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

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 2,596 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.