Hepatitis B immunoglobulins and/or lamivudine for preventing hepatitis B recurrence after liver transplantation: a systematic review
Journal of Gastroenterology & Hepatology. 2010;25((5):):872-9.
BACKGROUND Currently, hepatitis B immunoglobulins (HBIg) and/or lamivudine have become the main options for prevention of hepatitis B recurrence after liver transplantation. AIM: To assess the benefits of HBIg and/or lamivudine for prevention of hepatitis B recurrence after liver transplantation. METHODS We conducted a search of electronic databases and a manual search of bibliographical lists of relevant articles. All randomized clinical trials and non-randomized studies that meet the pre-specified criteria were included. However, results of non-randomized studies were reported under 'exploratory analyses' in the result section. The outcome measure was hepatitis B recurrence. RESULTS Two randomized and 44 non-randomized studies were included. Meta-analysis of two randomized studies shows one week HBIg combined with lamivudine regimen had equivalent effect compared with long-term high-dose HBIg regimen for preventing hepatitis B recurrence (RR 1.23; 95% CI 0.38-4.03; P = 0.73). For 44 non-randomized studies, only qualitative systematic review was performed. With long-term HBIg prophylaxis, hepatitis B recurrence rate ranged from 3.7% to 65%; with lamivudine prophylaxis, hepatitis B recurrence rate varied from 3.8% to 40.4%; Long-term high-dose HBIg plus lamivudine prophylaxis can reduce the risk of HBV recurrence to less than 10%. CONCLUSIONS Long-term HBIg prophylaxis or lamivudine prophylaxis can reduce the risk for hepatitis B virus recurrence. Long-term high-dose HBIg combined with lamivudine can further reduce HBV recurrence to less than 10%.
Prevention of recurrent hepatitis B virus infection after liver transplantation: hepatitis B immunoglobulin, antiviral drugs, or both? Systematic review and meta-analysis
Transplant Infectious Disease. 2010;12((4):):292-308.
OBJECTIVES To evaluate antiviral prophylaxis against hepatitis B virus (HBV) following liver transplantation. METHODS Systematic review and meta-analysis. Clinical trials and comparative cohort studies comparing the use of hepatitis B immunoglobulin (HBIg), antivirals, or both following liver transplantation for HBV infection were included. The primary outcome was reappearance of hepatitis B surface antigen (HBsAg). Other outcomes included all-cause and HBV-related mortality, HB-related active liver disease, and reappearance of HBV DNA after transplantation. Relative risks (RR) with 95% confidence intervals (CIs) are reported. RESULTS Twenty studies (22 comparisons) were included. Ten studies compared HBIg to combination treatment, 9 compared antivirals to combination treatment, and 3 compared lamivudine (LAM) to HBIg. Combination treatment reduced HBsAg reappearance (RR 0.28; 95% CI 0.12-0.66), and was superior to HBIg alone in all other outcome measures. Combination treatment was significantly better than antivirals in preventing reappearance of HBsAg (RR 0.31; 95% CI 0.22-0.44), even when low-dose HBIg was given. No significant difference was found between HBIg and LAM monotherapy for all measured outcomes. Major limitations with regard to comparability of the study groups in non-randomized trials were revealed. CONCLUSIONS Combination treatment with HBIg and LAM reduced HBV recurrence following liver transplantation, compared with HBIg or LAM alone, and reduced mortality compared with HBIg alone.
Lamivudine or adefovir dipivoxil alone or combined with immunoglobulin for preventing hepatitis B recurrence after liver transplantation
Cochrane Database of Systematic Reviews. 2010;((7):):CD006005.
BACKGROUND Recurrence of hepatitis B virus (HBV) infection in the liver graft is a grave complication following liver transplantation for HBV cirrhosis. Hepatitis B immunoglobulin (HBIg) seems effective in increasing survival after liver transplantation. HBIg and anti-viral drugs are given alone or in combination for its prevention. OBJECTIVES To assess the benefits and harms of different regimens for preventing HBV reactivation following liver transplantation. SEARCH STRATEGY We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until February 2010. We attempted to identify further trials by reviewing the reference lists and contacting the principal authors of identified trials. SELECTION CRITERIA Randomised clinical trials addressing benefits and harms of lamivudine or adefovir dipivoxil alone or in combination with hepatitis B immunoglobulins (HBIg) for preventing recurrent HBV infection in patients who are liver transplanted due to HBV infection with or without hepatocellular carcinoma. DATA COLLECTION AND ANALYSIS Two authors independently assessed the trials for risk of bias and extracted data. We contacted study authors whenever information was lacking. We collected information on adverse events. The primary outcomes were all-cause mortality and reappearance of hepatitis B surface antigen in serum after liver transplantation. Relative risks were calculated from individual trials. MAIN RESULTS Four trials, recruiting 136 participants, were included. Two trials compared lamivudine alone versus HBIg alone. Randomisation was performed one week after transplantation in one of the trials and after six months after transplantation in another; from transplantation until randomisation, HBIg alone was given to all patients in the two trials. A third trial compared combination treatment with lamivudine and HBIg versus lamivudine alone after one month of combination treatment, and a fourth trial compared the combination of lamivudine and HBIg versus a combination of lamivudine and adefovir dipivoxil after at least 12-month of lamivudine and HBIg combination treatment. Statistically significant differences were not detected in any of the comparisons and outcomes. All trials were open-labelled, and none of the trials were adequately powered to show a difference in HBV recurrence. No meta-analyses were performed since the identified trials assessed different comparisons. AUTHORS' CONCLUSIONS This review could not derive clear evidence from randomised clinical trials for the treatment of patients with chronic HBV following liver transplantation for preventing recurrence of HBV infection. Large randomised clinical trials comparing long-term combination treatment to each of the monotherapy alone, including the newer antiviral drugs, are needed.