AND THE ITALIAN GROUP FOR THE STUDY OF URSODEOXYCHOLIC ACID IN CYSTIC FIBROSIS* ment. Thus, we concluded that UDCA administration im-Liver disease is increasingly recognized as a major proves clinical and biochemical parameters in CF pacause of morbidity in cystic fibrosis (CF). Preliminary tients with liver disease. Taurine supplementation may data suggest that ursodeoxycholic acid (UDCA) may be be indicated in patients with severe pancreatic insuffibeneficial for treatment of this manifestation. We perciency and poor nutritional status. (HEPATOLOGY formed a double-blind, multicenter trial in these pa-1996;23:1484-1490.) tients to establish efficacy and safety of UDCA in terms of the improvement of clinical and nutritional indicators besides standard liver function tests. We also intended
It has been speculated that chronic liver disease deto establish whether taurine supplementation has a benvelops in patients with cystic fibrosis (CF) as a conseeficial effect in patients receiving UDCA. From June to quence of the plugging of intrahepatic bile ducts with December 1990, we enrolled in 12 centers 55 CF patients inspissated bile. [1][2][3] The lack of CF transmembrane regwith liver disease (39 male subjects; median age, 13.8 ulator in the apical membrane of bile duct cells, reyears). They were randomly assigned to receive for 1 cently documented in CF, 4 may lead to abnormalities year one of the following treatments: UDCA (15 mg/kg in biliary drainage, with chronic cholestasis and the body weight daily) plus taurine (30 mg/kg body weight daily), UDCA plus placebo, placebo plus taurine, or dou-development of multilobular biliary cirrhosis. Acble placebo. Clinical and laboratory evaluations were cording to data from the American CF registry in 1990, performed every 3 months. After 1 year, deterioration of liver disease is increasingly recognized as a cause of overall clinical conditions, as indicated by the Shwachmorbidity. 5,6 This probably reflects an increased prevaman-Kulczycki score (SKS), occurred in patients who relence of hepatobiliary complications because CF paceived placebo but not in those who received UDCA (P tients live longer. 5,6 A negative prognostic impact of Γ
.025). Patients treated with UDCA also showed an imliver disease is thus to be expected in CF, as also sugprovement in g-glutamyl transpeptidase (GGT) (P Γ
.004) gested by the recent identification of hepatomegaly as and 5-nucleotidase (P Γ
.006) levels. Treatment with tauan independent risk factor for early death in affected rine was followed by a significant increase in serum prepatients. 7 albumin levels (P Γ
.053), a trend toward a reduction in fat malabsorption, and no effect on the biochemical Over the last few years, we and others have found profile. No severe side effects occurred with any treatin open studies that treatment with ursodeoxycholic acid (UDCA) can improve serum liver enzyme levels, hepatic function, and nutritional status in patients Abbreviations: CF, cystic fibrosis; UDCA, ursodeoxycholic acid; GGT, g-with CF and liver disease. 8-17 UDCA is a hydrophilic glutamyl transpeptidase; SKS, Shwachman-Kulczycki score.
bile acid with choleretic properties. 18 In patients with
From the