A new type of cell therapy has been shown to dramatically reduce the risk of death or the need for a liver transplant in patients with advanced liver disease, offering what experts describe as a potential breakthrough for a condition that kills thousands every year.
The findings come from a clinical trial known as the MATCH study, a Phase 2 open-label randomised controlled trial led by researchers at the University of Edinburgh. The trial compared an autologous macrophage therapy — using a patient’s own immune cells — against standard medical care in 50 patients with compensated cirrhosis, the severe scarring of the liver that marks advanced disease.
After four years, 70% of patients who received the macrophage therapy were alive and had not required a liver transplant, compared with just 40% of those who received standard care. In the treatment group, there were eight deaths and no liver transplants, while in the control group there were nine deaths and five liver transplants. The researchers reported no serious side-effects among those treated with the cell therapy.
These results build on earlier data from the same trial. A three-year follow-up had already shown that 22 of 26 patients in the treatment group were alive and transplant-free, compared with 13 of 24 in the control group. A 360-day analysis also reported no liver-related severe adverse events or deaths in the treatment group, against three deaths (two liver-related) and ten severe adverse events (four liver-related) in the control arm. The primary endpoint — a significant difference in the change of the Model for End-Stage Liver Disease (MELD) score at 90 days — was not met, but the researchers said the data reinforced the safety and potential efficacy of the approach, supporting further investigation.
How the macrophage therapy works to repair the liver
The therapy works by harnessing the body’s own immune system to reverse the damage caused by cirrhosis. Although the liver has a unique ability to regenerate after injury, prolonged damage leads to extensive scarring — fibrosis — that eventually leaves the organ unable to function. Until now, the only curative option for end-stage liver disease has been a transplant, which is severely limited by a shortage of donor organs.
The treatment developed by scientists at the University of Edinburgh, in collaboration with the Scottish National Blood Transfusion Service (SNBTS), involves taking immune cells called monocytes from a patient’s blood. These cells are then cultured and differentiated in a laboratory to become mature macrophages — a type of white blood cell that acts as a “scavenger” in the immune system, engulfing and removing damaged or infected cells.
Once re-injected into the patient, these macrophages travel to the liver, where they perform several key functions. They break down existing scar tissue (fibrosis), reduce harmful inflammation, and promote the growth of healthy liver cells. This regenerative mechanism is what distinguishes the therapy from standard treatments, which can only manage complications of cirrhosis rather than addressing the underlying scarring.
The initial trial used what is known as non-engineered macrophages — cells that are matured but not genetically modified. However, a more advanced version of the therapy, called RTX001, is now being tested. This is an “engineered” regenerative macrophage therapy, modified with specific factors such as IL-10 and MMP-9 to enhance its anti-fibrotic and anti-inflammatory properties. RTX001 is being evaluated in the EMERALD clinical trial, a Phase I/II first-in-human, open-label, multi-centre study for patients with end-stage liver disease who have recovered from a recent hepatic decompensation. The first patient was dosed and cleared safety checks in September 2025, with initial clinical readouts expected in 2026. The study is actively recruiting patients in the UK and Spain.
Expert and charity reactions
Professor Stuart Forbes, from the University of Edinburgh’s Institute for Regeneration and Repair, who led the research, said: “Liver disease is a major cause of death of people of working age. Although we can use liver transplantation as a rescue treatment for a proportion of people who have advanced liver disease, this is restricted by a lack of suitable donor organs. Unfortunately, many patients may die whilst on the liver transplant waiting list. There is therefore a desperate need for alternative treatments for patients with advanced liver disease. We hope this type of approach could one day add to our treatment choices for patients with advanced liver disease, reducing the need for liver transplants.”
Professor Forbes co-founded the spinout company Resolution Therapeutics in 2020, with support from Edinburgh Innovations, the University’s commercialisation service. The company is behind the development of RTX001 and is also exploring regenerative macrophage therapy for other inflammatory and fibrotic conditions, such as lung fibrosis and graft-versus-host disease.
Pamela Healy, chief executive of the British Liver Trust, welcomed the findings. “For people living with cirrhosis, these results offer something that has been in desperately short supply for far too long: real hope,” she said. “Being told that a liver transplant may be your only option — and that one may never come — is devastating for patients and families. A treatment that could slow or reverse liver failure and reduce the need for transplantation would be truly life changing.”
The British Liver Trust has been involved in the research, working with people who have lived experience of cirrhosis to help shape the study and encourage trial participation.
The scale of the problem
The urgency of developing new treatments is underscored by the scale of liver disease in the UK. More than three-quarters of people are diagnosed with cirrhosis when it is too late for effective treatment, contributing to more than 11,000 deaths per year in the UK. Mortality rates from liver disease have risen dramatically — by over 400% in the last 50 years — and deaths have continued to climb, with a nearly 24% increase over a four-year period. The UK saw a record high of 12,367 liver disease-related deaths in 2023. Liver disease is now the fifth most common cause of death in the UK and the second biggest cause of mortality in terms of potential years of working life lost in England. Deaths are highest in midlife, between ages 45 and 64, and the condition is disproportionately higher in areas of socioeconomic deprivation, where people are up to six times more likely to die from it.
Common causes of cirrhosis in the UK include excessive alcohol consumption, long-term hepatitis C infection, and non-alcoholic steatohepatitis (NASH), which is rising due to obesity and inactivity. Currently, there are no approved therapies that can effectively halt or reverse the progression of cirrhosis itself, with most treatments focusing only on managing complications.
The MATCH study was funded by the Medical Research Council and the Chief Scientist Office, and is published in the journal Cell Stem Cell. The research team also included scientists from the University of Dundee, SNBTS, Resolution Therapeutics, Tayside Clinical Research Centre, and Glasgow Royal Infirmary.