Hepatobiliary Involvement in Cystic Fibrosis

The improved life expectancy of cystic fibrosis (CF) patients has increased the prevalence of extrapulmonary complications. Liver disease is present in about one-third of CF patients and presents in various forms. The clinically most relevant forms are cirrhosis, possibly arising from the pathognomonic focal biliary fibrosis, and non-cirrhotic portal hypertension. Various forms of liver disease may present in different age groups, including childhood. Cirrhosis mostly presents in the first or second decade of life. The pathogenesis of focal biliary fibrosis and cirrhosis in CF is incompletely understood, although the most accepted hypothesis envisions fibrosis as a response to stasis of inspissated bile, possibly with a second hit provided by increased pro-inflammatory responses of CF bile ducts to gut-derived microbial by-products. Since the disease is often subclinical until complications develop, and because serum liver enzymes are often nonspecifically elevated in CF, annual screening for structural liver disease is recommended. Once the diagnosis is established, treatment with ursodeoxycholate is often advised, although evidence for its efficacy remains a subject of discussion. The efficacy of CFTR modulators in preventing or reversing liver disease progression is not yet established. Complications of severe liver disease are related to portal hypertension, functional hepatic decompensation including exacerbation of malnutrition, and secondary complications of cirrhosis in other organs and may warrant liver transplantation. CF liver disease confers poorer survival and accounts for 2–3% of mortality among CF patients. Current research is aimed at diagnosing early, progressive disease noninvasively, as well as at the discovery of novel therapies.