(Prague, 12 November 2018) Scientists from the 1^st Faculty of Medicine of the Charles University used the protein osteopontin to improve the diagnostics and enable less invasive testing of patients suffering from cirrhosis of the liver.

Doctors from the IV Clinic of Internal Medicine (Clinic of Gastroenterology and Hepatology of the 1^st Faculty of Medicine and the General University Hospital) carried out a long-term study involving a large number of patients suffering from cirrhosis. Their results show that osteopontin among other things serves as a good predictor of the length of survival with this serious disease. In future, testing for osteopontin levels in blood could replace invasive and stressful tests, which patients with this serious liver disease have to undergo.

‘Our scientific team has been studying cirrhosis of the liver for many years. We started to systematically focus on it in the 1990s and many of our results stem from long-term observation of patients. This success is the outcome of a long-term investigation of the prognosis and future outlook of patients with cirrhosis of the liver,’ says head of this research project, Professor Radan Brůha.

The researchers have informed about this result in the World Journal of Gastroenterology already in 2016 and this year, the head of the grant project team, Professor Brůha, received a prize for the results in a prestigious international competition Dr. Bares Award.

Osteopontin is a signal protein which helps stabilise bone tissue. It was in this context that it was first described, but osteopontin also plays a role in a number of other processes in human body. For instance, it signalises information about inflammation and symptoms and severity of tissue damage. And it is this function that Czech scientists used in following patients with cirrhosis of the liver. The approach is utterly innovative.

‘The greater the damage to liver tissue, the more fibrous tissue it contains, the more it interacts with osteopontin production. The presence of osteopontin can be measured by a simple test, which is then significantly related to patient’s outcome. The higher the osteopontin levels, the worse the prognosis of cirrhosis,’ explains Professor Brůha, whose research is applauded also for involving an unusually large and therefore highly indicative group of 150 patients.

‘Outstanding results of long-term scientific activities of our team of specialists in internal medicine help provide less invasive care and thereby greater comfort to seriously ill patients during testing. It shows that the way from basic research to clinical practice requires in addition to inventiveness and financial means also a large amount of perseverance,’ adds Professor Aleksi Šedo, Dean of the 1^st Faculty of Medicine of the Charles University.

Cirrhosis of the liver develops over a long time. At first, a patient need not experience any problems and the disease can be diagnosed only by thorough testing. As cirrhosis progresses, however, blood pressure around the liver starts to rise. This results in a so-called portal hypertension, which leads to numerous complications and is in most cases also the cause of death in cirrhotic patients. Serious complications at this stage of the disease include bleeding from oesophageal varices, the presence of ascites (abnormal build-up of fluid in the abdomen), encephalopathy, changes to brain activity, and disorders of blood clotting.

At the IV Clinic of Internal Medicine in Prague, doctors try to diagnose these complications as soon as possible or even to prevent them, and testing for high osteopontin levels can indicate that a high-risk complication is likely to occur soon. Moreover, this test could replace various invasive examinations such as measuring of blood pressure around the liver, which is done by traditional catheterisation (invasive probe placed in the veins), or a gastroscopic examination, where doctors use endoscopy to detect oesophageal varices.

‘When osteopontin levels are low, we can claim with a high degree of confidence that the disease did not progress far enough to call for invasive and often stressful testing of the patient. Osteopontin also functions as a marker of liver cirrhosis as such, although the stage of cirrhosis is linked to osteopontin levels in a secondary manner. That is, the tissue reacts by releasing this protein and the more osteopontin is released, the more severe and further progressed cirrhosis is. Determination of osteopontin levels is also important in detecting primary cancer of the liver, which likewise presents a complication in cirrhosis,’ adds Professor Brůha.

Testing for osteopontin levels in the blood is so far not a standard examination covered by health insurance. At the moment, it is financed only from the funding of research projects. It is, however, a simple laboratory test which could in future replace invasive testing and provide more accurate prognosis for patients. Using osteopontin testing, doctors can already determine which patients with cirrhosis are stable and unlikely to suffer from complications and in which some of the complications of cirrhosis could appear and shorten their life.