Copyright: ©Author(s) 2026.
World J Hepatol. May 27, 2026; 18(5): 115047
Published online May 27, 2026. doi: 10.4254/wjh.v18.i5.115047
Published online May 27, 2026. doi: 10.4254/wjh.v18.i5.115047
Table 1 Differentiation between plasmapheresis (therapeutic plasma exchange) and hemodialysis[15]
| Characteristic | Hemodialysis | TPE-membrane filtration | TPE-centrifugation |
| Mechanism | Diffusion and/or convection | Convection | Centrifugal force |
| Blood flow, mL/minute | Continuous: 100-300; intermittent: 200 > 400 | 150-200 | 10-150 |
| Blood volume in circuit, mL | 160-280 | 125 | 180 |
| Plasma extraction, % | N/A | 30 | 80 |
| Molecular weight cutoff, Da | < 15000 | > 15000 | > 15000 |
| Vd, L/kg | Moderate (≤ 1.5-2) | Low (< 0.3) | Low (< 0.3) |
| Protein binding, % | < 80 | > 80 | > 80 |
| Anticoagulation | Heparin | Heparin | Citrate |
| Sterilisation | Ethylene oxide; steam; electron beam; γ-irradiation | γ-irradiation; ethylene oxide | γ-irradiation; ethylene oxide |
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) |
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) |
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) |
Table 5 Key studies on continuous renal replacement therapy in acute-on-chronic liver failure
| Ref. | Design | GRADE | Sample size | Etiology | CRRT regimen used | Key findings (detailed) | Effect estimates |
| Saraiva et al[8], 2020 | Retrospective cohort | Moderate | 120 | ACLF with AKI (mixed, predominantly alcohol and viral) | CVVHDF (dose 25-35 mL/kg/hour, RCA preferred, early vs late initiation) | CRRT in ACLF-AKI; early initiation improved renal recovery, reduced sepsis, and provided a survival benefit | 90-day survival 45% vs 25% (early vs late, P < 0.01) AKI recovery 55% |
| Zhang et al[21], 2019 | Meta-analysis | High | 500 (10 studies) | Liver failure (cirrhosis/ACLF with AKI) | Varied CRRT modes (mostly CVVHDF/CVVH, RCA vs heparin) | RCA is safer than heparin in liver failure CRRT; lower bleeding, effective clearance | Complication RR: 0.80 (95%CI: 0.65-0.99) I2 = 12% |
| Pourcine et al[71], 2021 | Prospective cohort | Moderate | 40 | Severe liver impairment (cirrhosis/ACLF) | RCA-CRRT (CVVHDF, citrate 3-4 mmol/L, dose approximately 30 mL/kg/hour) | RCA in liver impairment: Low toxicity, stable hemodynamics, prolonged filter lifespan | Citrate toxicity 5%. Filter lifespan increasing 20% (P < 0.05) |
| Ma et al[72], 2025 | Retrospective cohort | Low | 198 | ACLF-AKI (mixed, HBV predominant) | CRRT alone vs CRRT + TPE (CVVHDF, dose 30-40 mL/kg/hour) | No added benefit of TPE combo vs CRRT alone for MELD reduction or survival | MELD reduction similar (P > 0.05), 28-day survival approximately 50% (no difference) |
| Maiwall and Sharma[73], 2025 | Prospective cohort | High | 236 (AKI-3: 78) | ACLF with stage 3 AKI (mixed, alcohol/HBV predominant) | CRRT (mostly CVVHDF, dose not specified, initiated in 59%) | Rapid AKI-3 progression; CRRT modest AKI resolution benefit, but no significant TFS improvement; high mortality | CRRT use 59% AKI resolution 28% vs 9% (P = 0.04), 28-day TFS 23% vs 16% (P = 0.31), 90-day TFS 18% 90-day mortality 82% |
| Staufer et al[74], 2017 | Retrospective cohort | Moderate | 78 | Cirrhosis with ACLF (68% ACLF, mostly grade 2-3) | RRT (continuous and intermittent, predominantly CRRT in ICU) | High mortality independent of LT; low renal recovery; CLIF-C ACLF score best predictor | ICU mortality 82% 90-day mortality 91% 1-year mortality 92%. Renal recovery 13% bridged to LT 14% CLIF-C ACLF AUC: 0.866 |
Table 6 Key studies on therapeutic plasma exchange and continuous renal replacement therapy in acute liver failure (both combined and sequential)
| Ref. | Design | GRADE | Sample size | Etiology | TPE/CRRT regimen | Key findings (detailed) | Effect estimates |
| Thanh et al[62], 2023 | Case series | Low | 10 | Pediatric dengue-induced ALF | Combined TPE + CRRT (SV-TPE 1-1.5 volumes + CVVHDF 30-40 mL/kg/hour) | Vietnamese pediatric dengue-ALF; combined improved outcomes, rapid toxin/ammonia clearance | Survival 80%. Ammonia decreasing 50% in 24 hours (P < 0.05) |
