What are the current guidelines for managing Continuous Renal Replacement Therapy (CRRT) in Acute-on-Chronic Liver Failure (ACLF)?

Current Guidelines for CRRT Management in ACLF

Patients with ACLF who have urgent indications for CRRT should receive early initiation of therapy, specifically for persistent hyperammonemia, hyperkalemia, and other metabolic abnormalities. 1

Indications for CRRT Initiation

Early CRRT initiation is recommended as an urgent indication in ACLF patients presenting with:

• Persistent hyperammonemia that is refractory to medical management 1
• Hyperkalemia requiring urgent correction 1
• Other metabolic abnormalities including severe acidosis or electrolyte derangements 1
• Acute kidney injury meeting criteria for renal replacement therapy 1

The 2024 guidelines emphasize that timing is critical—CRRT should be initiated early when these urgent indications are present, rather than waiting for further deterioration 1. Recent meta-analysis data supports this approach, demonstrating that CRRT use in ALF/ACLF patients is associated with improved overall survival (RR 0.83,95% CI 0.70-0.99) and improved transplant-free survival (RR 0.65,95% CI 0.49-0.85) 2.

Setting and Monitoring Requirements

• ACLF patients requiring CRRT must be managed in intermediate care or intensive care settings with frequent monitoring of organ function 1
• Continuous monitoring should include: liver function, kidney function, brain function, lung function, coagulation status, and circulatory parameters 1
• Organ function assessment should occur frequently throughout hospitalization as ACLF is a dynamic condition with potential for rapid deterioration 1

Anticoagulation Considerations

Regional citrate anticoagulation (RCA) should be used with extreme caution in ACLF patients:

• Citrate clearance is significantly decreased in critically ill ALF and ACLF patients, creating substantial risk for citrate toxicity 3
• ACLF patients demonstrated citrate toxicity during standard citrate infusion (3 mmol/L dose) in clinical studies 3
• Alternative anticoagulation strategies (prostacyclin or no anticoagulation) may be preferable given the already deranged coagulation in liver failure 4

This is a critical safety consideration that differs from standard CRRT practice in other patient populations. The impaired citrate metabolism in liver failure creates a unique risk profile 3.

Circuit Management Challenges

CRRT circuits paradoxically clot in ACLF patients despite coagulopathy:

• Fresh frozen plasma (FFP) use is significantly associated with circuit blockade and should be minimized when possible 4
• Circuit changes occur frequently for reasons beyond clotting, including access catheter issues 4
• Expect mean circuit life of approximately 33 hours in pediatric liver failure patients, likely similar in adults 4

Dosing Considerations

Higher dialysis doses appear beneficial for survival outcomes:

• Continuous veno-venous hemodiafiltration (CVVHDF) with added dialysate (1-1.5 L/h) plus replacement fluid (1-2.5 L/h) demonstrates superior survival compared to hemofiltration alone 5
• Increasing dialysis dose for low molecular weight solutes (including ammonia) confers better survival in critically ill patients with acute renal failure 5

Integration with Overall ACLF Management

CRRT must be coordinated with other critical interventions:

• Early identification and treatment of precipitating factors (particularly bacterial infections) remains essential even when CRRT is initiated 1, 6
• Antiviral therapy with nucleoside analogues (tenofovir, entecavir) should be started immediately in HBV-related ACLF 1
• Early referral to liver transplant centers for immediate evaluation is mandatory for all ACLF patients requiring CRRT 1
• Terlipressin combined with albumin should be used for hepatorenal syndrome management 1

Futility Considerations

Withdrawal of intensive care support including CRRT can be considered in:

• Patients with ≥4 organ failures after one week of adequate intensive treatment who are not liver transplant candidates 1
• Patients with CLIF-C ACLF score >64 at days 3-7 after ACLF-3 diagnosis if transplant is contraindicated or unavailable 1

Key Caveats

The evidence base for CRRT in ACLF has important limitations. Most studies combine ALF and ACLF populations, and the optimal timing, dose, and duration remain incompletely defined 7. The 2018 EASL guidelines note that extracorporeal liver support systems (MARS, Prometheus) do not improve survival and should not be routinely used 1, though this differs from plasma exchange which shows promise as a bridging therapy 1, 6.

The primary goal of CRRT in ACLF is bridging to either liver transplantation or spontaneous liver regeneration, not definitive treatment of the underlying liver failure 1.