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. 2025 May 28;17(11):1808.
doi: 10.3390/cancers17111808.

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

Rodolfo Sacco  1 , Edoardo G Giannini  2 , Raffaella Tortora  3 , Giovan Giuseppe Di Costanzo  3 , Andrea Mega  4 , Luca Marzi  4 , Giulia Pieri  2 , Andrea Pasta  2 , Bruno Daniele  5 , Piera Federico  5 , Giuseppe Cabibbo  6 , Maurizio Russello  7 , Caterina Cocuzza  7 , Luca Giacomelli  8 , Marianna Silletta  9 , Paolo Gallo  10 , Umberto Vespasiani Gentilucci  10 , Andrea Casadei-Gardini  11 , Ernesto Claar  12 , Adriano Pellicelli  13 , Massimo Bellini  14 , Filomena Morisco  15 , Concetta Tatali  1 , Valeria Pace Palitti  16 , Antonio Izzi  17 , Marco Di Stefano  18 , Luca Rinaldi  19 , Antonio Facciorusso  20 ; A.I.G.O. (Italian Association of Hospital Gastroenterologists) and C.L.E.O. (Italian Association of Hospital Hepatologists)
Affiliations

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

Rodolfo Sacco et al. Cancers (Basel). .

Abstract

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.

Keywords: HCC; liver cancer; progression; propensity matching; survival.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Details of the propensity score matching model. (Left Panel) Jitter plot. (Right Panel) Histogram.
Figure 2
Figure 2
Kaplan–Meier curves comparing overall survival. Median overall survival was 21 months (95% CI: 20–23) in the group with MASH and 19 months (95% CI: 18–21) in the group with alcohol etiology (p = 0.18).
Figure 3
Figure 3
Kaplan–Meier curves comparing progression-free survival. Median progression-free survival 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).
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