Biochemical and histological changes after more than four years of treatment of ursodeoxycholic acid in primary biliary cirrhosis.

We report on three patients with symptomatic, anicteric, and noncirrhotic primary biliary cirrhosis (Ludwig histological stage III at first liver biopsy) who were treated orally with 600 mg/day of ursodeoxycholic acid (UDCA) for more than 4 years. Follow-up liver biopsy was performed twice (at 1-3 and 4-6 years) during treatment. In all cases, during the whole period of up to 4-6 years of UDCA treatment, transaminase, alkaline phosphatase, and gamma-glutamyltranspeptidase levels improved, remaining at subnormal levels compared with pretreatment levels. Moreover, histological stage did not change throughout the UDCA treatment of up to 6 years. The second liver biopsy (at 1-3 years) revealed decreased lymphocytic infiltration in all cases, and bridging fibrosis was decreased in two cases. However, in the third biopsy at 4-6 years, portal inflammation was increased in one case without fibrotic progression; in the other two cases, bridging fibrosis was slightly worsened without portal inflammatory progression. In summary, these three cases show that liver histology was found to be improved, as were blood chemistry and pruritus, during short-term UDCA treatment, but histology results were slightly worse after long-term treatment despite the sustained improvement in biochemistry and pruritus.