Alcohol-associated hepatitis induces hepatocyte senescence which is reduced following disease resolution II

Alcohol-associated hepatitis (AH) is an acute form of alcohol-related liver disease (ArLD) with high mortality rate. AH is histologically characterised by cellular processes including steatosis, inflammation and cell death. Apoptosis is the most studied form of cell death in AH; however, the role of cellular senescence, another response to cellular injury, in AH is unknown. Here we aim to explore the mechanisms of ArLD pathophysiology and define the role of senescence in AH. Transjugular liver biopsies were extracted from AH patients participating in the ISAIAH clinical trial (clinicaltrials.gov identifier NCT03775109) and flash frozen. Biopsies were taken for RNA sequencing at baseline (d0) and 28-days post treatment with either placebo or canakinumab (d28). N=65 samples sequenced.