Hepatobiliary complications of cystic fibrosis

Abstract

Cystic fibrosis (CF) is the most common potentially lethal genetic disease in the Caucasian population. The disease results from mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl(-) channel in the apical membrane of most secretory epithelia. In the liver, CFTR is located in biliary epithelial cells or cholangiocytes and gallbladder epithelia, where it appears to play a role in normal bile formation. However, how a defective CFTR protein leads to associated liver and biliary disease in a subset of patients with CF is unknown. Improvements in life expectancy have led to an increasing recognition of hepatobiliary complications from CF. Whereas the biliary tract disease is usually clinically evident, the liver involvement may progress silently, only manifesting as end-stage liver disease and portal hypertension. Unlike the pancreatic involvement in CF, a genotype-phenotype correlation is not apparent in the expression of liver disease, suggesting the presence of as yet unidentifiable "genetic modifiers" influencing disease expression. This review focuses on the pathogenesis, clinical manifestations, screening, diagnosis, and treatment of CF hepatobiliary disease.

Dental utilization for Medicaid‐enrolled children with cystic fibrosis

“…Bile, like other exocrine secretions is thickened and can obstruct the intrahepatic bile ducts progressing to periportal fibrosis and eventually cirrhosis (29). Clinical signs and symptoms may take years to manifest and include complications such as gastrointestinal hemorrhage, ascites, fatigue, weight loss, anorexia, jaundice and portal hypertension (30).…”

Unexpected diagnosis of cystic fibrosis at liver biopsy: a report of four pediatric cases

“…It is likely that the abnormal bile secretion which triggers this sequence of events is related to the expression of an abnormal CFTR protein by biliary epithelial cells [13,44]. However, the absence of genotype-phenotype correlations explaining the development of hepatobiliary manifestations in cystic fibrosis [18] suggests the existence of "modifier" genes [7,8,16], which remain, however, to be identified with certainty, even if several gene candidates have been proposed, including alpha1-antitrypsin, defensins, glutathione S transferase P1, mannose-binding lectin, and TGFbeta1 [2,14,21,23,43].…”

Liver Involvement in Iranian Children With Cystic Fibrosis: Ultrasonography and Biochemical Findings

“…Cystic fibrosis (CF) is the most common life-threatening genetic disorder in Caucasian children (1). CF is an inherited autosomal recessive disease of epithelial transport which affects most critically the lungs besides pancreas, liver and intestine (2).…”

“…Liver involvement in patients with CF is an early complication and relatively common which may progress silently (1). With improved survival of CF patients and reduced death from extra-hepatic causes, hepatobiliary involvement is increasingly recognized as a major manifestation of the disease.…”