What is the role of Continuous Renal Replacement Therapy (CRRT) and Plasma Exchange (PLEx) in managing acute liver cell failure?

Role of CRRT and PLEx in Acute Liver Cell Failure

Continuous Renal Replacement Therapy (CRRT) and Plasma Exchange (PLEx) serve as crucial bridge therapies in acute liver failure, providing temporary support until liver transplantation or native liver recovery occurs, with recent evidence showing improved survival rates of up to 83% when used in combination.

CRRT in Acute Liver Failure

Indications for CRRT

• CRRT should be considered in acute liver failure patients with acute kidney injury (AKI), regardless of the type of kidney injury 1
• CRRT is particularly indicated in patients with severe and/or refractory electrolyte or acid-base imbalances, volume overload, and symptomatic azotemia 1
• CRRT should be initiated in patients with hyperammonemia and/or hepatic encephalopathy, as it effectively reduces ammonia levels 2, 3

Benefits of CRRT in Liver Failure

• CRRT provides better hemodynamic stability compared to intermittent hemodialysis in critically ill patients with liver failure, who are often hemodynamically unstable 1
• CRRT allows for slower correction of severe or refractory hyponatremia than hemodialysis, reducing neurological complications 1
• CRRT facilitates management of fluid balance in hemodynamically unstable patients with liver failure 1
• CRRT removes water-soluble toxins (particularly ammonia) that accumulate in liver failure, potentially improving encephalopathy 4, 3

Technical Considerations

• A typical dose for CRRT in liver failure would be 20-25 mL/kg/hr of effluent generation 1
• CRRT causes significant loss of water-soluble nutrients (approximately 10-15g amino acids/day) and electrolytes, requiring careful monitoring and replacement 1
• Continuous venovenous hemofiltration (CVVH) and venovenous hemodiafiltration (CVVHD-F) are preferred modalities in critically ill patients with acute liver failure 1

Plasma Exchange (PLEx) in Acute Liver Failure

Indications for PLEx

• PLEx should be initiated for refractory coagulopathy in acute liver failure patients 2, 3
• PLEx is particularly beneficial for removing damage-associated molecular patterns (DAMPs) released from necrotic liver cells, which cause systemic inflammation resembling septic shock 3

Combined Approach of CRRT and PLEx

• The combination of CRRT and PLEx is rational and effective for simultaneously removing ammonia and inflammatory molecules in acute liver failure 3
• This combined approach improves survival for acute liver failure patients deemed not appropriate for liver transplantation despite poor prognostic criteria 3
• The combined therapy helps maintain stability of vital organs while awaiting liver transplantation 3

Prognostic Considerations

Mortality Risk Assessment

• Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure (CLIF)-SOFA scores perform better than liver-specific scores (Child-Pugh-Turcotte and MELD) in predicting mortality in patients requiring CRRT (AUROC 0.87 vs 0.67) 5
• Patients with acute-on-chronic liver failure (ACLF) and comorbidities have worse outcomes compared to those with acute liver failure alone 2, 5
• Despite extracorporeal support with CRRT, critically ill patients with ACLF and AKI have poor hospital survival (reported mortality rates up to 89.4%) 5

Liver Support Systems and Transplantation

Artificial Liver Support Systems

• Molecular adsorbents recirculating system (MARS) and Prometheus have shown promising beneficial effects in patients with hepatorenal syndrome but require further investigation 1
• The combination of CRRT with albumin dialysis tends to have similar effects as CRRT with plasma exchange 3

Liver Transplantation Considerations

• Liver transplantation remains the best therapeutic option for patients with hepatorenal syndrome 1
• CRRT and PLEx serve as bridge therapies to liver transplantation, with recent data showing survival rates approaching 90% post-transplantation 3
• For patients who receive liver transplantation or recover native liver function after CRRT and PLEx support, survival rates of up to 83% have been reported 2

Clinical Pitfalls and Considerations

• Avoid delaying CRRT initiation in acute liver failure patients with AKI, as early RRT may improve survival 1
• Be cautious with regional citrate anticoagulation in liver failure patients; while not absolutely contraindicated, it requires careful monitoring of ionized calcium levels and total calcium to ionized calcium ratio 1
• Monitor for significant nutrient losses during CRRT, particularly amino acids, water-soluble vitamins, and electrolytes (phosphate, magnesium) 1
• Recognize that CRRT alone may not be sufficient for complete liver support; consider combination with PLEx for optimal management 3
• Despite poor prognosis in some cases, do not limit CRRT and ICU treatment only to liver transplant candidates; base decisions on individual severity of illness, using prognostic scores, clinical judgment, and patient preferences 1