Immunopathogenesis of Primary Biliary Cholangitis, Primary Sclerosing Cholangitis and Autoimmune Hepatitis: Themes and Concepts

Abstract

Autoimmune liver diseases include primary biliary cholangitis, primary sclerosing cholangitis, and autoimmune hepatitis, a family of chronic immune-mediated disorders that target hepatocytes and cholangiocytes. Treatments remain nonspecific, variably effective, and noncurative, and the need for liver transplantation is disproportionate to their rarity. Development of effective therapies requires better knowledge of pathogenic mechanisms, including the roles of genetic risk, and how the environment and gut dysbiosis cause immune cell dysfunction and aberrant bile acid signaling. This review summarizes key etiologic and pathogenic concepts and themes relevant for clinical practice and how such learning can guide the development of new therapies for people living with autoimmune liver diseases.

Keywords: Bile Acids; Dysbiosis; Epidemiology; Fibrosis; Genetics; Homing; Microbiome; Tolerance; Transplantation.