J Pediatr 1994 Mar;124(3):393-9

Analysis of risk factors for the development of liver disease associated wit
cystic fibrosis

Colombo C, Apostolo MG, Ferrari M, Seia M, Genoni S, Giunta A, Sereni LP
Department of Pediatrics, University of Milan, Italy.

Abstract
We prospectively screened for liver disease patients with cystic fibrosis who
were more than 3 years of age and who were followed at the cystic fibrosis
center of the University of Milan. From January 1991 to December 1992, we
screened 189 patients; clinical, biochemical, and echographic abnormalities
suggestive of overt liver disease were present in 34 (18%). To define risk
factors for the development of liver disease associated with cystic fibrosis, we
evaluated the possible role of specific mutations of the CFTR (cystic fibrosis
transmembrane regulator) gene and of different clinical and demographic
characteristics (sex, pancreatic status, meconium ileus or its equivalent)
through a comparison of patients with cystic fibrosis and overt liver disease (n
= 34) and those without liver disease (n = 155). Genetic analysis failed to
reveal any significant difference in the allele frequencies of defined (delta
F508, 1717-1G-A, G542X, N1303K, W1282X, R553X) and undefined mutations of the
CFTR gene in the two groups of patients; genotype frequencies were also not
significantly different. Pancreatic insufficiency was present in all patients
with liver disease and in 87.3% of those without liver disease. A male
predominance was found in the group with liver disease. The frequency of
meconium ileus or its equivalent was significantly higher in patients with
cystic fibrosis and liver disease (35.3%) than in patients without liver disease
(12.3%) (p = 0.0025). In the 31 patients with a history of meconium ileus or its
equivalent, the following hepatic abnormalities occurred more frequently than in
the 155 patients with cystic fibrosis who did not have meconium ileus:
hepatomegaly, biochemical abnormalities, heterogeneous echographic pattern of
the liver, and microgallbladder. Twenty-four patients with a history of meconium
ileus or its equivalent underwent hepatobiliary scintigraphy (with
technetium-labeled iminodiacetic acid derivatives), which showed morphologic
abnormalities suggestive of impaired biliary drainage in 21 patients and
abnormalities in function in 11. The risk of acquiring liver disease was
increased almost fourfold in patients with a history of meconium ileus or its
equivalent, in comparison with patients who had cystic fibrosis but were
unaffected by these complications (odds ratio, 3.9043; 95% confidence interval,
1.666 to 9.149). We conclude that patients with cystic fibrosis and meconium
ileus or its equivalent may benefit from prophylactic treatment with
ursodeoxycholic acid; genetic analysis of the major mutations present in this
population failed to provide evidence of the existence of a specific genetic
marker for the development of liver disease in patients with cystic fibrosis