A ground-breaking cell treatment in Scotland has become the first viable therapeutic option for patients with end-stage liver disease, offering a disease-modifying alternative to orthotopic liver transplantation (OLT) that is beyond the reach of many due to donor shortage and limitations in recipient criteria.
Results from trials show that patients who received the treatment had a significantly lower risk of dying or needing to have their liver transplanted over four years than those receiving standard medical care.
Liver transplantation has historically been the only curative therapy for end-stage liver disease. But, due to restricted donor availability, prohibitive costs, and strict selection criteria, many patients never get to the operating table. Though the liver has an excellent capacity to regenerate, in cases of late liver disease, cirrhosis occurs, resulting in widespread scarring that makes it impossible to recover. Over three-quarters of patients are diagnosed too late to be treated effectively, and the disease is responsible for more than 11,000 deaths a year in the UK alone.
Now, researchers at the University of Edinburgh have developed a treatment that leverages the patient’s immune system to repair liver damage. It works by taking immune cells from a patient’s blood, developing them into mature macrophages (a type of specialized white blood cell that cleans up damaged tissues), and then injecting them back into the bloodstream. Macrophages have numerous sites of action, but when administered to the liver, they travel from the bloodstream to degrade scar tissue, reduce harmful inflammatory elements, and promote healthy liver regeneration.
The MATCH trial recruited 50 patients: 26 received macrophage therapy and 24 received standard care. After 4 years, 70% of the treated cohort were alive and not needing transplant compared with only 40% of controls. Of the patients treated with macrophages, eight died, and none received a transplant; in contrast, there were nine deaths and five transplants among those receiving standard care. No severe adverse effects were observed, which is worth remembering.
The four years of follow-up, the researchers stress, give important evidence of this therapy’s long-term safety and efficacy. This event has long been recognized by experts as a breakthrough in regenerative medicine.
Professor Stuart Forbes, from the University of Edinburgh’s Institute for Regeneration and Repair, who led the work, said:
Liver disease is a major cause of death among 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 while 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.”
Patient advocacy groups have hailed the breakthrough. Pamela Healy, Chief Executive of the British Liver Trust, said:
“For people living with cirrhosis, these results offer something that has been in desperately short supply for far too long: real hope. 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.
Patients have been at the heart of this research from the very beginning. The British Liver Trust has worked closely with the study team to support and involve people with lived experience of cirrhosis, helping to shape the research and encouraging participation in the trial. That patient voice is essential if new treatments are to meet the real needs of those facing this disease every day.”
This therapy embodies more than 10 years of research by Professor Forbes and colleagues, in collaboration with the Scottish National Blood Transfusion Service. Forbes co-founded Resolution Therapeutics—a spinout from the university backed by Edinburgh Innovations- in 2020 to take this science into the clinic. Meanwhile, an advanced version of the therapy, RTX001, is being investigated in the phase 1 EMERALD clinical trial.
Dr. Lara Campana, Scientific Co-Founder and Senior Vice President of Research & Translational Science at Resolution Therapeutics, added:
“This study not only highlights the significant potential of regenerative macrophage therapy in patients with advanced cirrhosis, but it also offers us a glimpse into the mechanism whereby these cells achieve their therapeutic effect: analysis of patients’ blood revealed a strong anti-inflammatory effect of this therapy, which correlates with transplant-free survival.”
The study was funded by the Medical Research Council and the Chief Scientist Office, and appears in Cell Stem Cell. Scientists from the University of Dundee, SNBTS, Resolution Therapeutics, Tayside Clinical Research Center, and Glasgow Royal Infirmary were all involved in the research consortium.
Given that thousands of people die each year from liver disease, finding a therapy able to restore liver function without relying on limited donor organs could be transformative. A note to patients and families facing the challenges of cirrhosis: There is a clear message: Hope is now truly possible.
