ORIGINAL RESEARCH article
Front. Gastroenterol.
Sec. Hepatology
Volume 4 - 2025 | doi: 10.3389/fgstr.2025.1585760
This article is part of the Research TopicWorld Hepatitis Day - Advances in Hepatitis Research: Bridging Gaps and Exploring New FrontiersView all 3 articles
Impact of nucleos(t)ide analogues on the risk of hepatocellular carcinoma in chronic hepatitis B patients: A time-dependent Cox regression analysis
Provisionally accepted
Makoto Moriyama1
Ryosuke Tateishi1*
Mizuki Nishibatake Kinoshita1Tsuyoshi Fukumoto1Tomoharu Yamada1Taijiro Wake1Ryo Nakagomi2Takuma Nakatsuka1
Tatsuya Minami1
Masaya Sato1Mitsuhiro Fujishiro1Kazuhiko Koike1,2- 1The University of Tokyo, Bunkyo, Japan
- 2Kanto Central Hospital of the Mutual Aid Association of Public School Teachers, Setagaya, Tōkyō, Japan
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The 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.In 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).The preventive effect of NA on hepatocarcinogenesis may be limited to cirrhotic patients.
Keywords: CHB, chronic hepatitis B, Hepatocellular carcinoma, Nucleosid analogs, time dependent covariate, cirrhois
Received: 01 Mar 2025; Accepted: 16 May 2025.
Copyright: © 2025 Moriyama, Tateishi, Kinoshita, Fukumoto, Yamada, Wake, Nakagomi, Nakatsuka, Minami, Sato, Fujishiro and Koike. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ryosuke Tateishi, The University of Tokyo, Bunkyo, Japan
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