Risk of de novo hepatitis in liver recipients from hepatitis-B core antibody-positive grafts - a systematic analysis

Many transplant programs utilize liver grafts from hepatitis-B core antibody (HBcAb)-positive and hepatitis-B surface antigen (HBsAg)-negative donors. However, there is risk for de novo hepatitis B (DNH) in recipients of these grafts. We reviewed 26 studies reporting the rates of DNH in recipients receiving HBcAb-positive liver grafts. Four hundred and sixty-two donor-recipient pairs were included to evaluate the risk of DNH stratified by the recipient's immune status to hepatitis B and type of prophylactic therapy given, if any. The rate of DNH was highest (58%) in the stratum of hepatitis-B (HBV) naive recipients who did not receive prophylaxis. In HBV naive recipients, prophylactic therapy (lamivudine and/or hepatitis-B immunoglobulin - HBIG) reduced DNH to 11% (odds ratio [OR] = 11.1, 95% CI 4.98-25, p < 0.0001 for DNH without prophylaxis). Recipients with hepatitis-B surface antibody (HBsAb) positivity had DNH rates of 18% without prophylaxis and 0% with prophylaxis (OR = 9.2, 95% CI 1.1-83.3, p = 0.039). Recipients with both HBsAb and HBcAb positivity had DNH rates of 4% without prophylaxis and 3% with prophylaxis (p = 1.00), while recipients with HBcAb positivity alone had DNH rates of 14% without prophylaxis and 3% with prophylaxis (p = 0.21). There was no significant difference between the types of HBV prophylaxis received whether lamivudine, HBIG or both. However, in the subgroup who received HBIG alone, rates of DNH were higher after cessation of HBIG prophylaxis compared to DNH rates with indefinite HBIG (p = 0.0002). In summary, the risk of DNH is highest for HBV naive liver recipients from HBcAb-positive donors. Recipients who are HBV naive as well as those recipients with isolated HBsAb positivity derive significant benefit from HBV prophylaxis after transplantation with a HBcAb-positive graft. The ideal prophylactic regimen for prevention of DNH is unclear, but based on our analysis of the literature, antivirals alone may suffice. More data are needed with the newer antivirals for hepatitis B.