., a viral load < 10000 IU/mL).
-hepatitis B antibody (anti-HBs) is a marker of immune status due to either naturally- or vaccine-acquired immunity.
-nucleic acid test (NAT), usually in the form of an HIV/HCV/HBV multiplex, has been proposed as an optional donor screening test.
▪︎RISK OF HBV TRANSMISSION AND INFECTION AFTER KT
*Donor factors and the role of HBV DNA
-HBV reactivation in the immunocompromised is a consern due to presence of HBV covalently closed circular DNA .
-Donors with HBV infections categorized into 2 groups:
•group 1 is the anti-HBc positive ,rate of transmission appears to be negligible.
• grop 2 is the HBsAg positive group where the HBV transmission remains a challenging problem
-Previously, it was generally believed to discard the use of these kidneys. However, several recent studies and guidelines suggested that kidneys from HBsAg (+) donors can be carefully considered to be transplanted to appropriate recipients after careful consideration of the risk and benefit with informed consent.
-KT from living HBsAg (+) donors can be donated to anti-HBs (+) recipients with protection ,who have no abnormalities of liver function test, no history of liver disease within the previous 28 days, and who are not living in the area of possible mutation strain of HBV.
-Use of antiviral medications to treat HBV add benefit to the treatment plan to use organs from HBsAg (+) donors.
-Studies of recipients who received hepatitis B immunoglobulin (HBIG) and antiviral medication as prophylaxis treatment showed that this treatment was associated with excellent graft and patient survival without excess HBV transmission when compared with the control group.
-Chancharoenthana et al ,reported that kidney transplants from HBsAg (+)/HBV DNA (-) (< 20 IU/mL) donors to 20 immune recipients (anti-HBs > 100 mIU/mL) was safe and was not associated with any HBV viremia, hepatitis or death despite the absence of antiviral prophylaxis.
▪︎ Recipient factors and the role of protective immunity
-Several guidelines and studies have suggested that an anti-HBs > 10 mIU/mL was protective.
one study that performed transplantation of HBsAg (+) kidney to four immunized patients with an anti-HBs ranged from 63 mIU/mL to > 1000 mIU/mL. The results showed that there was no HBsAg seroconversion, although the anti-HBc IgG was positive in all 4 cases at six months despite the presence of anti-HBs positivity.
▪︎MONITORING OF HBV INFECTION AFTER TRANSPLANTATION
For kidney transplant recipients, The American Association for the Study of Liver Diseases (AASDL) suggested periodic assessment of serum ALT, HBV DNA, and HBsAg during immunosuppressive therapy.
Reactivation of HBV infection was defined by detectable HBV DNAemia or positive HBsAg seroconversion.
hepatitis flare was defined by rising of serum ALT more than 3 folds and > 100 U/L with evidence of hepatitis B reactivation
It was advised monitoring liver enzymes, HBsAg, and HBV DNA every 3 mo for at least 12 mo post-transplantation.
In the case of naïve recipient receiving Anti-HBc (+) kidney without antiviral prophylaxis, the European guidelines recommend monitoring for HBsAg, and HBV DNA at least during the first year.
Also, most of the recipients from donors with HBV infection were suggested to receive lifelong monitoring
▪︎THE ROLE OF PROPHYLAXIS THERAPY
Vaccination and revaccination protocol
-Hepatitis B vaccination should be given to naïve recipients or previously immune recipients who have anti-HBs concentration below 10 mIU/mL
-KDIGO guideline suggested a concentration of Anti-HBs below 100 mIU/mL can be rapidly lowered down to a non-protective level and may require a booster dose .
Antiviral medications (nucleos(t)ide analogues) and HBIG
HBIG provides passive immunity for a high concentration of anti-HBs that are aimed to act as neutralizing antibodies to HBV.
the optimal dose of HBIG to be used for kidney transplant recipients from donors with HBV was not clearly known
Anti HBs (> 10 mIU/mL) and positive recipients can receive kidney transplants from anti-HBc (+) donors without a need for prophylaxis antiviral medications.
In contrast, naïve recipients who received kidneys from anti-HBc (+) donors should receive lamivudine prophylaxis without HBIG for at least 1 year.
HBs Ag (+) donors, recipients with protective anti-HBs (> 10 mIU/mL) were considered suitable.
If the anti-HBs is > 100 mIU/mL, one can proceed to KT without NA prophylaxis.
However, if HBV DNA was not measured NA may be prescribed to make the risk of HBV transmission as low as possible.
HBsAg (+)/HBV DNA (+) donor, most authors prescribed universal NA prophylaxis with or without HBIG as a prophylaxis regimen among patients with different levels of anti-HBs concentration
▪︎LONG TERM OUTCOMES AND SURVIVAL
Regarding HBsAg (-) anti-HBc (+) donors there were noHBsAg seroconversion and no excess risk of morbidity and graft failure
review of nine studies found the seroconversion rates of HBsAg, anti-HBc, anti-HBs were 4/1385, 32/1385, and 5/1385 recipients.
Those numbers were considered to be very low and the authors conclude that HBsAg (-) anti-HBc (+) kidneys can be transplanted safely to patients with ESKD
result of HBsAg (+) donor to anti-HBs (> 10 mIU/mL) recipient reported a ten-year actuarial graft survival rate of 84.6% and patient survival rate of 92.8% (with no hepatitis and hepatoma) provided that the recipients received no induction therapy
▪︎Benefits
Including donors with HBV to donor pool will help to expand the pool
Recipients who wil benefit are 3 groups:
The first group is patients with urgent need to receive KT.
as patients with exhausted vascular access , patients with ongoing uremia despite adequate dialysis, and patients who cannot remain in the dialysis treatment (hemodialysis or CAPD) due to any reason.
The second group is the recipients with positive HBsAg.
The third group is patients being registered as active waiting list who have waiting time longer than the median time to receive a kidney
recipients should be discussed about the willingness to receive a kidney from donors with HBsAg positivity
Level of evidence IV
Summary
· Rational behind the question to use HBV donors is the shortage of living donor pool. So, use of expanded donor criteria organs may help to solve this problem.
· HBV has high prevalence especially in Africa (up to 8%).
· Donors with positive hepatitis B core antibody-positive are safe to donate non liver organs to negative recipient (whatever his immune state to HBV), (with minimal risk of denovo infection).
· Many challenges exist as risk of transmission especially in HBsAg, with difficulty in diagnosis, treatment and need for special post transplant IS regimen and follow up.
· Suggested approach is the use of:
o Donor: HBsAg positive but HBV DNA negative PCR. so use of DNA detection for diagnosis can help in decreasing the missed diagnosis in the window phase (early phase before the development of anti HBV s antibodies).
o Recipient with low risk of acquiring infection (with protective anti HBSAb with titer > 10 mIU/m) plus the use of optimal nucleos(t)ide analog prophylaxis. close monitoring of HBV PCR. liver function test every 3 months in 1st year post transplant, which can further minimize risk of infection.
o This approach was not associated with any denovo infection or seroconversion and active hepatitis in the recipients.
o similarly, use of positive donors to donate HBVs Ag positive recipients.
· N.B:
o HBV sAg is the commonest screening serological test for HBV, but it miss early infection (in incubation period), so use of HBV DNA is essential in early 35-44 days.
o Anti-HBc IgM becomes positive after 4 – 6 wk of exposure indicating recent infection and active replication of virus. whereas total hepatitis B core antibody (anti-HBc) remains positive for life.
o HBeAg and anti-HBe are additional tests to identify viral replicative activity.
o anti-HBs is a marker of immune status due to either naturally- or vaccine-acquired immunity
· screening generally by: HBs Ag and anti-HBc. in endemic areas: additionally, anti-HBe and HBeAg are used.
· Risk of HBV transmission is lower in kidney than liver transplantation.
· Fulminant hepatitis B was reported in a naïve recipient who received kidneys from donors with HBsAg (+)/HBeAg (+) donors , Since this report, HBeAg and anti-HBe were routinely checked in HBsAg.
· Prophylactic therapy with lamivudine and HBIG achieved cure and eliminated the risk of development of HBV infection in kidney recipients from positive donors.
· Commonest HBV genotype was A in North America, B in Europe, C in Asia and Australia, and D in the middle east and central Asia.
· Reactivation occurred in about 2 % after 2 years of transplantation, especially in those received RTX, ATG, PEX for ABOi transplantation (massive IS).
· Role of vaccination:
o Routine vaccination for negative patients or those with lower (none protective) titer of anti HBVsAb), especially as CKD patients has immune dysregulation and defective memory B and T cells.
o Annual testing of antibody titer and booster doses required to maintain immune protection, in HD patients with defective immune response.
o vaccine characters as type, dose, and route of administration (subcutaneous injection route), third-generation vaccine containing pre s/s epitope vaccine, can increase efficacy.
· Role of antiviral therapy and immunoglobulins:
o lamivudine is most common used agent (few resistant cases)/
o Used together with IVIG, especially in patients with none protective antibody tier after vaccination.
· Conclusion: The use of HBV positive donors requires good allocation system and choice of appropriate donor for appropriate recipient. to provide certain recipients with better quality of life than being on waiting list (prolonged dialysis duration).
· Especially, those need urgent transplant as exhausted vascular access, those with positive HBV and those with very long duration on waiting list. the patient should be counseled and choose the most appropriate for him, written consent, vaccination with protective antibody titer are crucial before transplantation.
· level of evidence : v
· in our practice: we can not apply the current artcle conclusion(as week evidence) plus we need counseling of both recipient and donor, and involvement of expert hapatologist interested in the field of renal transplantation.
The main hope for the ESRD patients is the renal transplantation but unfortunately every patient has no access to this due to shortage of donors. Previously Hepatitis B donors were being discarded but according to few recent studies ,they can be considered utilizing the extended donor criteria organs’.The prevalence of hepatitis B is around 1.2-2.6% in Europe and up to 4.6-7.6% in Africa and varies according to geographical areas. The natural history of hepatitis B infection is ascertained by the virus replication and host immune response. In the window phase i.e.,( 35-44 days after acquiring the virus),HbsAg is not detected in the blood but viral DNA is detectable so serologic test needed at this time. Serologic testing includes hepatitis B core Ab IgM that becomes positive after 4-6 weeks, total anti HBcAb that appears at the start and continues life long. Some transplant centers also recommend HBeAg and antiHBe in areas where hepatitis is endemic to check for viral infectivity and replication. Some centers also recommend PCR to be done in all donors but due to cost not done widely. Liver transplant patients have more chances of acquiring HBV infection from donor compared to kidney transplant recipients. Donors with HBsAg can donate after special consideration of risks and benefit and increase the donor pool. Living donors with HbsAg with low evidence of infectivity (HBeAg and antiHBe status of the potential donor and undetectable HBV DNA)to antiHBs positive recipients with prophylaxis and having no liver disease and abnormalities of LFTs within the last 28 days and who are not living in an area of possible mutation strains of HBV.
AASLD suggest monitoring of LFTs ,HbsAg ,HBV DNA in kidney transplant recipients while they are on immunosuppression. However, AST recommend assessment every 03 months for 12 months post transplantation. Lifelong monitoring is recommended in recipients from donors with HBV infection. Vaccination should be given to all HbsAg negative recipients or previously immune recipients who have anti-HBs concentration below 10 mIU/mL. Prophylaxis in the form of anti-viral medication (entecavir or lamivudine)to all recipients of HBsAg (+) donors but PCR DNA negative and anti-HBc (+) with anti-Hbs<10miu/ml HbsAg positive donors can be considered for donation if there is an urgent need for KT (no vascular access, inadequate dialysis or recipients who have contraindications to dialysis)or expected very long time on waiting list. Active Hepatitis b infection is a contraindication to transplantation.
Narrative review level 5
Kidney donors from HbsAg positive donors can expand the donor pool and can be utilized safely but with counseling of the recipient about the risks and benefit, and also to continue prophylaxis and with close monitoring of the recipient
Introduction:
Kidney transplantation (KT) is the preferred treatment for end-stage kidney disease (ESKD) patients. It is associated with reduced mortality and improved quality of life compared to dialysis therapy.
According to current guidelines, there is an increasing trend of accepting non-liver
organs from total hepatitis B core antibody-positive [anti-HBc (+)] donors to be used in
any recipient, regardless of HBV immune status, without prophylaxis due to the
negligible risk of de novo infection
kidneys from donors with positive hepatitis B surface antigen (HBsAg) [HBsAg (+)] remains controversial, and it is generally suggested that such organs be discarded.
Objectives:
This review aims to summarize the current evidence regarding the use of kidneys from HBsAg (+) donors with an emphasis on the risk of HBV transmission, liver-related morbidities, and the outcomes of Kidnet tx
least 12 months then lifelong)
Reactivation of HBV infection was defined by detectable HBV DNAemia or positive HBsAg seroconversion
For naïve recipient receiving Anti-HBc+ kidney without antiviral prophylaxis, the European guidelines recommend monitoring for HBsAg, and HBV DNA at least during the first year
Resolved infection of HBV (defined by positive anti-HBc serology) should be aware of a possibility of HBV reactivation during a course of intensive immunosuppression particularly rituximab
The role of prophylaxis therapy
Vaccination and revaccination protocol
Hepatitis B vaccination should be given to naïve recipients or previously immune recipients who have anti-HBs concentration below 10 mIU/ml (KDIGO guideline suggested a level < 100 mIU/mL can be rapidly lowered down to a non-protective level and may require a booster dose). Monitoring of anti-HBs concentration should be done at least yearly and re-vaccine if anti-HBs were found to be below 10 mIU/mL
Strategies to improve vaccine efficacy may be related to the type, dose, and route of administration
Antiviral medications (nucleos(t)ide analogues) and HBIG
Used in combination with the aim to prevent recurrent infection of HBV after liver transplant (superior to HBIG or NA alone). Lamivudine was the first prophylaxis agent (lamivudine-resistant hepatitis B, increase with duration of treatment). Other drugs is entecavir
HBs Ag (+) donors, recipients with anti-HBs (> 10 mIU/mL) do NAT test and HBV DNA measurement. If NAT was negative and HBV DNA was undetectable , no NA prophylaxis (in the setting of no potent induction therapy), or prescription of NA alone without HBIG. If the anti-HBs is > 100 mIU/mL, one can proceed to KT without NA prophylaxis. If HBsAg +/HBV DNA + donor, NA prophylaxis with or without HBIG
CONCLUSION
long-term outcomes were favorable when compared with donors with no markers of HBV who received proper prophylaxis regimen.