| Jackson et al[75], 2024 | Retrospective cohort | Moderate | 50 | Pediatric ALF (mixed) | Combined TPE + CRRT (SV-TPE + CVVHDF, dose 35-50 mL/kg/hour) | United States pediatric; combined as a bridge to LT/recovery; improved neuro/renal function | Transplant-free survival 44% HE resolution 70% |
| Colak and Ocak[76], 2024 | Retrospective cohort | Low | 30 | Pediatric ALF (mixed, viral/toxin) | Combined TPE + CRRT (SV-TPE + CVVHDF) | Turkish pediatric; combined effective for stabilisation; low complications | The improvement 70%, survival 67% |
| Vo et al[77], 2023 | Prospective cohort | Moderate | 15 | Pediatric dengue-shock ALF | Combined TPE + CRRT (SV-TPE + high-volume CVVH) | Vietnamese; combined reduced shock duration and ammonia levels | Ammonia decreasing 50%, ICU stay decreasing 3 days (P = 0.04) |
| Trepatchayakorn et al[78], 2021 | Case series | Low | 5 | Pediatric ALF (dengue/toxin) | Combined TPE + CRRT | Thai pediatric; combined bridged to recovery; effective toxin clearance | Survival 60%, bilirubin decreasing 35% |
| Ruhatiya et al[79], 2025 | Retrospective observational (propensity-matched) | Low | 99 (after matching; original 222, exclusions 34) | ALF, excluding yellow phosphorus poisoning and Wilson’s disease | CRRT alone vs sequential CRRT + PLEX (plasma exchange, details not specified) | Indian adult ALF; no benefit from adding PLEX to CRRT; potential harm in transplanted patients; similar ICU/hospital stay | Non-transplant survival: 30.6% (CRRT) vs 16.1% (CRRT + PLEX), P = 0.251. Transplant survival: 100% (CRRT) vs 70.6% (CRRT + PLEX), P = 0.046. Overall, no benefit, possible harm |
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 |
Table 8 Consolidated summary of differentiation between use of therapeutic plasma exchange, continuous renal replacement therapy and therapeutic plasma exchange + continuous renal replacement therapy in acute liver failure and acute-on-chronic liver failure
| Aspect | TPE | CRRT | TPE + CRRT |
| Mechanism | Removes/replaces plasma; clears protein-bound toxins (> 15000 Da), cytokines, DAMPs/PAMPs (e.g., bilirubin, bile acids, HMGB1, LPS) via centrifugal (80% efficiency) or membrane filtration[15] | Convection/diffusion; clears water-soluble toxins (< 15000 Da), ammonia, urea, electrolytes, small cytokines (IL-6, IL-8) via CVVH/CVVH/CVVHDF[19,82] | Sequential TPE targets large/protein-bound toxins + CRRT for small solutes/ammonia; sequential avoids overload (TPE first for inflammation, then CRRT for AKI). Combined via integrated circuits (e.g., PrismaFlex) for rapid multi-toxin clearance[73,75] |
| Indications | ALF: Severe inflammation (IL-6 >100 pg/mL); coagulopathy (INR > 1.5), HE (grades III-IV), toxin-driven ALF (acetaminophen, viral), Wilson’s autoimmune ALF[16,18,32,33]. ACLF: Bilirubin > 20 mg/dL) or HE (grades II-IV), or systemic inflammation (MELD score > 20). HBV-ACLF flares. Severe alcoholic hepatitis refractory to corticosteroids[12,13,40] | ALF: Early in AKI, progressive or hyperammonemia or advanced grades of HE or electrolyte disturbances or volume management when needed[54-58]. ACLF: Stage 3 AKI with progression or non-response to vasoconstrictors within 12-24 hours[67] | ALF: Fulminant cases with cerebral oedema + AKI (e.g., post-TPE hyperammonemia rebound)[75-79]. ACLF: ACLF-3 with combined hyperbilirubinemia (> 20 mg/dL) + AKI-3 + ammonia > 200 μmol/L; septic shock (SOFA > 12)[42,75,80,81] |
| Preferred types | Centrifugal (e.g., SpectraOptia; low flow 50-150 mL/minute for instability); HV-TPE (8-12 L, ALF); SV-TPE (2-4.5 L, ACLF/ALF); DPMAS add-on for HBV[15,18,34] | CVVHDF (dual, 35-70 mL/kg/hour); CVVH (ammonia focus, 35-50 mL/kg/hour); high-volume for severe ALF; RCA (3-4 mmol/L) anticoagulation[19,82] | Sequential: TPE (1-3 sessions) → CRRT (within 12 hours post-TPE for preemptive ammonia control); combined: Integrated (TPE 2000 filter on PrismaFlex, post-oxygenator in ECLS). Preferred in low-resource ICUs for sequential[27,63,75] |
