Effect of plasma exchange with albumin replacement on albumin functionality and organ dysfunction in acute-on-chronic liver failure

Abstract

Background & aimsAcute-on-chronic liver failure (ACLF) in cirrhotic patients is characterized by severe inflammation, organ failure and high short-term mortality. This proof-of-concept pilot study was aimed at evaluating the effects of plasma exchange (PE) with human serum albumin 5% (PE-A5%) on the albumin functional capacity and organ dysfunction in ACLF patients.MethodsTen adult patients were enrolled in a single-center phase-2, prospective, open-label, non-controlled study. Six PE-A5% were performed in 10 days followed by a one-month follow-up visit. Albumin functional capacity, circulatory, renal, cerebral, liver dysfunction, and systemic inflammation were assessed. Main safety variable was the percentage of PE associated with at least one procedure-related adverse event (AE).ResultsACLF patients showed lower albumin binding capacity, lower antioxidant capacity, and lower levels of albumin with preserved structure with respect to healthy donors (n=19). PE-A5% treatment increased albumin levels and improved albumin binding capacity to Sudlow site II (15.3±1.6 mg/mL vs to 18.9±1.7 mg/mL; P=0.003), fatty acid binding capacity (8.2±1.4 μM vs to 3.1±1.5 μM; P=0.013) and antioxidant capacity (HMA 9.5±1.5mg/mL vs to 14.6±1.6 mg/mL; P=0.001). Native albumin levels were increased throughout day 1-11 PE-A5% sessions (6.5±1.0 mg/mL to 10.2±1.4 mg/mL (P=0.01). PE-A5% improved systemic hemodynamics (mean arterial pressure, heart rate, cardiac index), renal function (creatinine level, blood urea nitrogen), cerebral function (hepatic encephalopathy grade), liver parameters (transaminases, bilirubin) and inflammatory parameters (C-reactive protein, leukocyte count). All patients had at least one of the 78 AEs reported, mostly mild (product/procedure-related: 36%). Sixteen serious AEs were reported in 8 patients (procedure/product-related: none).ConclusionsPE-A5% was a safe procedure associated with positive effects on albumin functionality, circulatory, renal, cerebral, and liver functions in cirrhotic patients with ACLF.ClinicalTrials.gov IdentifierNCT01201720EudraCT number2010-021360-15Impact and implicationsAcute-on-chronic liver failure (ACLF) is a clinical condition characterized by severe systemic inflammation, organ failure, and high mortality. Plasma exchange removes patient’s plasma containing pathogenic substances, replacing it by 5% albumin and fresh frozen plasma (PE-A5%). In this study, cirrhotic patients with ACLF were treated with PE-A5%, which was a safe procedure that increased binding and antioxidant capacity of patients’ albumin, while improving circulatory, kidney, brain, and liver functions. These beneficial effects could impact survival in ACLF.

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