Comparison of 48-week efficacy of tenofovir vs entecavir for patients with chronic hepatitis B: A network meta-analysis

Both tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are accepted as first-line treatments for chronic hepatitis B (CHB). However, there are few randomized studies comparing their efficacy. The primary aim of this study was to compare the efficacy of TDF and ETV using a network meta-analysis of randomized trials. The secondary aim was to additionally include propensity-matched cohort studies in a conventional meta-analysis. We systematically searched PubMed, EMBASE, Cochrane Library and Web of Science for published English-language randomized and propensity-matched studies between 1/1/2000 and 4/2/2020. Outcomes included undetectable HBV DNA, ALT normalization and HBeAg seroconversion at 48 weeks. We excluded patients who had co-infection or significant prior treatment with antivirals. 13 517 participants from 16 studies (11 RCTs, n = 2675; five propensity-matched cohort studies, n = 10 842) were included. Virological response at 48 weeks was higher in patients receiving TDF compared to ETV using both the network meta-analytic approach (OR 1.69, P <.001) and the conventional meta-analysis including propensity-matched cohort studies (OR 1.40, P <.001). On subgroup analysis, this difference was only significant in HBeAg-positive patients (OR 1.81, P =.037). There was limited evidence to suggest a higher rate of ALT normalization with ETV (OR 0.74, P =.07). There was no difference in rates of HBeAg seroconversion between the two antivirals. TDF is more likely than ETV to induce virological response at 48 weeks in treatment-naïve CHB patients. Future studies should focus on elucidating associations between early and sustained virological response with adverse patient outcomes including development of HCC or cirrhosis.