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24-01-2025 | Liver Cirrhosis | News

Macrophage cell therapy may provide limited benefits to patients with chronic liver disease

Author: Dr. Jonathan Smith

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medwireNews: Autologous monocyte-derived macrophage therapy shows some therapeutic potential for patients with compensated liver cirrhosis, but further study is needed, suggests a phase 2 randomized controlled trial.

Patients randomly assigned to receive the therapy had a 0.87-point difference in Model for End-Stage Liver Disease (MELD) scores after 90 days of treatment relative to individuals who received standard medical care, but the difference was not significant and therefore the treatment did not meet the study’s primary endpoint.

The MELD predicts 3-month mortality in cirrhosis based on levels of serum creatinine, bilirubin, and international normalized ratio, and ranges from 6 to 40 points with higher scores indicating greater severity and higher mortality risk, the researchers explain.

They note that although results for the primary outcome were not statistically significant, their findings reinforced the safety of the cell therapy, as there were no deaths and just one serious adverse event (SAE) among those who received it during the full 360-day follow-up. In the control group, by contrast, there were 10 SAEs in five people and three participants died. Two of the deaths were linked to liver decompensation and the third was due to COVID-19.

Stuart Forbes (University of Edinburgh, UK) and colleagues say in Nature Medicine that their MATCH01 study “builds upon growing understanding of the role of macrophages in liver repair and provides a potential new therapeutic approach for liver disease.”

The multicenter, open-label trial enrolled 51 patients aged 18–75 years (mean age 59.3 years) with compensated cirrhosis, confirmed by clinical and/or radiologic features and transient elastography above 15 kPa.

The participants were given autologous macrophage therapy (n=27) or standard medical care (n=24). The cell therapy consisted of extracting leukocytes via leukapheresis, maturing the cells in the lab, and reinfusing them into the patient at a minimum dose of 1.25 × 10⁸ and a maximum of 1 × 10⁹ cells.

The protocol initially required three infusions in the treatment group, with three participants in the group receiving this procedure. However, the high demand of the infusions on the participants and time constraints led the investigators to change the treatment to a single infusion for the remaining patients.

The majority of patients were men (63%) and 35% were alcohol drinkers. Alcohol-related liver disease was the predominant cause of cirrhosis, seen in 52% of patients, followed by metabolic dysfunction-associated steatotic liver disease in 31%.

MELD scores fell by a mean of 0.46 points in the treatment group after 90 days, from 11.89 points at baseline to 11.43 points, whereas they increased from 12.00 to 12.40 points in the control group.

“It was assumed that a [change in] MELD of 1 point would represent a clinically meaningful change over the relatively short 90-d primary outcome interval,” the authors write. “It is, however, recognized that liver remodeling is not a rapid or linear process, and substantial fibrosis regression would likely take far longer than 90 d to occur.”

There were no significant differences between the treatment groups in terms of the study’s secondary endpoints, including changes in the type III collagen formation biomarker PRO-C3, liver stiffness, the United Kingdom Model for End-Stage Liver Disease score, and health-related quality of life.

However, patients receiving cell therapy showed transient anti-inflammatory effects, as signaled by significantly elevated interleukin (IL)-15 and IL-13 levels, and reduced IL-1β levels at day 90 relative to controls.

AEs occurred in 96% of participants in both groups, with 187 events in the treatment group and 104 in the control group. The single SAE in the treatment group was related to alcohol intoxication, which was not considered a clinical event. Meanwhile, the SAEs in the control group included four liver-related events, and a hospital admission for a hepatobiliary complication.

Forbes et al note that “[t]he absence of liver-related serious adverse events in the treatment group is a remarkable finding that underscores the safety of this novel therapy.”

The researchers acknowledge limitations in the study related to its size and open-label structure, which they used due to ethical considerations. Additionally, the study population had “limited geographical and ethnic diversity, predominantly comprising individuals of White Scottish descent,” they write.

They conclude: “Further trials are needed, particularly emphasizing the beneficial effects on clinical outcomes and elucidating the duration of response.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2025 Springer Healthcare Ltd, part of the Springer Nature Group

Nat Med 2025; doi:10.1038/s41591-024-03406-8

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