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.

Concise Review: Functional Roles and Therapeutic Potentials of Long Non-coding RNAs in Cholangiopathies

“…Biliary atresia is a progressive bile duct disorder in infants representing cholestasis, jaundice, and liver fibrosis (29). Although previous studies has suggested the association between perinatal viral infection and biliary atresia development in infants, detailed mechanisms of pathogenesis in biliary atresia are still undefined (30). Chen et al have performed genomewide association study using a cohort of 343 non-related biliary atresia patients and 1,716 healthy controls to identify susceptible loci to biliary atresia (31).…”

Gallbladder wall abnormality in biliary atresia of mouse Sox17+/− neonates and human infants

“…Biliary atresia (BA) occurs in one out of every 10,000-15,000 live births, and causes bile duct inflammation because of the blockage of bile flow during the perinatal period (Hartley et al, 2009;Mieli-Vergani and Vergani, 2009). Bile duct injury in extrahepatic bile ducts (EHBDs) may occur in the early pathogenesis of BA (Bezerra et al, 2018), possibly through viral infection (Averbukh and Wu, 2018), toxin exposure (Lorent et al, 2015) and/or individual genetic/epigenetic predisposition (Girard and Panasyuk, 2019) during fetal and perinatal periods (Mack and Sokol, 2005;Nakamura and Tanoue, 2013;Davenport, 2016). BA is traditionally classified into two forms: an 'embryonic' form in a minority (30%) of cases and a 'perinatal' form in the majority (70%) of patients (Balistreri et al, 1996;Bezerra, 2005;Makin and Davenport, 2017).…”

Clinicians should remain vigilant for biliary atresia as early diagnosis and surgery are vital

“…However, only the rotavirus ‐ induced murine BA is close to human BA, because it brings together the immune responses found in the human disease. Studies on human BA livers have reported contradictory results, with rotavirus rates ranging from 0% to 15% for rotavirus A and up to 40% for rotavirus C. One animal model showed that the rotavirus was no longer detectable shortly after having induced BA‐like disease, but its role can be witnessed by high serum titres of rotavirus immunoglobulin M and immunoglobulin G . However, the seroprevalence of group A immunoglobulin M in BA infants in one study did not differ from that of non‐BA matched‐age cholestatic controls .…”

“…Although the authors add to our knowledge about the link between the rotavirus vaccination and BA, their study had limitations, like most on this topic. The main inevitable limitation was the poor generalisability of the results as they only studied Korean subjects in the context of the still uncertain issue of BA seasonality in Korea . In addition to the unfortunate lack of information on which rotavirus group was associated with BA in their study, there were no details on feeding mode.…”

“…Then, there is the cystic variant and the form associated with viral markers, chiefly the variants with immunoglobulin M antibodies to the cytomegalovirus and rotavirus. The environmental insults that act as BA contributors in humans, namely the perinatal viral infections, have been more extensively studied and have been summarised by Averbukh et al …”