Transplantation involving HBsAg positive donors was a cost-effective.
LEVEL OF EVIDENCE – 5
1. Please summarise this article in your own words
INTRODUCTION
Kidney transplantation is the best available modality for patient with ESRD, it improves patient survival and quality of life. However, there is shortage of organs worldwide. This led to the introduction of expanding criteria donor, including donors with HBV infection.
The prevalence of chronic HBV infection varies greatly by geographical region:
1. 0.4% to 1.6% in the region of the Americas.
2. 1.2% to 2.6% in Europe,
3. 1.5% to 4.0% in Southeast Asia,
4. 2.6% to 4.3% in the Eastern Mediterranean,
5. 5.1 to 7.6 % in the Western Pacific, and
6. 4.6% to 8.5% in Africa
Discarding such number of kidneys, as the prevalence in donors is equivalent to general population with affect significantly the number of transplanted organs specially in endemic areas. Finding a way to transplant such organs to recipients with low risk for transmission will be useful.
Current guidelines allow transplanting organs from HBcAbs positive donors to any recipients regardless of their immune status against HBV, because the risk of transmission of the virus is very low, but transplanting organs from HBsAg positive is still controversial.
In this review, we aim to summarize the current evidence regarding the use kidneys from HBsAg (+) donors with an emphasis on the risk of HBV transmission, liver related morbidities, and the outcomes of KT.
SCREENING TESTS FOR HBV INFECTION IN ORGAN DONORS
· HBsAg: widely distributed, but it can fail to detect disease during a 35-44 d window period after inoculation or occult infection defined as detectable viral DNA in absence of HBsAg.
· Anti-HBc: IgM anti-HBc becomes positive after 4 wk to 6 wks.
· Total hepatitis B core antibody (anti-HBc) appear at the onset of symptoms and persists for life.
· HBeAg) : active viral replication (i.e.a viral load > 10000 IU/mL)
· Anti-HBe: presence of the non-replication phase (i.e., a viral load < 10000 IU/mL)
· Anti-HBs) is a marker of immune status due to either naturally- or vaccine-acquired immunity
In deceased donor setting screening with HbsAg and HBc Ab is done many centre as it is cost effective, some add to it, specially in endemic areas HBe Ag and HBe Abs. The result needs to be interpreted with caution, putting in mind the window period as well as sensitivity and specificity of each test.
RISK OF HBV TRANSMISSION AND INFECTION AFTER KT
Risk of transmission of HBV infection from liver transplant is more than from kidney transplant. Risk of transmission/seroconversion from HbcAb is very low, but from HBs Ag positive it is significant, however it may be reduced if transplanted to selected recipients.
Fulminant hepatitis B infection had been reported in a naïve recipient who received kidneys from donors with HBsAg (+)/HBeAg (+) donors. Since this report, HBeAg and anti-HBe were routinely checked in HBsAg (+) donors to ensure a low infectivity rate of HBV before performing KT.
A recent study performed 83 living KTs from HBsAg (+) donors to HBsAg (-) recipients. Before the transplant, 28% of the donor in the latter study were HBV DNA (+) and 24% of the recipients had no anti- HBs. All recipients in the latter study received hepatitis B immunoglobulin (HBIG) and antiviral medication as prophylaxis treatment. The results showed that this treatment was associated with excellent graft and patient survival without excess HBV transmission when compared with the control group.
KT from donors with HBsAg (+) donors is not a risk-free procedure. A careful allocation to appropriate recipients can be successfully performed. NAT for HBV is now accepted to be a useful screening test.
CONCLUSION
Within this era of several newer antiviral medications, the presence of positive HBsAg in potential organ donors should not preclude the use of kidney organs. Waiting list from those who accept to receive HBSag positive kidneys should be prepared by an experienced transplant team,
2. What is the level of evidence provided by this article?
Level 5
3. Will you accept living or deceased donations from HBV-positive donors?
Will accept if positive HBc Anti bodies as the risk is very low.
Regarding HBs Ag, we need to check HBe Ag and HBe antiboidies..need to follow result
1-Please summarize this article in your own words
Abstract:
Previously, it was generally believed to discard the use of these kidneys. However,
several recent studies and guidelines suggested that kidneys from HBsAg (+) donors
could be carefully considered to be transplanted to appropriate recipients after careful
consideration of the risk and benefit with informed consent.
Introduction:
Utilizing kidneys from donors with hepatitis B is one way to alleviate the current organ
shortage situation.
However, the risk of hepatitis B virus (HBV) transmission remains a challenge that
undermines the chance of organs being used. This is particularly true with hepatitis B
surface antigen (HBsAg) positive donors despite the comparable long-term outcomes
when compared with standard donors. To reduce the risk of HBV transmission, a
comprehensive approach is needed.
Possible solution is to expand the donor pool by utilizing “extended donor criteria
organs”. Such organs include those from donors with hepatitis B virus (HBV) infection.
There is an increasing trend of accepting non-liver organs from total hepatitis B core
antibody-positive [anti-HBc (+)] donors to be used in any recipient regardless of HBV
immune status without prophylaxis due to the negligible risk of de novo infection.
HBV TEST:
All serologic tests for HBV (HBsAg, anti-HBc, HBeAg, antiHBe) as well as other
essential infectious markers are done at the donor hospitals.
a universal NAT test for HBV (usually in combination with HIV and HCV) should be
conducted at the central or regional organ allocation center and the result should come
back before or at the time of organ retrieving.
RISK OF HBV TRANSMISSION AND INFECTION AFTER KT:
Donor factors and the role of HBV DNA:
Patients who have strong risk factors for HBV/ HCV/HIV combination should be tested
for HBsAg, HBV NAT, and then HBV DNA by a test with the highest sensitivity and
specificity.
test with a lower detection limit of less than < 0.1 ng/mL for HBsAg and 10 IU/mL for
HBV DNA.
Donors with HBV infections are generally categorized into two groups:
The first donor group is the anti-HBc positive group:
in which the rate of transmission appears to be negligible according to the recipient’s
protective immunity status. The overall seroconversion rate was 3.24% (antHBC mostly),
HBsAg seroconversion rate from this study was shown to be 0.28% with no symptoms of
hepatitis and no excess mortality.
The second donor group is the HBsAg positive group where the HBV transmission is
high.
KT from living HBsAg (+) donors can be donated to antiHBs (+) recipients with protection
who have no abnormalities of liver function test, no history of liver disease within the
previous 28 days, and who are not living in the area of possible mutation strain of HBV.
KT from this type of donor can be associated with a functional cure of HBV. The
functional cure was defined by a state of sustained loss of HBsAg with or without anti-
HBs seroconversion, which was usually associated with good clinical outcomes.
Transplant can be also to HBV negative recipient with no antibodies or with antibodies
more than 10 IU, with IVIG and antiviral.
Recipient factors and the role of protective immunity:
The recipients who received kidneys from donors with hepatitis B should have protective
anti-HBs. Several guidelines and studies have suggested that an antiHBs > 10 mIU/mL
was protective.
MONITORING OF HBV INFECTION AFTER TRANSPLANTATION:
AASDL suggested periodic assessment of serum ALT, HBV DNA, and HBsAg during
immunosuppressive therapy.
Reactivation of HBV infection:
Detectable HBV DNAemia or positive HBsAg seroconversion.
Hepatitis flare was defined by rising of serum ALT more than 3 times the baseline level
and > 100 U/L with evidence of hepatitis B reactivation.
The Infectious Disease Community of Practice of the American Society of
Transplantation advised monitoring liver enzymes, HBsAg, and HBV DNA every 3 month
for at least 12 month post-transplantation. Subsequent management was based on the
evolution of test results over the first year.
In the case of naïve recipient receiving Anti-HBc (+) kidney without antiviral prophylaxis,
the European guidelines recommend monitoring for HBsAg and HBV DNA at least
during the first year.
In addition, most of the recipients from donors with HBV infection were suggested to
receive lifelong monitoring.
Recipients who have a resolved infection of HBV (defined by positive anti-HBc serology)
should be aware of a possibility of HBV reactivation during a course of intensive
immunosuppression particularly rituximab.
THE ROLE OF PROPHYLAXIS THERAPY:
Vaccination and revaccination protocol:
Hepatitis B vaccination should be given to naïve recipients or previously immune
recipients who have anti-HBs concentration below 10 mIU/mL.
the KDIGO guideline suggested a concentration of Anti-HBs below 100 mIU/mL can be
rapidly lowered down to a non-protective level and may require a booster dose .
Anti-HBs concentration should be done at least yearly
.
A further booster dose of vaccine may be required.
This can be prescribed by either a single-shot high dose (40 µg) or a total complete
course with a follow-up level at 4-wk after a complete course of treatment.
Antiviral medications (nucleos (t) ide analogues) and HBIG:
Combined HBIG AND antiviral nucleos (t) ide analogs (NAs) that aim to prevent
recurrent infection of HBV is commonly used.
Lamivudine was the most popular prophylaxis. However, small number of lamivudine
-resistant hepatitis B hampered its efficacy Therefore; other drugs with a high genetic
barrier such as entecavir were considered as a better alternative.
Serologic markers of HBV infection may have some impact on the choice to prescribe
antiviral medications.
Anti HBs (> 10 mIU/mL) and positive recipients can receive kidney transplants from anti-
HBc (+) donors without a need for prophylaxis antiviral.
Naïve recipients who received kidneys from anti-HBc (+) donors should receive
lamivudine prophylaxis without HBIG for at least 1 year.
In the setting of HBs Ag (+) donors, recipients with protective anti-HBs (> 10 mIU/mL)
were considered suitable to receive the allocation of kidney grafts.
Further risk should be assessed by the result of the NAT test and HBV DNA
measurement.
If nucleic acid for HBV was negative and HBV DNA was undetectable, preventive
strategies varied from no NA prophylaxis (in the setting of no potent induction therapy),
or prescription of NA alone without HBIG.
If the anti-HBs is > 100 mIU/mL, one can proceed to KT without NA prophylaxis.
However, if HBV DNA was not measured by a method of optimum low detection limit or
the result of HBV DNA cannot be obtained due to any reason, NA may be prescribed to
make the risk of HBV transmission as low as possible.
In the setting of HBsAg (+)/HBV DNA (+) donor, most authors prescribed universal NA
prophylaxis with or without HBIG as a prophylaxis regimen among patients with different
levels of anti-HBs concentration
Use of HBsAg (+)/DNA (+) donors to recipients with naïve or anti-HBs < 10 mIU/mL was
the group with the highest risk being reported.
Another interesting issue is the use of HBsAg positive donors to recipients with HBsAg
positive serology. Have reported favorable outcomes of this treatment option if the
recipients received antiviral treatment before transplantation.
In addition, there is a suggestion that the recipients with positive HBsAg should have
the result of liver biopsy that did not show evidence of cirrhosis.
RISK BENEFIT OF TRANSPLANTATION AND PROPOSED CRITERIA FOR HBsAg (+)
DONOR UTILIZATION:
The criteria for utilization of kidneys from donors with HBsAg positivity
The first group is patients with urgent need to receive KT.
Exhausted vascular access for hemodialysis.
Patients with ongoing uremia despite adequate dialysis prescription.
Patients who cannot remain in the dialysis treatment (hemodialysis or CAPD) due to
any reason.
The second group is the recipients with positive HBsAg.
The third group is patients being registered as active waiting list who have waiting time
longer than the median time to receive a kidney in each national society.
The potential recipients should be discussed about the willingness to receive a kidney
from donors with HBsAg positivity.
Level of evidence 5
Yes carefully selected recipient :
The criteria for utilization of kidneys from donors with HBsAg positivity
The first group is patients with urgent need to receive KT.
Exhausted vascular access for hemodialysis.
Patients with ongoing uremia despite adequate dialysis prescription.
Patients who cannot remain in the dialysis treatment (hemodialysis or CAPD) due to any reason.
The second group is the recipients with positive HBsAg.
The third group is patients being registered as active waiting list who have waiting time
longer than the median time to receive a kidney in each national society.
The potential recipients should be discussed about the willingness to receive a kidney
from donors with HBsAg positivity.
This is a review article with level 5 of evidence
Summary
Expanded criteria donor including donor with Hepatitis B infection has been proposed to overcome the shortage of donor pools. It has been proposed that hepatitis B patients can serve as kidney donors in areas with high prevalence of Hep B infection- endemic areas. Selection of recipients is the best way to benefit from Hep B infected donors so that low risk patients of acquiring donor transmitted HBV infection are selected. Because the risk of transmission of infection from donor tissue, a comprehensive approach is needed.
Screening for HBV in potential donors
– HBsAg test is widely used, but can’t detect disease before 35-44 days, and pt become seropositive only 4-6 weeks after infection.
– The presence of anti-Hbc IgM type indicates acute infection. The total HBc-Ab appear at the onset of symptoms and can persist for life.
– Positive HBe-Ag indicates active replication (usually viral load >10000U/ml), while presence of anti-HBe Abs indicates non replication phase (viral load <10000U/ml).
– Positive anti-HBs Abs reflects immune status either due to previous infection or vaccination.
– For deceased kidney donors HBs-Ag and anti-HBc Abs tests are cost-effective screening tests, but additional tests are required in endemic areas.
– NAT can be used as an alternative test in the form of an HIV/HCV/HBV multiplex. Its advantage is that it shortens the windows period to 20-22 d compared to 35-44 d by conventional serology. In USA NAT is used routinely, however it is only reserved for high-risk population.
Risk of HBV transmission and infection post transplantation
The risk of HBV infection transmission is lower in kidney transplant recipient compared to liver transplant with similar serological marker positivity. Patients with strong risk factors for HBV, HCV & HIV combined infection should be tested with Abs-Ag, NAT then by HBV DNA.
