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

Background & Aims: Effective treatments for acute -on -chronic liver failure (ACLF) are a major unmet need. This proof -of concept pilot study was aimed at evaluating the effects of plasma exchange (PE) with albumin 5% (PE -A5%) on albumin functional capacity and organ dysfunction in patients with ACLF. Methods: Ten adult patients were enrolled in a single -center phase II, prospective, open -label, non -controlled study. Six PEA5% sessions were performed in 10 days followed by a 1 -month follow-up visit. Albumin functional capacity and circulatory function were assessed, as were renal, cerebral, and liver function, and systemic in flammation. The main safety variable was the percentage of PE sessions associated with at least one procedure -related adverse event (AE). Results: Patients with ACLF showed lower albumin binding capacity, lower antioxidant capacity, and lower levels of albumin with preserved structure compared to healthy donors (n = 19). From baseline to day 11, PE -A5% treatment increased albumin levels and improved albumin binding capacity to Sudlow site II (15.3 +/- 1.6 mg/ml to 18.9 +/- 1.7 mg/ml; p = 0.003), fatty acidbinding capacity (8.2 +/- 1.4 lM to 3.1 +/- 1.5 lM; p = 0.013) and antioxidant capacity (human mercaptalbumin 9.5 +/- 1.5 mg/ml 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 = 0.035). 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 in flammatory 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 eight patients (procedure/product-related: none). Conclusions: PE -A5% was a safe procedure associated with positive effects on albumin functionality, and circulatory, renal, cerebral, and liver function in patients with ACLF. Impact and implications: Acute -on -chronic liver failure (ACLF) is a clinical condition characterized by severe systemic in flammation, organ failure, and high mortality. Plasma exchange removes patient 's plasma containing pathogenic substances, replacing it with 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 bene ficial effects could impact survival in ACLF. ClinicalTrials.gov Identi fier: NCT01201720 EudraCT number: 2010-021360-15 (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).