The Beneficial Impact of Metabolic Dysfunction-associated Fatty Liver Disease on Lenvatinib Treatment in Patients with Non-viral Hepatocellular Carcinoma

Aim: Lenvatinib is used to treat advanced hepatocellular carcinoma (HCC). Metabolic dysfunction-associated fatty liver disease (MAFLD) is becoming a major etiology of HCC. We aimed to evaluate the impact of MAFLD on the efficacy of lenvatinib.

Methods: We enrolled 320 patients with HCC who were treated with lenvatinib. All patients were classified into the MAFLD (n = 155) and non-MAFLD (n = 165) groups. Independent factors for overall survival (OS) were analyzed. In the stratification analysis, HCC was categorized as non-viral (n = 115) or viral HCC (n = 205).

Results: The OS rate was significantly higher in the MAFLD group than in the non-MAFLD group (median 21.1 vs. 15.1 months, p = 0.002). Multivariate analysis demonstrated that, in addition to albumin-bilirubin grade and Barcelona Clinic Liver Cancer stage, MAFLD was identified as an independent factor for OS (HR 0.722, 95% CI 0.539-0.966, p = 0.028). In the stratification analysis, the OS rate was significantly higher in the MAFLD group than in the non-MAFLD group among patients with non-viral HCC (median 21.1 vs. 15.1 months, p = 0.002), but not in patients with viral HCC. Furthermore, MAFLD was an independent negative risk factor for OS in patients with non-viral HCC (HR 0.506, 95% CI 0.297-0.864, P < 0.01). However, MAFLD was not an independent factor for OS in patients with viral HCC.

Conclusions: MAFLD was a beneficial factor for survival in patients with HCC treated with lenvatinib. Moreover, the better OS of the MAFLD group was more pronounced in patients with non-viral HCC. Lenvatinib may be a suitable agent for patients with non-viral HCC and MAFLD.