What are the treatment options for pediatric liver failure, including artificial liver support systems like Molecular Adsorbent Recirculating System (MARS) or Prometheus?

Pediatric Artificial Liver Support Systems in Children with Liver Failure

Extracorporeal artificial liver support systems should only be used within the context of clinical trials in pediatric liver failure, as current evidence does not demonstrate significant survival benefit.

Current Treatment Options for Pediatric Liver Failure

Primary Management Approaches

• Urgent liver transplantation remains the definitive treatment for pediatric acute liver failure when prognostic indicators suggest a high likelihood of death 1
• N-acetylcysteine is strongly recommended for acetaminophen-induced acute liver failure 1
• For non-acetaminophen acute liver failure, N-acetylcysteine should only be used in clinical trial settings 1

Artificial Liver Support Systems

Available Systems

• Molecular Adsorbent Recirculating System (MARS)
• Fractionated Plasma Separation and Adsorption (Prometheus)
• Single-Pass Albumin Dialysis (SPAD)
• Plasma exchange combined with hemodialysis (PE/HD) 2

Evidence for Artificial Liver Support

• Multiple systematic reviews have assessed artificial liver support systems for acute liver failure and reported no clear effect on mortality 1
• Seven randomized controlled trials involving 415 patients with acute liver failure showed no significant improvement in survival with artificial liver support systems 1
• Large RCTs evaluating albumin dialysis (MARS) in Acute-on-Chronic Liver Failure have not demonstrated significant effects on survival 1, 3

MARS in Pediatric Patients

• MARS combines albumin dialysis with conventional hemodialysis to remove water and protein-bound toxins 2
• Limited pediatric data suggests MARS may temporarily improve clinical status in children awaiting liver transplantation 4
• However, comparative studies suggest that combined plasma exchange and hemodialysis (PE/HD) may be more effective than MARS for treating pediatric acute liver failure 5
• PE/HD demonstrated superior reduction of serum bilirubin (37% vs 2%), ammonia (39% vs 18%), and improved coagulation parameters compared to MARS in pediatric patients 5

Specific Clinical Scenarios

Wilson's Disease with Acute Liver Failure

• Liver transplantation is life-saving and required for patients with acute liver failure due to Wilson's disease 1
• MARS may be used along with plasmapheresis and hemofiltration to stabilize patients and delay, but not eliminate, the need for transplantation 1, 3
• Albumin dialysis has been shown to temporarily stabilize patients with acute liver failure due to Wilson's disease 1

Contraindications for Liver Transplantation

• Hemophagocytic lymphohistiocytosis (HLH) presenting as acute liver failure should be recognized, as chemotherapy and bone marrow transplantation are more appropriate treatments 1
• Liver transplantation is contraindicated in Niemann-Pick disease type C as it does not alter neurological disease progression 1

Clinical Considerations for Artificial Liver Support

Benefits vs. Risks

• Potential benefits include:

  • Bridge to transplantation or recovery 1
  • Temporary improvement in hepatic encephalopathy 2, 6
  • Reduction of protein-bound toxins 2

• Potential risks include:

  • Significant resource utilization and high costs 1
  • Potential toxicities including coagulation abnormalities 1
  • Volume and nitrogen overload if repeated plasma infusion is required 2

Practical Recommendations

• In cases of active bleeding, plasma exchange in combination with hemodialysis should be preferred over MARS 2
• For children with intractable cholestatic pruritus, MARS has been successfully applied but must be balanced against costs and risks 2
• Standard adult MARS sets can be used for children weighing >23 kg, while MARS Mini is available for smaller children (2.8-13 kg) 5

Future Directions

• Bioartificial systems that incorporate hepatocytes may address regulation and synthesis functions but still face developmental problems and high production costs 6
• A post-hoc analysis of the Prometheus study showed potential benefit in patients with MELD scores >30, which warrants further investigation 1, 3
• More pediatric-specific research is needed, as most evidence comes from adult studies 2, 6