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

Table 4 Key studies on continuous renal replacement therapy in acute liver failure

Ref.	Design	GRADE	Sample size	Etiology	CRRT regimen used	Key findings (detailed)	Effect estimates
Warrillow et al[1], 2020	Multicenter retrospective cohort	Moderate	62	Mixed ALF (Australasian)	CVVHDF/CVVH (effluent 20-40 mL/kg/hour, early initiation)	CRRT in hyperammonemic ALF reduced extreme hyperammonemia; prevented cerebral oedema progression; and was associated with transplant-free survival	Ammonia decreasing 50%-60% in 24-48 hours prevention of > 140 μmol/L ammonia associated with TFS 55% vs 13% (P = 0.05)
Cardoso et al[9], 2018	Multicenter cohort (United States ALFSG)	Moderate	Approximately 340 (RRT subgroup)	Mixed ALF	CRRT (preferred continuous modes, dose not specified)	CRRT associated with lower ammonia, reduced high-grade HE; improved mortality and transplant eligibility vs no RRT	RR: 0.65 (95%CI: 0.48-0.88) mortality ammonia decreasing 40%-60% (P < 0.001)
Dong et al[64], 2024	Systematic review and meta-analysis	High	Approximately 800 (8 studies)	Mixed ALF	Varied (mostly CVVHDF/CVVH, high-volume favoured)	CRRT improved overall and transplant-free survival; adequate ammonia clearance; low heterogeneity	Overall survival RR: 0.83 (95%CI: 0.70-0.99) TFS RR: 0.65 (95%CI: 0.49-0.85)
Fisher et al[59], 2022	Retrospective cohort	Moderate	40	Mixed ALF	CVVH vs CVVHD vs CVVHDF (dose approximately 30-35 mL/kg/hour)	All continuous modalities have similar ammonia clearance; no modality superiority	No difference in clearance/survival (P > 0.05), 28-day survival approximately 60%
Heyn et al[60], 2025	Retrospective cohort	Moderate	60	Paracetamol ALF	High-intensity CRRT (> 50 mL/kg/hour effluent)	Rapid ammonia/ICP reduction; improved survival in paracetamol ALF	Ammonia decreasing 75% (P < 0.001) mortality RR: 0.55 (95%CI: 0.35-0.85)
Roy et al[65], 2025	Multicenter retrospective cohort	Moderate	183 ALF (CRRT: 65)	Mixed ALF	CRRT (dose/regimen not detailed)	CRRT recipients have higher MELD scores; a nonsignificant trend to survival benefit	TFS 63.5% vs 47.6% (P = 0.07) lactate and KCC predicted mortality
Chaba et al[66], 2025	Single-center retrospective	Moderate	84	Paracetamol-induced ALF with hyperammonemia	High-intensity CRRT (median 54 mL/kg/hour in first 48 hours)	Early high-intensity CRRT improved TFS; a higher effluent dose was associated with better survival over time	Higher 48 hours dose HR: 0.67 (95%CI: 0.46-0.98) for survival. Improved TFS with increasing dose
Deep et al[61], 2016	Retrospective cohort (pediatric ALF)	Moderate	136 (CRRT: 45)	Pediatric ALF (mixed)	CRRT (high-volume preferred, dose approximately 35-50 mL/kg/hour)	Ammonia reduction by 48 hours improved survival; CRRT benefited non-LT patients	Every 10% ammonia decreasing at 48 hours increase survival likelihood 50% CRRT in non-LT HR: 4 (95%CI: 1.5-11.6)

GRADE: Grading of recommendations assessment, development and evaluation; CRRT: Continuous renal replacement therapy; ALF: Acute liver failure; CVVH: Continuous veno-venous hemofiltration; CVVHD: Continuous veno-venous hemodialysis; TFS: Transplant-free survival; ALFSG: Acute Liver Failure Study Group; RRT: Renal replacement therapy; HE: Hepatic encephalopathy; RR: Relative risk; CI: Confidence interval; ICP: Intracranial pressure; MELD: Model for end-stage liver disease; KCC: King’s College criteria; HR: Hazard ratio; LT: Liver transplantation.