26 August 2020When Professor Gerald Holtmann, from The University of Queensland, was pulled into a procedure room to perform a colonoscopy on a young patient, he had no idea it would lead to a major translational research project. Now, he is leading the development of an innovative treatment approach that could prevent liver failure and cancer in relatively young patients. The young patient was undergoing surveillance for ulcerative colitis and also had Primary Sclerosing Cholangitis (PSC), a condition frequently associated with colitis. PSC is a rare, chronic disease affecting one in 100,000 people. Over time, it causes permanent damage to the liver’s bile ducts, which gradually scars the liver, leading to liver failure or bile duct cancer. After 10-15 years with PSC, many people need a liver transplant. In this young patient’s case, the medical team observed that while the patient was on antibiotics, the colitis disappeared and the liver disease dramatically improved. Out of curiosity, the team reviewed the literature and found that others had made similar observations and even had published small patient cohorts. Pulling all the available data together, the team published a systematic review and meta-analysis. Encouraged by the clinical responses and the available data, the team developed a conceptional framework for antimicrobial therapy in PSC. This was published after peer review in the American Journal of Gastroenterology. Further encouraged by the clinical evidence and determined to show that antimicrobial therapy is a valuable therapy to reduce the long-term suffering of young people with PSC, the team at the Department of Gastroenterology and Hepatology at the Princess Alexandra Hospital joined forces with gastroenterologists across the state and successfully applied for funding from the National Health and Medical Research Council (NHMRC). The Queensland team secured a $1.6 million NHMRC Medical Research Future Fund grant to conduct a formal clinical trial. The project is coordinated by the team at the University of Queensland, based at the Princess Alexandra Hospital. It is part of the NHMRC Centre for Research Excellence (CRE) in Digestive Health. The CRE brings together world leaders in this field to prioritise improving the diagnosis and management of unexplained chronic gastrointestinal disorders. The research team is now busy establishing the state-wide clinical study network, which will involve all major hospitals in Queensland over the next four years. Professor Holtmann explained that collaboration is extremely important for research into this relatively rare disease. “Gastroenterologists are passionate about this area because there is currently no cure for PSC, and we want to make sure everyone with PSC in Queensland can access this new therapy. This is our opportunity to quickly translate our research findings into practice. This research trial has the potential to change the way we treat this chronic disease and drastically improve health outcomes for patients,” Professor Holtmann said. “As soon as a doctor identifies a patient with PSC, we can offer anti-microbial therapy straight away to prevent the inflammation that leads to permanent damage. This research will also help us to understand more about the microbiome involved, the patients’ immune response and, eventually, we may be able to cure patients with PSC.” https://youtu.be/lLX7sDHTrxY
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