New cell therapy shows progress in treating advanced liver disease
A new type of cell therapy to treat patients with liver scarring, or cirrhosis, shows promise of being the first medical treatment for this common and lethal condition.
Results from a clinical trial of the treatment was presented at the American Association for the Study of Liver Diseases (AASLD) conference (2023) in Boston.
The innovative new approach to treating cirrhosis uses macrophage immune cells – the cells associated with tissue repair – derived from the patient’s own cells. It was tested in a clinical study, called ‘MATCH Phase 2’, involving 50 patients in Scotland with cirrhosis caused by a variety of different factors, such as alcohol, fatty-liver disease and viral hepatitis.
The data shows the treatment - pioneered by Professor Stuart Forbes’ lab at the University of Edinburgh - helped dramatically reduce serious liver-related complications during this one-year study. These complications can lead to hospitalisation and death.
The results indicate the treatment might help delay the need for a liver transplant, which is currently the only treatment option available to patients with advanced liver disease, but is a highly invasive procedure severely limited by organ availability, patient eligibility and complex aftercare.
Professor Forbes who led the trial team said,
We are encouraged by the new results. This trial shows the treatment is well tolerated, and is associated with reducing the clinical complications in patients with end-stage liver disease.
Chronic liver diseases and associated cirrhosis account for approximately one million deaths per year globally, with 4,000 deaths per year in the UK alone.
In MATCH Phase 2, 26 patients received the macrophage treatment, and 24 patients in the control group received standard medical care only. After one year, there were no liver-related clinical events in any of the 26 patients treated with macrophages. In the control group, four patients out of the 24 developed liver-related severe adverse events, and there were three deaths.
Professor Stuart Forbes is a clinical hepatologist, IRR Director, and group leader in the Centre for Regenerative Medicine has spent over a decade researching macrophages, supported by Edinburgh Innovations, the University’s commercialisation service. He and his team, funded by the Medical Research Council, have been investigating ways to understand and enhance the natural regenerative features of macrophage cells to create more effective medicines for liver disease. The MATCH studies have been conducted in partnership with the Scottish National Blood Transusion Servce and the Cell and Gene Therapy Catapult.
Dr Robin Buckle, Chief Science Officer at the Medical Research Council said,
The results of this trial of a novel macrophage cell therapy show great promise and if successfully built upon should provide lasting benefit for patients with chronic liver disease, an area of significant and unmet clinical need. It is exciting to see MRC’s long-term investment in Centre for Regenerative Medicine bearing fruit, and we look forward to the next phase of development.
Co-investigator Professor Jonathan Fallowfield said:
Currently, there is little hope for patients with advanced cirrhosis, apart from a liver transplant and a life on immunosuppressants. Liver-related complications in cirrhosis can be fatal and put huge pressure on health services. We are cautiously optimistic that we can bring hope to patients with this neglected condition.
An initial smaller study led by Professor Forbes in 2019, MATCH Phase 1, showed the treatment was well tolerated, exhibiting none of the side effects commonly observed with immune cell therapy treatments. This was repeated in the MATCH Phase 2 results.
More about the Macrophage Cell Therapy Trials
Liver disease patients could one day benefit from a new cell therapy that has just completed its first clinical trial, published in Nature Medicine.
Researchers who tested the potential treatment in patients with liver cirrhosis – where long term damage produces scarring – found the therapy had no significant adverse effects.
Now the team, led by Professor Stuart Forbes, Director of the Institute for Regeneration and Repair and the MRC Centre for Regenerative Medicine, is to gauge the effectiveness of the treatment – which is based on white blood cells called macrophages, that are key to normal liver repair.
- Video: Cell therapy for liver cirrhosis
- Liver disease patients could one day benefit from a new macrophage cell therapy that has just completed its first clinical trial, published in Nature Medicine (07 October 2019). Professor Stuart Forbes (MRC Centre for Regenerative Medicine) describes the results of this safety clinical trial. Videography: Jessie Pearson, Robin Morton and Ellie Roger
The next stage of the trial will measure whether the therapy helps the liver to reduce scarring and stimulate regeneration. The results should be known within the next two years.
At present the only successful treatment for end-stage liver cirrhosis – which claims around 14,000 lives in the UK each year (British Liver Trust) – is an organ transplant. The safety trial is a vital step forward in finding an alternative therapy.
During the trial scientists took cells from the blood of nine patients with the disease and turned them into macrophages, in the Scottish National Blood Transfusion Service’s (SNBTS) cell therapy facility. The new cells were then re-injected into the patient with the hope of repairing the damaged organ from within.
The research, published in the journal Nature Medicine, received funding from the Medical Research Council. The study was conducted in partnership with the SNBTS and the Cell and Gene Therapy Catapult.
Causes of liver cirrhosis include infections such as hepatitis C, obesity, alcohol excess and some genetic and immune conditions.
Professor Stuart Forbes, who directed the trial, said:
“Liver cirrhosis is a major healthcare issue in the UK and is one of the top five killers. The results from this first safety trial are encouraging and we can now progress to testing how effective it is in a larger group of people. If this was found to be effective it would offer a new way to tackle this important condition.”
Dr Robin Buckle, Chief Science Officer, Medical Research Council, said:
“The goal of regenerative medicine is to drive the body to self-repair. This has the potential to provide long-lasting treatments for major and often untreatable health problems, such as liver cirrhosis. “MRC is proud to fund this study which is an important first step in transferring cutting-edge science to the clinic. This will pave the way for testing the effectiveness of this new cell therapy in patients who would otherwise require a liver transplant.”
Pamela Healy, CEO of the British Liver Trust, said:
“Across the UK we are facing a liver disease epidemic. The number of people affected has been rising at an alarming rate and liver disease is now the biggest killer of 35 to 49-year olds.
“Chronic liver disease occurs when the liver is damaged irreparably and becomes scarred (cirrhosis). At this stage, there are very few treatments available. This new innovative approach is an exciting development and could in the future reduce the need for transplantation. More research is needed and the next stage of this work will be to really test the potential benefit for patients.”
More about the Macrophage Cell Therapy Trial
Moroni et al (2019). Safety profile of autologous macrophage therapy for liver cirrhosis. Nature Medicine, 07 October 2019.