Immunoglobulin, nucleos(t)ide analogues and hepatitis B virus recurrence after liver transplant: A meta-analysis

Abstract

Background: Prophylaxis with hepatitis B immunoglobulin (HBIG) represents an efficient strategy for reducing the risk of hepatitis B virus (HBV) recurrence after liver transplantation (LT). Unfortunately, the long-term use of HBIG presents high costs. Therefore, the use of prophylaxis based only on nucleos(t)ide analogues (NUC) has been recently postulated. The present meta-analysis aimed to evaluate the impact of HBIG ± NUC vs HBIG alone or NUC alone in post-LT HBV recurrence prophylaxis.

Materials and methods: A systematic literature search was performed using PubMed and Cochrane databases. The primary outcome investigated was the HBV recurrence after LT. Three analyses were done comparing the effect of (a) HBIG + NUC vs HBIG alone; (b) HBIG+NUC vs NUC alone; and (c) HBIG alone vs NUC alone. Sub-analyses were also performed investigating the effect of low and high genetic barrierto-recurrence NUC.

Results: Fifty-one studies were included. The summary OR (95%CI) showed a decreased risk with the combination of HBIG + NUC vs HBIG alone for HBV recurrence, being 0.36 (95% CI = 0.22-0.61; P < .001). HBIG + NUC combined treatment reduced HBV reappearance respect to NUC alone (OR = 0.22; 95% CI = 0.16-0.30; P < .0001). Similarly, HBIG alone was significantly better than NUC alone in preventing HBV recurrence (OR = 0.20; 95% CI = 0.09-0.44; P < .0001).

Conclusions: Prophylaxis with HBIG is relevant in preventing post-LT HBV recurrence. Its combination with NUC gives the best results in terms of protection. The present results should be considered in light of the fact that also old studies based on lamivudine use were included. Studies exploring in detail high genetic barrier-to-recurrence NUC and protocols with definite use of HBIG are needed.

Keywords: adefovir; entecavir; lamivudine; liver transplantation; nucleos(t)ide analogues; prophylaxis.

FIGURE 1

PRISMA summarizing the trial flow

FIGURE 2

A‐C, Forest plot of odds ratios and 95% confidence intervals for the association between HBIG+NUC vs HBIG alone for the risk of HBV recurrence in patients undergoing liver transplantation. A, entire population; (B) HBIG +low genetic barrier‐to‐recurrence NUC vs HBIG alone.; (C) HBIG+high genetic barrier‐to‐recurrence NUC vs HBIG alone

FIGURE 3

A‐E, Forest plot of odds ratios and 95% confidence intervals for the association between HBIG+NUC and NUC alone for the risk of HBV recurrence in patients undergoing liver transplantation. A, entire population; (B) HBIG+low genetic barrier‐to‐recurrence NUC vs low genetic barrier‐to‐recurrence NUC alone; (C) HBIG +low genetic barrier‐to‐recurrence NUC vs high genetic barrier‐to‐recurrence NUC alone; D, HBIG+high genetic barrier‐to‐recurrence NUC vs low genetic barrier‐to‐recurrence NUC alone; E, HBIG+high genetic barrier‐to‐recurrence NUC vs high genetic barrier‐to‐recurrence NUC alone

FIGURE 4

A‐C, Forest plot of odds ratios and 95% confidence intervals for the association between HBIG alone and NUC alone for the risk of HBV recurrence in patients undergoing liver transplantation. A, entire population; (B) HBIG alone vs low genetic barrier‐to‐recurrence NUC alone; (C) HBIG alone vs high genetic barrier‐to‐recurrence NUC alone

FIGURE 5

Schematic representation of the results obtained from the meta‐analyses