Donors with HBV infection are categorized into 2 groups:
1- Negligible risk of transmission in patients with positive HBc-Ab – HBsAg seroconversion rate from this study was shown to be 0.28% with no symptoms of hepatitis and no excess mortality
2- Donors with positive HBs-Ag, remain a challenging problem
Historically it was believed to discard the use of kidneys with positive Hbs-Ag. However, several recent studies and guidelines suggested that kidneys from HBsAg (+) donors can be carefully considered to be transplanted to appropriate. Current guidelines suggest that HBs-Ag + donation is accepted if the recipients have protective antibodies HBs-Ab >10U/ml with normal liver function, no history of liver disease viral infection without mutation strain of HBV.
Monitoring of HBV infection after transplantation
– For kidney transplant recipients, The American Association for the Study of Liver Diseases (AASDL) suggested monitoring of ALT, HBV-DNA, & HBs-Ag in patients on immunosuppression.
– No consensus on the optimal frequency of monitoring for HBV infection. European guidelines recommend monitoring for HBsAg, and HBV DNA at least during the first year after transplantation. The Infectious Disease Community of Practice of the American Society of Transplantation advised monitoring liver enzymes, HBsAg, and HBV DNA every 3 mo for at least 12 mo post-transplantation.
– kidney transplant recipients who have a resolved infection of HBV (defined by positive anti-HBc serology) should be aware of a possibility of HBV reactivation during a course of intensive immunosuppression particularly rituximab.
Role of Prophylaxis therapy
Long term outcome & survival
HBs-Ag -ve/HBc-Ab+ve donors are considered immunized and can be transplanted safely with low risk of seroconversion andgraft loss. HBs-Ag+ve donor & HBs-Ab>10U recipient are considered protected and have a good long term outcome.Transplantation of HBs-Ag+ve donors to selected recipients is cost-effective comparing to patients waiting for long period on the waiting list.
Proposed criteria for HBs-Ag+ve donor utilization:
– Urgent need for transplantation such as those with no vascular access, inadequate dialysis or recipients who have contraindications to dialysis
– HBsAg positive transplant recipients
– Recipients with expected very long time on waiting list
☆Introduction
▪︎The donor pool can be expanded by utilizing “extended donor criteria organs”. Such organs include those from donors with hepatitis B virus (HBV) .The best utilization may involve allocating such kidneys to transplant candidates at low risk of acquiring a donor-transmitted hepatitis B infection.
▪︎According to current guidelines, there is an increasing trend of accepting non-liver organs from total hepatitis B core antibody-positive [anti-HBc (+)] donors to be used in any recipient regardless of HBV immune status without prophylaxis. However, utilizing kidneys from donors with positive hepatitis B surface antigen (HBsAg) [HBsAg (+)] remains controversial, and it is generally suggested that such organs be discarded.
☆The aim of the study:
▪︎To summarize the current evidence regarding the use kidneys from HBsAg (+) donors with an emphasis on the risk of HBV transmission, liver related morbidities, and the outcomes of KT.
☆ Screening test for HBV infection in organ donors
▪︎ By serologic screening tests which include: HBsAg, anti-HBc (previous HBV exposure).
▪︎ Hepatitis B e antigen (HBeAg) & hepatitis B e antibody (anti-HBe) are additional tests to identify viral replicative activity.
▪︎Hepatitis B antibody (anti-HBs) is a marker of immune status due to either naturally- or vaccine-acquired immunity.
▪︎To improve the sensitivity of screening tests, the nucleic acid test (NAT), which is usually in the form of an HIV/HCV/HBV multiplex, has been proposed as an optional donor screening test.
☆Risk of HBV transmission and infection after KT
Donor factors and the role of HBV DNA
▪︎Patients who have strong risk factors for HBV/ HCV/HIV combination should be tested for HBsAg, HBV NAT, and then HBV DNA by a test with the highest sensitivity & specificity.
▪︎Donors with HBV infections are generally categorized into two groups:
1. Anti-HBc positive group in which the rate of transmission appears to be negligible according to the recipient’s protective immunity status.
2. HBsAg positive group where the HBV transmission remains a challenging
problem.
▪︎kidneys from HBsAg (+) donors can be carefully considered to be transplanted to appropriate recipients after careful consideration of the risk and benefit with informed consent.
▪︎The role of NAT in reducing the window period of serological test.
▪︎KT from living HBsAg (+) donors can be donated to antiHBs (+) recipients with protection who have no abnormalities of liver function test, no history of liver disease within the previous 28 days, and who are not living in the area of possible mutation strain of HBV.
▪︎HBeAg and anti-HBe were routinely checked in HBsAg (+) donors to ensure a low infectivity rate of HBV before performing KT.
▪︎Use of antiviral medications to treat HBV add benefit to the treatment plan to use organs from HBsAg (+) donors.
Recipient factors and the role of protective immunity
In principle, the recipients who received kidneys from donors with hepatitis B should have protective anti-HBs.
Monitoring of HBV infection after transplantation
▪︎For kidney transplant recipients, AASDL suggested periodic assessment of serum ALT, HBV DNA, and HBsAg during immunosuppressive therapy.
▪︎Reactivation of HBV infection was defined by detectable HBV DNAemia or positive HBsAg seroconversion.
▪︎Hepatitis flare was defined by rising of serum ALT more than 3 times the baseline level and > 100 U/L with evidence of hepatitis B reactivation.
▪︎ The Infectious Disease Community of Practice of the American Society of Transplantation advised monitoring liver enzymes, HBsAg, and HBV DNA every 3 mo for at least 12 mo post-transplantation.
▪︎In the case of naïve recipient receiving Anti-HBc (+) kidney without antiviral prophylaxis, the European guidelines recommend monitoring for HBsAg, and HBV DNA at least during the first year. Also, most of the recipients from donors with HBV infection were suggested to receive lifelong monitoring. Besides, all kidney transplant recipients who have a resolved infection of HB (defined by positive anti-HBc serology) should be aware of a possibility of HBV
reactivation during a course of intensive immunosuppression particularly rituximab
THE ROLE OF PROPHYLAXIS THERAPY
Vaccination and revaccination protocol
Hepatitis B vaccination should be given to naïve recipients or previously immune recipients who have anti-HBs concentration below 10 mIU/mL. Also, the KDIGO guideline suggested a concentration of Anti-HBs below 100 mIU/mL can be rapidly lowered down to a non-protective level and may require a booster dose at this step.
Antiviral medications (nucleos(t)ide analogues) and HBIG
To prevent HBV transmission via kidney transplant organs, antiviral medications and HBIG can be used. Most prescriptions of HBIG were used in combination with antiviral nucleos(t)ide analogs (NAs) which suppress HBV virus replication eg:: Lamivudine and entecavir
Conclusion:
▪︎Low-risk hepatitis B surface antigen (HBsAg) positive kidney donor, defined by a negative test of hepatitis B virus (HBV) DNA being allocated to immunerecipients with anti-HBs at least 10 mIU/mL is a key factor in overcoming the risk of HBV transmission. ▪︎The risk may be further eliminated with optimal nucleos(t)ide analog prophylaxis. Blood tests for HBV DNA, HBs Ag, and liver function tests should be routinely monitored after transplantation and when there is a change of immunosuppression.
▪︎The excellent long-term outcomes being reported suggested that the outcomes of this treatment option are promising. This will lead to broader use of organs with positive HBsAg.
Summary
This study revolves around the decision of allowing HBV positive donors for transplant recipients, and in which circumstances this will have a good long term outcome.
Immunosuppressive regimen, prophylaxis and post transplant monitoring are crucial in giving good outcome after the donor has been accepted.
Donor risk assessment is important and has to be done first before accepting the donor. The donor also has to be fully aware of all the short and long term risks before signing the consent form for donation.
Nucleic acid testing with HBV DNA is essential.
In choosing the appropriate donor for the recipient, it is essential to make sure that only low risk HBsAg positive kidney donor having negative HBV DNA test is matched with recipient with anti-HB at least 10mIU/ml. This is essential to prevent HBV transmission to the recipient. Along with this, optimal nucleoside/nucleotide analog prophylaxis is to be given.
Non-liver organs are increasingly being accepted for donation for transplant recipients. This is even true of total hepatitis B core antibody positive donors, which are being used for all recipients regardless of HBV immune status without prophylaxis because of the negligible risk of de novo infection.
However, HBsAg positive organs continue to be discarded in many centers.
Prophylaxis involves high dose HBV vaccine more than 100 mIU/mL. Reactivation after kidney transplant is possible in cases who are given lesser than this concentration. KDIGO recommends annual screening for anti-HB and re-vaccination when anti-HB level is below 10 mIU/mL.
Prophylaxis with NA analogues are crucial especially if Rituximab is part of immunosuppressive regimen.
Multiple steps are essential from donor risk evaluation to recipient prophylaxis and post transplant monitoring to maintain low risk of transmission and good long term outcome.
Level of evidence
This article falls under the category of Narrative review and thus the level of evidence is 5.
HBV positive donors
Currently we do accept HBV positive donors for live donation when there are no other potential donors who are suitable for the recipient. However, prophylaxis is maintained strictly with HBV high dose vaccine.
Donor assessment regarding HBV status
Approach for transplanting a kidney from HBsAg positive donor
3 main factors should be considered before accepting HBsAg positive as a potential donor
A- factors related to the donor (screening tests results which include HBsAg HBcAb and PCR):
B- factors related to the recipient:
C- factors related to the virus itself and treatment availability
· No history of mutant virus infection with multidrug-resistant
· Availability of medications and medication insurance coverage.
Once these factors are fulfilled, and in the mentioned precautions, we can proceed with accepting this potential donor
Regarding postoperative care,
we have prophylactic, treatment with antiviral and IVIG, and also give booster dose of vaccination.
Indication of Prophylaxis(related to both donor and recipient status)
If the recipient didn’t achieve sufficient AB titer after immunization (antiHBs <10)
If the recipient achieved sufficient Ab titer after vaccination pretransplant
D- Close follow up
My center experience
We never accept donors with even only HBcAb (+). HBV is a DNA virus with a high risk of chronic infection and reactivation anytime a patient becomes over-immunosuppressed
Kidney failure remains a problem worldwide, and a larger pool of kidney donors is needed to reduce the numerous patients with ESRD. This article is based on using Hep B-positive persons as potential donors by using extended criteria. The prevalence of HEP varies from country to country and the use of donors with Hep B may help to reduce the problem facing the world currently. The use of Hep B surface antigen for a kidney transplant is still a controversial issue and it has not been accepted. So the objective of the article is to evaluate the evidence regarding the use of Hep HBsAg positive donors with an emphasis on the risk of HBV transmission, liver-related morbidities, and the outcomes in kidney transplantation.
To know if a patient has hepatitis B is via screening. Hep B has an incubation period of about 35-44 days and is difficult to test for HBsAg. Hep B core antigen (anti-HBc) becomes positive around a period of 4-6 weeks of exposure and the core B /anti-HBc remains permanent. Hep B e antigen and antibodies indicate viral replication activity. HBeAg positive indicate viral activity while the Anti-HBe positive indicates the presence of the non-replication phase of the virus. Hep B antibodies give details on immune status either naturally or via vaccination.
The test with improved sensitivity to detect the Hep B virus is a nucleic acid test (NAT) which is usually used for HIV/HCV/HBV multiplex. The limitation is the cost of the test. The other serologic test has limitations in terms of the long window period and the lack of sensitivity.
There are possible risks of transmission and infection after kidney transplantation as it relates to donor factors. Hep B reactivation is a risk factor for immunocompromised patients. Donors with HBV infection may have a co-infection with Hep Bc positive and a low risk of transmission or the presence of high risk of transmission HBsAg. Patients who are HBsAg donors can donate to a recipient AntiHBs. Also, HBeAg and Anti-HBe are the ones that can be used for a kidney transplant in HBsAg donors to reduce infectivity.
In light of the recipient, there must be anti-HBs greater than 10 IU/ml. The HBV transmission of the graft may not be associated clinically with Hep B infection. It is not certain if the higher anti-HBs concentration is associated with higher protection in kidney transplants. Due to the mutation in the determinant region of HBsAg, immune protection may reduce.
There must be measures to monitor the virus and its effects such as:
1) Serum ALT, HBV DNA, and HBsAg during immunosuppressive therapy should be done.
2) If one detects HBV-DNA or a positive HBsAg seroconversion it means reactivation of an infection
3) If there is an elevated of ALT more than 3 times the normal value it could be Hep B reactivation
4) Liver function tests must be always monitored every 3 months and every 12 months thereafter.
5) Drugs like rituximab can cause disease reactivation.
Giving patients a proper prophylaxis regimen can favor long-term benefits compared to donors with no markers for HBV. HBsAg can be cost-effective.
So we can conclude that long-term outcomes were more favorable, with donors with no markers of HBV who received prophylaxis. Patients that are transplanted with HBsAg were found to be more cost-effective.
The level of this article is 5
Due to the limited donors and the high demand for kidney transplantation needed I think it will be wise to accept it since we have seen it is possible.
Chronic hepatitis B virus (HBV) infection prevalence ranges from 0.4% to 8.5%. Organs from donors with HBV infection come under the extended donor criteria. The tests used for screening such donors include HBsAg (which fails to detect HBV infection in window period of 35-44 days), anti-HBc (IgM which becomes positive 4-6 weeks later, or total), HBeAg (if positive signifies a viral load of >10000 IU/ml). Anti HBs antibody (if positive, implies viral load of less than 10000 IU/ml) and anti-HBs antibody (signifying immunity). Nucleic acid testing (NAT) shortens the window period to 20-22 days.
The donor-transmitted HBV infection risk is lower in kidney transplant recipients as compared to that in liver transplant recipients. The risk of HBV transmission by donors having anti HBc positivity is negligible. The challenge lies with a donor with HBsAg positivity. The crucial factor in this scenario is the level of protection available to the recipient with respect to the anti-HBs antibody levels (>10 mIU/ml is protective). Post-transplant monitoring in form of Serum ALT, HBV DNA PCR and HBsAg should be done once in 3 months for 1 year, with later monitoring as per the test results.
