Impact of cirrhosis on the metabolic profile, tumor presentation, and management of MASLD-associated hepatocellular carcinoma: A systematic review and meta-analysis.

e16306 Background: Metabolically-dysfunction-associated steatotic liver disease (MASLD) affects nearly 38% of the adult world population and is a rapidly growing contributor to hepatocellular carcinoma. Unlike viral hepatitis–related HCC, MASLD-associated HCC frequently occurs in both cirrhotic and non-cirrhotic patients, creating uncertainty regarding risk stratification, presentation, and treatment eligibility. We conducted a systematic review and meta-analysis to evaluate the impact of cirrhosis on metabolic risk factors, tumor presentation, and treatment plan in MASLD-related HCC. Methods: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and performed a comprehensive literature search using PubMed, Cochrane, and Scopus. Data were extracted and pooled using random-effects models and Review Manager (V.5.4). Heterogeneity was assessed using the I² statistic. Results: Among the 2,873 article abstracts screened, 13 studies were analyzed. Cirrhotic MASLD-HCC patients had significantly higher odds of diabetes compared with non-cirrhotic patients (OR 2.16, 95% CI 1.84-2.54), while no significant associations were observed for obesity (OR 2.34, 95% CI 0.78-7.01), hyperlipidemia (OR 0.78, 95% CI 0.48-1.27), or hypertension (OR 1.07, 95% CI 0.90-1.27). At diagnosis, cirrhotic patients had greater tumor burden with higher odds of multifocal disease (OR 1.62, 95% Cl 1.09-2.42). Cirrhosis was strongly associated with reduced likelihood of surgical resection (OR 0.20, 95% Cl 0.13-0.29). Mortality did not differ significantly between cirrhotic and non-cirrhotic groups (OR 1.63, 95% Cl 0.94-2.81). Conclusions: Cirrhosis is associated with a distinct background metabolic risk profile in MASLD-associated HCC, affecting tumor presentation and treatment strategies. Differences in treatment patterns and metabolic risk factors emphasize the need for individualized surveillance and therapeutic protocols for this growing population. Further studies are warranted to improve risk stratification and to optimize a personalized treatment plan. Pooled odds ratio for metabolic risk factors, disease presentation, mortality, and treatment outcomes associated with HCC in cirrhotic MASLD compared to non-cirrhotic MASLD patients. Risk Factors, Presentation, Mortality and Treatment Pooled Odds Ratio (OR) 95% Cl Diabetes 2.16 1.84-2.54 Obesity 2.34 0.78-7.01* Hyperlipidemia 0.78 0.48-1.27* Hypertension 1.07 0.90-1.27* Number of Lesions: 1 0.61 0.41-0.89 Number of Lesions: 2-3 1.62 1.09-2.42 Mortality 1.63 0.94-2.81* Surgical Resection 0.20 0.13-0.29 All p<0.005 unless noted with *.