Evolving experience of hepatitis B virus prophylaxis in liver transplantation
Authors: Honaker M.R. , Shokouh‐Amiri M.H. , Vera S.R. , Alloway R.R. , Grewal H.P. , Hardinger K.L. , Kizilisik A.T. , Bagous T. , Trofe J. , Stratta R.J. , Egidi M.F. , Gaber A.O. 
Published: December 2004

Abstract:Passive immunoprophylaxis with hepatitis B immunoglobulin (HBIG) is important to prevent recurrence of hepatitis B virus (HBV) after orthotopic liver transplantation (OLT) for chronic HBV cirrhosis. With availability of lamivudine (3TC), the use of combination prophylaxis with long‐term HBIG/3TC has been shown to prevent short‐term HBV recurrence. This report compares HBV recurrence rates between groups receiving no/short‐term HBIG, long‐term HBIG alone, or HBIG/3TC prophylaxis, and describes HBIG requirements during the first 6 and 12 months in the latter two groups. This study involved patients undergoing OLT at the University of Tennessee‐Memphis between May 1990 and July 2001. During this period, 388 liver transplants were performed at our center. All hepatitis B surface antigen (HBsAg)‐positive recipients (n = 27) were included in this retrospective analysis. The groups were similar with regard to pre‐transplant demographic characteristics such as age, gender, weight, and pre‐transplant diagnosis. Owing to the retrospective study design, median follow‐up was longer for the no‐prophylaxis (5.6 years) and the HBIG‐alone (6.0 years) groups compared to the HBIG/3TC group (4.2 years). Patient survival was 50% in the no‐prophylaxis and 71% in the HBIG‐alone groups compared to 100% in the HBIG/3TC group (P = 0.09). When censored for death with a functioning graft, graft survival was 50% in the no‐prophylaxis and 86% in the HBIG‐alone group compared to 100% in the HBIG/3TC group (P = 0.07). The overall incidence of HBV recurrence in the no‐prophylaxis era was 100% and 21% in the HBIG‐alone era compared to 0% in the HBIG/3TC era (P < 0.001), despite similar mean and median HBIG trough titers in the HBIG‐alone and HBIG/3TC groups. The incidence of HBV recurrence in HBV DNA‐positive recipients was 100% in the no‐prophylaxis era, 30% in the HBIG‐alone era, and 0% in the HBIG/3TC era (P < 0.001). Recipients in the HBIG‐alone group had a nearly two‐fold increase in HBIG requirement at 6 and 12 months in order to maintain similar HBIG trough titers post‐transplant compared to recipients in the HBIG/3TC group despite similar pre‐transplant HBV serology. This increased HBIG requirement in the HBIG‐alone group resulted in a marked increase in the mean overall cost of HBV prophylaxis in this group ($47,367 at 6 months; $84,280 at 12 months) compared to the HBIG/3TC group ($25,931 at 6 months; $49,599 at 12 months). These data demonstrate an improvement in patient and graft survival rates in the group receiving combination HBIG/3TC prophylaxis compared to the HBIG‐alone and no‐prophylaxis groups. There was a significant reduction in HBV recurrence in the group receiving combination HBIG/3TC when compared to the groups receiving HBIG alone or no prophylaxis. Furthermore, we demonstrated that the addition of 3TC to the long‐term HBIG regimen led to elimination of the disparity previously described in HBV recurrence rates between HBV DNA‐positive and HBV DNA‐negative recipients. Importantly, our data demonstrates a complete lack of HBV recurrence in the HBIG/3TC group at a median follow‐up of 4.2 years. Additionally, the data show that the addition of 3TC to the post‐operative prophylaxis regimen resulted in a reduction in the requirement of HBIG at 6 and 12 months, which markedly reduced the overall cost of post‐transplant HBV prophylaxis.