Advertisement

Hepatitis B Immunoglobulin and Lamivudine Improve Hepatitis B–Related Outcomes After Liver Transplantation: Meta-Analysis

      Background & Aims: HBV recurrence increases morbidity and mortality in HBsAg+ patients undergoing liver transplantation. We aimed to estimate the relative efficacy of combined therapy with hepatitis B immunoglobulin (HBIG) and lamivudine (LAM) versus HBIG monotherapy for preventing HBV-related morbidity and mortality in this setting. Methods: We performed a meta-analysis of clinical trials that met the prespecified criteria and provided data for risk estimation of HBV recurrence in HBsAg+ liver transplant patients receiving HBIG and LAM versus HBIG alone. Databases searched until May 2007 included MEDLINE (Ovid), PubMed, Embase, Toxnet, Scopus, and Web of Science. Literature search and data extraction were conducted independently by 2 study investigators; then 2 other investigators reviewed and screened eligible studies. Odds ratios (ORs) for the risk reduction with HBIG and LAM versus HBIG alone were calculated by using a random-effects model. Results: Two prospective and 4 retrospective studies were included in the meta-analysis. The OR showing risk reduction in HBV recurrence with HBIG and LAM (n = 193) versus HBIG alone (n = 124) was 0.08 (95% confidence interval [CI], 0.03–0.21). HBV-related death and all-cause mortality could only be assessed in 3 studies each. The ORs showing HBV-related death and all-cause mortality reduction with HBIG and LAM versus HBIG alone were 0.08 (95% CI, 0.02–0.33) and 0.02 (95% CI, 0.06–0.82), respectively. Conclusions: Although this meta-analysis was limited by small studies and varying levels of immunosuppression, it is apparent that adding LAM to HBIG improved HBV-related morbidity and mortality in HBsAg+ recipients of liver transplants.

      Abbreviations used in this paper:

