HBIg And Lamivudine In Prevention Of HBV Recurrence After Liver Transplantation: A Systematic Review

Background: HBIg combined use with lamivudine has been proved to be short-term safe and effective in prevention of HBV recurrence after liver transplantation in patients with HBV-related liver disease by some observational researches. Because of different mechanisms of action and resistance profiles, combination therapy with HBIg and lamivudine may be more effective and less risk of resistance than monotherapy with either of them. Regretfully, there has no unified standard or optimal schedule and duration of HBIg. Its long-term outcome has also rarely been reported. Objectives: To access the benefit and adverse effect of combined use of HBIg and lamivudine in prevention of HBV infection after liver transplantation associated with HBIg's optimal schedule and duration and it's long-term outcome including YMDD mutants, liver function, quality of life, cost-effective analysis etc.Search strategy: We conducted a electronic search on MEDLINE disc, PubMed, EMBASE disc, EMbase.com (MEDLINE + EMBASE), CBM disc, and the Cochrane Central Register of Controlled Trials on the Cochrane Library 2005, Issue 2. Search engines like Google and other database and webpages like TRIP, clinicaltrials.gov were searched using related keywords. Reference lists of identified studies were searched manually. The latest search date: April 15, 2005.Selection criteria: Randomized or quasi-randomized trials comparing combination therapy of HBIg and lamivudine with their monotherapy or another combination schedule in prevention of HBV recurrence after liver transplantation.Data collection and analysis: Decisions on inclusion of studies and data extraction were performed by two reviewers independently. The outcome measures include HBV recurrence rate and its associated mortality, the rate of YMDD mutants and its associated outcome, liver function, quality of life, adverse events and cost-effective analysis.Main results: Four randomized studies, published between 1999 and 2003, involving 172 patients, and three different combination schedules were included. One study described that its randomization was performed at a central location while the other three didn't describe it's generation of the allocation sequence and allocation conceal. As HBIg is administrated by injection, all the studies were impossible to conduct the blinding. None of the four studies reported the server adverse effect, the quality of life and the death related to the HBV recurrence. All the four studies indicate that the combination therapy is effective and it's safe to replace HBIg with lamivudine at one week after transplantation as well as one month or six month. Two studies' short-term results, which reported the YMDD mutants, showed a low mutant rate (6%-25%) and it seemed that the mutants did not increase the risk of lamivudine resistance and HBV recurrence. All the four studies reported the combination therapy can reduce the costs with no detailed informations.Conclusion: The combination therapy is effective and cost saving; Replace HBIg with lamivudine at one week, one month or six month after transplantation is safe. However, more large studies with high quality and standard intervention schedules are needed to further evaluate the optimal schedule and duration of the combination therapy and its long-term outcome.