Shekhar Swaroop, Sagnik Biswas, Arnav Aggarwal, Poonam Coshic, Sonu Kumar, Samagra Agarwal, Hem Chandra Pandey, Gopal Kumar Patidar, Rahul Chaurasia, Umang Arora, Ayush Agarwal, Pragyan Acharya, Baibaswata Nayak, Deepak Gunjan, Viren Sardana, Ashwani Kumar Mishra, Shivanand Gamanagatti, Shalimar
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].