Is hepatitis B immunoglobulin necessary in prophylaxis of hepatitis B recurrence after liver transplantation? A meta-analysis

Background & Aims: Application of nucleoside analogues and hepatitis B immunoglobulin (HBIG) has reduced hepatitis B virus (HBV) recurrence rate after liver transplantation (LT) dramatically. Recent data suggests therapy without HBIG is also effective. We sought to evaluate the necessity of HBIG in prophylaxis of HBV recurrence after LT. Methods: A meta-analysis was performed. PubMed/MEDLINE, Web of Knowledge and other databases were searched for eligible literatures. The major end points were recurrence rate, patient survival, and YMDD mutant. Risk difference (RD) or risk ratio (RR) was calculated to synthesize the results. Results: Nineteen studies with a total of 1484 patients were included in this analysis. Application of HBIG was helpful to reduce HBV recurrence [P<0.001; RD = 0.16; 95% confidence interval (CI)(0.12, 0.20)] and virus mutants [P<0.001; RR = 3.13; 95%CI (1.86-5.26)], it also improved patients' 1-year [P = 0.03; RD = 0.08; 95%CI (0.01, 0.15)] and 3-year survival rates [P = 0.005; RD = 0.17; 95%CI(0.05, 0.28)]. No significant difference was found for patients' 5-year survival [P = 0.46; RD = -0.06; 95%CI (-0.21, 0.10)]. Sub-group analysis showed that in patients with positive pre-operative HBV DNA status, HBIG was necessary to reduce HBV recurrence rate (P<0.001; RD = 0.42; 95%CI (0.32, 0.52)). In patients with negative HBV DNA, combined therapy gained no significant advantages (P = 0.18; RD = 0.06; 95%CI (-0.03, 0.14)). Non-Lamivudine (non-LAM) antiviral drugs performed as well as combination therapy in prophylaxis of HBV recurrence after LT (P = 0.37; RD = 0.06; 95%CI (-0.02, 0.14)). Conclusions: HBIG with nucleoside analogues is helpful to reduce HBV recurrence and virus mutants. The necessity of HBIG in prophylaxis of HBV recurrence after LT when using new potent nucleoside analogues, especially for patients with negative pre-transplant HBV DNA status remains to be evaluated.