Prophylaxis therapy in form of vaccination of all potential recipients and those with dwindling immunity (Anti-HBs antibody levels less than 10 mIU/ml) should be immunized with the HBV vaccine using a 3-4 high-dose intramuscular vaccine protocol. If the response is inadequate, subcutaneous route can be used. The target is to achieve anti-HBs antibody >100 mIU/ml. Anti-HBs antibody levels in patients should be checked annually, and if found less than 10 mIU/ml, should be revaccinated.
Antiviral prophylaxis includes nucleoside and nucleotide analogues (NA) and HBIG. Use of prophylaxis depends on the donor and recipient factors.
a) Recipient anti-HBs > 10 mIU/ml and HBsAg positivity with donor anti-HBc positivity: No prophylaxis
b) Recipient HBsAg negativity with donor anti-HBc positivity: Lamivudine prophylaxis for at least one year.
c) Recipient with Anti-HBs >100mIU/ml and donor HBsAg positive: Prophylaxis not required.
d) Recipient with Anti-HBs >10mIU/ml and donor HBsAg positive: If donor is NAT negative and HBV DNA negative, prophylaxis in form of NA alone (if induction given). If no induction given, prophylaxis not required.
e) Recipient with Anti-HBs >10mIU/ml and donor HBsAg positive: If donor is HBV DNA positive, prophylaxis in form of NA with or without HBIG
f) Recipient with Anti-HBs <10mIU/ml and donor HBsAg positive: If donor is HBV DNA positive, the transplant should be avoided. If going ahead with transplant, prophylaxis in form of NA with or without HBIG should be offered.
g) Recipient and donor both HBsAg positive: antiviral treatment to be given to recipient prior to transplant.
h) Use of rituximab: NA prophylaxis should be used.
The long-term graft and patient survival rates in donors with HBsAg positivity have shown to be favourable.
The proposed criteria for utilizing HBsAg positive donors is in 3 settings: HBsAg positive recipients, recipients with very long waiting period on the wait-list, and those with urgent need of transplant due to reasons like absence of vascular access, not able to tolerate dialysis, persistent uremia etc.
The level of evidence: Level 5 – narrative review
For living donation: I will accept in situation with HBsAg positive recipient, treated with HBV DNA negative and no cirrhosis.
For cadaveric donation: I will accept if the recipient is adequately immunized (anti-HBs antibody >100 mIU/ml). Ours is a living donor transplant program, hence I will not be able to comment much on this.
Introduction
Utilizing kidneys from donors with hepatitis B is one way to alleviate the current organ shortage situation. However, the risk of hepatitis B virus (HBV) transmission remains a challenge that undermines the chance of organs being used
the number of ESKD patients awaiting KT far exceeds the number of organ donations globally and leads to a problem of organ shortage. This major barrier has led to a prolonged waiting time and subsequently excess mortality of patients in the waiting list pool
One possible solution is to expand the donor pool by utilizing “extended donor criteria organs”. Such organs include those from donors with hepatitis B virus (HBV) infection.
The best utilization may involve allocating such kidneys to transplant candidates at low risk of acquiring a donor-transmitted hepatitis B infection. Prophylactic therapy and appropriate monitoring will further eliminate the risk of HBV transmission.
SCREENING TEST FOR HBV INFECTION IN ORGAN DONORS
Screening for HBV infection usually relies on a panel of serologic tests. However, it can fail to detect disease during a 35-44 d window period after inoculation or occult infection defined as detectable viral DNA in absence of HBsAg
Another importance serologic screening test for previous HBV exposure is anti-HBc.
In acute hepatitis B infection, immunoglobulin M (IgM) antibody to hepatitis B core antigen (IgM anti-HBc) becomes positive after 4 wk to 6 wk of exposure indicating recent infection and active viral replication whereas total hepatitis B core antibody (anti-HBc) appear at the onset of symptoms and persists for life.
In acute hepatitis B infection, immunoglobulin M (IgM) antibody to hepatitis B core antigen (IgM anti-HBc) becomes positive after 4 wk to 6 wk of exposure indicating recent infection and active viral replication
total hepatitis B core antibody (anti-HBc) appear at the onset of symptoms and persists for life.
HBeAg positivity which indicates active viral replication (i.e., usually a viral load > 10000 IU/mL).
anti-HBe positivity indicates the presence of the non-replication phase (i.e., a viral load < 10000 IU/mL).
hepatitis B antibody (anti-HBs) is a marker of immune status due to either naturally- or vaccine-acquired immunity
In case of deceased kidney donation, HBs Ag and anti-HBc are generally accepted as cost-effective screening tools. The results should be integrated with additional essential information of the donors to assess the risk of donor-derived infection
Some transplant centers in endemic areas routinely add on anti-HBe and HBeAg to the donor screening platform as biomarkers of high viral replication and infectivity activity relating to a high viral burden
To improve the sensitivity of screening tests, the nucleic acid test (NAT), which is usually in the form of an HIV/HCV/HBV multiplex, has been proposed as an optional donor screening test. This test is advantageous, because it shortens the windows period to 20-22 d compared to 35-44 d by conventional serology
all serologic tests for HBV (HBsAg, anti-HBc, HBeAg, antiHBe) as well as other essential infectious markers are done at the donor hospitals. In parallel, a universal NAT test for HBV (usually in combination with HIV and HCV) should be conducted at the central or regional organ allocation center and the result should come back before or at the time of organ retrieval.
RISK OF HBV TRANSMISSION AND INFECTION AFTER KT Donor factors and the role of HBV DNA
The risk of donor-transmitted HBV infection is lower in kidney transplant recipients compared with liver transplant recipients with similar serologic marker positivity
Donors with HBV infections are generally categorized into two groups according to their serologic status.
The first donor group is the anti-HBc positive group in which the rate of transmission appears to be negligible according to the recipient’s protective immunity status. The overall seroconversion rate was 3.24% (mostly anti HBc seroconversion).
The second donor group is the HBsAg positive group where the HBV transmission remains a challenging problem[5]. In the current era, interesting information regarding the use of kidneys from HBsAg (+) donors is increasing. Previously, it was generally believed to discard the use of these kidneys. However, several recent studies and guidelines suggested that kidneys from HBsAg (+) donors can be carefully considered to be transplanted to appropriate recipients after careful consideration of the risk and benefit with informed consent
KT from living HBsAg (+) donors can be donated to antiHBs (+) recipients with protection who have no abnormalities of liver function test, no history of liver disease within the previous 28 days, and who are not living in the area of possible mutation strain of HBV
The results showed that this treatment was associated with excellent graft and patient survival without excess HBV transmission when compared with the control group
Recipient factors and the role of protective immunity
the recipients who received kidneys from donors with hepatitis B should have protective anti-HBs. Several guidelines and studies have suggested that an antiHBs > 10 mIU/mL was protective
Although cross-protection against other genotypes is observed, it has been suggested that a higher antibody concentration (> 50 mIU/mL) might be required
MONITORING OF HBV INFECTION AFTER TRANSPLANTATION
For kidney transplant recipients, The American Association for the Study of Liver Diseases (AASDL) suggested periodic assessment of serum ALT, HBV DNA, and HBsAg during immunosuppressive therapy. Reactivation of HBV infection was defined by detectable HBV DNAemia or positive HBsAg seroconversion. In addition, hepatitis flare was defined by rising of serum ALT more than 3 times the baseline level and > 100 U/L with evidence of hepatitis B reactivation
The Infectious Disease Community of Practice of the American Society of Transplantation advised monitoring liver enzymes, HBsAg, and HBV DNA every 3 mo for at least 12 mo post-transplantation.
all kidney transplant recipients who have a resolved infection of HBV (defined by positive anti-HBc serology) should be aware of a possibility of HBV reactivation during a course of intensive immunosuppression particularly rituximab
THE ROLE OF PROPHYLAXIS THERAPY Vaccination and revaccination protocol
Anti-HBs play a key role to minimize the risk of HBV transmission. Hepatitis B vaccination should be given to naïve recipients or previously immune recipients who have anti-HBs concentration below 10 mIU/mL[39]. Also, the KDIGO guideline suggested a concentration of Anti-HBs below 100 mIU/mL can be rapidly lowered down to a non-protective level and may require a booster dose at this step
monitoring of anti-HBs concentration should be done at least yearly. A further booster dose of vaccine may be required. This can be prescribed by either a single-shot high dose (40 µg) or a total complete course with a follow-up level at 4-wk after a complete course of treatment
A high dose of HBV vaccine was suggested to patients with ESKD who were receiving hemodialysis therapy. A protocol of three or four high-dose (40 µg) hepatitis B vaccine series with a target level of 10 mIU/mL at 4 wk post-treatment was suggested. Also, a second three doses of vaccination were suggested if the anti-HBs could not reach the desired level
Antiviral medications (nucleos(t)ide analogues) and HBIG
HBIG provides passive immunity for a high concentration of anti-HBs that are aimed to act as neutralizing antibodies to HBV
NAs are a group of antiviral medications that directly suppress HBV virus replication. Lamivudine was the most popular prophylaxis agent being used globally [5]. However, its efficacy was hampered by small number of lamivudine-resistant hepatitis B.
other drugs with a high genetic barrier such as entecavir were considered as a better alternative[19]. This was especially noteworthy in selected patients who were at risk of exposure to a lamivudine-resistant strain of HBV, including those who received kidneys from the donors previously treated by lamivudine.
Anti HBs (> 10 mIU/mL) and positive recipients can receive kidney transplants from anti-HBc (+) donors without a need for prophylaxis antiviral medications due to the negligible risk of HBV transmission
naïve recipients who received kidneys from anti-HBc (+) donors should receive lamivudine prophylaxis without HBIG for at least 1 year
HBs Ag (+) donors, recipients with protective anti-HBs (> 10 mIU/mL) risk should be assessed by the result of the NAT test and HBV DNA measurement.
If the result of nucleic acid for HBV was negative and HBV DNA was undetectable preventive strategies varied from no NA prophylaxis (in the setting of no potent induction therapy), or prescription of NA alone without HBIG.
If the anti-HBs is > 100 mIU/mL, one can proceed to KT without NA prophylaxis.
However, if HBV DNA was not measured by a method of optimum low detection limit or the result of HBV DNA cannot be obtained due to any reason, NA may be prescribed to make the risk of HBV transmission as low as possible.
In the setting of HBsAg (+)/HBV DNA (+) donor, most authors prescribed universal NA prophylaxis with or without HBIG as a prophylaxis regimen among patients with different levels of anti-HBs concentration
In the setting of HBsAg (+)/HBV DNA (+) donor, most authors prescribed universal NA prophylaxis with or without HBIG as a prophylaxis regimen among patients with different levels of anti-HBs concentration
Use of HBsAg (+)/DNA (+) donors to recipients with naïve or anti-HBs < 10 mIU/mL was the group with the highest risk being reported.
Another interesting issue is the use of HBsAg positive donors to recipients with HBsAg positive serology. A few studies[63-66] have reported favorable outcomes of this treatment option provided that the recipients received antiviral treatment before transplantation. Also, there is a suggestion that the recipients with positive HBsAg should have the result of liver biopsy that did not show evidence of cirrhosis.
Another interesting issue is the use of HBsAg positive donors to recipients with HBsAg positive serology. A few studies[63-66] have reported favorable outcomes of this treatment option provided that the recipients received antiviral treatment before transplantation. Also, there is a suggestion that the recipients with positive HBsAg should have the result of liver biopsy that did not show evidence of cirrhosis.
LONG TERM OUTCOMES AND SURVIVAL
Regarding HBsAg (-) anti-HBc (+) donors, historic studies found that there were no HBsAg seroconversion and no excess risk of morbidity and graft failure
RISK BENEFIT OF TRANSPLANTATION AND PROPOSED CRITERIA FOR HBsAg (+) DONOR UTILIZATION
As has been mentioned earlier, organs from HBsAg (+) donors are generally suggested to be discarded. However, with careful individual risk and benefit assessment, these organs may be utilized safely and serve as an alternative treatment to shorten waiting time rather than stay on a usual transplant waiting list
the criteria for utilization of kidneys from donors with HBsAg positivity depend on three groups of potential recipients.
The first group is patients with urgent need to receive KT
The second group is the recipients with positive HBsAg
The third group is patients being registered as active waiting list who have waiting time longer than the median time to receive a kidney in each national society.
all potential recipients should be vaccinated that aim to achieve anti-HBs at least > 10 mIU/mL. The potential recipients should not have HCV coinfection nor other cause of chronic liver disease which may worsen after KT. All recipients of HBsAg (+) donors should receive anti-viral medication, especially in the situation when the result of HBV DNA cannot be obtained before actual transplantation. HBIG may be considered for recipients with non-protective anti HBsAb level and/or in the situation of unknown HBV DNAemia of the donor. A protocol for close surveillance of viral reactivation and liver disease must be implemented. For HBsAg (+) recipient candidates, they must be treated with NA and evaluated by a specialist in liver disease. Untreated patients result in a higher mortality rate, with liver-related complications
CONCLUSION
the presence of positive HBsAg in potential organ donors should not preclude the use of kidney organs. Several additional steps and experienced transplant teams are specifically required to prepare waiting list candidates who are willing to receive a kidney from such donors.
2-What is the level of evidence provided by this article?
Level 5
3-Will you accept living or deceased donations from HBV-positive donors?
I will accept living or deceased donor with HBV positive for recipient need urgent transplantation in case of exhausted vascular access and not fit for CAPD
Kidney transplant remains the best possible option for patients with chronic kidney disease. Organ shortage is a world wide problem and efforts are being made to overcome this problem. Extended criteria donor is one such effort where kidneys which otherwise were considered unfit for donation are used in view of current evidence. This article has also looked into suitability of HbsAg + donors
The risk of using HbSAg+ donors if appropriately screened is negligible and transplant programs should look into this aspect carefully.
To reduce the risk of HBV transmission, a comprehensive approach is needed. This includes assessment of donor risk, optimal allocation to the proper recipient, appropriate immunosuppressive regimen, optimizing the prophylactic therapy, and post-transplant monitoring.
