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Background and Aims Patients with cirrhosis who recover from a hepatic decompensation event face high morbidity and mortality with no therapeutic options beyond etiological treatment or transplantation. Pro-regenerative macrophages with anti-inflammatory and anti-fibrotic effects modulate liver fibrosis and stimulate regeneration, as shown in animal models and the MATCH trials ( ISRCTN10368050). EMERALD, a Phase1/2 trial, aims to evaluate engineered macrophages in patients with end stage liver disease.Method This first-in-human trial will enrol patients in the UK and Spain with cirrhosis due to steatotic liver disease (MASLD, Met-ALD and ALD), who have stabilized after a recent hepatic decompensation event or have developed refractory ascites, and have a baseline MELD 3.0 score of 12–20. Exclusion criteria include hepatocellular carcinoma, portal vein thrombosis, significant hydrothorax, splenomegaly ≥16 cm, platelets <50x10 9/L and PEth>200 ng/ml. Patients receive G-CSF (10 µg/kg/day for 5 days) followed by apheresis to collect monocytes, which are then differentiated into pro-regenerative macrophages engineered to express interleukin-10 (IL-10) and matrix metalloproteinase-9 (MMP-9). Cryopreserved autologous cells (108 per 10 mL) are infused for four cycles.Results Patients will be monitored for major clinical events (including further hepatic decompensation, death and transplant), over two years, with additional exploratory biomarker analysis including proteomic, transcriptomic and fibrosis biomarkers. Safety data from a sentinel patient will guide treatment progression. Clinical outcomes will be compared to the OPAL observational cohort with similar inclusion/exclusion criteria and patient characteristics conducted at mainly the same sites. Safety is the primary endpoint, time to event is the primary efficacy measure.Abstract P68 Figure 1Conclusion EMERALD will explore the safety and efficacy of autologous engineered macrophages in mitigating inflammation and fibrosis in decompensated cirrhosis, potentially offering a novel therapeutic option for high-risk cirrhotic patients.