AUTHOR=Moriyama Makoto , Tateishi Ryosuke , Kinoshita Mizuki Nishibatake , Fukumoto Tsuyoshi , Yamada Tomoharu , Wake Taijiro , Nakagomi Ryo , Nakatsuka Takuma , Minami Tatsuya , Sato Masaya , Fujishiro Mitsuhiro , Koike Kazuhiko 

TITLE=Impact of nucleos(t)ide analogues on the risk of hepatocellular carcinoma in chronic hepatitis B patients: a time-dependent Cox regression analysis

JOURNAL=Frontiers in Gastroenterology

VOLUME=Volume 4 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/gastroenterology/articles/10.3389/fgstr.2025.1585760

DOI=10.3389/fgstr.2025.1585760

ISSN=2813-1169

ABSTRACT=Background and aimsThe preventive effect of nucleos(t)ide analog (NA) use on HCC development in patients with chronic hepatitis B (CHB) is controversial due to the difficulty of conducting randomized controlled trials.Approach and resultsIn this single-center, retrospective study, NA-naïve CHB patients without a history of HCC were enrolled and followed-up from the first visit on or after January 2000 to December 2020. Patients were categorized into the NA group, including those who started NA after study enrollment, and the non-NA group, including patients who were never administered NA during the follow-up period. After propensity score matching (PSM) to balance the confounding factors, we applied a multivariable time-dependent Cox proportional regression analysis with the initiation of NA as a time-dependent covariate. We further performed a subgroup analysis according to the presence or absence of cirrhosis. The baseline characteristics of 212 pairs of patients retrieved by PSM were comparable. During the mean follow-up of 12.9 and 6.8 years in the NA and non-NA groups, respectively, 25 and 28 patients developed HCC, respectively. Multivariable analysis with time-dependent covariates showed that NA did not affect HCC risk (HR, 0.68; 95% CI, 0.36–1.31; p = 0.25) after adjusting for other risk factors, including age, sex, and HBV viral load. Subgroup analysis showed that NA use significantly reduced the risk of HCC in cirrhotic patients (HR, 0.26; 95% CI, 0.08–0.85; p = 0.03).ConclusionsThe preventive effect of NA on hepatocarcinogenesis may be limited to cirrhotic patients.