Primary sclerosing cholangitis (PSC) is a puzzling, chronic, cholestatic liver disease. Inflammation of the intra-and/or extrahepatic
bile ducts leads to the formation of fibro-sclerotic strictures interspersed with dilatations. Destruction of the biliary
tree results in cholestasis, biliary cirrhosis, and eventually liver failure.
Despite over two decades of research in
PSC, to date, there are no medical therapies that can alter the natural disease course. To find an adequate treatment, a measurable
treatment effect is important. The most reliable way to measure treatment effect is by means of clinical – solid – endpoints,
such as survival and liver transplantation. However, using such endpoints can be inefficient, and an indirect measurement
(a biomarker) as a surrogate for clinical response can reduce the size, duration, and costs of clinical studies. In addition,
biomarkers for disease progression in PSC may be used for risk stratification – identification of patients that would potentially
have the most benefit of treatment with a novel therapy. The importance of risk stratification in PSC is not restricted to
clinical trials, and can be extrapolated to patient care where stratification of patients into low versus high risk of poor
outcome can resulting in a more patient tailored counselling, and treatment.
In this thesis the prognostic value of several
potential biomarkers for disease progression in PSC have been studied. This concerns biochemical biomarkers (alkaline phosphatase,
enhanced liver fibrosis test), liver histology, and the identification of a genetic marker for disease progression PSC. Ultimately,
clinical and biochemical biomarkers for disease progression have been integrated to establish a novel prognostic model for