HEPATOLOGY Elsewhere 973 6 mo of the study. Furthermore, six study patients treated with ursodeoxycholic acid failed therapy, indicating that not all PBC patients treated with ursodeoxycholic acid therapy respond. Of equal importance, no patient in either group was noted to have a complete clinical, biochemical and histological remission, which remains the gold standard by which we judge treatment efficacy.
Thus, in summary, the results of this study evaluating ursodeoxycholic acid therapy in PBC suggest we may have yet another drug that is associated with hepatic biochemical improvements and that may have some modest effect on reducing pruritus. However, with regard to hepatic fibrosis, little or no effect was apparently seen. Furthermore, the study falls short in telling us whether a difference exists in response in subgroups of patients based on disease severity. Patients in the clinically most advanced stages of disease were excluded from this study, and the investigators failed to address whether patients with histologically early stage disease responded better than patients who had histologically advanced (fibrotic/cirrhotic) stage disease. It is important to point out that preliminary studies from other centers (10) have suggested that those patients with histological stage 3-4 disease (fibrotic/cirrhotic) have little or no response to ursodeoxycholic acid therapy. Furthermore, studies (11) have suggested that the beneficial biochemical effect of ursodeoxycholic acid therapy may be only temporary and that after a certain period of time hepatic biochemistries again worsen and the disease appears to progress. Finally, other studies (12) have suggested no beneficial effect of ursodeoxycholic acid is seen in PBC patients after 1 yr of therapy.
Clearly, a major advantage of ursodeoxycholic acid therapy is its low toxicity rate. However, its substantial cost will make it important to clearly establish the efficacy of this drug before widespread use in the treatment of PBC. Thus the major questions not answered by this study are the following: (a) Are the beneficial effects of ursodeoxycholic acid in PBC sustainable? (b) Will treatment with ursodeoxycholic acid prolong time to development of cirrhosis, prevent or prolong time to development of complications of portal hypertension and prolong survival time free of liver failure? It appears essential to continue to evaluate ursodeoxycholic acid therapy in long-term, controlled clinical trials to further address these very important questions concerning efficacy.