Similar Long‐Term Incidence of Hepatocellular Carcinoma in Chronic Hepatitis B Initiating Entecavir Versus Tenofovir Alafenamide: A REAL ‐B Study

Data on potential differences in hepatocellular carcinoma (HCC) incidence between entecavir (ETV) and tenofovir alafenamide (TAF) in chronic hepatitis B (CHB) patients are limited. This retrospective multinational study included treatment-naïve adults with CHB without a history of HCC who initiated ETV or TAF therapy since 2016 at 23 centres in 4 countries. Baseline characteristics were balanced using inverse probability of treatment weighting (IPTW) and propensity score matching (PSM). HCC incidence and the association between antiviral regimen and HCC were analysed using competing-risk analysis. A total of 1437 patients (710 ETV, 727 TAF) were included, with similar mean follow-up durations (55.5 ± 29.8 vs. 58.0 ± 25.5 months; p = 0.077). ETV-treated patients were older, more frequently male, and more likely to have cirrhosis. After IPTW, both groups had balanced characteristics (all standardised differences < 0.1). After IPTW adjustment, during follow-up, 23 patients on ETV and 20 on TAF developed HCC, with incidence rates of 0.67 and 0.65 per 100 person-years, respectively (p = 0.853). There was no statistically significant difference in HCC risk between the groups (SHR: 1.09; 95% CI: 0.44-2.65; p = 0.851), with consistent findings across subgroups by age, sex, cirrhosis, hepatic steatosis, HBeAg, baseline liver enzymes, HBV DNA levels, diabetes mellitus and in sensitivity analysis using PSM. In this real-world multinational study of treatment-naïve CHB patients, HCC incidence did not significantly differ between ETV and TAF groups, suggesting therapeutic selection should consider cost and patient-specific factors.