Similar Long‐Term Incidence of Hepatocellular Carcinoma in Chronic Hepatitis B Initiating Entecavir Versus Tenofovir Alafenamide: A
REAL
‐B Study
Haruki Uojima, Rui Huang, Huy Trinh, Akito Nozaki, Philip Vutien, Hidenori Toyoda, Takashi Honda, Hiroshi Abe, Masanori Atsukawa, Tsunamasa Watanabe, Toru Ishikawa, Masaru Enomoto, Yasuhito Tanaka, Koichi Takaguchi, Pei‐Chien Tsai, Wan‐Long Chuang, Chia‐Yen Dai, Jee‐Fu Huang, Chung‐Feng Huang, Ming‐Lun Yeh, Tomonori Senoh, Mayumi Maeda, Ramsey Cheung, Takanori Ito, Manabu Morimoto, Ming‐Lung Yu, Chao Wu, Mindie H. Nguyen ABSTRACT
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.