Format

Send to

Choose Destination
Cell Mol Gastroenterol Hepatol. 2019 May 7;8(2):197-207. doi: 10.1016/j.jcmgh.2019.04.013. [Epub ahead of print]

Pathophysiology of Cystic Fibrosis Liver Disease: A Channelopathy Leading to Alterations in Innate Immunity and in Microbiota.

Author information

1
Section of Digestive Diseases, Yale Liver Center, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut. Electronic address: romina.fiorotto@yale.edu.
2
Section of Digestive Diseases, Yale Liver Center, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.

Abstract

Cystic fibrosis (CF) is a monogenic disease caused by mutation of Cftr. CF-associated liver disease (CFLD) is a common nonpulmonary cause of mortality in CF and accounts for approximately 2.5%-5% of overall CF mortality. The peak of the disease is in the pediatric population, but a second wave of liver disease in CF adults has been reported in the past decade in association with an increase in the life expectancy of these patients. New drugs are available to correct the basic defect in CF but their efficacy in CFLD is not known. The cystic fibrosis transmembrane conductance regulator, expressed in the apical membrane of cholangiocytes, is a major determinant for bile secretion and CFLD classically has been considered a channelopathy. However, the recent findings of the cystic fibrosis transmembrane conductance regulator as a regulator of epithelial innate immunity and the possible influence of the intestinal disease with an altered microbiota on the liver complication have opened new mechanistic insights on the pathogenesis of CFLD. This review provides an overview of the current understanding of the pathophysiology of the disease and discusses a potential target for intervention.

KEYWORDS:

CFTR; Inflammation; Modulators; Toll-Like Receptor 4; cholangiocyte; gut

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center