ABSTRACT
Liver disease associated with cystic fibrosis has been increasingly diagnosed during
recent years probably due to the combined effect of systematic hepatic assessment
and reduced death from extra-hepatic causes of CF patients. In a group of 173 CF patients
regularly followed at our Center, cumulative incidence of liver disease was 17% over
a mean period of 10 years. Although it generally runs a mild course, it is considered
a major complication of CF which may limit survival and quality of life of affected
patients. CF-associated liver disease should be considered as the first inherited
liver disorder in which the primary defect affects cholangiocyte transport systems.
Although data assessing the effects of defective CFTR on cholangiocyte pathobiology
are not yet available, the impaired secretory function of the biliary epithelium is
considered responsible for reduced biliary fluidity and alkalinity and for subsequent
bile duct damage by cytotoxic compounds or infectious agents. No clear association
with specific CFTR mutations has been observed. Treatment with ursodeoxycholic acid,
aimed at improving biliary secretion in terms of bile viscosity and bile acid composition,
is currently the most useful therapeutic approach in CF-associ-ated liver disease.
Beneficial effects on liver biochemistry, hepatic excretory function, liver histology,
and essential fatty acid status have been reported, but no long-term data exist on
its effectiveness on clinically relevant outcomes, such as death or need for transplantation.
The effectiveness of bile acid therapy may be higher if started in patients with early
stage liver disease, before symptoms have become clinically evident. Early diagnosis
and identification of CF patients who are more liable to develop liver disease should
be actively pursued.
KEY WORDS
cystic fibrosis - CFTR (cystic fibrosis transmembrane regulator) - cholangiocytes
- liver disease - ursodeoxycholic acid
