Primary sclerosing cholangitis

Conclusion In this article, evidence has been presented that immune mechanisms play a major role in the pathogenesis of PSC. Although considerable progress has been made in our understanding of the pathogenesis and treatment of this disease, many questions remain unanswered. The factors that trigger the disease in a susceptible host are unknown and it is unclear whether an exogenous agent such as retroviral infection is involved or if there is an intrinsic abnormality in the immune system. It is unknown if the pathogenetic mechanisms are the same for patients with PSC alone or patients with PSC and IBD or whether these represent separate clinical entities. Moreover it is unclear if immunosuppressants as high-dose single agents or in combination may halt or slow disease progression. To answer some of these questions, the disease must be identified in patients early in its pathogenesis, perhaps even before the characteristic cholangiographic changes have occurred. Although new noninvasive techniques, such as magnetic resonance cholangiography, may allow screening of patients with UC, early diagnosis is likely to remain difficult. Animal models provide a way of exploring the relationship of PSC and IBD and the early events in pathogenesis. Previous animal models (144, 145) have provided limited insight into PSC because the hepatobiliary damage was more representative of acute rather than the chronic insidious damage of PSC. However studies of colitis in the “knockout” mouse offer the opportunity to explore the relationship between host genetic susceptibility, colitis, and hepatobiliary damage.