Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly recognized as a leading cause of hepatocellular carcinoma (HCC), the third-leading cause of cancer mortality worldwide, driven by the global obesity epidemic. Projected to become the primary cause of HCC by 2030, MASH-HCC presents unique clinical challenges. This review examines its clinical management, including surveillance strategies and treatment advances, and discusses prospects to overcome existing challenges. MASH-HCC accounts for 10%–20% of HCC cases, particularly in Western countries, with a rising incidence due to obesity. Risk factors include cirrhosis, diabetes, obesity, alcohol, smoking, genetic polymorphisms (e.g., PNPLA3), and microbiome alterations. The pathogenesis involves fibrosis, immune dysfunction (e.g., T-cell impairment), and molecular changes. Prevention focuses on lifestyle modifications. Surveillance in patients with MASH cirrhosis is crucial but is hindered by poor ultrasound sensitivity in obese patients, necessitating alternative methods. Treatment mirrors that of other HCC types, but comorbidities and potentially reduced efficacy of immunotherapy necessitate tailored approaches. MASH is becoming the leading cause of HCC, necessitating lifestyle interventions for prevention. Improved surveillance and early detection are critical but challenging due to obesity-related factors. Treatments align with those for other HCC types, but comorbidities and potential differences in immunotherapy efficacy due to T-cell dysfunction require careful consideration. Key needs include identifying molecular drivers in non-cirrhotic metabolic dysfunction-associated steatotic liver disease, developing preventive therapies, refining surveillance methods, and tailoring treatments. Trials should specifically report MASH-HCC outcomes to enable personalized therapies. Further research is needed to understand T-cell dysfunction, optimize immunotherapies, and identify predictive biomarkers.

The major risk factors of hepatocellular carcinoma include hepatitis B or C virus infection and alcohol consumption in Korea which lead to liver cirrhosis development and progression. However, prevalence of non-alcoholic fatty liver disease related hepatocellular carcinoma is rising worldwide and hepatocellular carcinoma cases in patients with non-cirrhotic non-alcoholic steatohepatitis are increasing. A hypoechoic nodule was incidentally detected in a 52-year-old woman, with no evidence of liver cirrhosis or specific hepatocellular carcinoma findings on radiological examination. Non-cirrhotic non-alcoholic steatohepatitis-associated hepatocellular carcinoma was diagnosed based on clinical, laboratory, and histopathological findings of liver biopsy. To our knowledge, this is the first such case report in Korea.