Lenvatinib Is Highly Effective in Patients with Hepatocellular Carcinoma Related to Both Metabolic Dysfunction-Associated Steatohepatitis and Alcoholic Etiology: A Propensity Score Analysis

Background and aims: Metabolic dysfunction-associated steatotic liver disease (MASLD)-related hepatocellular carcinoma (HCC) may have distinct biological characteristics influencing systemic treatment response. However, the prognostic impact of MASLD vs. alcohol-related HCC in patients receiving lenvatinib remains unclear. This study aimed to assess lenvatinib’s effectiveness and safety in these populations. Methods: A multicenter cohort of 378 HCC patients treated with lenvatinib (2019–2024) was analyzed. Propensity score matching was performed based on age, sex, tumoral stage, alpha-fetoprotein levels and Child–Pugh class. Survival was estimated using Kaplan–Meier analysis and compared with the log-rank test. Results were expressed as HR and 95% CI. Results: After matching, 115 patients per group were compared. Median OS was 21 months (95% CI: 20–23) in the group with metabolic dysfunction-associated steatohepatitis (MASH) and 19 months (95% CI: 18–21) in the group with alcohol etiology (p = 0.18). In multivariate analysis, only Child–Pugh class (HR 2.67, 95% CI: 1.84–5.41) and tumor stage (HR 2.18, 95% CI: 1.57–6.93) resulted as significant predictors of OS. Median PFS was 9 months (95% CI: 8–9) in patients with MASH and 9 months (95% CI: 7–10) in patients with alcohol etiology (p = 0.33). Only the Child–Pugh class was a significant predictor of PFS in univariate analysis (HR 1.56, 95% CI: 1.15–3.41; p = 0.03). No difference in terms of adverse event rate was observed between the two groups. Conclusions: Lenvatinib is effective in patients with both MASH- and alcohol-related HCC, with no difference in oncological outcomes between the two groups.