Cystic Fibrosis

Cystic fibrosis is an autosomal recessive disorder of ion transport, inducing clinical disease in a variety of organs including lungs, exocrine pancreas, liver and gut &. There are more then 600 mutations described in the transmembrane regulator (CFTR) gene, located on the long arm of chromosome 7 which result in failure of the cAMP chloride channel transport mechanism &. CFTR is a glycoprotein located at the apical region of epithelial cells in different organs including airways, intestine, pancreatic ducts, and bile ducts &. Lack or dysfunction of CFTR in the epithelial cell lining the intrahepatic bile ductules is deemed responsible for the production of abnormally inspissated secretions which plug the bile ductules thus leading to focal biliary cirrhosis, the typical hepatic lesion of cystic fybrosis &. Pronounced liver disease on the basis of clinical, biochemical , and ultrasonographic criteria develops in about 20% of patients with cystic fibrosis &. Risk factors are pancreatic insufficiency &, possession of human leucocyte antigen (HLA) type DQ6 &, male sex &, and presentation with meconium ileus or its equivalent &. Different CFTR mutations appear not to play a role in the development of liver disease &. The liver injury in patients with cystic fibrosis is likely one of an ongoing nature, and the increased longevity of survival among patients with cystic fibrosis may lead to increasing prevalence of advanced liver disease in these patients &. In recent years, improvement in liver biochemistry, quantitative liver function tests and hepatobiliary scintigraphy has been documented after ursodeoxycholic acid administration &. The rationale for treatment of cystic fibrosis-associated liver disease with ursodeoxycholic acid, a non-toxic bile acid with choleretic properties, is based on its ability to stimulate cholangiocyte calcium dependent chloride efflux and hepatocellular secretion and to protect hepatocyte and cholangiocytes from damage caused by citotoxic bile acids &. 
Because the deficiency of the CFTR affects biliary epithelial cells and not hepatocytes the initial manifestation of the liver disease is portal hypertension rather than hepatocellular failure.
In children with life-threatening hepatic cirrhosis-complicating cystic fibrosis, liver transplantation offers a good chance of prolonged survival with a greatly improved quality of life and improved  respiratory function &. The debate is now focused on the difficult problem of judging the optimal time for liver transplantation in these children. Liver transplantation should be considered as a last resort only when there is evidence of progressive hepatocyte loss. Liver transplantation is an elective choice that can improve nutritional status and pulmonary function when there is established portal hypertension, before signs of hepatocellular failure are prominent &.