Low-risk hepatitis B surface antigen (HBsAg) positive kidney donor, defined by a negative test of hepatitis B virus (HBV) DNA being allocated to immune- recipients with anti-HBs at least 10 mIU/mL is a key factor in overcoming the risk of HBV transmission. The risk may be further eliminated with optimal nucleos(t)ide analog prophylaxis. Blood tests for HBV DNA, HBs Ag, and liver function tests should be routinely monitored after transplantation and when there is a change of immunosuppression. The excellent long-term outcomes being reported suggested that the outcomes of this treatment option are promising. This will lead to broader use of organs with positive HBsAg.
Will we accept such donors at our ceter?
Sometimes, the available donor may be an individual with chronic HBV infection (HBsAg positive). Recipients with HBV immunity due to vaccination may receive a kidney transplant from donors with chronic HBV infection (HBsAg positive). The risk of de novo infection is low but not zero which may be due in part to a decrease in anti-HBs titer over time and with immunosuppression.
We can only accept such donors in our center which deals with only living donors if there is no other donor available and recipient has Anti HBc AB titer more than10 and donor is HbSAg negative though AntiHbc Ab positive.Frankly speaking transplant is a costly affair in my country and patients have to pay from their pocket and they are not ready to take any risks as well.
In order to overcome the shortage of donors kidneys , ECD was proposing to include HBV infected donors. Particular approach was stipulated to includ extensive assessment of donor with HBS antigen to verify the infectivity of the donor and risk of HBV Transmission .
This approach includes selection of proper recipient, immunosuppressive medications, risk of transmission, prophylaxis and close follow up plan.
HBV immunological markers:
Anti HBC antibody with negative HBS antigen is carrying negligible risk and proceed for transplantation.
HBs antigen positive donor has to be assessed for infectivity and activity .
NAT study is pivotal to diagnose active infection, in the window period which persist up to 33 to 44 days post inoculation or in occult infection where the NAT is positive and negative HBS antigens.
HBe antigen is reflective of infectivity and replicative state equivalent to NAT of more than 10000.
HBe antibody is indicative of nonrplicative state with NAT of less than 10000
The marker of active replicative viral infection Hbe antigen and viral DNA are the indicators of subsequent step in the management of HBV donors and the plan of kidney transplantation.Therefor, when Hbe antigen and DNA are positive ,it’s not recommended for kidney donation.But ,when DNA is positive and HBe antigen is negative ,then depending on Anti HBV antibodies titer the decision of transplant is planned, in a way that if titer of antibodies below 10 miu/ml, then it’s contraindicated, but if it’s urgently indicated then HBIG is indicated with 6 months prophylactic medication with Lamivudine or Enticavir with close observation of liver function test and virology markers.
When HBs antibody is more than 10 miu/ml in the setting of positive DNA and negative Hbe antigen its recommended to proceed with transplantation with
Prophylactic cover..
This paper is a review article with level of evidence 5.
In my opinion ,transplantation with hbv donor kidney is a challenging option for highly critical patients with limited options. I would for each case options as per it’s merits.
Title:
Kidney transplant from donors with hepatitis B: A challenging treatment option
Method :
Review article
Main ideas of article:
-Utilizing kidneys from donors with hepatitis B is one way to alleviate the current organ shortage situation. However, the risk of hepatitis B virus (HBV) transmission remains a challenge that undermines the chance of organs being used. This is particularly true with hepatitis B surface antigen (HBsAg) positive donors despite the comparable long-term outcomes when compared with standard donors
-To reduce the risk of HBV transmission, a comprehensive approach is needed. This includes assessment of donor risk, optimal allocation to the proper recipient, appropriate immunosuppressive regimen, optimizing the prophylactic therapy, and post-transplant monitoring
-topics include donor risk assessment by adopting the nucleic acid test coupled with HBV DNA as the
HBV screening, optimal recipient selection, importance of hepatitis B immunity, role of nucleos(t)ide analogues, and hepatitis B immunoglobulin
SCREENING TESTS :
hepatitis B core antigen (IgM anti-HBc) becomes positive after 4 wk to 6 wk of exposure indicating recent infection and B core antibody (anti-HBc) appear at the onset of symptoms and persists for life.
Hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) indicate viral replicative activity. In this situation HBeAg positivity indicates active viral replication Whereas anti-HBe positivity indicates the presence of the non-replication phase
Hepatitis B antibody (anti-HBs) is a marker of immune status due to either naturally- or vaccine acquired immunity.
nucleic acid test (NAT) :HIV/HCV/HBV multiplex.
has been proposed as an optional donor screening test. This test is advantageous, because it shortens the windows period to 20-22 d compared to 35-44 d by conventional serology
However, cost effectiveness and logistic issues are main problems in regular implementation of nucleic acid tests (NAT)
RISK OF HBV TRANSMISSION AND INFECTION AFTER KT
Donor factors :
The risk of donor-transmitted HBV infection is lower in kidney transplant recipients
compared with liver transplant recipients with similar serologic marker positivity
Donors with HBV infections are generally categorized into two groups according to their serologic status.
The first donor group is the anti-HBc positive group in which the rate of transmission appears to be negligible according to the recipient’s protective immunity status
The second donor group is the HBsAg positive group where the HBV transmission remains a challenging problem
– In the current era, interesting information regarding the use of kidneys from HBsAg (+) donors is increasing. Previously, it was generally believed to discard the use of these kidneys. However, several recent studies and guidelines suggested that kidneys from HBsAg (+) donors can be carefully considered to be transplanted to appropriate recipients after careful consideration of the risk and benefit with informed
consent
Recipient factors
Recipients who received kidneys from donors with hepatitis B should have protective anti-HBs> 10mIU /ML.
It is important to note that HBV transmission may not necessarily lead to clinical evidence of HBV infection
For KT, it was unclear whether a higher level of anti-HBs concentration was
associated with a higher level of protection of HBV transmission as was shown in liver
transplantation. Immunity to hepatitis B was crucial to prevent donor-derived infection. However, it was suggested that an anti-HBs concentration of > 10 mIU/mL was protective[
Monitor and f/u :
ALT, HBV DNA and HBsAg during immunosuppressive therapy
Detectable HBV DNAemia or positive HBsAg seroconversion is defined as infection reactivation.
Hepatitis flare was defined by rising of serum ALT more than 3 times the baseline level and > 100 U/L with evidence of hepatitis B reactivation.
Liver enzymes, HBsAg, and HBV DNA should be monitored every 3 month for at least 12 month after transplantation.
Vaccination and revaccination protocol
Anti-HBs play a key role to minimize the risk of HBV transmission. Hepatitis B vaccination should be given to naïve recipients or previously immune recipients who have anti-HBs concentration below 10 mIU/mL
A further booster dose of vaccine may be required. This can be prescribed by either a single-shot high dose (40 µg) or a total complete course with a follow-up level at 4-wk after a complete course of treatment
A high dose of HBV vaccine was suggested to patients with ESKD who were receiving hemodialysis therapy. A protocol of three or four high-dose (40 µg) hepatitis B vaccine series with a target level of 10 mIU/mL at 4 wk post-treatment was suggested
Antiviral medications
HBIG provides passive immunity for a high concentration of anti-HBs that are aimed to act as neutralizing antibodies to HBV
Most prescriptions of HBIG were used in combination with antiviral nucleos(t)ide analogs (NAs) that aim to prevent recurrent infection of HBV after liver transplantation. This regimen was found superior to HBIG or NA alone[59]. However, the optimal dose of HBIG to be used for kidney transplant recipients from donors with HBV was not clearly known.
LONG TERM OUTCOMES AND SURVIVAL
Regarding HBsAg (-) anti-HBc (+) donors, historic studies found that there were no HBsAg seroconversion and no excess risk of morbidity and graft failure
Subsequent studies that examined the outcomes in children have shown a similar
result in terms of patient survival and graft surviva
CHALLENGING PERSPECTIVE
KT from donors with HBsAg (+) donors is not a risk-free procedure. A careful
allocation to appropriate recipients can be successfully performed. NAT for HBV is
now accepted to be a useful screening test. The result of a sensitive HBV DNA test is of
prime importance in the organ allocation and the design of the prophylactic protocol.
The rate of HBV transmission from this treatment option was reported to be low and
manageable. HBV reactivation can occur in resolved HBV infection. Thus, a regular
monitoring schedule for HBV is an essential part of post-transplant care
Level 5
In our center no they will not accept
Summary:
The prevalence of chronic HBV infection is quite variable geographically. Using donors with markers of HBV infections may significantly help in endemic areas since the prevalence in donors is similar to that of the general population.
As per recent evidence, non-liver organs from total hepatitis B core antibody-positive [anti-HBc (+)] donors are being routinely used in
any recipient irrespective of his/her HBV immune status without prophylaxis as there is minimal risk of de novo infection. But using kidneys from HBsAg positive persons is still controversial.
In window period it is quite difficult to test for HBsAg. hepatitis B core antigen (IgM anti-HBc) becomes positive after 4 wk to 6 wk of exposure indicating recent infection and B core antibody (anti-HBc) appear at the onset of symptoms and persists for life.
Hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) indicate viral replicative activity. In this situation HBeAg positivity indicates active viral replication (i.e., usually a viral load > 10000 IU/mL). Whereas anti-HBe positivity indicates the presence of the non-replication phase (i.e., a viral load < 10000 IU/mL).
Hepatitis B antibody (anti-HBs) is a marker of immune status due to
either naturally- or vaccine-acquired immunity.
Compared to liver transplant recipients the risk of donor transmitted HBV infection is quite low in kidney transplant recipient
Living HBsAg (+) donors can be donated to anti-HBs (+) recipients who dont have any abnormalities of liver function.
Before transplantation HBeAg and anti-HBe are routinely checked in HBsAg (+) donors to ensure a low infectivity rate.Donation from HBsAg (+)/HBV DNA (-) (< 20 IU/mL) donors to immune recipients (anti-HBs > 100 mIU/mL) was found safe safe and was not associated with any HBV viremia in quite a few studies.
Recipients should have protective anti-HBs> 10mIU /ML.
long-term outcomes were favorable when compared with donors with no markers of HBV who received proper prophylaxis regimen.
Level of Evidence: 5
Can be accepted in a situation-
Can be condidered with-
Utilizing kidneys from donors with hepatitis B is one way to alleviate the current organ shortage situation. However, the risk of hepatitis B virus (HBV) transmission remains a challenge that undermines the chance of organs being used.
There are several proposed rationales to solve the problem of organ shortage. One possible solution is to expand the donor pool by utilizing “extended donor criteria organs”. Such organs include those from donors with hepatitis B virus (HBV) infection.
RISK OF HBV TRANSMISSION AND INFECTION AFTER KT
Donor factors and the role of HBV DNA
The risk of donor-transmitted HBV infection is lower in kidney transplant recipients compared with liver transplant recipients with similar serologic marker positivity.
Patients who have strong risk factors for HBV/ HCV/HIV combination should be tested for HBsAg, HBV NAT, and then HBV DNA by a test with the highest sensitivity and specificity.
Donors with HBV infections are generally categorized into two groups according to their serologic status. The first donor group is the anti-HBc positive group in which the rate of transmission appears to be negligible according to the recipient’s protective immunity status.
The second donor group is the HBsAg positive group where the HBV transmission remains a challenging problem
several recent studies and guidelines suggested that kidneys from HBsAg (+) donors can be carefully considered to be transplanted to appropriate recipients after careful consideration of the risk and benefit with informed consent.
The role of NAT in reducing the window period of serological test in combination with a careful evaluation of the donor behavioral risk factors has been increasingly emphasized.
KT from living HBsAg (+) donors can be donated to antiHBs (+) recipients with protection who have no abnormalities of liver function test, no history of liver disease within the previous 28 days, and who are not living in the area of possible mutation strain of HBV
Use of antiviral medications to treat HBV add benefit to the treatment plan to use organs from HBsAg (+) donors. Unlike liver transplantation, KT from this type of donor can be associated with a functional cure of HBV.
The functional cure was defined by a state of sustained loss of HBsAg with or without anti-HBs seroconversion which was usually associated with good clinical outcomes
Recipient factors and the role of protective immunity
In principle, the recipients who received kidneys from donors with hepatitis B should have protective anti-HBs. Several guidelines and studies have suggested that an antiHBs > 10 mIU/mL was protective
MONITORING OF HBV INFECTION AFTER TRANSPLANTATION
For kidney transplant recipients, The American Association for the Study of Liver Diseases (AASDL) suggested periodic assessment of serum ALT, HBV DNA, and HBsAg during immunosuppressive therapy. Reactivation of HBV infection was defined by detectable HBV DNAemia or positive HBsAg seroconversion. In addition, hepatitis flare was defined by rising of serum ALT more than 3 times the baseline level and > 100 U/L with evidence of hepatitis B reactivation
Besides, all kidney transplant recipients who have a resolved infection of HBV (defined by positive anti-HBc serology) should be aware of a possibility of HBV reactivation during a course of intensive immunosuppression particularly rituximab
A high incidence of reactivation was observed in recipients with ABO incompatibility, who received plasmapheresis, received acute rejection therapy, and received induction therapy with rituximab
THE ROLE OF PROPHYLAXIS THERAPY
Vaccination and revaccination protocol
Anti-HBs play a key role to minimize the risk of HBV transmission. Hepatitis B vaccination should be given to naïve recipients or previously immune recipients who have anti-HBs concentration below 10 mIU/mL.Also, the KDIGO guideline suggested a concentration of Anti-HBs below 100 mIU/mL can be rapidly lowered down to a non-protective level and may require a booster dose at this step
Antiviral medications (nucleos(t)ide analogues) and HBIG
Another modality to prevent HBV transmission via kidney transplant organs was the use of antiviral medications and HBIG. HBIG provides passive immunity for a high concentration of anti-HBs that are aimed to act as neutralizing antibodies to HBV.
Most prescriptions of HBIG were used in combination with antiviral nucleos(t)ide analogs (NAs) that aim to prevent recurrent infection of HBV after liver transplantation. This regimen was found superior to HBIG or NA alone.
