Rosanna Villani, Gaetano Serviddio
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and a major risk factor for hepatocellular carcinoma. Compared with viral-related liver cancer, MASLD-associated hepatocellular carcinoma occurs at older age, is often diagnosed at more advanced stages, and may develop in a significant proportion of patients without established cirrhosis. These features profoundly affect surveillance strategies, which have largely been based on cirrhosis-driven eligibility criteria. This review summarizes current evidence on hepatocellular carcinoma risk in MASLD, with a focus on surveillance. We discuss the epidemiology of MASLD-related hepatocellular carcinoma, the clinical relevance of non-cirrhotic disease, and the limitations of current surveillance approaches, particularly in individuals with obesity and hepatic steatosis. Across international guidelines, routine surveillance is recommended for patients with MASLD-related cirrhosis, whereas surveillance in non-cirrhotic MASLD is generally not advised because of the absence of validated selection criteria. Recent epidemiological and real-world data highlight the marked heterogeneity of HCC risk in MASLD populations and the suboptimal performance of ultrasound-based surveillance strategies. Future research should focus on validating risk stratification tools, refining eligibility criteria for surveillance beyond cirrhosis, and evaluating surveillance strategies tailored to individual risk profiles.