Published online Oct 21, 2017. doi: 10.3748/wjg.v23.i39.7191
Peer-review started: July 26, 2017
First decision: August 10, 2017
Revised: August 23, 2017
Accepted: September 5, 2017
Article in press: September 5, 2017
Published online: October 21, 2017
Primary biliary cholangitis (PBC) is an idiopathic autoimmune liver disease characterized by chronic cholestasis and destruction of the intrahepatic bile ducts. Similar to other autoimmune diseases, the pathogenesis of PBC is considered to be a complex etiologic phenomenon involving the interaction of genetic and environmental factors. Although a number of common variants associated with PBC have been reported from genome-wide association studies, a precise genetic mechanism underlying PBC has yet to be identified. Here, we describe a family with four sisters who were diagnosed with PBC. After the diagnosis of the index patient who was in an advanced stage of PBC, one sister presented with acute hepatitis, and two sisters were subsequently diagnosed with PBC. Notably, one half-sister with a different mother exhibited no evidence of PBC following clinical investigation. Our report suggests the possibility of a maternal inheritance of PBC susceptibility. Moreover, judging from the high-penetrance of the disease observed in this family, we inferred that a pathogenic genetic variant might be the cause of PBC development. We describe a family that exhibited diverse clinical presentations of PBC that included asymptomatic stages with mildly increased liver enzyme levels and symptomatic stages with acute hepatitis or advanced liver fibrosis. Additional studies are needed to investigate the role of genetic factors in the pathogenesis of this rare autoimmune disease.
Core tip: The precise genetic mechanism underlying primary biliary cholangitis (PBC) has yet to be identified. Here, we describe a family with four siblings who were diagnosed with primary biliary cholangitis. This is the first case report to provide evidence of a maternal inheritance mechanism for PBC based on the identification of a non-PBC half-sibling. This report also highlights the occurrence of all clinical presentations of PBC in one family. Identification of a causal variant is important for a better understanding of the mechanism underlying PBC pathogenesis.