However, the optimal dose of HBIG to be used for kidney transplant recipients from donors with HBV was not clearly known.
Lamivudine was the most popular prophylaxis agent being used globally
The incidence of lamivudine-resistance can be increased with longer durations of exposure (as high as a fifty percent increase after 2 years).
In chronic hepatitis B liver transplant recipients, high genetic barrier nucleos(t)ide analog combined with HBIG was superior to lamivudine combined with HBIG in the prevention of recurrent HBV infection (disease recurrent rate 1.0% compare to 6.1%)
Use of HBsAg (+)/DNA (+) donors to recipients with naïve or anti-HBs < 10 mIU/mL was the group with the highest risk being reported.
A study in 20 naïve recipients who received prophylactic NA or HBIG or combination showed that the incidence of acute liver injury, anti-HBc seroconversion, and HBV DNAemia was 20 %, 10%, and 10% respectively.
Thus the use of this treatment option should be restricted to patients with an urgent need for KT (exhausted multiple vascular access, with ongoing uremia despite adequate hemodialysis prescription)
LONG TERM OUTCOMES AND SURVIVAL
Regarding HBsAg (-) anti-HBc (+) donors, historic studies found that there were no HBsAg seroconversion and no excess risk of morbidity and graft failure
These results suggested that kidney transplants from HBsAg positive donors to appropriate recipients was a cost-effective option when compared with keeping the potential recipient in the waiting list pool
RISK BENEFIT OF TRANSPLANTATION AND PROPOSED CRITERIA FOR HBsAg (+) DONOR UTILIZATION
As has been mentioned earlier, organs from HBsAg (+) donors are generally suggested to be discarded.
However, with careful individual risk and benefit assessment, these organs may be utilized safely and serve as an alternative treatment to shorten waiting time rather than stay on a usual transplant waiting list. Shortened waiting time was also beneficial in improving 10-year graft survival in both living and deceased donor KTs.
Moreover, recipients can benefit from excellent graft survival without excess risk of liver disease as aforementioned
It has long been shown and recently confirmed that kidney transplants promoted both longer life expectancy and better quality of life at a lower cost relative to staying on dialysis treatment
However, the criteria for utilization of kidneys from donors with HBsAg positivity has not been well described. We would like to describe our proposed criteria to define three groups of potential recipients.
The first group is patients with urgent need to receive KT.
The second group is the recipients with positive HBsAg.
The third group is patients being registered as active waiting list who have waiting time longer than the median time to receive a kidney in each national society. The potential recipients should be discussed about the willingness to receive a kidney from donors with HBsAg positivity. They may choose not to take this opportunity and continue to wait for HBsAg negative donors.
CHALLENGING PERSPECTIVE
KT from donors with HBsAg (+) donors is not a risk-free procedure. A careful allocation to appropriate recipients can be successfully performed. NAT for HBV is now accepted to be a useful screening test. The result of a sensitive HBV DNA test is of prime importance in the organ allocation and the design of the prophylactic protocol. The rate of HBV transmission from this treatment option was reported to be low and manageable. HBV reactivation can occur in resolved HBV infection. Thus, a regular monitoring schedule for HBV is an essential part of post-transplant care. Differentiation between donor-derived HBV infection and reactivation of recipient strain HBV infection may be difficult. We believe that the use of kidney organs from donors with HBV infection in the area where the national organ donation rate is less than the rate of endemic HBV infection is a better alternative than discarding the organs.
CONCLUSION
Within this era of several newer antiviral medications, the presence of positive HBsAg in potential organ donors should not preclude the use of kidney organs. Several additional steps and experienced transplant teams are specifically required to prepare waiting list candidates who are willing to receive a kidney from such donors. These steps should be regularly assessed for each individual during his or her registration as active waiting list to receive KT from deceased donors.
———————————————————-
What is the level of evidence provided by this article?
Level V
——————————
Will you accept living or deceased donations from HBV-positive donors?
I will not accept such donor still we need a globally recognized protocols to such donors and receipts to be in safe area for both
as there is no enough studies about the outcomes for both living donors and receipts
Please summarise this article in your own words
# INTRODUCTION
*The number of ESKD patients awaiting KT far exceeds the number of organ donations globally and leads to a problem of organ shortage, one possible solution is to expand the donor pool by utilizing “extended donor criteria organs”. Such organs include those from donors with (HBV) infection.
*According to recent guidelines, there is a high tendency for accepting non-liver organs from total hepatitis B core antibody-positive donors to be used in any recipient regardless of HBV immune condition without prophylaxis due to the negligible risk of de novo infection, even so, receiving kidneys from donors with positive hepatitis B surface antigen still controversial, and it is generally suggested that such organs be refused.
*So the aim of this article to summarize the current evidence regarding the use kidneys from HBsAg (+) donors with an emphasis on the risk of HBV transmission, liver related morbidities, and the outcomes of KT.
# SCREENING TEST FOR HBV INFECTION IN ORGAN DONORS
*Usually relies on a panel of serologic tests.
*Serologic testing alone still has limitations due to the long window period and the lack of sensitivity to detect occult infections.
* HBsAg is widely distributed. It can fail to detect disease during a 35-44 d window period post inoculation or occult infection defined as detectable viral DNA in absence of HBsAg.
*Anti-HBc. In acute hepatitis B infection, (IgM anti-HBc) becomes positive after 4 wk to 6 wk of exposure indicating recent infection and active viral replication whereas total hepatitis B core antibody (anti-HBc) appear at the onset of symptoms and persists for life.
*(HBeAg) and (anti-HBe) identify viral replicative activity as HBeAg positivity which indicates active viral replication, In contrast, anti-HBe positivity indicates the presence of the non-replication phase.
*Anti-HBs is a marker of immune status due to either naturally- or vaccine-acquired immunity.
*In the deceased kidney donation, HBs Ag and anti-HBc are generally accepted as cost-effective screening tools.
*Transplant centers in endemic areas routinely add on anti-HBe and HBeAg to the donor screening platform as biomarkers of high viral replication and infectivity activity relating to a high viral burden.
*To improve the sensitivity of screening tests, the nucleic acid test (NAT), which is usually in the form of an HIV/HCV/HBV multiplex, because it shortens the windows period to 20-22 d compared to 35-44 d by conventional serology and promising solution, obstacles to its implementation include whether it is cost effective
RISK OF HBV TRANSMISSION AND INFECTION AFTER KT
Donor factors and the role of HBV DNA.
*The risk is lower in kidney transplant recipients compared with liver transplant recipients with similar serologic marker positivity. Important behavioral risk factors to acquire HBV infections should be carefully reviewed.
* Donors with HBV infections are generally categorized into two groups according to their serologic status:
*The anti-HBc positive group in which the rate of transmission appears to be negligible according to the recipient’s protective immunity status. The overall seroconversion rate was 3.24%.
*The HBsAg positive group where the HBV transmission remains a challenging
problem.
*Guidelines suggested that kidneys from HBsAg (+) donors can be carefully considered to be transplanted to appropriate recipients after careful consideration of the risk and benefit with informed consent
*Chancharoenthana et al reported that kidney transplants from HBsAg (+)/HBV DNA (-) (< 20 IU/mL) donors to 20 immune recipients (anti-HBs > 100 mIU/mL) was safe and was not associated with any HBV viremia, hepatitis or death despite the absence of antiviral prophylaxis.
Recipient factors and the role of protective immunity
*Several guidelines and studies have suggested that an anti- HBs > 10 mIU/mL was protective. It is important to note that HBV transmission may not necessarily lead to clinical evidence of HBV infection.
*Study showed evidence of HBV transmission by the kidney grafts without any clinical manifestations of HBV infection.
*It was unclear whether a higher level of anti-HBs concentration was associated with a higher level of protection of HBV transmission as was shown in liver transplantation.
* Tuncer et al and Asuman et al reported that kidney transplants from HBsAg (+) donors to 146 recipients with anti-HBs > 10 mIU/mL were not associated with any de novo HBV infection or active liver diseases.
MONITORING OF HBV INFECTION AFTER TRANSPLANTATION
*The (AASDL) suggested periodic assessment of serum ALT, HBV DNA, and HBsAg during immunosuppressive therapy.
* Reactivation of HBV infection was defined by detectable HBV DNA or positive HBsAg seroconversion.
Hepatitis flare was defined by rising of serum ALT more than 3 times the baseline level and > 100 U/L with evidence of hepatitis B reactivation.
*The monitoring of liver enzymes, HBsAg, and HBV DNA was advised every 3 mo for at least 12 mo post-transplantation.
* Native recipients from donors with HBV infection were suggested to receive lifelong monitoring.
*Resolved infection of HBV may have a possibility of HBV reactivation during a course of intensive immunosuppression particularly rituximab.
THE ROLE OF PROPHYLAXIS THERAPY
Vaccination and revaccination protocol
*Hepatitis B vaccination should be given to naïve recipients or previously immune recipients who
have anti-HBs concentration below 10 mIU/mL.
* As an antibody concentration is likely to wane over time, monitoring of anti-HBs concentration should be done at least yearly.
* A protocol of three or four high-dose (40 μg) hepatitis B vaccine series with a target level of 10 mIU/mL at 4 wk post-treatment was suggested. Also, a second three doses of vaccination were suggested if the anti-HBs could not reach the desired level.
*Antiviral medications and HBIG another modality to prevent HBV transmission via kidney transplantation.
*HBIG provides passive immunity for a high concentration of anti-HBs that are aimed to act as neutralizing antibodies to HBV.
*Most prescriptions of HBIG were used in combination with antiviral nucleos(t)ide analogs (NAs) that aim to prevent recurrent infection of HBV after liver transplantation.
CONCLUSION
Within this era of several newer antiviral medications, the presence of positive HBsAg in potential organ donors should not preclude the use of kidney organs.
*What is the level of evidence provided by this article?
Level 5
*Will you accept living or deceased donations from HBV-positive donors?
No, I will not accept such donation in my center. Still we need further study.
I will accept this donors group although level evidence is low
▪︎ anti-HBc (+) donors with negative HBs Ag , negative HBe Ag , and undetectable DNA
▪︎ urgent recepiants whose have anti-HBs (> 10 mIU/mL) after discussion their willingness and the risks arising therefrom
▪︎ HBsAg positive recipients with no HCV coinfection nor other cause of chronic liver disease
Organ shortage is a major barrier to transplantation and results in prolonged waiting time, extended donor criteria organs including those from donors with HBV infection is a possible solution.
In endemic areas, those donors can increase the donor pool, however, accepting kidneys from donors with HBsAg+ is controversial.
Screening test for HBV infection in organ donors:
HBsAg: widely used, give false negative result during window phase and with occult infection
Anti-HBc: test for previous HBV exposure and persist for life
HBeAg: indicate active viral replication
Anti-HBe: indicate presence of non-replication phase
Anti-HBs: marker of immune status naturally or vaccine acquired immunity.
In deceased donor, HBsAg and anti-HBc are cost effective for screening. in endemic areas, some centers add anti-HBe & HBeAg to determine viral replication and infectivity
However, serological tests lack sensitivity in detection of occult infections
NAT increase sensitivity of screening but has several limitations and may be added when using organ with discordant results, the use of NAT is individualized according to each country
Risk of HBV transmission and infection after kidney transplantation:
Donor factors and the role of HBV DNA:
The risk in kidney transplantation is lower than liver transplantation.
HBV reactivation is a risk in immunocompromised patients with acute and chronic HBV infection even after clearance of HBsAg in blood.
Important behavioral risk factors should be reviewed and testing for HBsAg, HBV NAT and HBV DNA by high sensitivity and specificity tests should be performed for patient at risk for HBV infection.
Donors with HBV infection are either having anti-HBc positive and low risk of transmission or having HBsAg+ with high risk of transmission.
Recently, studies suggested that kidneys from donors with HBsAg+ are accepted after assessing the risk and benefit with informed consent.
Living HBsAg+ donors can donate to antiHBs+ recipients provided liver function tests are normal, no history of recent liver disease and not living in place with possible mutation strain of HBV.
HBeAg and anti-HBe are routinely done in HBsAg+ donors to ensure low infectivity rate.
Recipient factors and the role of protective immunity:
Recipients should have anti-HBs>10mIU/mL
HBV transmission by kidney graft may not be associated clinical manifestations of HBV infection
It is unclear if higher anti-HBs concentration is associated with higher protection in kidney transplants.
The immune protection may decrease in cases with HBV antigenic variation due to mutation in the determinant region of HBsAg.
Monitoring of HBV infection after kidney transplantation:
Periodic assessment of serum ALT, HBV DNA and HBsAg during immunosuppressive therapy, however the optimal frequency of monitoring is variable
Detection of HBV DNAemia or HBsAg seroconversion is considered reactivation of HBV infection.
Kidney recipients with resolved infection of HBV (positive anti-HBc) are at risk of HBV reactivation with immunosuppressive therapy especially rituximab and incidence of reactivation increases with induction, plasmapheresis or rejection treatment.
Role of prophylaxis therapy:
Vaccination and revaccination protocols:
Vaccination should be given to naïve recipients or those with anti-HBs concentration <10mIU/mL.
KDIGO suggested that anti-HBs <100mIU/mL may decrease rapidly and require a booster dose
Patients with CKD may have insufficient immune response to HBV with low or absent antibody titer
Anti-HBs concentration should be monitored yearly and it is suggested to be kept at level >100mIU/mL to avoid reactivation
Antiviral medications(nucleotide analogues) and HBIG:
HBIG provide passive immunity and act as neutralizing antibodies to HBV, the optimal dose is unclear in kidney transplant recipients from donors with HBV.
NA are antiviral medications suppress viral replication as lamivudine may be associated with resistance, increase with longer duration of exposure,
entecavir an alternative with higher genetic barrier.
Choice of NA is according to serologic markers of HBV infection and according to NAT test and HBV DNA measurement and use of potent induction therapy.
NA should be prescribed in recipient of kidney from HBV donor who will receive rituximab.
