Lee, Teng-YuTeng-YuLeeYang, Sheng-ShunSheng-ShunYangTsai, Pei-ChienPei-ChienTsaiHuang, Chung-FengChung-FengHuangChen, Chi-YiChi-YiChenHung, Chao-HungChao-HungHungChen, Chien-HungChien-HungChenTai, Chi-MingChi-MingTaiCheng, Pin-NanPin-NanChengKuo, Hsing-TaoHsing-TaoKuoTseng, Kuo-ChihKuo-ChihTsengMo, 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-HueyTzeng-HueyYangPeng, 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-LongChuangLee, Shou-WuShou-WuLeeYu, Ming-LungMing-LungYu2026-04-012026-04-012026-01https://scholars.lib.ntu.edu.tw/handle/123456789/736994Background: The survival benefit of direct-acting antiviral (DAA) in hepatitis C virus (HCV)-infected patients with or without active hepatocellular carcinoma (HCC) remains debated. This study aimed to clarify this issue. Methods: This retrospective nationwide cohort study utilized data from the Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) to identify adults with HCC who received DAA therapy for HCV between December 2013 and December 2020. Patients with other viral infections, prior liver transplantation, non-HCC malignancies, or terminal-stage HCC were excluded. The primary outcome was overall survival (OS). The adjusted odds ratio (aOR) for sustained virological response (SVR) and the adjusted hazard ratio (aHR) for OS were calculated. Findings: A total of 2205 patients were included: 1771 (80.3 %) without active HCC and 434 (19.7 %) with active HCC. SVR was independently associated with improved OS (aHR 0.45, 95 % CI: 0.31-0.66; p < 0.001). In Barcelona Clinic Liver Cancer (BCLC) stage 0/A, the 3-year OS rate was significantly higher in the SVR group amongst patients with active HCC (71.7 %, 95 % CI 64.6-77.7 % vs. 39.9 %, 95 % CI 15.6-63.5 %; p = 0.007) but non-significantly higher amongst those without active HCC (84.2 %, 95 % CI 81.7-86.4 % vs. 70.0 %, 95 % CI 44.2-85.6 %; p = 0.181). In BCLC stage B/C, the 3-year OS rate was significantly higher in the SVR group amongst patients without active HCC (76.2 %, 95 % CI 70.2-81.2 % vs. 24.7 %, 95 % CI 5.3-51.3 %; p < 0.001) but not amongst those with active HCC (58.6 %, 95 % CI 47.9-67.7 % vs. 57.1 %, 95 % CI 17.2-83.7 %; p = 0.922). Conclusion: For BCLC stage 0/A HCC, early DAA initiation is recommended, even with active HCC. In BCLC stage B/C, DAA therapy appears most beneficial after tumor control.enChronic hepatitis CEradicationLiver cancerSustained virological responsejournal article10.1016/j.ejca.2025.11610941274170