Evolution of Hepatocellular Carcinoma Treatment Outcomes Over Two Decades in Japan: Improvements in Early‐Stage Viral Disease

Background and Aims Hepatocellular carcinoma (HCC) management has markedly evolved in Japan. We evaluated temporal changes in patient characteristics and outcomes between 2004–2013 and 2014–2023. Methods In this multicenter retrospective study, 7275 treatment‐naïve HCC patients were analyzed (3832 vs. 3443). Propensity score matching (PSM) for age, sex, albumin‐bilirubin (ALBI) score, and viral status yielded 4754 patients. Overall survival (OS) was compared by the Barcelona Clinic Liver Cancer (BCLC) stage and treatment modality. Cox regression identified independent prognostic factors. Results After PSM, baseline characteristics were balanced. OS significantly improved in BCLC‐0/A patients in 2014–2023 ( p < 0.0001), but not in BCLC‐B, C, or D. Among BCLC‐A patients, surgical resection ( p = 0.0042) and ablation ( p = 0.0019) showed improved outcomes in the recent era, whereas TACE and systemic therapy did not. Subgroup analysis revealed survival gains were confined to viral HCC, with minimal improvement in nonviral HCC. Multivariate analysis confirmed the recent era (HR 0.800, 95%CI 0.658–0.972, p = 0.025), curative therapy, and ALBI score as independent prognostic factors. Conclusions Survival outcomes in Japan improved primarily for early‐stage viral HCC, reflecting advances in curative treatments and antiviral management. Nonviral HCC showed minimal improvement, highlighting the need for novel therapeutic strategies for this growing population. Clinical trial registration This study is a retrospective study using anonymized database data, and clinical trial registration was not performed.