Navigating the therapeutic tightrope: Precision use of plasmapheresis and continuous renal replacement therapy in liver failure

Table 2 Key studies on therapeutic plasma exchange in acute liver failure

Ref.	Design	Etiology	TPE protocol	GRADE	Sample size	Key findings (detailed)	Effect estimates
Stahl et al[14], 2019	Retrospective cohort	Mixed (idiopathic, viral, drug-induced, autoimmune)	LV-TPE (1-1.5 plasma volumes/session, median three sessions)	Moderate	45	Retrospective; TPE in severe ALF led to neurological improvement in 60%, bridging 40% to transplant; effective in viral/toxin etiologies	HE improvement 60% (grades III-IV to I-II); 90-day survival 55%
Larsen et al[16], 2016	Open label RCT	Mixed (indeterminate 38% paracetamol 23%, viral 14%, DILI 12%, others)	HV-TPE (8-12 L, 3 sessions)	High	182	Open-label RCT comparing HV-TPE + SMT vs SMT; TPE improved transplant-free survival at 90 days, with faster HE resolution and reduced bilirubin/INR; no increase in adverse events	59% vs 48% transplant-free survival (P = 0.0083); bilirubin decreasing 30%-40% (P < 0.01)
Pinceaux et al[17], 2025	Retrospective cohort (21-year single centre)	Mixed ALF (acetaminophen-40%, viral-20%, drug induced, indeterminate)	High-volume plasma exchange (8-12 L/session,1-3 sessions)	Moderate	199 total (HVPE-45, controls-126)	Severe ALF meeting LT criteria; HVPE significantly improved transplant-free survival vs no/short support; low adverse events; effective HE and biochemical control	Day-21 transplant-free survival 55.6% vs 30.4% (P = 0.003); adjusted HR: 0.54 (95%CI: 0.32-0.93), P = 0.0257
Goel et al[18], 2023	Meta-analysis	Mixed	Varied (mostly HV-TPE; 8%-15% plasma volumes, 1-5 sessions)	High	1200 (12 studies)	Pooled RCTs/cohorts; TPE associated with survival benefit, toxin clearance, and reduced transplant waitlist mortality; heterogeneity is low	OR: 1.5 (95%CI: 1.2-1.9) for survival; I2 = 18%
Maiwall et al[34], 2022	Open-label RCT	Non paracetamol (viral-45%, drug induced-25%, autoimmune-15%, indeterminate)	SV-TPE (2-4.5 L, 2-3/week)	High	60	SV-TPE vs SMT in non-acetaminophen ALF; TPE reduced 28-day mortality, improved biochemistry (ammonia, INR), and HE grades; safe with low complications	RR: 0.65 (95%CI: 0.45-0.94) for mortality; INR decrease 20%-30% (P = 0.02)
Gasca-Aldama et al[36], 2025	Retrospective cohort	Mixed (predominantly viral, drug-induced, autoimmune)	SV-TPE (1-1.5 plasma volumes/session, median four sessions)	Low	25	Mexican real-world; TPE + SMT improved 30-day survival vs SMT alone, especially in viral ALF; reduced HE and coagulopathy	92% vs 50% survival (P = 0.02); INR decrease 25% (P < 0.05)
Burke et al[37], 2025	Multicentre retrospective cohort	Mixed (paracetamol 55%, paracetamol 45%, drug induced, viral, indeterminate)	Varied (mostly HV-TPE, 8-10 LFFP, 1-3 sessions)	Moderate	150	Real-world United Kingdom cohort; TPE frequent but no overall survival benefit; transient biochemistry improvements in 70%; higher use in non-paracetamol ALF	HR: 1.1 (95%CI: 0.8-1.5) for mortality; no difference in transplant rates
Swaroop et al[38], 2026	Pilot open-label RCT	Mixed (drug-induced, toxin, viral, indeterminate predominant)	SV-TPE (1.2-1.5 plasma volumes/session, up to 5 sessions)	High	40	Open-label 11 RCT (SMT vs SMT + SV-TPE); identical 30-day mortality but transient day 3 improvements in bilirubin/INR/ammonia; no survival association; safe profile	65% mortality both arms (ITT, P = 1.0); HR: 0.92 (95%CI: 0.43-1.99, P = 0.83); bilirubin decrease (P = 0.002)
Panda et al[39], 2025	Meta-analysis	Pediatric ALF (mixed: Indeterminate, viral, metabolic, drug induced)	Varied (mostly SV-TPE, 1-1.5 volumes/session, 3-7 sessions)	High	80 (pediatric)	Pediatric ALF; TPE improved survival as a bridge to transplant/recovery; effective in 70% for HE resolution; low adverse events	Overall survival 75% (vs 45% historical); OR: 2.1 for bridge success (95%CI: 1.3-3.4)

TPE: Therapeutic plasma exchange; GRADE: Grading of recommendations assessment, development and evaluation; LV: Low-volume; ALF: Acute liver failure; HE: Hepatic encephalopathy; DILI: Drug-induced liver injury; HV: High volume; RCT: Randomized controlled trial; SMT: Standard medical therapy; INR: International normalised ratio; HVPE: High-volume plasma exchange; LT: Liver transplantation; HR: Hazard ratio; CI: Confidence interval; OR: Odds ratio; RR: Relative risk; SV: Standard volume; LFFP: Low-volume fresh frozen plasma; ITT: Intention-to-treat.