Based on the efficacy of ursodeoxycholic acid (URSO) for PBC and the fact that patients with this disease have autoimmune features, these authors evaluated the addition of prednisone and azathioprine to URSO therapy in PBC patients. They carried out a double-blind randomized placebo-controlled 1 year study in 50 patients with PBC who had previously received URSO but had not achieved remission. 26 patients received prednisone 30 mg daily tapered to 10 mg after 8 weeks and azathioprine 50 mg daily in addition to URSO, while 24 patients took URSO alone. The short term benefits were assessed by the primary end points of the drug effects on symptoms, chemistry, histology, bone mass and adverse effects. In the combination group, pruritus, serum aminotransferases, alkaline phosphatase, IgM, and histologic disease activity (necrosis, portal and lobular infiltrate) improved significantly but improvement in fibrosis was less impressive. Since patients received cyclic etidronate and calcium, the adverse effects of combination therapy on bone density could not be determined. These results suggest that the beneficial role of combination therapy in this disease needs to be confirmed by further studies.