Cholestatic insult triggers alcohol-associated hepatitis in mice

Alcohol-associated hepatitis (AH) is a severe, potentially life-threatening form of alcohol-associated liver disease with limited therapeutic options. Existing evidence shows that biliary dysfunction and cholestasis are common in AH patients and are associated with poorer prognosis. However, the role of cholestasis in the development of AH is largely unknown. We aimed to examine the hypothesis that cholestasis can be an important etiology factor for AH. To study the interaction of cholestasis and alcohol, chronically ethanol (EtOH)-fed mice were challenged with a sub-toxic dose of a-naphthylisothiocyanate (ANIT), a well-studied intrahepatic cholestasis inducer. RNAseq was performed to determine hepatic transcriptomic changes.