Abstract
BACKGROUND/AIMS: Acute liver failure (ALF) is a life-threatening condition with high short-term mortality without liver transplantation (LT). Prior studies on therapeutic plasma exchange (TPE) have yielded mixed survival results. In this randomized controlled trial (RCT), we evaluated the safety and efficacy of TPE on the 30-day outcomes in ALF. METHODS: In this single-center, open-label, pilot RCT, 40 adults with ALF were randomized in a 1:1 ratio to receive either standard medical therapy (SMT) alone or SMT plus TPE. TPE was performed daily for up to five days or stopped as per the predefined criteria (improvement in hepatic encephalopathy or the development of shock or sepsis), using standard-volume centrifugation-based with a 1:1 fresh frozen plasma and albumin replacement. The primary outcome was 30-day mortality. Secondary outcomes included changes in biochemical parameters and adverse events. RESULTS: Median age was 24 (20-28) years; 57.5% were female; 57.5% had viral hepatitis-related ALF. Among TPE-assigned patients, 14 of 20 received ≥1 sessions. Thirty-day mortality was identical in both arms (65%; intention-to-treat, P = 1.000), with similar results on per-protocol analysis (TPE: 78.6% vs SMT: 65.0%, P = 0.393). By day 3, TPE recipients showed greater reductions in bilirubin (P = 0.002), international normalized ratio (P = 0.013), and ammonia (P = 0.340), but survival was unchanged. Rates of infection and electrolyte disturbances were similar. TPE was not independently associated with survival (hazard ratio: 0.92, 95% confidence interval [CI]: 0.43-1.99, P = 0.83). CONCLUSION: In our study, standard-volume TPE led to transient biochemical improvements but did not improve 30-day transplant-free survival. Future large, adequately powered multicentric RCTs are needed to clarify the potential role of TPE in ALF. This trial was prospectively registered with the Clinical Trials Registry of India (CTRI/2017/08/009525).