Supplementary Material for: Etiology of hepatocellular carcinoma may influence the pattern of progression under atezolizumab-bevacizumab.

Background: Preclinical models have shown that metabolic dysfunction-associated steatotic liver disease (MASLD)-related hepatocellular carcinoma (HCC) may exhibit reduced responsiveness to immunotherapy, especially for intrahepatic lesions due to liver tumour microenvironment. Radiological pattern of progression has been validated in clinical studies as a useful tool for predicting outcomes in HCC undergoing systemic treatments.
Aims. To determine whether MASLD influences the pattern of progression in patients treated with atezolizumab-bevacizumab.
Methods: This multicenter, prospective study included patients with unresectable HCC receiving atezolizumab-bevacizumab. Progression patterns were defined as previously proposed. Patients were categorized as either MASLD or controls based on a recent multisocietal Delphi consensus statement. Multivariable models analyzed the risk of specific progression patterns and their impacts on post-progression survival (PPS) and overall survival (OS). A historical cohort treated with sorafenib was also analyzed to determine whether observed patterns were specific for atezolizumab-bevacizumab.
Results: Four-hundred-twenty patients were included (MASLD: n=88, 21.0%). Time-to-progression (TTP) was shorter in MASLD compared to controls, due to an increased risk of intrahepatic growth [IHG – hazard ratio (HR) 1.739, 95% confidence interval (CI) 1.206-2.507, p=0.003)]. Neither etiology nor IHG predicted a different PPS. No differences between etiologies were found in OS. Etiology did not influence the pattern of progression under sorafenib in the historical cohort.
Conclusion: IHG was more frequently associated with MASLD-HCC compared to controls, confirming preclinical data and suggesting biological differences between tumors, with potential implications for future research. MASLD should not be seen as a contraindication to immunotherapy.