DHCR7 inhibition ameliorates MetALD and HCC in mice and human 3D liver spheroids

This study demonstrates the critical role of <i>de novo</i> lipogenesis and cholesterol synthesis in the pathogenesis of metabolic dysfunction and alcohol-associated liver disease (MetALD) and its progression to hepatocellular carcinoma (HCC). Our findings identified that the upregulation of DHCR7 contributes to the pathogenesis of MetALD and its inhibition suppresses hepatic steatosis, inflammation, fibrosis, and tumor proliferation. These findings are significant for researchers and clinicians, as they establish that genetic and pharmacological inhibition of DHCR7 is effective in both experimental models and translational 3D human liver spheroids. The results uncover the translational potential of DHCR7-targeted therapies for MetALD and HCC, offering practical implications for the development of novel treatment strategies. Further studies are necessary to optimize these approaches and address potential methodological limitations.