Elevated serum bilirubin level correlates with the development of cholangiocarcinoma, subsequent liver transplantation, and death in patients with primary sclerosing cholangitis

Introduction: Predicting the clinical course of primary sclerosing cholangitis (PSC) is difficult. There are currently a paucity of studies evaluating serum chemistries as predictors of conventional clinical endpoints. The purpose of this study was to prognosticate key clinical endpoints in patients with PSC who had elevated serum liver chemistries at the time of their initial presentation. Methods: We performed a retrospective cohort study of PSC patients at our institution. The aim of our study was to determine the association between elevated liver chemistries at initial presentation - bilirubin, alanine transaminase, aspartate transaminase, or alkaline phosphatase - with a primary outcome of either cholangiocarcinoma, liver transplantation, death, or composite of the 3. The secondary endpoints examined were development of severe biliary ductal disease and need for biliary stent placement. Results: Eighty-one PSC patients (61 males and 20 females) were included in this study. By univariate analysis, there was a significant association between initial bilirubin elevation >2x the upper limit of normal (ULN) and death (P<0.009). Multivariate regression analysis revealed that an elevated initial serum total bilirubin >2xULN (P<0.017) significantly predicted the composite endpoint. By univariate analysis of pre-endoscopic retrograde cholangiopancreatography labs, serum bilirubin level elevation >2xULN showed an association with severity of biliary ductal disease (P<0.0001). A logistic regression of outcome variables also proved that >2xULN serum bilirubin levels predicted the ductal disease severity (P<0.0001). Conclusions: An initial elevation of serum total bilirubin >2xULN in PSC patients correlates positively with the development of cholangiocarcinoma, subsequent liver transplantation, and death. Elevated bilirubin also correlates positively with the severity of cholangiographic findings.