Evidence for Viral Induction of Biliary Atresia: A Review

Abstract

Biliary atresia (BA) is a childhood disease which manifests with abnormal narrowing, blockage or complete absence of bile ducts within the liver. Many possible etiologies have been reported for the development of BA, including congenital, perinatal and acquired conditions. Since the 1970's, there has been increasing evidence linking BA development to viral perinatal infections. The viral vectors most commonly implicated include members of the herpesviridae family (cytomegalovirus and Epstein-Barr virus) as well as those of the reoviridae family (reovirus and rotavirus). While extensive work has been done on a murine model of disease, the current review focuses primarily on evidence from human studies of viral vectors in children afflicted with BA.

Keywords: Biliary atresia; Cytomegalovirus; Epstein-Barr virus; Reovirus; Rotavirus.

Fig. 1.. Immunopathogenesis of biliary atresia.

Viral infection of cholangiocytes leads to activation of the innate immune system and bystander damage. Toll-like receptor-pathogen-associated molecular pattern complexes subsequently lead to CD4+ activation for viral antigens as well as cross-reactive bile duct epithelial antigen.

Fig. 2.. Bystander damage of cholangiocytes and associated release of cross-reactive bile duct epithelial antigens induces autoreactive T cells.

Depressed Treg numbers fail to regulate autoreactive T cells, leading to increased stimulation of downstream effector cells and resulting in chronic inflammation and continued biliary injury post-viral clearance. Abbreviations: Treg, T regulatory cells.