People suffering sudden liver failure could one day benefit from a treatment that may reduce the need for transplants.
Studies with mice found a class of drugs under development as a cancer treatment can help prompt the liver to regenerate after injury.
The team, led by CRM Director Prof Stuart Forbes, say further tests will be needed before clinical trials can begin, but the discovery brings fresh hope to people affected by liver failure each year.
Acute Liver Failure occurs when a healthy liver is so seriously damaged it can no longer regrow and recover, leaving patients in urgent need of transplant.
In the study, researchers found that liver injury triggers a process called senescence, which is usually associated with aging or chronic disease. The team found that treatment with a class of drugs called TGF-beta inhibitors blocked the spread of senescence. Treatment helped the liver to regenerate after injury and improved survival in mice.
Lead author, Mr Tom Bird, Wellcome Trust Fellow at the Medical Resarch Council Centre for Regenerative Medicine at the University of Edinburgh, said:
“Our research has identified a potential treatment for acute liver failure, which may prevent the need for transplant. This could make a huge difference for patients with Acute Liver Failure and could also help free up donor livers for people with other forms of disease, who might otherwise die whilst waiting for a suitable organ.”
Paracetamol overdose is the most common cause of acute liver failure. There are around 200 life-threatening cases in the UK and 2,000 in the US each year. Often the damaged liver can regrow and recover on its own. When the injury is severe, however, regeneration may fail. A liver transplant is the only option in such cases. Healthy livers can also fail as a result of infections with some Hepatitis viruses. Recreational drug use is another cause of sudden liver failure. The study did not investigate these.
Professor Stuart Forbes, Director of the Medical Research Council Centre for Regenerative Medicine at the University of Edinburgh, said,
“These results are encouraging but it will be some time before we are in a position to begin trialling these therapies in patients.”
Around 300 adults and children in the UK are waiting for a liver transplant at any one time. Treatments that can reduce the need for liver transplants are urgently needed.
The study was led by researchers at the University of Edinburgh and the Cancer Research UK Beatson Institute in Glasgow and was funded by The Wellcome Trust, the Medical Research Council, The Jules Thorn Trust and Scottish Enterprise. It is published in Science Translational Medicine.
Bird et al. (2018). TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence. Science Translational Medicine, 15 Aug 2018: Vol. 10, Issue 454, eaan1230. DOI: 10.1126/scitranslmed.aan1230