Metabolic hepatic steatosis and hepatocellular carcinoma

Metabolic dysfunction–associated steatotic liver disease (MASLD) has emerged as the fastest-growing cause of hepatocellular carcinoma (HCC) worldwide. HCC arising in this context is characterized by several adverse prognostic features, including higher tumor burden and, consequently, more advanced stage at diagnosis, as well as its occurrence even in the absence of underlying cirrhosis. Some of these unfavorable characteristics may reflect the lack of established screening programs for at-risk populations. Moreover, recent evidence suggests that the rising prevalence of cardiometabolic comorbidity may significantly influence therapeutic interventions, particularly in advanced disease stages, thereby posing a major clinical challenge. In this review, we provide a comprehensive narrative synthesis of the current evidence, aiming to analyze and integrate the available knowledge on MASLD related HCC. A systematic literature search was performed in PubMed/MEDLINE, Embase, and Cochrane Controlled Register of Trials (CENTRAL), considering studies published in English and Spanish between 2005 and 2025. Evidence selection was guided by the hierarchy of the evidence pyramid, prioritizing systematic reviews with or without meta-analyses, randomized controlled trials, interventional studies, observational cohorts, and, finally, case reports and expert opinion. The retrieved data were organized and synthesized across seven thematic domains: epidemiology, risk factors, pathogenesis, diagnosis, treatment, prevention, and future perspectives.