What is the evidence for using plasmapheresis (plasma exchange) in patients with Acute Liver Failure (ALF)?

Evidence for Plasmapheresis in Acute Liver Failure

Primary Recommendation

Plasmapheresis should be used specifically for Wilson disease-related acute liver failure as a bridge to transplantation, but is NOT recommended for routine use in other causes of ALF based on current guideline consensus. 1

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Guideline-Based Framework

When Plasmapheresis IS Indicated

Wilson Disease-Related ALF:

• The AASLD explicitly recommends plasmapheresis (or plasma exchange) as part of the treatment strategy to acutely lower serum copper and limit hemolysis in Wilson disease-related ALF while awaiting liver transplantation 1
• Alternative acceptable options include albumin dialysis, continuous hemofiltration, or plasma exchange 1
• Wilson disease-related ALF is considered uniformly fatal without transplantation 1

When Plasmapheresis is NOT Recommended

General ALF Management:

• The 2017 AGA guidelines make no recommendation for extracorporeal artificial liver support systems (including plasmapheresis) in general ALF, stating they should only be used within clinical trials 2
• Two well-designed RCTs including 115 patients with ALF failed to demonstrate significant mortality reduction with liver support systems (pooled RR = 0.82; 95% CI 0.42–1.59) 2
• The place of liver support systems in ALF management needs better definition, and these techniques should not delay transfer to a liver transplantation center 2

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Critical Distinction: ALF vs ACLF

Important caveat: The evidence you may encounter regarding plasmapheresis benefits often pertains to acute-on-chronic liver failure (ACLF), not acute liver failure (ALF) 3, 4:

• EASL and AASLD recommend against routine plasma exchange for ACLF outside research trials 3, 4
• AASLD suggests plasma exchange only for ALF with hyperammonemia (ammonia >150 μmol/L), though this is a conditional recommendation based on low-quality evidence 3, 4

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Emerging Research Evidence (Not Yet Guideline-Supported)

While guidelines do not support routine use, recent observational studies show potential benefits:

High-Volume Plasma Exchange (HVPE) Studies

Definition: HVPE involves exchange of 8-12 L per day or 15% of ideal body weight with fresh frozen plasma 5, 6, 7

Observed Benefits in Research:

• A 2021 retrospective study of 32 ALF patients showed HVPE improved coagulopathy (INR decreased from 4.46 to 1.48), total bilirubin, ALT, and ammonia levels 5
• Among patients with high CLIF-SOFA scores (≥13), 30-day survival was significantly better with HVPE (91% vs 29%, P < 0.05) 5
• Overall survival was 94% at 30 days in HVPE patients versus 69% in non-HVPE patients (P = 0.068) 5

Low-Volume TPE:

• A 2019 study showed low-volume TPE improved mean arterial pressure, reduced vasopressor requirements, and decreased multi-organ dysfunction (CLIF-SOFA score improved from 17 to 7) 8
• 30-day survival was 65% with LV-TPE versus 50% with standard medical therapy alone (not statistically significant) 8

Pediatric Experience:

• A 2001 study of 49 children with ALF showed TPE effectively prevented bleeding complications and maintained euvolemia, but had no effect on neurologic complications or liver regeneration 9
• Three patients recovered spontaneously, 32 underwent transplantation, and 14 were not transplant candidates 9

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Practical Algorithm for Decision-Making

Step 1: Determine Etiology

• If Wilson disease: Use plasmapheresis as bridge to transplantation 1
• If other etiology: Proceed to Step 2

Step 2: Assess Transplant Status

• If NOT a transplant candidate: Standard medical therapy only; plasmapheresis not indicated per guidelines 2
• If transplant candidate: Proceed to Step 3

Step 3: Consider Research Protocol

• If available research protocol AND center with expertise: May consider HVPE as investigational bridge to transplantation 5, 6, 7
• If no research protocol: Standard medical therapy and expedite transplant evaluation 2

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Common Pitfalls and Caveats

Do Not Delay Transplant Evaluation:

• Any consideration of plasmapheresis should not delay transfer to a liver transplantation center 2
• The "transplantation window" is often narrow in ALF 1

Monitoring Requirements:

• If plasmapheresis is used in Wilson disease, carefully monitor for HCV/HBV infection evolution, particularly when combined with immunosuppressants 1

Coagulation Management:

• Fresh frozen plasma should be reserved for active bleeding or invasive procedures, not given prophylactically 2
• Prophylactic coagulation factor administration precludes assessment of natural disease evolution 2

No Impact on Encephalopathy:

• Plasmapheresis has not been shown to improve neurologic complications of liver failure 9
• Do not use plasmapheresis as treatment for hepatic encephalopathy 9

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Standard Medical Therapy Priorities

While plasmapheresis remains investigational for most ALF cases, focus on proven interventions:

Hemodynamic Support:

• Maintain mean arterial pressure ≥50-60 mm Hg with fluid resuscitation (prefer albumin over crystalloid) 1
• Use vasopressors (epinephrine, norepinephrine, or dopamine—NOT vasopressin) if fluids fail 1

Metabolic Management:

• Monitor glucose every 2 hours and manage hypoglycemia with continuous glucose infusions 2, 1
• Maintain serum sodium at 140-145 mmol/L 1

Renal Support:

• Use continuous renal replacement therapy rather than intermittent hemodialysis if dialysis needed 2, 1

Infection Prevention:

• Provide stress ulcer prophylaxis with H2 blockers or proton pump inhibitors 2, 1
• Screen aggressively for infections and treat early 1