Primary sclerosing cholangitis (PSC) is an idiopathic, heterogeneous cholestatic liver disease that is characterized by persistent, progressive biliary inflammation and fibrosis. It is strongly associated with inflammatory bowel disease. There is no effective medical therapy. PSC affects predominantly male patients (60%) and the median age at diagnosis is 41 years. This is a rare disease with increasing incidence (0-1.3 cases per 100.000 persons/year) and prevalence (0-16.2 per 100.000 persons). Despite being an official rare disease, in developed countries PSC is the most common risk factor for cholangiocarcinoma (CCA).  The annual risk of CCA in this population is 2%, and the 30-year cumulative incidence is 20%. The risk of CCA is 400 times as high in PSC patients compared to the general population.

CCA has always presented a challenging tumor with poor diagnostic and therapeutic tools, associated with low patient survival, despite its increasing incidence. It represents 15% of all primary liver cancers .

There is no consensus on effective surveillance strategies for CCA in PSC patients , as current strategies lack the required sensitivity and specificity for early diagnosis of CCA. Guidelines suggest yearly MRI/MRCP in large-duct PSC patients . Nevertheless, a recent well performed prospective study showed that 2% of CCA were detected using annual MRI follow up in PSC patients, but only 62% were eligible for curative treatment and the majority of the patients developed tumour recurrence and died . A recent review of novel biomarkers to increase the success of surveillance identified some promising biomarker signatures (miRNAs, proteomic and metabolomic profiles), but most of them are based on complex and expensive technologies and all of them require prospective clinical validation.

Taken together, there is a clear need for

1.       An effective, reliable and affordable diagnostic tool for CCA, in a very early stage amenable to curative treatment

2.       A prognostic tool that stratifies patients according to the risk of CCA development

Our team has been studying for the last 20 years changes in N-glycosylation in liver disease, liver transplantation and liver tumours as a source of biomarker development. 

Based on (unpublished) preliminary findings glycomic signatures should be able to provide further guidance in diagnosis and prognosis in CCA in PSC patients. Furthermore, this technology is affordable and can easily be transferred to a routine medical lab environment, as comparable biomarkers based on the same technology exist already for other liver diseases .