I 73
has been reported to recur after liver transplantation (Hepatology 1993;18:1392).
The authors of the current study state that based on the results of their study, they "would not recommend empirical therapy with ursodiol for patients with primary sclerosing cholangitis." The results of the study are discouraging, because the medical therapy for this disease is limited. Many earlier studies using ursodiol in PSC appeared to demonstrate a beneficial effect, although the majority of these studies involve small numbers of patients and have a relatively short follow-up (Hep- . Lindor and colleagues do comment that the lack of a beneficial effect of ursodiol may relate to thc advanced stage of PSC of many of their study participants. One can postulate that perhaps the drug would be efficacious in earlier stages of the disease, although Lindor's study did not demonstrate a statistically significant difference between patients at different stages of the disease. The follow-up, however, may not have been lengthy enough to illustrate a favorable outcome in this group of patients.
The lack of a beneficial effect of ursodiol on the outcome of patients with PSC, as shown in this study, elucidates the need for ongoing, long-term, clinical therapeutic trials. The natural history of this disease is still not well known, and the disease may actually have a more protracted asymptomatic stage than initially believed. A recent study by Metcalf et al. discussed a subset of asymptomatic patients with a positive antimitochondrial antibody (AMA), normal liver function tests, and a liver biopsy suggestive of early PSC (Lancet 1996;348: 1399-401).
These individuals were followed for up to 1 0 years, and appeared to have slow progression of their disease.
As more knowledge is acquired regarding the natural history, pathogenesis, and etiology of this disease, we can be cautiously optimistic that further therapeutic options will be available for patients with primary sclerosing cholangitis before the need for orthotopic liver transplantation.