What is the role of plasma exchange (plex) in the management of acute on chronic liver failure (ACLF)?

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

Plasma exchange (PLEX) should be considered as a therapeutic option in patients with acute-on-chronic liver failure (ACLF) who have hyperammonemia, as it may improve survival outcomes when standard medical therapy is insufficient. 1

Understanding ACLF and the Rationale for PLEX

ACLF is characterized by:

• Acute onset with rapid deterioration in clinical condition
• Presence of liver failure (elevated bilirubin and INR)
• At least one extrahepatic organ failure (neurologic, circulatory, respiratory, or renal) 1

The pathophysiology of ACLF involves:

• Systemic inflammation
• Accumulation of toxins
• Multiple organ dysfunction
• High short-term mortality (30-50% at 28 days)

Evidence Supporting PLEX in ACLF

The most recent evidence strongly supports PLEX as an effective intervention:

• The 2023 Critical Care Medicine guidelines suggest using plasma exchange in critically ill ALF patients who develop hyperammonemia (conditional recommendation, low-quality evidence) 1

• A 2025 meta-analysis of 23 studies (5,336 ACLF patients) demonstrated:

  • Significant reduction in mortality at 30 days (RR 0.70; 95% CI, 0.60-0.81)
  • Improved survival at 90 days (RR 0.81; 95% CI, 0.77-0.86)
  • Better 1-year outcomes (RR 0.85; 95% CI, 0.79-0.92)
  • Benefits across different etiologies (HBV-related and alcohol-related ACLF) 2

Clinical Application of PLEX in ACLF

Indications for PLEX

• Hyperammonemia not responding to standard medical therapy
• Hepatic encephalopathy
• Refractory coagulopathy
• Patients who are not immediate candidates for liver transplantation

Timing and Protocol

• Consider early initiation (within 2-3 days of ICU admission)
• Standard volume plasma exchange is typically used
• Multiple sessions may be required (average 3-4 procedures per patient) 3

Expected Benefits

• Reduction in serum bilirubin, ammonia, and coagulation parameters
• Improvement in clinical severity scores (ACLF Research Consortium score, MELD)
• Potential bridge to recovery or transplantation 3

Limitations and Considerations

• Safety profile: Generally well-tolerated with minimal adverse events (skin rash and allergic reactions reported in approximately 14% of cases) 2

• Bridge to transplant vs. bridge to recovery:

  • More effective as a bridge to transplantation
  • Limited efficacy as a standalone bridge to recovery in severe cases 4

• Patient selection is crucial:

  • Most beneficial in moderate severity ACLF (Grade II)
  • Less effective in patients with multiple comorbidities 5

Integration with Other Management Strategies

PLEX should be considered within a comprehensive management approach that includes:

1. Early identification and treatment of precipitating factors
2. Organ support (hemodynamic, respiratory, renal)
3. Management of hepatic encephalopathy with lactulose/rifaximin
4. Consideration for liver transplantation in appropriate candidates
5. Palliative care consultation for all ACLF patients 6

Algorithm for PLEX Implementation in ACLF

1. Assessment:

   • Confirm ACLF diagnosis
   • Evaluate severity (CLIF-C ACLF score)
   • Assess transplant candidacy

2. Consider PLEX when:

   • Hyperammonemia persists despite standard therapy
   • Hepatic encephalopathy grade 3-4
   • Refractory coagulopathy
   • Patient is awaiting transplant evaluation

3. Protocol:

   • Standard volume plasma exchange
   • Monitor ammonia levels, coagulation parameters, and clinical response
   • Reassess after 2-3 sessions

4. Decision point:

   • If clinical improvement: continue supportive care
   • If transplant candidate with stabilization: bridge to transplant
   • If no response and not a transplant candidate: consider palliative approach

Conclusion

While PLEX shows promise in improving survival in ACLF patients, it should be viewed as part of a comprehensive management strategy rather than a definitive treatment. The decision to implement PLEX should consider the patient's clinical status, transplant candidacy, and goals of care.