Long term outcome and survival:
Kidney transplantation from donors with HBsAg- and anti-HBc+ donors is not associated with HBsAg seroconversion nor increased comorbidity and can be transplanted safely.
Proper prophylaxis regimen is associated with favorable long term outcomes compared to donors with no markers of HBV
It is suggested that kidney transplantation from HBsAg+ donors is cost effective when compared with keeping potential recipient in the waiting list.
Risk benefit of transplant and proposed criteria for HBsAg+ donor utilization:
Benefits include shortened waiting time through expanding donor pool with good graft survival in living and deceased donor kidney transplants without increased risk of liver disease.
It is associated with better patient survival and improved quality of life at a lower cost than dialysis.
However, criteria of utilization of kidneys from donors with HBsAg is not well determined.
Potential recipients should be discussed about receiving kidney from donor with HBsAg.
All potential recipients should be vaccinated to keep anti-HBs >10, they shouldn’t have HCV coinfection nor other cause of chronic liver disease.
All recipients of HBsAg donors should receive antiviral medication
Close follow up for viral reactivation and liver diseases.
Level of evidence: 5 (Review article)
I will not accept donor with HBV infection as there is no enough evidence about safety of transplantation, no clear regimen for monitoring post transplant and all available studies included small sample size.
Q1: to overcome the organ shortage problem, donors with HBV infection are considered as “extended criteria donors” in endemic areas. This utilization needs specific consideration. Anti-HBV positive donors could be utilized due to low risk of infection; however, HBV AG positive donors are more controversial.
In cadaveric kidney donors, HBS AG and anti-HBC are used for screening. NAT test (HIV/HCV/HBV multiplex) is an optimal screening test beside serological tests. Kidney TX has lower risk for HBV-infection from donors.
Donors with only anti-HBS positivity have a seroconversion rate of 3.24%. For HBS Ag positive donors, screening by NAT, HBeAg, anti- HBe, donor risk factors and recipient’s Anti-HBs Ab situation are important to determine risk of transmission. Nowadays, using antiviral treatment would result in a functional cure. Using HBIG and antiviral treatment as prophylaxis was associated with excellent graft survival without HBV transmission. Outcome of kidneys from HBS Ag+ and HBV DNA – donors to recipients with protective anti- HBS Ab titers was excellent. Anti- HBS Ad titers more than 10 IU/ml was protective. Protective titers depend on genotype. ALT, HBV DNA and HBS Ag are used to monitor HBV infection after transplantation. There is an increased risk of HBV reactivation after receiving rituximab. Anti-HBS Ab concentration should be done at least yearly and if is low, 3-4 dose of 40 µg HBV vaccine is recommended at 0,1, and 6 months. Titers of at least 10 IU/ml and preferably more than 100 IU/ml are protective. Use of HBIG and antiviral drugs are another option. Lamivudine or entecavir for lamivudine- resistant strains are considered as another treatment. If both HBS Ag and HBV DNA are positive, prophylaxis with NA±HBIG are prescribed. But, there is still a risk of positivity especially with potent induction therapy. After TX regular monitoring for HBV is necessary in these recipients.
Q2: This is a review article with the level of evidence of 5.
Q3: No, in our center HBS-positive donors are not accepted for HBS Ag-negative children.
Please summarize this article in your own words
INTRODUCTION
There is ever increasing need for kidney donation globally due to increasing cases of ESRD. Current review article evaluates possible options of using Hepatitis B positive individuals as potential donors by utilizing “extended donor criteria organs”.
The prevalence of chronic HBV infection is quite variable geographically. Using donors with markers of HBV infections may significantly help in endemic areas since the prevalence in donors is similar to that of the general population. But in such cases major challenge is to determine the optimal use of kidneys.
As per the current guidelines, non-liver organs from total hepatitis B core antibody-positive [anti-HBc (+)] donors are being routinely used in
any recipient irrespective of his/her HBV immune status without prophylaxis as there is minimal risk of de novo infection. But using kidneys from HBsAg positive persons is still controversial.
SCREENING TESTS IN ORGAN DONORS
During the window period of 35-44 days after inoculation or occult infection it is quite difficult to test for HBsAg. hepatitis B core antigen (IgM anti-HBc) becomes positive after 4 wk to 6 wk of exposure indicating recent infection and B core antibody (anti-HBc) appear at the onset of symptoms and persists for life.
Hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) indicate viral replicative activity. In this situation HBeAg positivity indicates active viral replication (i.e., usually a viral load > 10000 IU/mL). Whereas anti-HBe positivity indicates the presence of the non-replication phase (i.e., a viral load < 10000 IU/mL).
Hepatitis B antibody (anti-HBs) is a marker of immune status due to
either naturally- or vaccine-acquired immunity.
But serologic tests have two major limitations i.e. long window period
and lack of sensitivity to detect occult infections. To overcome this hurdle and improve the sensitivity of testing, it is proposed to use nucleic acid test (NAT), which is usually in the form of an HIV/HCV/HBV multiplex.
However, cost effectiveness and logistic issues are main problems in regular implementation of nucleic acid tests (NAT) but still adding NAT led to a gain in overall organ utilization.
RISK OF HBV TRANSMISSION AND INFECTION AFTER KT
DONOR FACTORS –
RECIPIENT FACTORS
MONITORING
CONCLUSION
LEVEL OF EVIDENCE – 5
Please summarise this article in your own words
-The number of ESKD patients awaiting KT far exceeds the number of organ donations globally and leads to a problem of organ shortage. There are several
proposed rationales to solve the problem of organ shortage. One possible solution is to expand the donor pool by utilizing “extended donor criteria organs”. Such organs include those from donors with hepatitis B virus (HBV) infection.
– According to current guidelines, there is an increasing trend of accepting non-liver organs from total hepatitis B core antibody-positive [anti-HBc (+)] donors to be used in any recipient regardless of HBV immune status without prophylaxis due to the negligible risk of de novo infection. However, utilizing kidneys from donors with positive hepatitis B surface antigen (HBsAg) [HBsAg (+)] remains controversial, and it is generally suggested that such organs be discarded.
-The test for HBsAg is widely distributed but it can fail to detect disease during a 35-44 d window period after inoculation or occult infection defined as detectable viral DNA in absence of HBsAg.
-Another importance serologic screening test for previous HBV exposure is anti-HBc. In acute hepatitis B infection, immunoglobulin M (IgM) antibody to hepatitis B core antigen (IgM anti-HBc) becomes positive after 4 wk to 6 wk of exposure indicating recent infection and active viral replication whereas total hepatitis
B core antibody (anti-HBc) appear at the onset of symptoms and persists for life.
– HBeAg positivity which indicates active viral replication (i.e., usually a viral load > 10000 IU/mL). In contrast, anti-HBe positivity indicates the presence of the non-replication phase (i.e., a viral load < 10000 IU/mL). Lastly, hepatitis B antibody (anti-HBs) is a marker of immune status due to either naturally- or vaccine-acquired immunity.
-In the situation of deceased kidney donation, HBs Ag and anti-HBc are generally
accepted as cost-effective screening tools.
-Isolated anti-HBc is commonly observed : in the early window period of acute hepatitis B , a resolved HBV infection with waning of anti-HBs titer , a false positive anti-HBc and an occult chronic HBV infection with low viremia and undetectable HBsAg.
-To improve the sensitivity of screening tests, the nucleic acid test (NAT)has been proposed as an optional donor screening test. This test is advantageous, because it shortens the windows period to 20-22 d compared to 35-44 d by conventional serology.
-The risk of donor-transmitted HBV infection is lower in kidney transplant recipients compared with liver transplant recipients with similar serologic marker positivity.
– Donors with HBV infections are generally categorized into two groups
according to their serologic status:
The first donor group is the anti-HBc positive group in which the rate of transmission appears to be negligible according to the recipient’s protective immunity status. The overall seroconversion rate was 3.24% (mostly anti HBc seroconversion).
The second donor group is the HBsAg positive group where the HBV transmission remains a challenging problem. Several recent studies and guidelines suggested
that kidneys from HBsAg (+) donors can be carefully considered to be transplanted to appropriate recipients after careful consideration of the risk and benefit with informed consent .
– KT from living HBsAg (+) donors can be donated to anti- HBs (+) recipients with protection who have no abnormalities of liver function test, no history of liver disease within the previous 28 days, and who are not living in the area
of possible mutation strain of HBV.
– HBeAg and anti-HBe were routinely checked in HBsAg (+) donors to ensure a low infectivity rate of HBV before performing KT.
-Use of antiviral medications to treat HBV add benefit to the treatment plan to use organs from HBsAg (+) donors.
-Unlike liver transplantation, KT from this type of donor can be associated with a functional cure of HBV. The functional cure was defined by a state of sustained loss of HBsAg with or without anti-HBs seroconversion which was usually associated with good clinical outcomes.
– A recent study performed 83 living KTs from HBsAg (+) donors to HBsAg (-) recipients. Before the transplant, 28% of the donor in the latter study were HBV DNA (+) and 24% of the recipients had no anti- HBs. All recipients in the latter study received hepatitis B immunoglobulin (HBIG) and antiviral medication as prophylaxis treatment. The results showed that this treatment was associated with excellent graft and patient survival without excess HBV transmission when compared with the control group.
-Chancharoenthana et al[14] reported that kidney transplants from HBsAg
(+)/HBV DNA (-) (< 20 IU/mL) donors to 20 immune recipients (anti-HBs > 100
mIU/mL) was safe and was not associated with any HBV viremia, hepatitis or death despite the absence of antiviral prophylaxis.
– The recipients who received kidneys from donors with hepatitis B should
have protective anti-HBs. Several guidelines and studies have suggested that an anti-HBs > 10 mIU/mL was protective .
– For kidney transplant recipients, The American Association for the Study of Liver
Diseases (AASDL) suggested periodic assessment of serum ALT, HBV DNA, and
HBsAg during immunosuppressive therapy.
– Reactivation of HBV infection was defined by detectable HBV DNAemia or positive HBsAg seroconversion.
– Hepatitis flare was defined by rising of serum ALT more than 3 times the baseline level and > 100 U/L with evidence of hepatitis B reactivation.
– The Infectious Disease Community of Practice of the American Society
of Transplantation advised monitoring liver enzymes, HBsAg, and HBV DNA every 3 mo for at least 12 mo post-transplantation.
-All kidney transplant recipients who have a resolved infection of HBV
(defined by positive anti-HBc serology) should be aware of a possibility of HBV
reactivation during a course of intensive immunosuppression particularly rituximab.
-As an antibody concentration is likely to wane over time, monitoring of anti-HBs concentration should be done at least yearly.
– The results of long-term outcomes being reported showed favorable outcomes when compared with donors with no markers of HBV with proper prophylaxis regimen.
-Kidney transplants from HBsAg positive donors to appropriate recipients was a cost-effective option when compared with keeping the potential recipient in the waiting list pool.
– The potential recipients should be discussed about the willingness to receive a kidney from donors with HBsAg positivity. The risk of infection transmission before undergoing KT, recipients should be fully informed and consent must be obtained from each individual.
What is the level of evidence provided by this article?
Level 5
Will you accept living or deceased donations from HBV-positive donors?
Yes, I will accept due to shortage of the donor pool.
-Kidney transplantation (KT) is the preferred treatment for patients with end-stage
kidney disease (ESKD).
-It is associated with reduced mortality and improved quality
of life when compared to dialysis therapy.
-The number of ESKD patients awaiting KT far exceeds the number of organ donations globally, utilizing “extended donor criteria organs” including donors with HBV infection is one of the solution. Thus, one challenge is determining the optimal use of kidneys from such donors.
-The prevalence of chronic HBV infection varies greatly by geographical region,
ranging from 0.4% to 1.6% in the region of the Americas, 1.2% to 2.6% in Europe, 1.5% to 4.0% in Southeast Asia, 2.6% to 4.3% in the Eastern Mediterranean, 5.1 to 7.6 % in the Western Pacific, and 4.6% to 8.5% in Africa.
-Prophylactic therapy and appropriate monitoring will further eliminate the risk of HBV transmission.
-There is an increasing trend of accepting non-liver organs from anti-HBc (+) donors. The utilizing kidneys from donors with HBsAg (+) remains controversial.
Screening test for HBV infection in organ donors.
Serological tests:-
1– HBsAg, anti-HBc, HBeAg, anti-HBe
2– Can be negative in window period and lack of sensitivity to detect occult infections.
3– HBs Ag and anti-HBc are generally accepted as cost effective screening tools.
4– In endemic areas; add on anti-HBe and HBeAg as biomarkers of high viral replication and infectivity activity relating to a high viral burden.
The nucleic acid test :
1–Usually in the form of an HIV/HCV/HBV multiplex.
2– It shortens the windows period to 20-22 d compared to 35-44 d by conventional serology.
3– Its implementation is limited by it is cost effective, and the logistic challenges.
Risk for HBV transmission and infection after KT
Donor factors and the role of HBV DNA:
1– Important behavioral risk factors to acquire HBV should be carefully reviewed when assessing the risk of transmission.
2– Donors with HBV infections are generally categorized into two groups according to their serologic status.
### The first donor group is the anti-HBc positive group; the rate of transmission appears to be negligible according to the recipient’s protective immunity status.
-The overall seroconversion rate was 3.24%.
-The second donor group is the HBsAg positive group where the HBV transmission remains a challenging problem.
– KT from living HBsAg (+) donors can be donated to anti-HBs (+) recipients with protection who have no abnormalities of liver function test, no history of liver disease within the previous 28 days, and who are not living in the area of possible mutation strain of HBV.
–Use of antiviral medications to treat HBV add benefit to the treatment plan to use organs from HBsAg (+) donors, which lead to functional cure of HBV, means sustained loss of HBsAg with or without anti-HBs seroconversion which was usually associated with good clinical outcomes.
####Recipient factors and the role of protective immunity:
– The recipients who received kidneys from donors with hepatitis B should have protective anti-HBs, level > 10 mIU/mL was protective, higher antibody concentration (> 50 mIU/mL) might be required related to global variation in HBV genotypes.
###Monitoring of HBV infection after transplantation.
