EFFECT OF URSODEOXYCHOLIC ACID THERAPY ON HEPATIC-FUNCTION IN CHILDREN WITH INTRAHEPATIC CHOLESTATIC LIVER-DISEASE

Background: Ursodeoxycholic acid (UDCA) has been shown to improve prur itus, alanine aminotransferase (ALT), and cholesterol levels in childr en with intrahepatic cholestatic liver disease. However, the effect of UDCA on quantitative tests of hepatic function in children is uncerta in. Methods: A 2.5-year, open label, crossover study, was desired to d etermine the effect of UDCA (15-20 mg/kg per day for 12 months, off fo r 6 months, and on again for 12 months) on clinical symptoms, biochemi cal test results, galactose and caffeine elimination half-lives (t(1/2 )), and quantitative hepatic scintigraphy in 13 subjects aged 13.1 +/- 2.1 years (10 of whom completed the entire study), with intrahepatic cholestasis. Results: Pruritus improved with UDCA in the 6 patients wi th pruritus on entry into the study. At 12 months, there was a signifi cant decline in ALT, gamma-glutamyl transpeptidase, and plasma levels of copper and manganese, with no further decline in these levels at 24 months. There were no changes in bilirubin or cholylglycine levels. A fter therapy was discontinued at 12 months, UDCA was restarted within 1 month in 9 of 12 patients in response to a doubling of ALT (n = 6) o r worsening pruritus (n = 3). Galactose t(1/2) increased after 12 mont hs, with no further increases after 24 months of UDCA therapy, whereas caffeine t(1/2), did not change. There were no significant changes in hepatic scintigraphy throughout the study. Conclusions: These data su ggest that although UDCA therapy improves pruritus and results in a re duction in ALT and gamma-glutamyl transpeptidase, UDCA therapy did not improve quantitative measures of hepatic function in children with in trahepatic cholestasis.