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

Table 3 Key studies on therapeutic plasma exchange in acute-on-chronic liver failure

Ref.	Design	GRADE	Sample size	Etiology	TPE protocol	Definition	Key findings (detailed)	Effect estimates
Ramakrishnan et al[41], 2022	Prospective interventional-non-randomised study	Moderate	TPE-14, SMT-14	Alcohol ACLF	Standard-volume TPE (not specified volume/sessions; along with SMT)	APASL	TPE + SMT vs SMT alone in nonresponders without immediate LT prospects; reduced bilirubin, ammonia, coagulation parameters, and severity scores; lower 90-day mortality in the TPE group; well-tolerated with minimal AEs	Reduced bilirubin/ammonia/INR (P < 0.05); 90-day mortality lower in cases (significant); procedure AEs in 2%
Yao et al[42], 2019	Retrospective cohort	Moderate	80 (DPMAS + TPE: 40, SMT: 40)	HBV-ACLF	DPMAS + sequential SV-TPE (1.5-2 plasma volumes, 3-5 sessions)	APASL criteria	DPMAS + TPE improved biochemistry, reduced mortality/sepsis, and enhanced HBV antigen clearance	RR: 0.70 (95%CI: 0.50-0.98) mortality; viral load decreasing 1-2 log10 (P < 0.05)
Chen et al[43], 2021	Multicenter prospective cohort	Moderate	200 (TPE: 100, SMT: 100)	HBV-ACLF	TPE-based support (2-4 L plasma, response-guided, median four sessions)	APASL criteria	TPE shortened hospital stay, improved short-term survival; safe in cirrhosis	90-day survival 55% vs 40% (P = 0.03); bilirubin decreasing 20%-30%
Schumacher et al[44], 2025	Propensity-matched cohort	Moderate	150 (TPE: 75, SMT: 75)	Mixed (alcohol 50%, HBV 30%, other)	SV-TPE (1.5-2 plasma volumes, 3-4 sessions)	EASL-CLIF criteria	TPE improved multiorgan function (liver/kidney), reduced inflammatory markers; no excess AEs	MELD decreasing 5 points (P < 0.05); SOFA score decreasing 2.1 (95%CI: 1.2-3.0)
Beran et al[45], 2024	Systematic review and meta-analysis	High	Approximately 1500 (15 studies)	Mixed (HBV, alcohol, viral, indeterminate)	Varied (SV-TPE and HV-TPE, 1-5 sessions)	Mixed (EASL-CLIF, APASL)	TPE survival benefit in ACLF, especially HBV/alcoholic; improved LT eligibility; low bias	OR: 1.4 (95%CI: 1.1-1.8); I2 = 22%
Tan et al[46], 2020	Systematic review	High	Approximately 1000 (10 studies)	Mixed (HBV, alcohol, viral, drug-induced)	Varied (mostly SV-TPE, 1-2 plasma volumes, 3-7 sessions)	Mixed (EASL-CLIF, APASL)	TPE reduced waiting-list mortality, stabilised hemodynamics, and was effective as a bridge therapy	HR: 0.75 (95%CI: 0.60-0.95) for death
Kumar et al[47], 2025	Case series	Low	5	Alcoholic ACLF	SV-TPE (1-1.5 plasma volumes, three sessions) + steroids	APASL criteria	TPE + steroids in steroid-failed ACLF improved survival, reduced inflammation; pediatric-adapted	90-day survival 80%; IL-6 decreasing 40% (P < 0.05)
Kumar et al[40], 2025	Systematic review and meta-analysis	High	5336 (23 studies, 2724 TPE vs 2612 SMT)	Mixed (HBV 40%, alcohol 35%, other)	Varied (SV-TPE and HV-TPE, 1-7 sessions)	Mixed (EASL-CLIF, APASL, CMA)	Largest meta-analysis; TPE improved 30-day, 90-day, 1-year survival; strong benefit in HBV/alcohol ACLF; acceptable safety	30-day RR: 0.70 (95%CI: 0.60-0.81); 90-day RR: 0.81 (95%CI: 0.77-0.86); 1-year RR: 0.85 (95%CI: 0.79-0.92)
