YAP overexpression in hepatocytes influences a specific fibrosis profile in alcohol-related hepatitis

Objective: YAP impairs hepatocyte regeneration in alcohol-related hepatitis (AH) but its impact on fibrogenesis remains unknown. Our aim was to describe fibrogenesis during AH and the relationship between impaired hepatocyte regeneration and fibrogenesis. Design: Fibrosis distribution and colocalization of YAP and αSMA were assessed by immunostaining. Extracellular matrix (ECM) composition in patients with severe AH (n=22) or alcohol-related cirrhosis (Cirrh, n=24) and healthy livers (Ctrl, n=15) was assessed by bulk and spatial proteomics and PCR. We generated organoids from AH and Cirrh livers and evaluated their impact on myofibroblasts in a 3D coculture model. Cirrh organoids were transduced with an active YAP and cocultured with myofibroblasts. Myofibroblasts were also cultured with medium from transduced (YAP medium) or not-transduced hepatocytes (CTRL medium).