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Cystic fibrosis (CF) is a genetic multisystem disorder that is discussed in greater detail in Chapter 512.

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Epidemiology

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Cystic fibrosis–associated liver disease is increasingly recognized as mortality from lung disease decreases. In many cases the course is benign and does not contribute significantly to morbidity or mortality. However, in a minority of cystic fibrosis (CF) patients, liver disease may directly affect survival. The incidence of CF liver disease appears to peak during adolescence and it is rare for liver disease to have its onset after 20 years of age. Symptomatic liver disease is observed in 20% to 50% of patients, and it can be the presenting or dominant feature of CF. Pathologic evidence of liver disease is found at autopsy in more than 75% of patients. Cirrhosis complicates CF in 1.4% of patients, with a peak frequency of 2.7% in those 16 to 20 years of age. Cirrhosis now accounts for virtually all nonpulmonary causes of death in patients with CF.1

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Pathophysiology

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Cystic fibrosis transmembrane regulator (CFTR) is a chloride channel on epithelial cells. In the liver, it is expressed on biliary tract cells, and is involved in chloride and water secretion into bile. There are no clear genotype associations with CF liver disease, although it is less common in those patients with pancreatic sufficiency. The factors that initiate, accentuate, and perpetuate the development of liver disease in patients with CF have not been identified. A 3:1 male preponderance of liver disease is seen in patients with CF.2 One study has suggested an association with particular histocompatibility antigens, thus implicating a possible role for altered immune responses in patients with CF and liver disease.3 Another study demonstrated an association of a specific polymorphism of glutathione S-transferase with liver disease in CF patients.4 The variability in time of presentation, severity of liver disease, and rate of progression may be due to as yet unknown polymorphisms for other genes.

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Although the precise pathogenetic effects of the CFTR defect in the liver are unknown, it results in the production of thick, tenacious secretions in the hepatobiliary system. Secretion of viscous bile results in impaired bile flow and consequent sludge and potential gallstone formation. Over time, these abnormalities in bile lead to persistent focal microscopic or macroscopic obstructions in the intrahepatic biliary tree causing chronic inflammation, bile duct proliferation, fibrosis with extension and coalescence. The resulting lesion is called focal biliary cirrhosis.

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Clinical Features

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Several forms of liver disease are seen in patients with CF1 (Table 423-1). Neonatal cholestasis occurs in 2% to 10% of affected infants, most commonly in those with meconium ileus, and may persist for several months. It is generally attributed to viscous bile with sludging. Hepatic steatosis is common, seen in up to 30% of patients, but its cause has not been clearly elucidated. Steatosis ...

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