Therapeutic plasma exchange improves short-term survival in patients with acute-on-chronic liver failure: A randomized controlled trial

Background: This randomized controlled trial (RCT) evaluated the efficacy and safety of Therapeutic plasma exchange (TPE) versus standard medical therapy (SMT) in ACLF. Methods: In this single-center, open-label RCT (February 2022-March 2025), we randomly (1:1) assigned 194 adult patients (aged 18-60 y) with ACLF (European Association for the Study of the Liver-Chronic Liver Failure Consortium EASL CLIF-C Grades 1–3b) to receive SMT plus 5 sessions of TPE (n=97) or SMT alone (n=97). The primary outcome was all-cause mortality at 28 days. Secondary outcomes included 90-day mortality, changes in prognostic scores and resolution of organ failures, infections and adverse events. Findings: Baseline characteristics were comparable between groups. Seventy-two (74.2%) patients completed 3 sessions of TPE while 56 (57.7%) received all 5 sessions. Hemodynamic instability was the leading cause for discontinuation of TPE (18/41 patients, 43.9%). The 28-day mortality was significantly lower with TPE (43 patients, 44.3%; 95%CI: 34.2%-54.8%) than SMT (62 patients, 63.9%; 95%CI: 53.5%-73.4%), p =0.006; absolute risk reduction: 19.6% (95% CI: 5.8% to 33.3%). Ninety-day mortality was similar between groups. TPE resulted in greater reductions in ammonia, and higher rates of resolution of hepatic and coagulation failure by day 7 as compared to SMT. Subgroup analysis did not reveal significant heterogeneity across ACLF grade or etiology. Dyselectrolytemia and shivering were the most common complications after TPE. Interpretation: TPE significantly improves 28-day survival and organ failure resolution in patients with ACLF, but does not reduce 90-day mortality. CTRI/2022/01/039094