| Pros | Rapid large-toxin clearance (bilirubin 30%-40% reduction); protein replenishment (INR drop 20%-50%); immunomodulation (IL-6/TNF-αdecreasing 20%-40%); survival increasing 10%-15% ALF, 5%-10% ACLF; bridge to transplant (eligibility increasing 15%)[16,18,34,38,40,45] | Ammonia clearance 40%-75% in 24-48 hours; hemodynamic stability (ICP decreasing 15-20 mmHg); AKI/fluid management (sepsis risk decreasing 15%); mortality RR: 0.65 ALF, 5%-10% survival increasing ACLF[64,65,71-73,82] | Ammonia decreasing 60%-80% + bilirubin decreasing 40%-60% (48 hours); fastest MOF reversal (SOFA decreasing 3-5 points in 72 hours); survival increasing 15%-25% vs monotherapy in ACLF-3; better bridge to LT (increasing 30% eligibility); reduced vasopressor needs (norepinephrine decreasing 20%-30% in sequence)[62,72,75,76] |
| Cons | Bleeding (5%-10%), infections (5%-15%), hypocalcemia (1.5%-9%), allergic reactions (2%-5%); hemodynamic instability (membrane type); high cost ($5-10K/session); limited access (20%-40% low-resource centres)[16,18,34,38,40,45] | Bleeding (22%), infections (15%), citrate toxicity (12%); slower for protein-bound toxins; circuit clotting (10%-20%); rebound ammonia risk (SLED 10%-15%)[64,65,71-73,82] | Fluid load increasing 10%-15% (combined), citrate accumulation increasing 12% (liver impairment), complexity/cost increasing 50%; hemodynamic dips (MAP decreasing 5-10 mmHg in 10% combined); infection increasing 8% if prolonged (> 7 days). Sequential mitigates (complications decreasing 5%-10%)[62,72,75,76] |
| Monitoring | Daily: INR, bilirubin, ammonia, cytokines (IL-6/TNF-α), neuro status (West Haven); biomarkers (NGAL for AKI); adjust per MELD/HE trends[16,18,34,38,40,45] | q4-6 hours: Ammonia, electrolytes, Ca2+ circuit pressures; NGAL/IL-6 for progression; hemodynamics/fluid balance[71-73] | Hybrid model: TPE: Same as TPE column + hourly ionised Ca2+, CRRT (or simultaneous): Same as the CRRT column, additional daily: Total bilirubin, INR, ammonia, lactate, SOFA/CLIF-SOFA citrate monitoring intensified: Post-filter iCa 0.25-0.35 mmol/L, systemic iCa 1.0-1.3 mmol/L, total/iCa ratio < 2.5; q12 hours neuro checks if HE present, NGAL/cystatin C q24 hours for early AKI recovery[62,72,75-77] |
| Survival benefit | ALF: Improve TFS by 10%-25% at 21-90 days compared with standard medical therapy alone[16,17,18,34]. Swaroop et al[38] in 2026 pilot RCT in ALF: No overall 30-day survival benefit (65% mortality in both arms, P = 1.0). ACLF: Significant reduction in mortality at 30 days (RR: 0.70; 95%CI: 0.60-0.81; P < 0.001) and at 90 days (RR: 0.81; 95%CI: 0.77-0.86; P < 0.001)[40]. Six studies (1495 patients; 2 RCTs) with data for 1-year survival showed better outcomes in the PLEX group (RR: 0.85; 95%CI: 0.79-0.92; P < 0.0001) compared to SMT[40] | ALF: A single systematic review to date shows: CRRT improve TFS (RR: 0.73, 95%CI: 0.57-0.94, P = 001, I2 = 54.74%)[64] may improve overall survival (RR: 0.83, 95%CI: 0.73-0.93, P < 0.001, I2 = 18.77%)[64]. However, most studies are limited by serious confounding and overall bias[64]. ACLF: 90-day TFS ranges from 6% to 23%; hospital mortality: 80%-90%. Non-transplant patients exhibit mortality of 90%-94% with intervention[71-74] | ALF: TPE + CRRT (mostly sequential/tandem) markedly improves transplant-free survival in pediatric ALF (44%-83%) vs single modality (approximately 30%-60%), with rapid ammonia clearance and HE resolution. In adults, however, adding TPE to CRRT shows no benefit and may even worsen outcomes post-transplant[62,75-79]. ACLF: Modest short-term survival gain (48%-65% at 28-90 days) over single therapy, mainly in HBV-related ACLF, with better MELD/SOFA reduction and sepsis control. In non-HBV and general ACLF-AKI cohorts, combined therapy is equivalent or inferior to TPE or CRRT alone, providing no consistent added survival advantage[42,72,75,80,81] |
- Citation: Manrai M, Pachisia AV, Dawra S, Shukla S, Jha AA. Navigating the therapeutic tightrope: Precision use of plasmapheresis and continuous renal replacement therapy in liver failure. World J Hepatol 2026; 18(5): 115047
- URL: https://www.wjgnet.com/1948-5182/full/v18/i5/115047.htm
- DOI: https://dx.doi.org/10.4254/wjh.v18.i5.115047