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

Table 7 Key studies on therapeutic plasma exchange and continuous renal replacement therapy in acute-on-chronic liver failure (both combined and sequential)

Ref.	Design	GRADE	Sample size	Etiology	CRRT+TPE regimen	Key findings (detailed)	Effect estimates
Yao et al[42], 2019	Retrospective cohort	Moderate	135 (PE: 44, DPMAS: 44, PE + DPMAS: 47)	HBV-related ACLF	DPMAS + sequential half-dose PE (low-volume TPE, 1-1.5 plasma volumes/session, 3-5 sessions)	Combined DPMAS + PE improved short-term survival and biochemistry (bilirubin, coagulation) vs monotherapies, especially in mild ACLF; reduced sepsis/AKI progression	28-day survival 65% combined vs 45%-50% mono (P < 0.05) MELD decreasing 6 points (P < 0.01)
Ma et al[72], 2025	Retrospective cohort	Low	198 (medication: 68, PE: 56, PE + CRRT: 74)	ACLF with AKI (mixed etiologies)	PE + CRRT (SV-TPE 2-4 L + CVVHDF 30-40 mL/kg/hour, sequential/combined)	PE alone is as effective as PE + CRRT for organ function recovery and short-term survival in ACLF-AKI; no added benefit from CRRT addition	No difference in MELD/SOFA reduction (P > 0.05), 28-day survival 48% (PE + CRRT) vs 45% (PE), P > 0.05
Bañares et al[80], 2013	Multicenter RCT	High	189 (MARS: 95, SMT: 94; PP: 156)	ACLF (mixed, hyperbilirubinemia/HE/renal failure)	MARS (albumin dialysis with CRRT elements, five sessions over 6 days)	RELIEF trial; MARS + SMT vs SMT; modest biochemical improvements (bilirubin, HE) but no significant 30-day survival benefit; reduced complications	30-day survival 40% vs 30% (P = 0.08). Bilirubin decreasing 25% (P < 0.05)
Schönfelder et al[81], 2025	Retrospective cohort	Moderate	142 (CytoSorb + CVVHDF: 71, ADVOS: 71; ACLF subgroup: 97)	ACLF with hyperbilirubinemia (mixed)	CytoSorb integrated with CVVHDF (24 hours sessions, CytoSorb replaced q12-24 hours)	CytoSorb + CVVHDF is superior to ADVOS for bilirubin removal in ACLF; improved organ function, but high mortality; better creatinine/urea removal with ADVOS	Bilirubin reduction 35% vs 15% (P < 0.0001), SOFA decreasing 4.2 (P < 0.001), 28-day survival 55%
Jackson et al[75], 2024	Retrospective cohort	Moderate	23	Pediatric ALF/ACLF (mixed)	CRRT + TPE (combined, sequential/tandem; TPE for coagulopathy, CRRT for hyperammonemia)	Pediatric liver failure; 83% survived with LT or native recovery; worse outcomes in ACLF/comorbidities	Overall survival 83%. Mortality aOR: 2.5 (95%CI: 1.1-5.7, P = 0.028) with comorbidities, 4/13 ACLF died pre-discharge

GRADE: Grading of recommendations assessment, development and evaluation; TPE: Therapeutic plasma exchange; CRRT: Continuous renal replacement therapy; PE: Plasma exchange; DPMAS: Double plasma molecular adsorption system; HBV: Hepatitis B virus; ACLF: Acute-on-chronic liver failure; AKI: Acute kidney injury; RCT: Randomised controlled trial; MELD: Model for end-stage liver disease; SV-TPE: Standard-volume therapeutic plasma exchange; CVVHD: Continuous veno-venous hemodialysis; SOFA: Sequential organ failure assessment; MARS: Molecular adsorbent recirculating system; PP: Per-protocol; SMT: Standard medical therapy; ADVOS: Advanced organ support; LT: Liver transplantation; ALF: Acute liver failure; aOR: Adjusted odds ratio; CI: Confidence interval.