Update on Etiology and Pathogenesis of Biliary Atresia

Abstract

Biliary atresia is a rare inflammatory sclerosing obstructive cholangiopathy that initiates in infancy as complete choledochal blockage and progresses to the involvement of intrahepatic biliary epithelium. Growing evidence show that biliary atresia is not a single entity with a single etiology, but a phenotype resulting from multifactorial events whose common path is obliterative cholangiopathy. The etiology of biliary atresia has been explained as resulting from genetic variants, toxins, viral infection, chronic inflammation or bile duct lesions mediated by autoimmunity, abnormalities in the development of the bile ducts, defects in embryogenesis, abnormal fetal or prenatal circulation and susceptibility factors. It is increasingly evident that the genetic and epigenetic predisposition combined with the environmental factors to which the mother is exposed are potential triggers for biliary atresia. There is also indication that a progressive thickening of the arterial middle layer occurs in this disease, suggestive of vascular remodeling and disappearance of the interlobular bile ducts. It is suggested that hypoxia/ischemia process can affect portal structures in biliary atresia and is associated with both the extent of biliary proliferation and thickening of the medial layer.

Trisomy 22 Mosaicism from Prenatal to Postnatal Findings: A Case Series and Systematic Review of the Literature

“…While a definitive causal link between TCA, malrotation, and mT22 has not been established, it is reasonable to think that malrotation and TCA share a common ground [ 54 ]. Biliary atresia (BA) or choledochal malformations are rarely caused by an underlying genetic abnormality [ 60 ]. A case series of five infants affected by various forms of chromosome 22 aneuploidies along with congenital biliary tract anomalies has been reported.…”

Progress in Biomarkers Related to Biliary Atresia

“…Specifically, the main viruses investigated in BA include cytomegalovirus (CMV), human herpesvirus-5, human papillomavirus, Epstein-Barr virus, and rotavirus rhesus. 5 CMV infection is thought to be the most closely related to BA. This infection may cause disequilibrium of cytokine expression and reduction of regulatory T cells, resulting in an inflammatory response and subsequent bile duct injury.…”

“…This infection may cause disequilibrium of cytokine expression and reduction of regulatory T cells, resulting in an inflammatory response and subsequent bile duct injury. 5 Biliatresone, a natural toxin found in plants, can damage extrahepatic cholangiocytes through decreased glutathione and SOX17 levels. 19 Immune responses led by Th1, Th17, and Treg cells can also participate in the injury of the bile duct.…”

“… 19 Immune responses led by Th1, Th17, and Treg cells can also participate in the injury of the bile duct. 5 Genome-wide association studies were carried out and identified several genes as susceptibility factors of BA. A previous review has summarized common genetic variants in BA.…”

“… 1 The etiology of BA is currently unknown. It may be associated with viral infection, 2 environmental toxins like biliatresone, 3 , 4 immune responses, 5 and genetic susceptibility. 6 BA is currently the main reason for liver transplantation in children, 7 with a high incidence in East Asian countries.…”