Cholestatic biomarkers and symptoms in primary sclerosing cholangitis: a post-hoc analysis of the DILSTENT

Primary sclerosing cholangitis (PSC) lacks validated surrogate endpoints, impeding the development of new therapies. This study assessed the association between cholestatic biochemical markers and clinical symptoms to evaluate their construct validity as surrogate endpoints.

Cholestatic biochemical markers and clinical symptoms measured by the simple cholestatic complaint score were collected from non-end-stage PSC patients that participated in the DILSTENT trial. Associations between each biochemical marker and clinical symptom were explored using a univariable and multivariable mixed-effect ordinal logistic regression analysis. Measures of associations were expressed as odds-ratio (OR).

Data from 65 patients were included. Alkaline phosphatase (ALP), bilirubin and Aspartate Aminotransferase (AST) levels were significantly associated with pruritus levels (OR 1.01 (p < 0.001); OR 1.02 (p = 0.02); OR 1.01 (p = 0.01), respectively) in univariable analysis. Bilirubin was significantly associated with abdominal right upper quadrant pain (OR 1.01, p = 0.02. Only ALP remained significantly associated with pruritus in multivariable analysis (OR 1.01, p < 0.001)).

This study shows a significant association between ALP and pruritus, the most prominent cholestatic symptom. Our results corroborate the hypothesis that ALP has construct validity as cholestatic marker, thereby supporting its role as potential surrogate endpoint for clinical trials.