The Strategy and Efficacy of Prophylaxis Against Hepatitis B Virus Recurrence After Liver Transplantation in the Era of High Potent Nucleos(t)ide Analogues: A Meta-Analysis

Abstract Background: High potent nucleos(t)ide analogues (HP NAs) with or without hepatitis B immunoglobulin (HBIG) is the standard prophylactic therapy for avoiding the HBV recurrence after liver transplantation (LT). While the clinical impact of HP NAs-based prophylaxis has not been well documented, the optimal treatment strategy is currently debated. This meta-analysis aims to evaluate clinical outcome of LT recipients under HP NAs-based regimens and investigate different prophylaxis schemes. Methods: We followed PRISMA statement to conduct this study. Two reviewers independently searched relevant literature via PubMed, EMBAES, MEDLINE, Web of Science, and Google Scholar. Studies were included if they observed HBV recurrence under HP NAs-based regimens in patients who received HBV-related LT. Primary and secondary outcome were HBV recurrence, HCC recurrence, all-cause and HBV-recurrence related mortality. Incidence with 95% confidence intervals was aggregated and assess by fixed effect model/random effect model. Subgroup analysis was applied to examine the impact of different treatment strategies. Results: 26 studies (n=2374) were included, with a pooled HBV recurrence rate of 0.92% (95% CI 0.47%-1.48%). Studies with and without HBV viremia or HDV superinfected patients demonstrated comparable HBV recurrence (p=0.25, p=0.69). Recurrence rate under indefinite combination of HP NAs and HBIG was lower than that under HP NAs monotherapy (p=0.0003), and similar to that under NAs plus finite course of HBIG (p=0.53). Pooled HCC recurrence rate was 5.34% (95% CI 0.78%-12.48%). HBV-recurrence related mortality and all-cause mortality were 0.17% (95% CI 0.00%-1.51%) and 7.29% (95% CI 4.42%–10.71%) respectively. Conclusion: Our study suggests HP NAs-based regimens provide satisfactory HBV antiviral prophylaxis and improved long-term outcome for LT recipients. Finite combination of HP NAs and HBIG is an alternative to lifelong dual therapy.