Efficacy and Safety of Nafamostat Mesilate Versus Heparin for Anticoagulation During Artificial Liver Support Therapy in Patients with Acute-on-Chronic Liver Failure: A Prospective Real-World Cohort Study

Abstract

Background: Evidence regarding the use of nafamostat mesilate (NM) for anticoagulation during artificial liver support system (ALSS) therapy in patients with acute-on-chronic liver failure (ACLF) remains limited. The bleeding risk associated with heparin (HP) underscores the need for safer anticoagulation strategies. Objectives: This study aimed to evaluate the anticoagulation efficacy and short-term safety of NM versus HP in patients with ACLF undergoing treatment with a double plasma molecular adsorption system (DPMAS) combined with plasma exchange (PE). Methods: This prospective real-world cohort study included 122 consecutive patients with ACLF who underwent DPMAS combined with PE between November 2024 and December 2025. Patients received NM (n = 60) or HP (n = 62) according to routine clinical practice. Only the first treatment session per patient was analyzed. The primary endpoint was anticoagulation efficacy, and secondary safety outcomes included bleeding events and overall adverse events (AEs). Results: Effective anticoagulation rates were comparable between the NM and HP groups (91.7% vs 90.3%, P = 0.796). After treatment, the NM group had a shorter activated partial thromboplastin time (40.3 vs 48.4 s, P = 0.013), higher prothrombin activity (36.5% vs 32.1%, P = 0.034), and a higher platelet count (106.5 vs 82.5 × 109/L, P = 0.008). The incidences of bleeding events (3.3% vs 19.4%; relative risk [RR] = 0.172, 95% confidence interval [CI], 0.040 - 0.737; P = 0.006) and overall AEs (36.7% vs 58.1%; RR = 0.631, 95% CI, 0.426 - 0.937; P = 0.018) were significantly lower in the NM group. Multivariable logistic regression showed that NM remained associated with lower odds of bleeding (adjusted odds ratio [OR] = 0.150, 95% CI, 0.030 - 0.746; P = 0.020) and overall AEs (adjusted OR = 0.397, 95% CI, 0.185 - 0.855; P = 0.018). No serious AEs or treatment discontinuations occurred in either group. Conclusions: Treatment with NM achieved anticoagulation efficacy comparable to that of HP and was associated with lower incidences of bleeding events and overall AEs in patients with ACLF undergoing DPMAS combined with PE. These associations remained significant after adjustment for selected baseline characteristics. Nafamostat mesilate may represent an alternative to HP for anticoagulation during ALSS therapy. However, these findings should be interpreted with caution, given the nonrandomized design and the potential for residual confounding. Prospective, multicenter randomized controlled trials are warranted to confirm these findings.