Consistent with our functional data in mouse models of MASLD and ALD, we observed that RSPO3 conferred protection in patients, revealing an association of high RSPO3 expression with reduced mortality, HCC and liver-related events in patients with MASLD, as well as a trend towards lower mortality in patients with alcohol-associated hepatitis (Fig. 5l,m and Extended Data Fig. 12h,i). This evidence concerns the gene RSPO3 and hepatocellular carcinoma.