What is the role of Plasma Exchange (PLEX) in treating Acute-on-Chronic Liver Failure (ACLF)?

Role of Plasma Exchange (PLEX) in Acute-on-Chronic Liver Failure (ACLF)

Plasma exchange (PLEX) may be considered for selected patients with ACLF, particularly those with high risk of end-stage kidney disease (ESKD) and those who are not liver transplant candidates or as a bridge to transplantation. 1, 2, 3

Definition and Context of ACLF

ACLF is characterized by:

• Acute onset with rapid deterioration in clinical condition
• Presence of liver failure (elevated bilirubin and INR) in patients with chronic liver disease with/without cirrhosis
• At least one extrahepatic organ failure (neurologic, circulatory, respiratory, or renal) 1

Current Guidelines on PLEX in ACLF

There are conflicting recommendations regarding PLEX in ACLF:

• Asian Pacific Association for the Study of the Liver (APASL) and Chinese guidelines support PLEX as a promising treatment for ACLF patients awaiting liver transplants or experiencing spontaneous regeneration 1

• European Association for the Study of the Liver (EASL) advises against routine use of PLEX for ACLF outside of research trials 1

• American Association for the Study of Liver Diseases (AASLD) suggests using plasma exchange in critically ill ALF patients who develop hyperammonemia (conditional recommendation, low quality evidence), but does not make specific recommendations for ACLF 1

Evidence Supporting PLEX in ACLF

Recent meta-analyses show promising results:

• A 2025 meta-analysis including 23 studies (5,336 ACLF patients) demonstrated that PLEX was associated with:

  • Significant reduction in mortality at 30 days (RR 0.70; 95% CI, 0.60-0.81)
  • Improved survival at 90 days (RR 0.81; 0.77-0.86)
  • Better 1-year survival (RR 0.85; 0.79-0.92) 2

• A 2024 meta-analysis of 20 studies (5,705 ACLF patients) showed:

  • Higher 30-day survival with PLEX (RR 1.36; 95% CI 1.22-1.52)
  • Higher 90-day survival with PLEX (RR 1.21; 95% CI 1.10-1.34) 3

• A 2021 propensity-score matched study showed PLEX:

  • Improved resolution of systemic inflammatory response syndrome
  • Lowered and delayed development of multiorgan failure
  • Reduced liver-failure-related deaths compared to standard medical therapy
  • Cleared inflammatory cytokines and improved monocyte function 4

Mechanism of Action

PLEX appears to work by:

• Clearing inflammatory cytokines, damage-associated molecular patterns, and endotoxins
• Improving monocyte phagocytic function and mitochondrial respiration
• Increasing anti-inflammatory cytokines 4

Patient Selection for PLEX

PLEX may be most beneficial for:

• Patients with HBV-related ACLF (RR 0.79; 0.74-0.85 for 90-day mortality reduction) 2
• Patients with alcohol-related ACLF (RR 0.69; 0.52-0.92 for 90-day mortality reduction) 2
• Patients who are not liver transplant candidates 3
• Patients as a bridge to liver transplantation 3

Safety Profile

• Most common adverse effects: skin rash and allergic reactions (14%) 2
• PLEX is associated with fewer adverse effects compared to Fractional Plasma Separation and Adsorption (FPSA) 4

Limitations and Considerations

• Subgroup analysis of randomized controlled trials shows inconsistent results in ACLF 3
• The optimal timing, frequency, and volume of plasma exchange remain unclear 5
• PLEX should be considered within the broader context of ACLF management, including:
  • Early identification and treatment of precipitating factors (especially bacterial infections)
  • Organ support
  • Consideration for liver transplantation in eligible patients 1

Practical Approach to PLEX in ACLF

1. Consider PLEX for:

   • Patients with ACLF who are not immediate transplant candidates 3
   • Patients awaiting liver transplantation as a bridge therapy 3
   • Patients with HBV or alcohol-related ACLF 2

2. Monitor for:

   • Allergic reactions and skin rash during treatment 2
   • Improvement in organ function and inflammatory markers 4

3. Integrate with standard care:

   • Continue standard medical therapy including management of precipitating factors 1
   • Provide appropriate organ support 1
   • Early referral to liver transplant centers for evaluation 1

While more high-quality randomized controlled trials are needed to definitively establish the role of PLEX in ACLF, current evidence suggests it may improve survival in selected patients with ACLF, particularly those with specific etiologies and those awaiting liver transplantation.