Objectives Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality and limited therapeutic options. Therapeutic plasma exchange (PLEX) may improve outcomes by removing inflammatory mediators, but randomized evidence in ACLF is limited. This study evaluated the efficacy of PLEX in alcohol-related ACLF (A-ACLF). Methods In this randomized controlled trial, 100 patients with A-ACLF were randomized (1 : 1) to PLEX plus standard medical therapy (SMT) or SMT alone. PLEX was performed for up to three sessions. Coprimary outcomes were in-hospital mortality and 30-day survival. Secondary outcomes included hospital stay, ventilator requirement, and longitudinal changes in disease severity scores and laboratory parameters. Results All 100 patients (PLEX n = 50; SMT n = 50) completed follow-up. In-hospital mortality was lower with PLEX [24 vs. 52%; P = 0.007], with an absolute risk reduction of 28% (number needed to treat: 3.6). Thirty-day survival was higher with PLEX (72 vs. 36%; P < 0.001), with an adjusted hazard ratio for mortality of 0.43 ( P = 0.003). Significant improvements were observed in the model for end-stage liver disease sodium, Asian Pacific Association for the Study of the Liver ACLF Research Consortium, and Child–Turcotte–Pugh scores, and in international normalized ratio, creatinine, lactate, ammonia, and von Willebrand factor (all P < 0.001 for interaction). Hospital stay was shorter with PLEX (19 vs. 24 days; P = 0.023). No major PLEX-related adverse events were observed. Conclusion PLEX improves short-term survival and disease severity in A-ACLF and may be a valuable therapeutic option where transplantation is limited.
