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 acute-on-chronic liver failure (ACLF). APPROACH AND RESULTS: 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, resolution of organ failures, infections, and adverse events. 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%-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 with SMT. Subgroup analysis did not reveal significant heterogeneity across ACLF grade or etiology. Dyselectrolytemia and shivering were the most common complications after TPE. CONCLUSION: 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].