MASLD-related HCC: Multicentre Study Comparing Patients with and Without Cirrhosis

Background and Aims Despite its growing incidence, hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) in non-cirrhotic liver remains poorly characterized. We compared the characteristics, management, survival, and trends of MASLD-related HCC in patients with or without underlying cirrhosis in a large multicenter cohort. Methods 354 patients with MASLD-related HCC presented at the liver tumor meetings of four French university hospitals between 2007 and 2018, were included in the study. Data were extracted from the meetings’ databases and from the French Birth and Death Registry. Results 35% of HCC cases occurred in the absence of cirrhosis. HCC was diagnosed through screening in 60% of patients with cirrhosis, and incidentally in 72% of patients without it. Non-cirrhotic patients were older, had a greater tumor burden, but also better liver function than cirrhotic patients. Non-cirrhotic patients showed better overall survival than those with cirrhosis (p=0.043). However, cirrhosis was not independently associated with overall survival, the independent predictors were age, liver function, tumor burden and BCLC classification. Non-cirrhotic patients underwent surgery more frequently than cirrhotic patients did (41% versus 11%, p<0.001), even in cases where the largest tumors were ≥5 cm (42% versus 14%, p=0.002) or there were four or more lesions (19% versus 2%, p=0.024). Among the cirrhotic and non-cirrhotic patients who underwent surgery, survival was not significantly different. The cirrhosis / no cirrhosis ratio remained stable over the study period. Conclusions In MASLD-related HCC, non-cirrhotic patients account for 35% of cases and have poor prognostic factors (higher age and larger tumors) but also better liver function, resulting in more aggressive management of advanced tumors and better survival compared to cirrhotic patients. Impact and implications The incidence of hepatocellular carcinoma related to MASLD is projected to increase by 47% to 130% by year 2030 with one third occurring in non cirrhotic livers, making them inaccessible to screening with tumors more advanced at diagnosis. Our study shows that survival in MASLD patients with hepatocellular carcinoma relies on age, tumor burden and underlying liver function and the preserved liver function of these non-cirrhotic patients allows them to be managed surgically. A better understanding of the pathophysiological processes driving HCC occurrence in non-cirrhotic MASLD patients to screen and early management of these patients.