£30M study paves the way for new treatments for people with cirrhosis

The ADVANCE (Accelerating Discovery: Actionable NASH Cirrhosis Endpoints) study will be the most detailed observational study of its kind enrolling 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 to identify translational biomarkers that will accelerate the development of future therapies.

Approximately 444 million people worldwide (1) are estimated to live with a condition referred to as nonalcoholic or metabolic dysfunction-associated steatohepatitis (NASH/MASH), an inflammatory liver disease that is caused by accumulation of fat in the liver. Over time, NASH causes the formation of scar tissue leading in many cases to liver cirrhosis. This can result in serious complications, including liver failure or liver cancer and may result in the patient needing a liver transplant. Currently there are no approved medicines for cirrhosis and so there is an urgent need for earlier diagnosis and new medicines to prevent MASH cirrhosis progression to liver failure, or to reverse the scarring of the liver once cirrhosis is established.

This £30M study is funded by Boehringer Ingelheim and reflects the company’s commitment to improve the lives of people living with cardiovascular, renal and metabolic diseases (CRM). The study will be led by researchers at Newcastle University and the University of Edinburgh, along with collaborators across Europe. 

Professor Quentin Anstee, Professor of Experimental Hepatology at Newcastle University and Consultant Hepatologist at 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 reveal the fundamental disease processes driving cirrhosis”.

“We aim to work out why, even at the most advanced stages of liver disease, there is substantial variation in how the disease progresses with some people remaining well for many years whilst others rapidly experience liver failure or develop liver cancer. Working internationally with our collaborators, we will then use this knowledge to improve how patients are diagnosed, and to help develop new medicines.”

“Cardiovascular, renal, and metabolic diseases are the leading cause of death worldwide, accounting for up to 20 million deaths annually (2,3,4),“ said Lykke Hinsch Gylvin, M.D., Chief Medical Officer at Boehringer Ingelheim. “At Boehringer Ingelheim we are focusing on understanding the whole patient and how to target specific disease mechanisms to address interconnected CRM diseases. We are very excited to work with our partners in the ADVANCE study to better understand the underlying disease processes and to bring much needed new treatments to patients with liver cirrhosis.”

Professor Neil Henderson, Professor of Tissue Repair and Regeneration at the University of Edinburgh and co-lead on the study, said; “Liver disease has reached epidemic proportions worldwide. Therefore, there is a huge need to develop potent, new treatments for liver scarring. To help address this, over the last several years we have harnessed a new technology in Edinburgh called single cell RNA sequencing. Using this new technology has allowed us to study human liver scarring in high definition for the first time, and we hope that this state-of-the-art approach will allow us to accelerate the discovery of much-needed new treatments for patients with liver disease.” His team is being supported by Edinburgh Innovations, the University’s commercialization service.

The study will include 200 patients with cirrhosis. Participating patients will be recruited at specialist liver clinics at hospitals throughout the UK and Europe or through referral by their own GP or doctors’ surgery. This study will enroll patients, who have been diagnosed with or are thought to be at risk of advanced fibrosis or cirrhosis due to fatty liver disease (Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD), formerly termed Non-Alcoholic Fatty Liver Disease (NAFLD)).

Participants will initially undergo a biopsy to collect a small sample of liver tissue so that detailed changes in gene expression in the liver can be assessed using advanced scientific techniques. They will then have blood tests and state-of-the-art MRI scans performed at regular time points over the next two years. The data generated will be combined to allow researchers to see how disease-related changes evolve in the body as cirrhosis progresses. 

The international research consortium is led by doctors at Newcastle University (UK) and Edinburgh University (UK), working closely with scientists at Boehringer-Ingelheim, and includes specialist doctors and researchers at universities and hospitals across Europe from Antwerp University Hospital (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). 

Anyone interested in taking part should discuss it with their treating physician. 
 

About Boehringer Ingelheim

Boehringer Ingelheim is working on breakthrough therapies that transform lives, today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units Human Pharma and Animal Health. Learn more at www.boehringer-ingelheim.com

About ADVANCE

ADVANCE will track the course of advanced liver cirrhosis to discover why some but not all patients experience liver failure or go on to develop cancer. The aim is to find new treatment targets to enable earlier diagnosis and the development of novel, more precise and effective treatments to improve patient outcomes.

The international research consortium is led by doctors at Newcastle University (UK) and University of Edinburgh (UK), working closely with scientists at Boehringer-Ingelheim International GmbH, and includes specialist doctors and researchers at universities and hospitals across Europe including: Antwerp University Hospital (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). Visit http://www.research.ncl.ac.uk/advance for more information.


(1) Spengler EK, Loomba R. Recommendations for Diagnosis, Referral for Liver Biopsy, and Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Mayo Clin Proc. 2015;90(9):1233-1246. doi:10.1016/j.mayocp.2015.06.013
(2) Non communicable diseases. https://www.who.int/news-room/fact-sheets/detail/noncommunicable-diseases. Last accessed: October 2023. 
(3) Vos T, Lim SS, Abbafati C, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet. 2020;396(10258):1204-1222. doi:10.1016/S0140-6736(20)30925-9
(4) Wang H, Naghavi M, Allen C, et al. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet. 2016;388(10053):1459-1544. doi:10.1016/S0140-6736(16)31012-1