Primary Biliary Cholangitis (PBC): Joint Model Selection for Alkaline Phosphatase and Serum Bilirubin

Primary Biliary Cholangitis (PBC) is a chronic autoimmune disease of the liver. Currently, there is no cure available for PBC and most patients are treated with Ursodeoxylic Acid (UDCA) that slows down the course (Parés et al. (2006)). Retrieving measurable indicators associated with the progression of the disease is important to evaluate the prognosis and the effect of (new) medical therapies. This thesis shows the prognostic significance of two biomarkers, Alkaline Phosphatase and Serum Bilirubin, in a joint modeling framework. Two joint models are constructed, one for each marker. Relating the true levels of the biomarker to the risk of an event (death or liver transplantation) through a weighted cumulative function shows the best fit and accuracy up to 15 years of follow-up, with exception of the joint model regarding longitudinal measurements of Serum Bilirubin at 15 years of follow-up. To validate the discriminative ability of the fitted joint model and its alternative association structures for Alkaline Phosphatase and Serum Bilirubin, the Area Under the Curve (AUC) of both models is computed. The accuracy of the fitted joint models regarding the prediction of future events is quantified by an estimate of its Prediction Error (PE). The accuracy measures show that both models are performing considerably well in the discrimination between patients and the prediction of future events.