New potential approaches to treatment for primary sclerosing cholangitis

(Vienna, 14th April 2015) Primary sclerosing cholangitis (PSC) is a currently incurable liver disease that mostly affects younger people, and especially young men, aged between 30 and 40. It is considered a rare condition which is usually detected as an incidental finding or as part of a work-up for jaundice, and is caused by a problem with bile production. Over time, this condition can develop into liver cirrhoses and bile duct cancer. Its cause is as yet unknown.

Researchers from the Clinical Department of Gastroenterology and Hepatology at the MedUni Vienna have gained new insights into the development of the disease and its causes over recent years through experimental approaches. It has been possible to demonstrate, for example, that problems with the balance of bile composition can lead to cholangitis and that these processes can also be influenced by medication.

At the forefront of the current research is the development of new therapeutic options aimed at changing this "imbalanced" bile composition which leads to increased toxicity and aggressiveness of the bile, resulting in puzzling inflammation, and thereby have a positive influence on the progress of the condition, explains MedUni Vienna expert Emina Halilbasic from the research team led by Michael Trauner in the University Department of Internal Medicine III's Clinical Department of Gastroenterology and Hepatology at the MedUni Vienna. Trials have clearly shown that an improvement in the bicarbonate component of the bile liquid can reduce or prevent irritation. Says Halilbasic: "Bicarbonate anions act like a shield for bile duct cells, and by improving this shield with medications (note: such as modified bile acids, activators of the bile acid nuclear receptor FXR), we have a new, highly promising therapeutic approach for this liver condition that still remains incurable."

The cause of PSC is still believed to lie in a problem with the intestinal-liver axis. "People who develop this condition often have inflammation of the bowel," explains Trauner, Head of the Clinical Department of Gastroenterology and Hepatology at the MedUni Vienna. Problems with the microbiome, i.e. the micro-organisms that inhabit humans, and especially the gut, are also believed to play a role.

The MedUni Vienna is one of the world's leading centres in the research of cholangitis and is carrying out intensive research into new medication-based treatment strategies for the condition, such as nor-ursodeoxycholic acid (norUrso), which is already undergoing clinical testing in a multi-centre European study led by Trauner, following very promising results in fundamental research. Pre-clinical models were able to demonstrate that norUrso works directly on the biliary tract and flushes the bile ducts of toxins by increasing bicarbonate-rich bile secretion.

Symposium: Cholestasis research - past, present and future
In light of the fact that cholestasis (stagnation of the bile secretion inside the bile ducts or liver), the conditions associated with it and their causes remain largely unresearched, the MedUni Vienna is organising the first international expert symposium entitled "Cholestasis - Past, Present and Future", to be held on Tuesday, 21 April 2015 (MedUni Vienna van Swieten Suite, van Swieten Gasse 1a, 1090 Vienna, 10.00 a.m. - 7 p.m.). See http://www.profbriefings.co.uk/ppfcholestasis2015/. The symposium will bring together international experts and up-and-coming researchers in order to drive the progress of innovative approaches to curing bile duct conditions forward.

Research clusters at the MedUni Vienna
Research into chronic inflammatory bile duct diseases, including sclerosing cholangitis, is part of the MedUni Vienna’s Allergology / Immunology / Infectious Diseases research cluster. The MedUni Vienna is increasingly focusing in this, and the other four specialist domains, on fundamental and clinical research. The research of transport processes for bile production and their dysfunction in the context of liver disease carried out in the Hans Popper Laboratory for Molecular Hepatology within the Clinical Department of Gastroenterology and Hepatology (headed by Michael Trauner) is also the focus of a special area of FWF research (SFB 35, Transmembrane Transporters in Health and Disease), which is based at the MedUni Vienna. The other four research clusters are Cancer Research / Oncology, Vascular / Cardiac Medicine, Neurosciences and Imaging.