Something fishy about primary sclerosing cholangitis? Development of an LC-MS assay to quantify serum 5-cyprinol-sulfate levels.

Using an innovative approach (imaging mass spectrometry), we investigated the spatial distribution of individual bile salt species in intact human liver with (non)cholestatic parenchyma, and identified specific lipid markers for the structural elements of the liver (i.e. parenchyma, connective tissue, and bile ducts). This resulted in the identification of sulfatides as specific markers of the bile ducts. Of note, bile ducts in patients with PSC and severe cholestatic liver injury were devoid of sulfatides, and extraductular localization of (atypical) bile salts was apparent in these cases. This is reminiscent of bile regurgitation from leaky bile ducts in experimental PSC. 5-Cyprinolsulfate (5-CS) was among the atypical bile salts observed in liver tissue of patients with PSC and severe cholestatic liver injury, but was lacking in liver tissue of patients with hepatobiliary malignancies or PSC without cholestatic liver injury. 5-CS is a bile alcohol found in certain freshwater fishes but not in man. Apart from food poisoning by ingestion of dried gallbladders of cyprinid fish (a rich source of 5-CS, and occasional ingredient of traditional Chinese medicine), 5-CS has not been previously linked with human disease, nor considered as a biomarker. Likewise, it is unknown whether 5-CS (in essence a toxic bile salt) has a pathogenic contribution in PSC. Potential of 5-CS as an informative marker of PSC stage, disease progression or therapy response, requires a quantitative assay and investigation of a larger set of biospecimens of patients and (disease) controls. The purpose of project is to develop a quantitative assay for 5-CS based on liquid chromatography and mass spectrometry detection (LC-MS).