Association of Metabolic‐Associated Steatotic Liver Disease With Clinical Outcomes of Durvalumab and Tremelimumab in Advanced Hepatocellular Carcinoma Patients: A Multicenter Study

ABSTRACT Aim This study aimed to evaluate the association between the efficacy of durvalumab plus tremelimumab (Dur/Tre) and metabolic dysfunction‐associated steatotic liver disease (MASLD) in patients with hepatocellular carcinoma (HCC). Methods A total of 239 patients with HCC who received Dur/Tre between March 2023 and October 2024 at multiple institutions in Japan were retrospectively analyzed. Patients were categorized into three groups based on underlying liver disease: viral‐related HCC ( n = 126), MASLD‐related HCC ( n = 30), and nonviral, non‐MASLD HCC ( n = 83). Results The overall response rates (ORR) were 17.5%, 16.7%, and 19.3% in viral‐related HCC, MASLD‐related HCC, and nonviral, non‐MASLD HCC, respectively. The disease control rates (DCR) were 44.4%, 46.7%, and 51.8%, respectively. No significant differences in ORR ( p = 0.6) or DCR ( p = 0.9) were observed among the three groups. The median PFS was 3.7 months (95% CI, 2.8–4.9) in patients with viral‐related HCC, 3.6 months (95% CI, 2.3–4.8) in patients with MASLD‐related HCC, and 4.4 months (95% CI, 2.6–5.8) in patients with nonviral, non‐MASLD HCC. The median OS was 14.4 months (95% CI, 9.8–NA) in patients with viral‐related HCC and 11.0 months (95% CI, 6.4–NA) in patients with MASLD‐related HCC, whereas it was not reached in patients with nonviral, non‐MASLD HCC. No statistically significant differences in PFS ( p = 1.0) and OS ( p = 0.3) were found among the groups. Conclusions Dur/Tre showed comparable efficacy in MASLD‐related HCC and other etiologies, warranting confirmation in larger cohorts.