Hepatobiliary disease in cystic fibrosis

Cystic Fibrosis (CF) is an inherited, multisystem disease characterised by defective salt and water transport across the secretory epithelia of the respiratory and gastrointestinal tracts. Much of the morbidity and mortality in CF results from inflammation and infection of the airways. However, since the introduction of more intensive therapies and Centre-based care, life expectancy has increased significantly. This has led to the recognition of other life limiting conditions in CF including liver disease which is now the 2nd commonest cause of death in CF patients. Defective function of the cystic fibrosis transmembrane conductance regulator (CFTR) gene impairs bile secretion at the hepatocellular and cholangiocellular levels leading to cholestasis. However, this alone fails to explain the broad spectrum of hepatobiliary problems seen in cystic fibrosis, and why only a proportion of patients develop clinically significant liver disease. It is now believed that the development of CF-related liver disease may reflect the influence of modifier genes on CFTR function.The characteristic lesion is focal biliary cirrhosis, resulting from biliary obstruction and progressive periportal fibrosis. The focal fibrogenic process progresses in about 10% of patients to multilobular biliary cirrhosis, portal hypertension and eventually liver failure. Careful evaluation of all CF patients needs to be made to ascertain the presence of liver disease with the majority of patients developing liver disease by 10 years of age. Aggressive treatment of malnutrition and portal hypertension is required but some children may progress to liver transplant.