Alcohol Plays a Detrimental Role in the Prognosis of Hepatocellular Carcinoma Related to Steatotic Liver Disease

Introduction: The recently adopted nomenclature of steatotic liver disease (SLD) introduces new diagnostic categories, including metabolic dysfunction-associated steatotic liver disease (MASLD), the intermediate metabolic dysfunction and alcohol-related liver disease (MetALD), and alcohol-associated liver disease (ALD). However, their specific impact on the outcomes of hepatocellular carcinoma (HCC) remains unclear. This study aimed to evaluate how alcohol consumption influences prognosis in patients with SLD-related HCC. Methods: We analyzed data from 2,864 HCC patients enrolled in the nationwide ITA.LI.CA database (2008-2022), stratifying those with SLD based on alcohol intake into MASLD, MetALD, and ALD. A comparator group with hepatitis B virus (HBV)-related HCC was also included. Multivariable Cox regression and competing risk analyses were employed to assess survival and cause-specific mortality. Results: Among SLD-related HCC, MASLD accounted for 47.1%, ALD 18.7%, and MetALD 7.2%. Patients with ALD showed the poorest liver function, more advanced tumor stage, and the highest mortality risk. Alcohol use progressively worsened prognosis from MASLD to ALD. MetALD and ALD were both associated with increased liver failure- and extrahepatic-related deaths compared to MASLD. In multivariable models, tumor burden, liver decompensation, and alcohol intake were significant predictors of mortality. Notably, metabolic comorbidities impacted prognosis predominantly in MetALD and ALD, suggesting an interaction between alcohol and systemic metabolic dysfunction. Conclusion: Alcohol consumption exerts a dose-dependent detrimental effect on clinical outcomes in SLD-related HCC. These findings support a distinct prognostic stratification for HCC patients with MetALD and ALD, reinforcing the need for alcohol abstinence in individuals with metabolic liver disease.