Impact of metabolic dysfunction-associated steatotic liver disease on the development of hepatocellular carcinoma after HCV cure.

Abstract

Introduction and objectives: The impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on hepatocellular carcinoma (HCC) development after hepatitis C virus (HCV) elimination remains incompletely understood. This study aimed to clarify this association in a cohort of patients stratified by fibrosis severity.

Patients and methods: We analyzed the data of 2596 eligible patients obtained from a multicenter database between 2014 and 2025. The FIB-4 index was used to assess fibrosis status, with patients categorized into three groups: <1.45, 1.45-3.25, and >3.25. Cox proportional hazards and Fine-Gray subdistribution hazards models were used to evaluate factors independently associated with HCC development.

Results: The median follow-up duration was 6.7 years. MASLD was present in 975 patients (36.3%) and was more frequent among men and patients with diabetes. During follow-up, 156 patients (6.0%) developed de novo HCC. Patients with MASLD had a higher cumulative incidence of HCC than those without MASLD (log-rank test, P<0.001); however, no HCC occurred in patients with FIB-4<1.45. MASLD was associated with HCC development in multivariable analysis of the overall cohort and in patients with FIB-4 1.45-3.25 and >3.25. Older age, male sex, lower albumin level, and higher AFP level at post-treatment week 12 were also independently associated with HCC development, whereas individual cardiometabolic risk factors were not significant after adjustment.

Conclusions: MASLD was significantly associated with an increased risk of HCC after HCV cure, even among patients with intermediate FIB-4 values of 1.45-3.25. These findings support the need for tailored surveillance and management strategies.