EFFECT OF URSODEOXYCHOLIC ACID ON SERUM ENZYMES AND LIVER HISTOLOGY IN PATIENTS WITH CHRONIC ACTIVE HEPATITIS - A 12 MONTH DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

A reduction in serum enzymes has been already observed by administerin g ursodeoxycholic acid to patients with chronic active hepatitis. The aim of this study was to assess whether the Liver histological activit y of inflammation was modified by a 12-month treatment with ursodeoxyc holic acid. Thirty-six patients with chronic active hepatitis, fulfill ing the inclusion criteria, were admitted to the trial. Patients were randomly allocated to receive double blind either 600 mg/day of ursode oxycholic acid (Group A: 18 patients) or placebo (Group B: 18 patients ). Clinical and biochemical follow-up was performed at 3-month interva ls. A percutaneous liver biopsy was performed before and after 1 year of treatment. Histological hepatitis activity was assessed using Knode ll's numerical scoring system, while biliary damage was evaluated by a n appropriate scoring system. Sixteen and 12 patients in Groups A and B, respectively, completed the clinical and biochemical follow-up. Alt hough a reduction in serum enzymes was found in both groups, multifact orial covariance analysis showed that the reductions in alanine aminot ransferase, aspartate aminotransferase and gamma glutamyl transpeptida se were significantly higher in Group A than in Group B. Biochemical r emission was not observed in either group. Histological analysis showe d a dichotomy between the results from the hepatitis and the biliary c omponents of the disease process. No differences were found in the two groups before or after treatment in histological activity index, whic h measures the ''hepatitic'' component. Nor were there any significant differences in baseline values. Furthermore, no relationship was foun d between changes in biochemical parameters and the histological activ ity indices. In contrast, the ''biliary'' component showed significant improvement after ursodeoxycholic acid treatment for certain cholesta tic parameters: ductular metaplasia, bile duct damage and phenotypic c ytokeratin changes. These changes were significantly associated with c hanges in gamma glutamyl transpeptidase serum levels. This study has c onfirmed that ursodeoxycholic acid administration in patients with chr onic active hepatitis reduces transaminases and gamma glutamyl transpe ptidase. The morphological substrate of this biochemical improvement c an be traced to the biliary component of the process. (C) Journal of H epatology.