Effects of ursodeoxycholic acid therapy for liver disease associated with cystic fibrosis.

The hydrophilic bile acid ursodeoxycholic acid (UDCA) has recently been shown to improve indexes of liver function in adult patients with various liver diseases. The clinical and biochemical responses to UDCA administration (10 to 15 mg/kg body weight per day) were therefore investigated in nine patients with cystic fibrosis and evidence of liver disease. All patients were receiving pancreatic enzymes and taurine supplementation. Liver function tests were done and serum bile acid concentrations and biliary bile acid composition were determined before and during UDCA therapy; fat balance studies and fecal bile acid excretion were carried out before and 6 months after UDCA treatment. After 2 months of bile acid therapy, biliary bile acid composition was enriched in UDCA from approximately 5% before treatment to 25%, at the expense of cholic and chenodeoxycholic acids, thus making the pool more hydrophilic. This enrichment is lower than that reported for adults with chronic liver diseases. Serum concentrations of UDCA increased significantly but variably. UDCA became the predominant fecal bile acid excreted (12% to 67%), indicating a variable absorption of the administered bile acid. Liver function improved in all patients after 2 to 6 months of therapy, although the degree of improvement (aspartate aminotransferase, -34%; alanine aminotransferase, -41%; gamma-glutamyltranspeptidase, -41% alkaline phosphatase, -19%) was lower than that observed in adults with chronic liver diseases. Mean coefficient of fat absorption and growth rate were, on average, unaffected by UDCA therapy, although an improvement was noted for three patients with greater severity of steatorrhea. The study indicates that UDCA can be used safely in this patient population but that higher doses of UDCA may be of greater benefit in the treatment of the liver disease associated with cystic fibrosis.

Effect of taurine supplementation on fat and bile acid absorption in patients with cystic fibrosis.

Eleven children with cystic fibrosis (CF) and pancreatic insufficiency were given supplementation with taurine (30-40 mg/kg/day) for 2 months, while taking their usual dosage of enzymatic therapy. One patient dropped out of the study because she developed severe constipation. In the other 10 patients, urinary taurine excretion (88 +/- 30.1 mg/m2s.a./24 h) was similar to that of controls (86.2 +/- 6 mg/m2s.a./24 h) before taurine and increased markedly after supplementation (618.2 +/- 79.97 mg/m2s.a./24 h), indicating efficient intestinal absorption. Their coefficient of fat absorption was 81.2 +/- 2.3% and increased significantly after taurine (91.3 +/- 1.13%; p less than 0.01); the area under the curve of plasma triglyceride postprandial levels (1 +/- 0.1 mg X min/ml) also increased significantly after taurine (1.4 +/- 0.3 mg X min/ml; p less than 0.05), showing values very similar to those of controls. Conversely, no change was observed in the serum postprandial levels of glycocholic acid: the maximum postprandial peak before (1.2 +/- 0.3 mumol/l) and after taurine (1 +/- 0.1 mumol/l) remained significantly lower than in controls (2.4 +/- 0.3 mumol/l); p less than 0.01 and p less than 0.001, respectively. Mean total fecal bile acid (BA) excretion was 10.24 +/- 2.15 mg/kg/day before taurine and 12.8 +/- 4.27 mg/kg/day after taurine (normal pediatric values, 2.91 +/- 1.1 mg/kg/day); however, in the individual patients we found a variable trend, four of them showing a net increase in fecal BA excretion.(ABSTRACT TRUNCATED AT 250 WORDS)