Chen, Yen-ChunYen-ChunChenTsai, Pei-ChienPei-ChienTsaiHuang, Chung-FengChung-FengHuangChen, Chi-YiChi-YiChenHung, Chao-HungChao-HungHungChen, Chien-HungChien-HungChenTai, Chi-MingChi-MingTaiCheng, Pin-NanPin-NanChengKuo, Hsing TaoHsing TaoKuoMo, Lein-RayLein-RayMoLo, Ching ChuChing ChuLoHuang, Yi-HsiangYi-HsiangHuangLin, Han-ChiehHan-ChiehLinLee, Pei-LunPei-LunLeeBair, Ming-JongMing-JongBairChang, Te-ShengTe-ShengChangLin, Chun-YenChun-YenLinWang, Szu-JenSzu-JenWangHsieh, Tsai-YuanTsai-YuanHsiehYang, Tzeng-HueTzeng-HueYangPeng, Cheng-YuanCheng-YuanPengYang, Chi-ChiehChi-ChiehYangChong, Lee-WonLee-WonChongHuang, Chien-WeiChien-WeiHuangLin, Chih-WenChih-WenLinChu, Cheng-HsinCheng-HsinChuTsai, Ming-ChangMing-ChangTsaiJIA-HORNG KAOCHUN-JEN LIUChuang, Wan-LongWan-LongChuangTseng, Kuo-ChihKuo-ChihTsengYu, Ming-LungMing-LungYu2025-04-052025-04-052025-02-06https://scholars.lib.ntu.edu.tw/handle/123456789/726253The risk of hepatocellular carcinoma (HCC) is increased in patients with chronic hepatitis C (CHC) and elevated alanine transaminase (ALT) levels. The association between HCC and ALT levels after interferon (IFN) or direct-acting antivirals (DAA) therapy is unclear. Patients with CHC receiving antiviral therapy were included in two large-scale cohorts in Taiwan (T-COACH and TACR). Posttreatment ALT levels were assessed at 24-weeks/12-weeks after the end-of-treatment with IFN/DAA. HCC risk after antiviral therapy were identified for evaluation. Of 29,926 CHC patients enrolled in the study, 64%, 22.5%, and 13.5% had posttreatment healthy-normal (female, ≤19 U/L; male ≤30 U/L), high-normal (female, 19-40 U/L; male, 30-40 U/L), and abnormal (>40 U/L) ALT levels, respectively. During a median follow-up of 2.4 years, 1245 patients developed HCC. The 5-year cumulative HCC incidence was 11.2% and 5.2% in the abnormal and high-normal ALT groups, respectively, compared to 2.7% in the healthy ALT group. In Cox regression analysis, factors associated with a higher HCC risk were advanced fibrosis, abnormal and high-normal posttreatment ALT levels, cirrhosis, and old age; whereas a sustained virological response (SVR) was associated with a lower HCC risk. The aforementioned impacts of abnormal and high-normal posttreatment ALT levels were observed across the SVR, non-SVR, and non-cirrhotic subgroups. Patients with CHC with high-normal and abnormal posttreatment ALT levels have an increased risk of HCC; thus, HCC surveillance is still necessary in this population.enChronic hepatitis CDirect-acting antiviralsHepatocellular carcinomaInterferon[SDGs]SDG3journal article10.1016/j.jfma.2025.01.02639919992