Primary biliary cirrhosis: specific treatment.

No single agent or combination of agents has been shown to unequivocally delay the need for liver transplantation or reduce mortality in patients with PBC. Given this uncertainty, what, if any, specific therapy should be recommended? The agents with the strongest scientific proof of efficacy in well-designed clinical trials are ursodiol, azathioprine, and cyclosporine. Ursodiol is clearly the least toxic of these three. Other agents, such as methotrexate, have shown impressive results in anecdotal studies but have never been adequately tested in randomized clinical trials. Thus, based on the current evidence, imperfect as it is, ursodiol appears to be the safest and potentiaily the most effective specific therapy for patients with PBC. Azathioprine and methotrexate may be the best alternatives for patients who cannot tolerate or do not respond to ursodiol therapy, primarily because their safety has been established in large and lengthy clinical trials. Cylosporine could be considered in patients who fail other treatments (Table 3). We can hope that a safe, highly-effective treatment for patients with PBC will ultimately be discovered. Trials to unequivocally demonstrate the efficacy of new agents will have to be extremely well designed, however, and will require large numbers of patients followed for an extended period of time.