      CI (confidence interval), HBIG (hepatitis B immunoglobulin), LAM (lamivudine), OR (odds ratio)
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Alter M.J.
        Epidemiology of hepatitis B in Europe and worldwide.
        J Hepatol. 2003; 39: S64-S69
        • Hoofnagle J.H.
        • Doo E.
        • Liang T.J.
        • et al.
        Management of hepatitis B: summary of a clinical research workshop.
        Hepatology. 2007; 45: 1056-1075
        • Lai C.L.
        • Ratziu V.
        • Yuen M.F.
        Viral hepatitis B.
        Lancet. 2003; 362: 2089-2094
        • Seehofer D.
        • Rayes N.
        • Neuhaus P.
        Prophylaxis and treatment of hepatitis B recurrence after liver transplantation in the antiviral era.
        Expert Rev Anti Infect Ther. 2003; 1: 307-318
        • Konig V.
        • Hopf U.
        • Neuhaus P.
        • et al.
        Long-term follow-up of hepatitis B virus-infected recipients after orthotopic liver transplantation.
        Transplantation. 1994; 58: 553-559
        • Samuel D.
        • Muller R.
        • Alexander G.
        • et al.
        Liver transplantation in European patients with the hepatitis B surface antigen.
        N Engl J Med. 1993; 329: 1842-1847
        • Fontana R.J.
        • Lok A.S.
        Combination of HBIG and lamivudine-resistant mutations: a formula for trouble?.
        Liver Transpl. 2002; 8: 1082-1084
        • Dumortier J.
        • Le Derf Y.
        • Guillem P.
        • et al.
        Favorable outcome of liver transplantation despite a high hepatitis B virus replication: beyond the limits?.
        Transpl Infect Dis. 2006; 8: 182-184
        • Loomba R.
        • Liang T.J.
        Novel approaches to new therapies for hepatitis B virus infection.
        Antivir Ther. 2006; 11: 1-15
        • Gane E.J.
        • Angus P.W.
        • Strasser S.
        • et al.
        Lamivudine plus low-dose hepatitis B immunoglobulin to prevent recurrent hepatitis B following liver transplantation.
        Gastroenterology. 2007; 132: 931-937
        • Bradburn M.J.
        • Deeks J.J.
        • Berlin J.A.
        • et al.
        Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events.
        Stat Med. 2007; 26: 53-77
        • Yusuf S.
        • Peto R.
        • Lewis J.
        • et al.
        Beta blockade during and after myocardial infarction: an overview of the randomized trials.
        Prog Cardiovasc Dis. 1985; 27: 335-371
        • Huedo-Medina T.B.
        • Sanchez-Meca J.
        • Marin-Martinez F.
        • et al.
        Assessing heterogeneity in meta-analysis: Q statistic or I2 index?.
        Psychol Methods. 2006; 11: 193-206
        • Breslow N.E.
        • Day N.E.
        Statistical methods in cancer research.
        Analysis of case-control studies. International Agency for Research on Cancer, Lyon, France1980
        • Egger M.
        • Davey Smith G.
        • Schneider M.
        • Minder C.
        Bias in meta-analysis detected by a simple, graphical test.
        BMJ. 1997; 315: 629-634
        • Lee S.K.
        • Park J.H.
        • Joh J.W.
        • et al.
        Prophylaxis against hepatitis B recurrence following liver transplantation in HBs Ag(+) patients.
        Transplant Proc. 2000; 32: 2248-2249
        • Anselmo D.M.
        • Ghobrial R.M.
        • Jung L.C.
        • et al.
        New era of liver transplantation for hepatitis B: a 17-year single-center experience.
        Ann Surg. 2002; 235 (discussion 619–620): 611-619
        • Dumortier J.
        • Chevallier P.
        • Scoazec J.Y.
        • et al.
        Combined lamivudine and hepatitis B immunoglobulin for the prevention of hepatitis B recurrence after liver transplantation: long-term results.
        Am J Transplant. 2003; 3: 999-1002
        • Han S.H.
        • Ofman J.
        • Holt C.
        • et al.
        An efficacy and cost-effectiveness analysis of combination hepatitis B immune globulin and lamivudine to prevent recurrent hepatitis B after orthotopic liver transplantation compared with hepatitis B immune globulin monotherapy.
        Liver Transpl. 2000; 6: 741-748
        • Honaker M.R.
        • Shokouh-Amiri M.H.
        • Vera S.R.
        • et al.
        Evolving experience of hepatitis B virus prophylaxis in liver transplantation.
        Transpl Infect Dis. 2002; 4: 137-143
        • McCaughan G.W.
        • Spencer J.
        • Koorey D.
        • et al.
        Lamivudine therapy in patients undergoing liver transplantation for hepatitis B virus precore mutant-associated infection: high resistance rates in treatment of recurrence but universal prevention if used as prophylaxis with very low dose hepatitis B immune globulin.
        Liver Transpl Surg. 1999; 5: 512-519
        • Sousa J.M.
        • Pareja F.
        • Serrano J.
        • et al.
        Comparison between levels of anti-HBS with a fixed administration dose of HBIG and a combination of HBIG and lamivudine for the prophylaxis of hepatitis B after liver transplantation.
        Transplant Proc. 2003; 35: 723-724
        • Burbach G.J.
        • Bienzle U.
        • Neuhaus R.
        • et al.
        Intravenous or intramuscular anti-HBs immunoglobulin for the prevention of hepatitis B reinfection after orthotopic liver transplantation.
        Transplantation. 1997; 63: 478-480
        • Neff G.W.
        • Nery J.
        • Lau D.T.
        • et al.
        Tenofovir therapy for lamivudine resistance following liver transplantation.
        Ann Pharmacother. 2004; 38: 1999-2004
        • Schreibman I.R.
        • Schiff E.R.
        Prevention and treatment of recurrent hepatitis B after liver transplantation: the current role of nucleoside and nucleotide analogues.
        Ann Clin Microbiol Antimicrob. 2006; 5: 8
        • Buti M.
        • Mas A.
        • Prieto M.
        • et al.
        A randomized study comparing lamivudine monotherapy after a short course of hepatitis B immune globulin (HBIg) and lamivudine with long-term lamivudine plus HBIg in the prevention of hepatitis B virus recurrence after liver transplantation.
        J Hepatol. 2003; 38: 811-817
        • Wong S.N.
        • Chu C.J.
        • Wai C.T.
        • et al.
        Low risk of hepatitis B virus recurrence after withdrawal of long-term hepatitis B immunoglobulin in patients receiving maintenance nucleos(t)ide analogue therapy.
        Liver Transpl. 2007; 13: 374-381