Liver transplantation for primary sclerosing cholangitis: screening for biliary malignancy and the role of preemptive transplantation

Primary sclerosing cholangitis is a chronic, progressive, cholestatic disorder of the intrahepatic and extrahepatic bile ducts with a median life expectancy of less than 10 years from the time of diagnosis. Medical treatment is ineffective, and transplantation, with a 5-year survival rate of 80 to 85%, is the only curative treatment for those who develop cirrhosis. Although the progression of liver disease is predictable, a significant number of patients develop cholangiocarcinoma. The cumulative incidence of cholangiocarcinoma is thought to be 15 to 20%. The prognosis for patients with clinically apparent cholangiocarcinoma is poor; thus, they do not benefit from liver transplantation. The outcome of patients with primary sclerosing cholangitis and incidental cholangiocarcinoma is better. It is difficult to make an early diagnosis of cholangiocarcinoma in the presence of primary sclerosing cholangitis. Although the use of brush cytology, DNA cytometry, tumor and molecular markers, or a combination of these appears promising, these tests do not have the accuracy to identify high-risk patients who are likely to develop or who already have early cholangiocarcinoma. In the future, these newer diagnostic modalities may undergo further refinement, allowing identification of high-risk patients. Based on current knowledge, there is no justification for preemptive transplantation in patients who have well compensated liver disease and a reasonable quality of life. However, early transplantation is advisable in patients who have other indications for transplantation such as severe ascites, variceal bleeding, hepatic encephalopathy, intermittent sepsis, severe pruritus, or fatigue. This review focuses on the recent developments in the management of primary sclerosing cholangitis, the search for early markers of cholangiocarcinoma, and the role of preemptive transplantation in patients with primary sclerosing cholangitis.