Swaroop et al[48], 2023	Retrospective cohort	Low	76 (TPE: 38, SMT: 38)	Mixed (alcohol 65%, HBV 20%, other)	SV-TPE (1-1.5 plasma volumes, median three sessions)	EASL-CLIF criteria	TPE improved 30-day survival but no long-term (90-day) benefit; reduced inflammation	30-day mortality 21% vs 50% (P = 0.008); 90-day mortality 36.8% vs 52.6% (P = 0.166)
Maiwall et al[49], 2021	Retrospective cohort	Low	183 (TPE: 94, SMT: 89)	Alcohol (65%), HBV, other	SV-TPE (1-2 plasma volumes, 2-4 sessions)	APASL criteria	TPE reduced systemic inflammation, MOF, and mortality vs SMT in the propensity-matched cohort	30-day mortality HR: 0.07 (95%CI: 0.03-0.18)
Xu et al[50], 2023	Open-label RCT	High	96 (DPMAS + TPE: 48, SMT: 48)	HBV-ACLF (100%)	DPMAS + sequential low-volume TPE (1-1.5 plasma volumes, 3-5 sessions)	CMA + APASL criteria	DPMAS + TPE safe, improved 12-week survival in intermediate-stage HBV-ACLF	12-week survival 64% vs 36% (P = 0.048)
Xu et al[51], 2019	Open-label RCT	High	60 (TPE: 30, SMT: 30)	HBV-ACLF (100%)	SV-TPE (1-1.5 plasma volumes, median three sessions)	Bilirubin ≥ 10 × ULN, INR > 1.5	TPE is safe but has no significant short-term survival benefit vs SMT	30-day survival 80% vs 63.3%; 90-day 56.7% vs 50%; 1-year 53.3% vs 43.3% (P > 0.05)
Qin et al[52], 2014	Open-label RCT	High	234 (ALSS: 104, SMT: 130)	HBV-ACLF (100%)	ALSS (including TPE, 2-4 L plasma, 2-3 sessions/week)	CMA criteria	ALSS (including TPE) improved short/Long-term survival vs SMT; reduced viral load	90-day survival 60% vs 47% (P = 0.016); 5-year survival improved (P < 0.05)
Yu et al[53], 2008	Open-label RCT	High	280 (TPE: 140, SMT: 140)	HBV-ACLF (100%)	SV-TPE (1-2 plasma volumes, response-guided, median four sessions)	CMA 2006 criteria	TPE reduced mortality in MELD 30-40; low viral load pre-TPE predicted better survival	MELD 30-40: 3-month mortality 49.4% vs 86.1% (P < 0.01); MELD > 40: No benefit (91.5% vs 98.4%, P > 0.05)

GRADE: Grading of recommendations assessment, development and evaluation; TPE: Therapeutic plasma exchange; ACLF: Acute-on-chronic liver failure; SMT: Standard medical therapy; APASL: Asian Pacific Association for the Study of the Liver; LT: Liver transplantation; AE: Adverse event; INR: International normalised ratio; DPMAS: Double plasma molecular adsorption system; HBV: Hepatitis B virus; SV: Standard volume; RR: Relative risk; CI: Confidence interval; EASL-CLIF: European Association for the Study of the Liver-Chronic Liver Failure; MELD: Model for end-stage liver disease; SOFA: Sequential organ failure assessment; HV: High volume; LT: Liver transplantation; OR: Odds ratio; HR: Hazard ratio; IL-6: Interleukin-6; CMA: Chinese Medical Association; MOF: Multiorgan failure; RCT: Randomised controlled trial; ULN: Upper limit of normal; ALSS: Artificial liver support system.