What is the role of Molecular Adsorbent Recirculating System (MARS) in managing hepatic encephalopathy?

Role of MARS in Hepatic Encephalopathy

MARS (Molecular Adsorbent Recirculating System) therapy shows significant improvement in hepatic encephalopathy symptoms but does not improve overall survival in patients with liver failure, making it primarily useful as a bridge therapy rather than a definitive treatment. 1

Mechanism and Clinical Effects

• MARS functions as an albumin dialysis system that selectively removes both protein-bound and water-soluble toxins from the patient's blood, enabling regeneration of the patient's albumin and increasing albumin binding capacity 2

• Post-hoc analysis of randomized European studies demonstrated significant improvement in hepatic encephalopathy when using albumin dialysis with MARS versus standard medical therapy 1

• MARS therapy also shows improvement in hepatorenal syndrome, which frequently coexists with hepatic encephalopathy in advanced liver disease 1

Clinical Applications

Primary Indications for MARS in Hepatic Encephalopathy:

• Bridge to liver transplantation: MARS can temporarily improve neurological status while awaiting a donor organ 1, 3

• Bridge to recovery: In potentially reversible cases of liver failure with hepatic encephalopathy, MARS may support the patient until native liver function recovers 2

• Acute-on-Chronic Liver Failure (ACLF): Short-term survival improvement (14-day and 28-day) has been observed in patients with ACLF and multiple organ failure, potentially allowing access to transplantation 1

Efficacy in Hepatic Encephalopathy:

• Meta-analysis shows MARS results in significant improvement in West-Haven grade of hepatic encephalopathy (OR 3.0; 95% CI 1.9,5.0; p < 0.001) 4

• MARS therapy leads to significant reduction in total bilirubin levels (net change -7.0 mg/dl; 95% CI -10.4, -3.7; p < 0.001), which may contribute to improved neurological status 4

• Despite improvements in encephalopathy, MARS has not demonstrated a significant benefit on overall survival (OR 0.91; 95% CI 0.64,1.31; p = 0.62) 4

Patient Selection and Treatment Considerations

• Optimal candidates include:

  • Patients with severe hepatic encephalopathy (grade III-IV) 3
  • Patients with bilirubin > 15 mg/dL and ammonia > 160 μg/dL 3
  • Patients awaiting liver transplantation with deteriorating neurological status 1, 3

• Treatment protocol:

  • Average treatment duration: approximately 8 hours per session 3
  • Multiple sessions may be required (average 6.4 sessions per patient in clinical studies) 3
  • Careful anticoagulation management is necessary, with heparin as standard and citrate recommended for patients at risk of bleeding 2

Important Caveats and Limitations

• European Association for the Study of the Liver (EASL) does not currently recommend MARS as a routine treatment for hepatic encephalopathy despite its potential therapeutic value 5

• Aggressive treatment of infections and sepsis is critical for safe and efficient use of MARS therapy 2

• Thrombocytopenia is a reported adverse effect of MARS treatment that requires monitoring 6

• Patient referral to specialized centers with experience in liver support systems is strongly recommended for optimal outcomes 1

• The "transplantation window" is often narrow in these patients, requiring rapid decision-making by a multidisciplinary team 1

Conclusion for Clinical Practice

• For patients with hepatic encephalopathy, MARS should be considered primarily as a bridge therapy rather than a definitive treatment 1, 2

• Despite not improving overall survival, the significant improvement in hepatic encephalopathy symptoms may provide valuable clinical benefits in selected patients 4

• Current evidence supports referring patients to expert centers at an early stage after decompensation of cirrhosis for evaluation of MARS therapy as part of a comprehensive management approach 1