– AASDL suggested periodic assessment of serum ALT, HBV DNA, and HBsAg during immunosuppressive therapy, every 3 mo for at least 12 mo post-transplantation. Lifelong monitoring in naïve recipient.
-Reactivation of HBV infection was defined by detectable HBV DNAemia or positive HBsAg seroconversion.
###The Role of prophylaxis therapy Vaccination and revaccination protocol
1- HBsAg (-) anti-HBc (+) kidneys can be transplanted safely to patients with ESKD, there were no HBsAg seroconversion and no excess risk of morbidity and graft failure.
2- The amount of information on KT from HBsAg (+) donors is much less than anti-HBc (+) donors, the results of long-term outcomes being reported showed favorable outcomes when compared with donors with no markers of HBV with proper prophylaxis regimen.
3- The previous report of fulminant hepatitis B infection in the setting of HBsAg (+)/HBeAg (+) donor to anti-HBs (-) recipients has been a major concern.
###Risk benefit of transplantation and proposed criteria for HBsAg (+) donor utilization:
###The potential recipients should be discussed about the willingness to receive a kidney from donors with HBsAg positivity.
All potential recipients should:-
###For HBsAg (+) recipient candidates:
What is the level of evidence provided by this article?
level 5.
Will you accept living or deceased donations from HBV-positive donors?
Introduction:
Kidney transplantation (KT) is the preferred treatment for end-stage kidney disease (ESKD) patients. It is associated with reduced mortality and improved quality of life compared to dialysis therapy.
According to current guidelines, there is an increasing trend of accepting non-liver
organs from total hepatitis B core antibody-positive [anti-HBc (+)] donors to be used in
any recipient, regardless of HBV immune status, without prophylaxis due to the
negligible risk of de novo infection
kidneys from donors with positive hepatitis B surface antigen (HBsAg) [HBsAg (+)] remains controversial, and it is generally suggested that such organs be discarded.
Objectives:
This review aims to summarize the current evidence regarding the use of kidneys from HBsAg (+) donors with an emphasis on the risk of HBV transmission, liver-related morbidities, and the outcomes of Kidnet tx
Screening for HBV infection:
1-detectable viral DNA in the absence of HBsAg
2-test for previous HBV exposure is anti-HBc.
3-immunoglobulin M (IgM) antibody to hepatitis B core antigen (IgM anti-HBc)
4-Hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) are additional tests to identify the viral replicative activity as HBeAg positivity which indicates active viral replication (i.e., usually a viral load > 10000 IU/mL
5-anti-HBe positivity suggests the presence of the non-replication phase
6-deceased kidney donation, HBs Ag and anti-HBc are generally accepted.
7-Some transplant centers in endemic areas routinely add on anti-HBe and HBeAg to the donor screening
8-For practical purposes, we suggest that all serologic tests for HBV (HBsAg, anti-HBc, HBeAg, anti- HBe) and other essential infectious markers are done at the donor hospitals. A universal NAT test for HBV (usually in combination with HIV and HCV) should be conducted at the central or regional organ allocation center. The result should come back before or at the time of organ retrieval.
Risk of hepatitis B virus transmission and infection after kidney transplant :
Donor factors and the role of HBV DNA:
The risk of donor-transmitted HBV infection is lower in kidney transplant recipients compared with liver transplant recipients with similar serologic marker positivity
Specific HBV receptor recognition may play an essential role in this hepatotropism phenomenon
Patients with solid risk factors for HBV/ HCV/HIV combination should be tested for HBsAg, HBV NAT, and HBV DNA by a test with the highest sensitivity and specificity.
A previous study had suggested a test with a lower detection limit of less than < 0.1 ng/mL for HBsAg and 10 IU/mL for HBV DNA
.
Depending on their serologic status, donors with HBV infections are generally categorized into two groups.
The first donor group is the anti-HBc positive group, in which the transmission rate appears negligible according to the recipient’s protective immunity status.
The overall seroconversion rate was 3.24% (mostly antiHBc seroconversion). Showed HBsAg seroconversion rate from this study to be 0.28%, with no symptoms of hepatitis and no excess mortality
The second donor group is the HBsAg positive group, where the HBV transmission.
remains a challenging problem
several recent studies and guidelines suggested that kidneys from HBsAg (+) donors can be carefully considered to be transplanted to appropriate recipients after careful consideration of the risk and benefit with informed consent
KT from living HBsAg (+) donors can be donated to anti- HBs (+) recipients with protection who have no abnormalities of liver function test, no history of liver disease within the previous 28 days, and who are not living in the area of possible mutation strain of HBV
fulminant hepatitis B infection had been reported in a naïve recipient who received kidneys from donors with HBsAg (+)/HBeAg (+) donors
HBeAg and anti-HBe were routinely checked in HBsAg (+) donors to ensure a low infectivity rate of HBV before performing KT
Using antiviral medications to treat HBV benefits the treatment plan to use organs from HBsAg (+) donors. Unlike liver transplantation, KT from this type of donor can be associated with a functional cure of HBV
Practical medicine was defined by a state of sustained loss of HBsAg with or without anti-HBs seroconversion, which was usually associated with good clinical outcomes
Recipient factors and the role of protective immunity:
The recipients who received kidneys from donors with hepatitis B should have protective anti-HBs.
Several guidelines and studies have suggested that an anti- HBs > 10 mIU/mL were protective
definitions of HBV transmission may include anti-HBc IgM seroconversion, HBsAg
Seroconversion, and HBV DNAemia.
Monitoring of HBV infection after kidney transplantation:
Ø The American Association for the Study of Liver Diseases (AASDL) suggested periodic assessment of serum ALT, HBV DNA, and HBsAg during immunosuppressive therapy
Ø Reactivation of HBV infection was defined by detectable HBV DNAemia or positive HBsAg seroconversion
Ø hepatitis flare was defined by rising in serum ALT more than three times the baseline level and > 100 U/L with evidence of hepatitis B reactivation
Ø The Infectious Disease Community of Practice of the American Society of Transplantation advised monitoring liver enzymes, HBsAg, and HBV DNA every 3mo for at least 12 mo post-transplantation
Ø all kidney transplant recipients who have a resolved infection of HBV (defined by positive anti-HBc serology) should be aware of the possibility of HBV reactivation during a course of intensive immunosuppression, particularly rituximab
Vaccination and revaccination protocol
Ø Anti-HBs play a crucial role in minimizing the risk of HBV transmission. Hepatitis B vaccination should be given to naïve or previously immune recipients with anti-HBs concentrations below ten mIU/mL. Also, the KDIGO guideline suggested that a concentration of Anti-HBs below 100 mIU/mL can be rapidly lowered to a non-protective level and may require a booster dose at this step.
Ø Suggest A high dose of HBV vaccine to patients with ESKD who were receiving hemodialysis therapy.
Ø Suggested A protocol of three or four high-dose (40 μg) hepatitis B vaccine series with a target level of 10 mIU/mL at 4 wk post-treatment. Also, a second three doses of vaccination were suggested if the anti-HBs could not reach the desired level.
Antiviral medications (nucleos(t)ide analogs) and HBIG :
Ø Modality to prevent HBV transmission via kidney transplant organs was the use of antiviral medicines and HBIG
Ø Lamivudine was the most popular prophylaxis agent being used globally
Ø Serologic markers of HBV infection may impact the choice to prescribe antiviral medications (NA).
Ø Anti HBs (> 10 mIU/mL) and positive recipients can receive kidney transplants from anti-HBc (+) donors without a need for prophylaxis antiviral medications due to the negligible risk of HBV transmission
Ø naïve recipients who received kidneys from anti-HBc (+) donors should receive lamivudine prophylaxis without HBIG for at least one year
Ø HBs Ag (+) donors and recipients with protective anti-HBs (> 10 mIU/mL) were considered suitable to receive the allocation of kidney grafts
Ø If the result of nucleic acid for HBV was negative and HBV DNA was undetectable (by a method with a detection limit as low as 20 copies per mL), preventive strategies varied from no NA prevention (in the setting of no potent induction therapy), or prescription of NA alone without HBIG. If the anti-HBs are> 100 mIU/mL, one can proceed to KT without NA prophylaxis.
Ø If HBV DNA was not measured by a method of optimum low detection limit or the result of HBV DNA cannot be obtained for any reason, NA may be prescribed to make the risk of HBV transmission as low as possible.
Ø HBsAg (+)/HBV DNA (+) donor, most authors prescribed universal NA prophylaxis with or without HBIG as a prophylaxis regimen among patients with different levels of anti-HBs concentration.
LONG-TERM OUTCOMES AND SURVIVAL:
Ø The amount of information on KT from HBsAg (+) donors is much less than from anti- HBc (+) donors. However, the reported long-term outcomes were favorable when compared with donors with no markers of HBV with a proper prophylaxis regimen.
Ø The result of HBsAg (+) donor to anti-HBs (> 10 mIU/mL) recipient reported a ten-year actuarial graft survival rate of 84.6% and patient survival rate of 92.8% (with no hepatitis and hepatoma) provided that the recipients received no induction therapy.
RISK-BENEFIT OF TRANSPLANTATION AND PROPOSED CRITERIA FOR
HBsAg (+) DONOR UTILIZATION:
It has long been shown and recently confirmed that kidney transplants promote both longer life expectancy and better quality of life at a lower cost relative to staying on dialysis treatment
the criteria for utilization of kidneys from donors with HBsAg positivity have not been well described
1-The first group is patients with an urgent need to receive KT. Patients with exhausted vascular access
2-The second group is the recipients with positive HBsAg
3-The third group is patients being registered on an active waiting list
CONCLUSION
Within this era of several newer antiviral medications, positive HBsAg in potential organ donors should not preclude the use of kidney organs.
The level of evidence provided by this article: is level 5.
Will you accept living or deceased donations from HBV-positive donors?
NO, Because we do not have all markers for HBV screening, deficiency in prophylaxis regimen, and medication, we have no clear guidelines for HBV infection in transplant patients.
Introduction:
KTx is the treatment of choice for ESRD patients.
The problem of organ shortage is still affecting access to such important treatment.
Extended criteria donor is one solution to this problem, and this includes donors with hepatitis B infection.
According to current guidelines, there is an increasing trend of accepting non-liver organs from total hepatitis B core antibody-positive donors to be used in any recipient regardless of HBV immune status without prophylaxis due to the negligible risk of de novo infection.
However, utilizing kidneys from donors with positive hepatitis B surface antigen remains controversial, and it is generally suggested that such organs be discarded.
Screening for hepatitis B infection in organ donors:
In the case of deceased kidney donation, HBs Ag and anti-HBc are generally accepted as cost-effective screening tools; some transplant centers in endemic areas routinely add on anti-HBe and HBeAg.
Serologic testing alone still has limitations due to the long window period and the lack of sensitivity to detect occult infections, raising concerns over risk misclassification.
To improve the sensitivity of screening tests, the nucleic acid test has been proposed as an optional donor screening test; it shortens the window period but has certain limitations such as concerns about its cost-effectiveness, need for an expert technician, long time for testing, and the reliability of home testing.
Risk of HBV transmission and infection after KTx:
Donor factors and the role of HBV DNA:
Recipient factors and the role of protective immunity:
Monitoring of HBV infection after Tx:
The role of prophylaxis therapy:
Vaccination and revaccination protocol:
Hepatitis B vaccination should be given to naïve recipients or previously immune recipients who have anti-HBs concentrations below 10 mIU/mL.
The KDIGO guideline suggested a concentration of Anti-HBs below 100 mIU/mL can be rapidly lowered down to a non-protective level and may require a booster dose at this step.
Monitoring of anti-HBs concentration should be done at least yearly.
High doses of vaccines are required to patients with ESRD.
Reactivation after KT has been reported in patients with antibody titers less than 100 mIU/mL.
Efforts are made to improve vaccine efficacy but it needs a long time to be proved.
Antiviral medications (nucleos(t)ide analogues) and HBIG:
HBIG provides passive immunity for a high concentration of anti-HBs that are aimed to act as neutralizing antibodies to HBV.
The optimal dose of HBIG to be used for kidney transplant recipients from donors with HBV was not clearly known.
NAs are a group of antiviral medications that directly suppress HBV virus replication. Lamivudine was the most popular prophylaxis agent being used globally, its efficacy was hampered by small number of lamivudine-resistant hepatitis B.
Serologic markers of HBV infection may have some impact on the choice of antiviral medications (NA). Anti HBs (> 10 mIU/mL) and positive recipients can receive kidney transplants from anti-HBc (+) donors without a need for prophylaxis antiviral medications due to the negligible risk of HBV transmission. In contrast, naïve recipients who received kidneys from anti-HBc (+) donors should receive lamivudine prophylaxis without HBIG for at least 1 year.
In the setting of HBsAg (+) donors, recipients with protective anti-HBs (> 10 mIU/mL) were considered suitable to receive the allocation of kidney grafts.
Further risk should be assessed by the result of the NAT test and HBV DNA measurement.
For HBsAg (+)/HBV DNA (+) donors, most authors prescribed universal NA prophylaxis with or without HBIG as a prophylaxis regimen.
Long-term outcomes and survival:
For HBsAg (-) anti-HBc (+) donors, historic studies found that there were no HBsAg seroconversion and no excess risk of morbidity and graft failure.
The amount of information on KT from HBsAg (+) donors is much less than anti-HBc (+) donors. However, the results of long-term outcomes being reported showed favourable outcomes when compared with donors with no markers of HBV with a proper prophylaxis regimen.
The previous report of fulminant hepatitis B infection in the setting of HBsAg (+) /HBeAg (+) donor to anti-HBs (-) recipients has been a major concern. However, A review of published articles from 2005 onwards has shown there were a total of at least 412 KTs from HBsAg (+) donors to HBsAg (-) recipients with good outcomes.
A proposed criteria for receiving donors with HbsAg +ve:
Level 5 ( review article ).
Although the risk of infection transmission is low, the process is not free of risk and carries ethical concerns; if I should accept such an offer, I would only do it for patients with either HbsAg +ve or those with exhausted accesses with no compatible donor and no chance to be on CAPD.