Changes in clinical outcomes in Japanese patients with hepatocellular carcinoma due to hepatitis C virus following the development of direct‐acting antiviral agents

Background and Aim Direct‐acting antivirals (DAAs) have been accessible in Japan since 2014. The aim of this study is to compare how the prognosis of patients with hepatitis C virus (HCV)‐associated hepatocellular carcinoma (HCV‐HCC) changed before and after DAA development. Methods A retrospective analysis of 1949 Japanese HCV‐HCC patients from January 2000 to January 2023 categorized them into pre‐DAA (before 2013, n = 1169) and post‐DAA (after 2014, n = 780) groups. Changes in clinical features and prognosis were assessed. Results Despite no significant differences in BCLC stage between groups, the post‐DAA group exhibited higher rates of sustained virological response (SVR) (45.6% vs. 9.8%), older age (73 vs 69 years), lower levels of AST (40 vs 56 IU/L), ALT (31 vs 46 IU/L), and AFP (11.7 vs 23.6 ng/mL), higher platelet count (13.5 vs 10.8 × 10 4 /μL), better prothrombin time (88.0% vs 81.9%), and better ALBI score (−2.54 vs −2.36) (all P < 0.001). The post‐DAA group also showed higher rates of curative treatments (74.1% vs 65.2%) and significantly improved recurrence‐free survival (median 2.8 vs 2.1 years). Adjusted for inverse probability weighting, overall survival was superior in the post‐DAA group (median 7.4 vs 5.6 years, P < 0.001). Subanalysis within the post‐DAA group revealed significantly shorter overall survival for patients without SVR (median 4.8 years vs NA vs NA) compared to pre‐SVR or post‐SVR patients (both P < 0.001). No significant difference in OS was observed between the pre‐SVR and post‐SVR groups ( P = 1.0). Conclusion The development of DAA therapy has dramatically improved the prognosis of HCV‐HCC patients.