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Positive suggestions about the anti-HBc positive donor
  1. D Mutimer
  1. Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, UK
  1. Correspondence to:
    D Mutimer;
    david.mutimer{at}university_b.wmids.nhs.uk

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What to do with the anti-hepatitis B virus core antigen positive donor liver

The paper by Roque-Afonso et al in this issue of Gut1 describes the outcome of recipients following transplantation of livers from organ donors who have detectable antibody to the hepatitis B virus (HBV) core antigen (HBc) but undetectable serum hepatitis B surface antigen (anti-HBc positive, HBsAg negative) (see 95). Serum anti-HBc positivity simply confirms exposure to HBV. Its presence in the absence of serum HBsAg identifies the patient with resolved infection. Frequently, antibodies to HBsAg (anti-HBs) will be absent, fading in titre for many patients from the time of acute infection. Thus the patient with a past resolved HBV infection will be anti-HBc positive and HBsAg negative, and anti-HBs may or may not be present. Irrespective of the anti-HBs status of the donor, it is known that the use of anti-HBc positive (HBsAg negative) donor livers will transmit HBV to the recipient and will establish chronic infection and graft damage.2–5 This is termed de novo HBV infection. Occasionally, aggressive infection with graft failure and patient death may be observed.6 In general, the other organs of the anti-HBc positive donor can be used with little risk of de novo infection to the recipient.2 This observation suggests that potentially infectious HBV is present in the liver, but not in other organs, and that reactivation of the virus occurs following transplantation in the context of immunosuppression.

There is considerable geographic variation in the frequency of organ donor anti-HBc positivity. In the UK, reflecting a relatively low lifetime risk of exposure to HBV, donor anti-HBc positivity is uncommon. However, de novo infection causes significant morbidity for the few unlucky recipients.4 In Southern Europe and Japan, the frequency is high, reflecting past exposure to HBV of a large proportion of the potential organ donor pool.5,7 Of consecutive organ donors used by the liver transplant surgeons at Hospital Paul Brousse, 22/315 (7%) were anti-HBc positive. Roque-Afonso et al from Hospital Paul Brousse present the pretransplant HBV serological status and post-transplant outcome (with or without passive immunoprophylaxis) of the 22 recipients of those anti-HBc positive liver donations. The results are nicely organised and presented in table 1 of their manuscript. Detailed analysis of the data in the table emphasises the important and accepted principles that should be applied to the use of anti-HBc positive livers.

Patient Nos 1–4 are the ideal recipients for these organs. These recipients had HBV associated liver failure as the indication for liver transplantation and required immunoprophylaxis to prevent graft reinfection by HBV. Under this circumstance, it appears that immunoprophylaxis prevented both reinfection and de novo infection by HBV. Thus with no added cost or effort, the anti-HBc positive liver was suitably and safely placed.

Patient Nos 19–22 provide confirmation that the anti-HBc positive liver, when placed into a recipient who lacks pretransplant HBV immunity and who does not receive post-transplant prophylaxis, will establish de novo infection in the majority of instances.

The outcome of patient Nos 5–9 suggests that passive immunoprophylaxis can prevent de novo infection of most non-immune recipients (only 1/5 treatment failures observed). A similar beneficial impact was observed by Uemoto et al who used immunoprophylaxis for three paediatric recipients of living related anti-HBc positive livers.5 Recent published work suggests that lamivudine prophylaxis, with or without immunoprophylaxis, may also prevent de novo recipient infection in this at-risk group.8,9 Yu et al have published a small study using lamivudine (without immunoprophylaxis) to prevent de novo infection of nine recipients of anti-HBc positive livers. However, four recipients were HBV immune pretransplant and three of the remaining patients died soon after transplantation. Thus a sustained effect of lamivudine prophylaxis for non-immune recipients of anti-HBc positive livers was confirmed for only three patients.9 Dodson et al reported successful results with the combination of lamivudine and immunoglobulin given to 15 recipients, of whom seven were non-immune.8 Compared with immunoprophylaxis, lamivudine is inexpensive and easier to administer. Immunoglobulin is plasma derived and therefore its use raises microbiological concerns. Thus patient and doctor acceptance of lamivudine is superior, and compliance with lamivudine prophylaxis is good.

The outcome of patient Nos 10–18 poses more questions than provides answers. These recipients were either anti-HBc or anti-HBs positive pretransplant, most received immunoprophylaxis, and none developed de novo infection. However, the contribution of passive immunoprophylaxis to the favourable outcome of these recipients cannot be determined. Patient Nos 10–16 may have been protected from de novo infection by their own pre-existing HBV immunity. For these recipients, immunoprophylaxis may represent an unnecessary and costly addition to their care. Indeed, the outcome of patient Nos 17 and 18, who were anti-HBs positive pretransplant, who did not receive prophylaxis, and who did not experience de novo infection, suggests that anti-HBc positive livers may be suitably placed (without the need for prophylaxis) in recipients who have serological evidence of HBV immunity. Other reports support this possibility that recipient anti-HBs and/or anti-HBc positivity may prevent de novo infection from anti-HBc positive livers.7

In summary, the data presented by Roque-Afonso et al in this issue of Gut support the following conclusions and recommendations.

  • The use of anti-HBc positive livers without prophylaxis for non-immune recipients can and must be avoided (it follows that the anti-HBc status of the donor and recipient must be known).

  • If possible, the anti-HBc positive liver should be used for a HBsAg positive recipient (who receives the combination of lamivudine and immunoprophylaxis to prevent graft reinfection and de novo infection). If a liver unit does not have a suitable HBsAg positive recipient for the anti-HBc positive donor, then the donor liver might be offered to a unit that does.

  • For the HBsAg negative recipient of the anti-HBc positive liver, it appears that pretransplant immunity to HBV, immunoprophylaxis, or lamivudine (or combinations) significantly reduce the risk of de novo infection. Probably, and despite the fact that conclusive efficacy data are scarce, lamivudine without immunoprophylaxis will be preferred by many transplant units.

Above all, the anti-HBc positive liver can and must be used. In these times of donor organ shortage, a suitable and grateful recipient can always be found.

What to do with the anti-hepatitis B virus core antigen positive donor liver

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