A review of the medical treatment of primary sclerosing cholangitis in the 21st century.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that progresses to end-stage liver disease and cirrhosis. Recurrent biliary inflammation is thought to lead to dysplasia, and as such PSC confers a high risk of cholangiocarcinoma. PSC accounts for 10% of all UK liver transplants, although transplantation does not guarantee a cure with 20% recurrence in the graft. At present there are no effective medical treatment options for PSC, and trials of novel therapeutic agents are limited by the time taken to reach clinically significant endpoints with no well defined early surrogate markers for disease outcome. Moreover, PSC appears to be a heterogeneous disease with regards to disease distribution, associated inflammatory bowel disease and subsequent disease outcome, further compounding the issue. Thus existing trials have taken place in heterogeneous groups, are likely to be underpowered to detect any individual subgroups effect. The current mainstay of medical treatment is still with ursodeoxycholic acid, although there is no evidence that it alters long-term outcome. Small pilot studies of immunosuppressive agents have taken place, but despite evidence that may support studies in larger groups, these have not been conducted. Recent advances in our understanding of the disease pathogenesis may therefore pave the way for trials of novel therapeutic agents in PSC, even given the limitations described. This review explores the controversial evidence underlying current treatment strategies and discounted treatments, and explores prospective agents that may bring new hope to the treatment of PSC in the 21st century.