How does plasma exchange (PLEX) help in acute liver failure?

How Plasma Exchange (PLEX) Helps in Acute Liver Failure

Direct Answer

Plasma exchange improves transplant-free survival in acute liver failure by removing toxic substances, inflammatory mediators, and damage-associated molecular patterns while simultaneously replacing deficient coagulation factors and synthetic proteins, thereby attenuating systemic inflammation and preventing multi-organ failure. 1, 2, 3

Primary Mechanisms of Benefit

Removal of Toxic Substances

• PLEX removes the entire plasma volume, including ammonia, inflammatory cytokines (TNF-α, IL-6, IL-8), damage-associated molecular patterns (DAMPs), and endotoxin that accumulate in liver failure 4, 5
• This complete plasma removal distinguishes PLEX from other artificial liver support systems that only perform dialysis-based corrections 4
• The removal of inflammatory cytokines and DAMPs modulates early innate immunity and restores monocyte phagocytic function 3, 5

Replacement of Essential Functions

• Fresh frozen plasma replacement provides coagulation factors, albumin, and other synthetic proteins that the failing liver cannot produce 4
• This replacement fulfills metabolic, detoxification, and synthetic functions of the liver 4
• PLEX increases anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1RA) in responders 5

Evidence-Based Indications

Hyperammonemia (Primary Indication)

• The American College of Critical Care Medicine conditionally recommends PLEX for acute liver failure patients with ammonia levels >150 μmol/L 1
• Hyperammonemia independently predicts intracranial hypertension and hepatic encephalopathy, with 55% of patients developing intracranial hypertension when ammonia exceeds 200 μmol/L 1
• Acute liver failure patients are more vulnerable to cerebral edema from hyperammonemia compared to acute-on-chronic liver failure patients 1

Wilson Disease (Immediate Indication)

• The American Association for the Study of Liver Diseases recommends initiating PLEX immediately in Wilson disease-related acute liver failure as a bridge to transplantation 1, 2
• Wilson disease-related acute liver failure is uniformly fatal without transplantation 1, 2
• PLEX protects kidneys from copper-mediated tubular damage while awaiting transplantation 2

Acute Fatty Liver of Pregnancy

• PLEX should be considered in acute fatty liver of pregnancy, though expeditious delivery remains the primary treatment 1

Survival Benefit Data

Transplant-Free Survival

• High-volume plasma exchange (8-12 or 15% of ideal body weight) improves overall hospital survival to 58.7% versus 47.8% in controls (HR 0.56; 95% CI 0.36-0.86; p=0.0083) 3
• This survival benefit is attributable to attenuation of innate immune activation and amelioration of multi-organ dysfunction 3
• PLEX is the only artificial liver support device that improves survival in acute liver failure patients 4

Prevention of Multi-Organ Failure

• PLEX significantly reduces systemic inflammatory response syndrome (SIRS) scores and sequential organ failure assessment (SOFA) scores compared to standard medical therapy (p<0.001) 3
• PLEX lowers and delays the development of multi-organ failure (HR 7.1,4.5-11.1) 5
• Resolution of SIRS occurs more frequently with PLEX (OR 9.23,3.42-24.8) 5

Clinical Algorithm for Implementation

Step 1: Identify Candidates

• Measure ammonia levels in all acute liver failure patients; consider PLEX if >150 μmol/L 1
• Initiate PLEX immediately for Wilson disease regardless of ammonia level 1, 2
• Consider PLEX for acute fatty liver of pregnancy after arranging expeditious delivery 1

Step 2: Protocol Selection

• Use high-volume plasma exchange: 8-12 or 15% of ideal body weight with fresh frozen plasma 3
• Perform PLEX for three consecutive days as the standard protocol 3
• Consider combining PLEX with continuous hemodiafiltration (CHDF) in parallel circuit to suppress citrate toxicity and enhance inflammatory cytokine removal 6

Step 3: Bridge to Definitive Therapy

• Simultaneously list appropriate candidates for liver transplantation, as PLEX is bridge therapy, not definitive treatment 1, 2
• PLEX stabilizes patients and delays, though does not eliminate, the need for transplantation 2
• PLEX prior to transplantation does not improve post-transplant survival compared to standard medical therapy alone (CI 0.37 to 3.98; p=0.75) 3

Step 4: Monitor Response

• Track SIRS and SOFA scores to assess treatment response 3
• Monitor for improvement in monocyte phagocytic function and mitochondrial respiration in responders 5
• Watch for citrate toxicity, particularly if not using combined CHDF 6

Important Caveats and Pitfalls

Evidence Quality Limitations

• The guideline recommendation is conditional with low-quality evidence, meaning clinical circumstances and resource availability should heavily influence the decision 1
• The incidence of severe adverse events is similar between PLEX and standard medical therapy groups 3

Technical Considerations

• PLEX is readily available in intensive care units, dialysis units, or blood banks 4
• Combining PLEX with CHDF in parallel circuit effectively suppresses blood citrate elevation and removes inflammatory cytokines more completely than PLEX alone 6
• Citrate levels increase significantly after PLEX treatment, but the increase is lower when combined with CHDF 6

What NOT to Use

• Traditional therapies for chronic liver failure, such as lactulose and rifaximin, have not demonstrated benefit in acute liver failure and should not be relied upon 1
• Penicillamine is not recommended in acute liver failure due to risk of hypersensitivity 2
• Other artificial liver support systems like Fractional Plasma Separation and Adsorption (FPSA) show inferior outcomes compared to PLEX 5