https://www.ncbi.nlm.nih.gov/pubmed/29604222

Hepatology. 2018 Mar 31. doi: 10.1002/hep.29905. [Epub ahead of print]

BILIARY ATRESIA: Clinical and Research Challenges for the 21st Century. Bezerra JA, Wells RG, Mack CL, Karpen SJ, Hoofnagle JH, Doo E, Sokol RJ.

Abstract

Biliary atresia (BA) is a fibroinflammatory disease of the intra- and extrahepatic biliary tree. Without medical treatment, surgical hepatic portoenterosmy (HPE) may restore bile drainage, but progression of the intrahepatic disease results in complications of portal hypertension and advanced cirrhosis in most children. Recognizing that further progress in the field is unlikely without a better understanding of the underlying cause(s) and pathogenesis of the disease, the National Institutes of Diabetes and Digestive and Kidney Diseases sponsored a research workshop focused on innovative and promising approaches and on identifying future areas of research. Investigators discussed recent advances using gestational ultrasound and results of newborn BA screening with serum direct (conjugated) bilirubin that support a pre-natal onset of biliary injury. Experimental and human studies implicate the toxic properties of environmental toxins (e.g. biliatresone) and of viruses (e.g. CMV) to the biliary system. Among host factors, sequence variants in genes related to biliary development and ciliopathies, a notable lack of a cholangiocyte glycocalyx and of submucosal collagen bundles in the neonatal extrahepatic bile ducts, and an innate pro-inflammatory bias of the neonatal immune system contribute to an increased susceptibility to damage and obstruction following an epithelial injury. These advances form the foundation for a future research agenda focused on identifying the environmental and host factor(s) that cause BA, the potential use of population screening, studies of the mechanisms of prominent fibrosis in young infants, determinations of clinical surrogates of disease progression, and the design of clinical trials that target subgroups of patients with initial drainage following HPE. This article is protected by copyright. All rights reserved.