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