Autologous macrophage therapy increases transplant-free survival in cirrhosis: Long-term follow-up of a phase 2 clinical trial

Abstract

Liver cirrhosis is a major contributor to global morbidity and mortality, and transplantation remains the only cure for end-stage disease. Preclinical studies have indicated that macrophage injections reduce inflammation, resolve fibrosis, and stimulate liver regeneration. The phase 1/2 Macrophage Therapy for Liver Cirrhosis trial (MATCH01; ISRCTN10368050) demonstrated the safety and potential efficacy of autologous monocyte-derived macrophage therapy in cirrhosis. Following MATCH01, participants were re-enrolled in a long-term follow-up (LTFU) study, extending observation to up to 4 years from randomization. Macrophage-treated patients in MATCH01 phase 2 demonstrated a significantly lower risk of death or transplant within the LTFU period (30.8%) compared with standard medical care (58.3%); macrophage-treated patients had an additional 252 days of restricted mean survival time within the LTFU period. There was no evidence of increased serious adverse events attributable to cell therapy. These results support the continued advancement of macrophage-based regenerative strategies as a promising therapeutic option for end-stage liver disease.

Keywords: cell therapy; liver cirrhosis; liver fibrosis; long-term follow-up; macrophage; regenerative macrophage.