GLP-1 and its analog extendin-4 can prevent cholangiocyte from apoptosis and facilitate its proliferative repair in response to cholestasis.24,25 Therefore, bile acid sequestrant applied in this PBC cohort probably act to augment intestinal TGR5 signaling and colonic production of GLP-1, which then exert cholangioprotective effects. Here, GPBAR1 is linked to cholestasis.