The Oral Cholate Challenge Test Quantifies Risk for Liver-Related Clinical Outcomes in Primary Sclerosing Cholangitis

Abstract

Background and Aims: We quantified hepatic functional impairment using quantitative function tests and linked severity of functional impairment to liver-related complications and outcome in primary sclerosing cholangitis. Methods: Forty-seven patients had baseline testing, and 40 were retested after 1 year. For each test, cholates labeled with cold, nonradioactive isotopes were administered orally (DuO, SHUNT tests) and intravenously (SHUNT test), and blood was analyzed at 20 and 60 minutes (DuO), or 0, 5, 20, 45, 60, and 90 minutes (SHUNT). Disease severity index (DSI), hepatic reserve (HR%), and portal-systemic shunting (SHUNT%) were calculated. Results: Three subgroups with low, moderate, and high disease severity were defined from the age-adjusted results for DSI, HR%, and SHUNT%. Standard laboratory tests, clinical scores, cytokine levels, and clinical outcome correlated with these subgroups. In univariate analysis of baseline tests, SHUNT% was a strong predictor of clinical outcome (n = 13 of 47; areas under the receiver operating characteristic curve, 0.84DuO, 0.90SHUNT). A model combining SHUNT%, DSI (or HR%), platelet count, and changes from baseline was most predictive of outcome (n = 10 of 40; areas under the receiver operating characteristic curve, 0.95DuO, 0.96SHUNT). Conclusion: DSI, HR%, and SHUNT% identified subgroups of primary sclerosing cholangitis based on the age-related severity of hepatic impairment that predicted risk for liver-related clinical outcome. Further study is warranted to confirm and validate these intriguing findings both in studies of natural progression of primary sclerosing cholangitis and in clinical trials. DuO enhances the utility of quantitative liver function testing.

Keywords

• Cholate Clearance
• Portal Hypertension
• Portal-Systemic Shunting
• Quantitative Liver Function Test