What is the preferred treatment between Continuous Renal Replacement Therapy (CRRT) and Plasma Exchange (PLEX) in patients with Acute-on-Chronic Liver Failure (ACLF)?

CRRT vs PLEX in Acute-on-Chronic Liver Failure

Plasma exchange (PLEX) appears to be a more promising and effective therapy for patients with ACLF compared to continuous renal replacement therapy (CRRT), particularly for improving survival outcomes when initiated early in the course of disease. 1

Indications and Evidence-Based Approach

PLEX in ACLF

• PLEX has demonstrated significant survival benefits in ACLF patients:

  • Associated with 30% reduction in 30-day mortality (RR 0.70) 2
  • Improved 90-day survival (RR 0.81) 2
  • Better 1-year outcomes (RR 0.85) 2
  • Effective across different ACLF etiologies including HBV-related and alcohol-related ACLF 2

• Mechanistic benefits of PLEX:

  • Significantly improves systemic inflammation 3
  • Resolves systemic inflammatory response syndrome (SIRS) (Odds ratio 9.23) 3
  • Reduces development of multiorgan failure (MOF) (Hazard ratio 7.1) 3
  • Clears inflammatory cytokines, damage-associated molecular patterns, and endotoxins 3

CRRT in ACLF

• CRRT is primarily indicated for:

  • Persistent hyperammonemia 1
  • Hyperkalemia and other metabolic abnormalities 1
  • Renal failure management in ACLF 1

• CRRT outcomes are less favorable:

  • High mortality rates (89.4% in one study) despite CRRT support 4
  • Limited effectiveness as a standalone therapy 1

Decision Algorithm for ACLF Management

1. Initial Assessment

   • Confirm ACLF diagnosis
   • Evaluate severity using CLIF-SOFA or SOFA scores (better predictors than MELD/CPT) 4
   • Identify and treat precipitating factors (especially infections) 1
   • Assess transplant candidacy

2. First-Line Therapy

   • For ACLF with predominant hyperammonemia and hepatic encephalopathy:

     • Choose PLEX as primary extracorporeal support 1, 5, 2
     • Initiate early (within 2-3 days of ICU admission) 5
     • Standard volume plasma exchange with multiple sessions (3-4 procedures) 5

   • For ACLF with predominant renal failure (HRS-AKI):

     • First try vasoconstrictors (terlipressin or norepinephrine) with albumin 1
     • If no response, then consider CRRT 1

3. Special Considerations

   • For transplant candidates: Both PLEX and CRRT can serve as bridge to transplantation 6
   • For HBV-related ACLF: PLEX shows significant mortality reduction (RR 0.79) 2
   • For alcohol-related ACLF: PLEX demonstrates improved survival (RR 0.69) 2

Practical Implementation

• PLEX Protocol:

  • Most beneficial in moderate severity ACLF (Grade II) 5
  • Monitor for common adverse effects: skin rash and allergic reactions (14% of cases) 2
  • Consider discontinuation if no improvement after 3-4 sessions

• CRRT Protocol:

  • Preferred in hemodynamically unstable patients 1
  • Continuous RRT is preferable to intermittent RRT 1
  • Not recommended as stand-alone therapy unless patient is transplant candidate 1

Caveats and Pitfalls

1. Avoid delayed initiation of extracorporeal therapies - early intervention with PLEX shows better outcomes 5, 3

2. Don't rely solely on CRRT for non-transplant candidates with ACLF - high mortality rates despite therapy 4

3. Recognize futility - consider withdrawal of intensive care support in non-transplant candidates with ≥4 organ failures after one week of adequate treatment 1

4. Don't overlook transplant evaluation - early referral to transplant centers is critical for ACLF patients 1

5. Consider combination approaches - some patients may benefit from both PLEX and CRRT, particularly those with multiple organ dysfunction 6

In conclusion, while both PLEX and CRRT have roles in ACLF management, current evidence suggests PLEX offers superior survival outcomes and should be prioritized when available, particularly for patients with systemic inflammation and those who are candidates for liver transplantation.