Effects of Tenofovir vs Entecavir on Risk of Hepatocellular Carcinoma in Patients With Chronic HBV Infection: A Systematic Review and Meta-analysis

Abstract

Background & aims: Tenofovir disoproxil fumarate (TDF) and entecavir are recommended as first-line treatments for chronic hepatitis B virus (HBV) infection. However, there is debate over the comparative effectiveness of these drugs in preventing hepatocellular carcinoma (HCC). We performed a systematic review and meta-analysis of the effectiveness of TDF vs entecavir in reducing the incidence of HCC among patients with chronic HBV infection.

Methods: We performed a systematic review of the MEDLINE, EMBASE, Web of Science, and Cochrane Library from 2010 through 2019 for full-text articles and conference abstracts on studies of effects of TDF vs entecavir in patients with HBV infection. Extracted data were analyzed with the random-effects model. Potential sources of heterogeneity were investigated using sensitivity, meta-regression, and subgroup analyses.

Results: Our final analysis comprised 15 studies (61,787 patients; 16,101 patients given TDF and 45,686 given entecavir). TDF treatment was associated with a significantly lower risk of HCC than entecavir (hazard ratio, 0.80; 95% CI, 0.69-0.93; P = .003; I² = 13%). The lower risk of HCC in patients given TDF compared with entecavir persisted in sensitivity and subcohort analyses performed with propensity score-matched cohorts and cirrhosis subcohorts. Inclusion of patients with decompensated cirrhosis and the sample size were the factors with the largest effects on between-study heterogeneity in meta-regression analyses. Subsequent subgroup analyses showed no statistical differences in the incidence of death or transplantation (hazard ratio, 0.93; 95% CI, 0.73-1.17; P = .519; I² = 6%) between patients given TDF vs entecavir.

Conclusions: In a meta-analysis of studies of patients with chronic HBV infection, we found that TDF treatment was associated with a significantly lower (20%) risk of HCC than entecavir treatment. Randomized trials are needed to support this finding.

Keywords: CHB; Comparison; Liver Cancer; Therapy.