Fresh insights could lead to new treatments for liver disease

The fight against liver disease could be helped by the discovery of cells that cause liver scarring, thanks to a study by the University of Edinburgh in collaboration with BHP researchers. 

The study has identified new sub-types of cells that, when they interact, accelerate the scarring process in diseased livers.

Experts hope that by understanding more how these cells behave, new treatments can be developed more quickly for liver diseases.

One in five people in the UK are at risk of developing liver disease, which is predicted to become the most common cause of premature death in the UK. It can occur as a result of a number of conditions such as obesity, alcohol excess, viral infections, autoimmune diseases or genetic disorders. Long-term damage leads to the formation of scar tissue within the liver, eventually causing liver failure. There are currently no treatments available to prevent or reverse this.

Scientists from the University of Edinburgh used a new technology called single cell RNA sequencing to study liver scarring in high definition.

They discovered sub-types of three key cells: white blood cells called macrophages, endothelial cells – which line blood vessels – and scar-forming cells known as myofibroblasts.

The study, published in Nature, was funded by the Wellcome Trust, Medical Research Council, Guts UK, Children’s Liver Disease Foundation, AbbVie pharmaceuticals, Tenovus Scotland, British Heart Foundation, and NIHR.

Dr Prakash Ramachandran, an MRC clinician scientist at the University of Edinburgh’s Centre for Inflammation Research and Consultant Liver Specialist at the Royal Infirmary of Edinburgh said: “Identifying new treatments for liver scarring is critical to tackling the epidemic of liver disease that we are currently facing. For the first time, we now have an in-depth understanding of how cells behave and talk to each other in diseased livers and, importantly, how we might block their activity as a treatment for liver scarring.”

Professor Neil Henderson, a Wellcome Trust Senior Research Fellow at the Centre for Inflammation Research and Consultant Liver Specialist at the Royal Infirmary of Edinburgh, said: “Using this new technology has allowed us to study human liver scarring in high definition for the first time. We hope that this new cutting-edge approach will rapidly accelerate the discovery of much-needed new treatments for patients with liver disease.”

Dr Sarah Teichmann, from the Wellcome Sanger Institute, University of Cambridge and co-chair of the Human Cell Atlas Organising Committee, said: “The discovery of three new sub-types of cell involved in human liver scarring is another important moment in the fight against liver disease and for the Human Cell Atlas initiative. The data is now publicly available for other researchers to use and will be a great resource as we attempt to tackle this epidemic.”

Dr Chris Weston

Dr Chris Weston, Senior Research Fellow at the University of Birmingham's Institute of Immunology and Immunotherapy, commented:

“Liver cirrhosis develops from an established background of inflammation and fibrosis and results in a high rate of mortality. However, our understanding of the cellular interactions that drive these processes is not complete; animal models do not fully recapitulate the human disease and reductionist single cell population models lacking the complex interplay that occurs within a highly organised tissue environment.

“Our paper addresses this shortfall through the use of single-cell RNA sequencing to not only identify key populations of liver cells in both healthy and cirrhotic human tissue, but also determine disease-associated pathways and interactions that may prove to be druggable targets for the treatment of liver disease.

“Our research team based in the Centre for Liver and Gastrointestinal Research, University of Birmingham played a key role in supporting this ground-breaking study. We used our expertise in the isolation and maintenance of human liver cells and access to human liver tissue to identify, purify and grow specific cell populations from patient specimens in the laboratory.

“Molecular pathways and binding partners identified by single-cell RNA sequencing were then explored in these culture systems to validate the observations arising from the transcriptomics data. When combined, these data provide a detailed map of the processes underlying human fibrotic disease, with the potential to guide not only stratification of patients with fibrotic disease but also provide real opportunities for novel treatment strategies.

“This study was supported by the dedication of the transplant team and associated clinical colleagues and QEHB and the generosity of patients who donated liver tissue.”