Is Hepatitis B Immunoglobulin Necessary in Prophylaxis of Hepatitis B Recurrence after Liver Transplantation? A Meta-Analysis

Abstract

Background & AimsApplication 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.MethodsA 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.ResultsNineteen 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)).ConclusionsHBIG 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.

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

“…152 Conversely, lifelong combination therapy should be given to patients who are at a high risk for HBV recurrence, namely those who are HBV DNA positive at the time of liver transplantation, who are HBeAg-positive, have HCC, and HDV or HIV co-infection. [153][154][155] In the setting of liver transplantation, nephrotoxicity should always be considered and renal function should be carefully monitored because of the concomitant use of calcineurin inhibitors. When the immune system is therapeutically suppressed in the context of liver transplantation, there is potential for HBV reactivation in HBsAg-negative patients receiving donor organs with evidence of past HBV infection (anti-HBc positive).…”

Management of special patient groups with hepatitis B virus infection: The EASL 2017 Clinical Practice Guidelines

“…Treatment with a combination of nucleos(t)ide analogs (NAs) and hepatitis B immunoglobulin (HBIG) has dramatically decreased HBV recurrence and improved the clinical outcome after LT (5)(6)(7)(8)(9)(10). Entecavir (ETV) or tenofovir disoproxil fumarate (TDF) and HBIG combination therapy decrease the risk of graft infection to <5% (1,8).…”

Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation

“…Therefore, a combination of HBIg with potent nucleos(t)ide analogues (NA) is considered as gold standard in prophylaxis of recurrent HBV [62][63][64][65][66][67] . Currently, the combination of anti-HBs Ig with tenofovir or entecavir is under clinical evaluation [62,68] . These novel drugs are characterized by higher antiviral potency than lamivudine (Lam) or adefovir and, thus, decrease the risk of viral resistances [68] .…”

“…Currently, the combination of anti-HBs Ig with tenofovir or entecavir is under clinical evaluation [62,68] . These novel drugs are characterized by higher antiviral potency than lamivudine (Lam) or adefovir and, thus, decrease the risk of viral resistances [68] . In combination with high costs and inconvenience of HBIg treatment, strategies of HBIg minimization/withdrawal or even anti-HBs Ig-free prophylaxis may be reasonable.…”

“…In addition, most trials were predominantly focusing on virologic outcome results, but not on survival data. It became, however, evident in recent years that, with availability of very effective antimicrobial agents, recurrent viral disease no longer reduces patients' long-term prognosis [58,60,[68][69][70][71][72][73][74][75][76][77][78][79] . In order to appropriately assess the prognostic value of HBIg, the focus should, thus, be rather turned on variables like organ acceptance, graft rejection, infectious complications and survival [21,22] .…”