The most comprehensive clinical study on liver cirrhosis ever conducted worldwide has been announced by Newcastle University, the University of Edinburgh, and leading research-driven global biopharmaceutical company, Boehringer Ingelheim.
The ADVANCE study (Accelerating Discovery: Actionable NASH Cirrhosis Endpoints) will be the most detailed observational study of its kind, including the largest number of patients and providing a detailed analysis of liver health.
This will not only enhance the understanding of NASH cirrhosis, but also help identify translational biomarkers that will accelerate the development of future therapies.
It is estimated that around 444 million people worldwide are living with a condition known as non-alcoholic or metabolic dysfunction-associated steatohepatitis (NASH/MASH), an inflammatory liver disease caused by fat accumulation in the liver. Over time, NASH leads to the formation of scar tissue, often resulting in liver cirrhosis. This can lead to serious complications like liver failure or liver cancer, necessitating the need for a liver transplant. Currently, there are no approved drugs for liver cirrhosis. Therefore, there is an urgent need for earlier diagnosis and new medications to prevent the progression of MASH cirrhosis to liver failure or to reverse liver scarring once liver cirrhosis has been identified.
This £30 million study is funded by Boehringer Ingelheim, reflecting the company’s commitment to improving the lives of people with cardiovascular, kidney, and metabolic diseases (CRM). The study will be led by researchers from Newcastle University and the University of Edinburgh, as well as staff from across Europe.
Professor Quentin Anstee, Professor of Experimental Hepatology at Newcastle University and Consultant Hepatologist at the Newcastle Hospitals NHS Foundation Trust, who is coordinating the global study, explained, „Building on Newcastle’s internationally recognized expertise in translational liver research, this study will uncover the fundamental disease processes triggering liver cirrhosis.“
„We want to find out why, even in the most advanced stages of liver disease, there are substantial differences in disease progression, with some people remaining healthy for many years, while others quickly experience liver failure or develop liver cancer. We are collaborating internationally with our partners to then use this knowledge to improve patient diagnosis and help in the development of new medications.“
„Cardiovascular, kidney, and metabolic diseases are the leading cause of death worldwide, accounting for up to 20 million deaths annually,“ said Lykke Hinsch Gylvin, MD, Chief Medical Officer at Boehringer Ingelheim. „At Boehringer Ingelheim, we focus on understanding the whole patient and specifically addressing disease mechanisms to address interconnected CRM diseases. We are very excited to collaborate with our partners in the ADVANCE study to better understand the underlying disease processes and achieve much-needed results for new treatment opportunities for patients with liver cirrhosis.“
Professor Neil Henderson, Professor of Tissue Repair and Regeneration at the University of Edinburgh and Co-Principal Investigator of the study, said, „Liver diseases have reached epidemic proportions worldwide, and there is an enormous need for the development of effective new treatment methods for liver scarring. To address this issue, we have been using a new technology called single-cell RNA sequencing in Edinburgh in recent years.“ The use of this new technology has allowed us, for the first time, to examine the scarring of human liver at a high resolution, and we hope that this state-of-the-art approach will enable us to accelerate the discovery of urgently needed new treatment methods for liver disease.“ His team is supported by Edinburgh Innovations, the university’s commercialization service.
The study will involve 200 patients with liver cirrhosis, who will be recruited from specialized liver clinics in hospitals across the UK and Europe or through referral by their treating physician. The study will include patients who have been diagnosed with advanced fibrosis or liver cirrhosis due to metabolic dysfunction-associated steatotic liver disease (MASLD) and those at risk of advanced fibrosis or cirrhosis.
Participants will undergo a biopsy to obtain a small sample of liver tissue for a detailed assessment of changes in liver gene expression using advanced scientific techniques. Subsequently, blood tests and advanced MRI scans will be conducted at regular intervals over the next two years. The data generated will be combined to enable researchers to see how disease-related changes in the body develop with advancing cirrhosis.
The international research consortium is led by physicians from Newcastle University (UK) and the University of Edinburgh (UK) and works closely with scientists from Boehringer Ingelheim. It includes specialist physicians and researchers at universities and hospitals across Europe, from the University Hospital Antwerp (Belgium), Assistance Publique Hopitaux de Paris (France), Edinburgh Royal Infirmary (UK), Newcastle upon Tyne Hospitals NHS Trust (UK), University of Seville (Spain), University of Turin (Italy), and Vall d’Hebron University Hospital (Spain).
For those interested in participating, they should discuss this with their treating physician.
Retired primary school headteacher Yvonne Gray was diagnosed with metabolic-dysfunction associated steatohepatitis (MASLD) over a decade ago.
The 68-year-old from Sunderland, UK, is a governor of the national liver patient charity for adults, LIVErNORTH, and strongly supports the ADVANCE study.
She said, „When my liver condition was diagnosed in 2010, not much was generally known about MASLD, let alone research being conducted in this regard.“
„Although quite common, MASLD is a largely silent disease that sneaks up on patients. Other than fatigue and constant discomfort in the upper right side of my abdomen, I was only aware of the symptoms of my other conditions, without realizing that my liver disease was silently advancing.“
„I had ’subtle changes‘ in my liver function blood tests and was only referred to a liver specialist after another consultant dealing with my other conditions sought his opinion. After a biopsy, I was shocked to be told that my liver was at stage three of a four-stage condition – the fourth stage being cirrhosis.“
„I am thrilled and relieved that this research gives hope for better diagnostic tests to identify people earlier, and for the potential discovery of treatments that could prevent or even reverse liver cirrhosis.“
As an active member of LIVErNORTH and a mother to a 39-year-old daughter recently diagnosed with MASLD, Yvonne is keen to engage more patients in research to raise awareness and find better treatments.
Yvonne added, „I am so thankful, grateful, and happy to live in a region where Newcastle University is at the forefront of MASLD research worldwide.“
„I want to encourage all liver patients to discuss with their own doctors about getting involved in this innovative research.“