Autologous macrophage therapy for liver cirrhosis: a phase 2 open-label randomized controlled trial

Abstract

Cirrhosis is a major cause of morbidity and mortality; however, there are no approved therapies except orthotopic liver transplantation. Preclinical studies showed that bone-marrow-derived macrophage injections reduce inflammation, resolve fibrosis and stimulate liver regeneration. In a multicenter, open-label, parallel-group, phase 2 randomized controlled trial (ISRCTN10368050) in n = 51 adult patients with compensated cirrhosis and Model for End-Stage Liver Disease (MELD) score ≥10 and ≤17, we evaluated the efficacy of autologous monocyte-derived macrophage therapy (n = 27) compared to standard medical care (n = 24). The primary endpoint was the difference in baseline to day 90 change in MELD score (ΔMELD) between treatment and control groups (ΔΔMELD). Secondary endpoints included adverse clinical outcomes, non-invasive fibrosis biomarkers and health-related quality of life (HRQoL) at 90 d, 180 d and 360 d. The ΔΔMELD between day 0 and day 90 in the treatment group compared to controls was −0.87 (95% confidence interval: −1.79, 0.0; P = 0.06); therefore, the primary endpoint was not met. During 360-d follow-up, five of 24 participants in the control group developed a total of 10 severe adverse events, four of which were liver related, and three deaths (two liver related), whereas no liver-related severe adverse events or deaths occurred in the treatment group. Although no differences were observed in biomarkers or HRQoL, exploratory analysis showed anti-inflammatory serum cytokine profiles after macrophage infusion. This study reinforces the safety and potential efficacy of macrophage therapy in cirrhosis, supporting further investigation.