What is the role of Molecular Adsorbent Recirculating System (MARS) therapy in managing chronic liver disease?

Role of Molecular Adsorbent Recirculating System (MARS) in Chronic Liver Disease

Based on current evidence, MARS therapy is not recommended as a standard treatment for chronic liver disease as it has not demonstrated significant survival benefits compared to standard medical therapy.

Overview of MARS Therapy

• MARS is an extracorporeal liver support system that uses albumin dialysis to remove albumin-bound toxins through a specialized membrane transport system 1
• The system allows for selective regeneration of the patient's albumin, increasing albumin binding capacity and removing toxins that accumulate in liver failure 2
• MARS therapy can remove albumin-bound molecules such as bilirubin, bile acids, aromatic amino acids, and copper 1

Clinical Applications in Chronic Liver Disease

Alcoholic Liver Disease (ALD)

• In patients with severe alcoholic hepatitis who are poor responders to corticosteroids (Lille score >0.45), early switch to MARS therapy appears not to modify outcomes 3
• A single-center experience with MARS in acutely decompensated ALD showed improvement in laboratory parameters of hepatic detoxification and renal function, but patient mortality remained unsatisfactorily high at 78.6% 4
• MARS should not be used indiscriminately in acutely decompensated ALD without further controlled studies 4

Acute-on-Chronic Liver Failure (ACLF)

• Large randomized controlled trials evaluating albumin dialysis (MARS) and fractionated plasma separation and adsorption (Prometheus) in ACLF have not demonstrated significant effects on survival 3
• Based on these results, extracorporeal liver support systems do not improve survival of patients with ACLF and should not be recommended for this indication 3
• A sub-analysis of the Prometheus study showed a potential beneficial effect on survival in patients with MELD scores higher than 30, which may warrant further investigation 3

Hepatorenal Syndrome (HRS)

• MARS may have promising beneficial effects in patients with type 1 HRS, but further investigation is needed 3
• MARS therapy has been shown to improve liver, cardiovascular, and renal functions in some studies, but these improvements have not translated to consistent survival benefits 1

Evidence from Meta-analyses and Controlled Trials

• A meta-analysis of 4 randomized controlled trials with 67 patients found that MARS treatment did not significantly reduce mortality compared to standard medical treatment (relative risk 0.56; 95% CI, 0.28-1.14; P = 0.11) 5
• Subgroup analyses for acute liver failure and acute-on-chronic liver failure also did not reveal survival benefits with MARS treatment 5
• A case-control study showed that MARS therapy improved short-term response in patients with acute liver injury and graft dysfunction but did not improve 28-day mortality 6

Specific Clinical Scenarios Where MARS May Be Considered

Bridge to Liver Transplantation

• MARS may be considered as a bridge therapy to liver transplantation in carefully selected patients 2
• The treatment can potentially contribute to stabilization of vital organ functions while waiting for a donor organ 2

Wilson's Disease with Acute Liver Failure

• In patients with acute liver failure due to Wilson's disease, MARS may be used along with plasmapheresis, hemofiltration, or exchange transfusion to stabilize patients and delay, but not eliminate, the need for transplantation 3

Hepatic Encephalopathy

• MARS appears to be a valuable therapeutic tool for the treatment of hepatic encephalopathy in liver failure 2
• However, it should be noted that MARS is not mentioned in the EASL guidelines for hepatic encephalopathy as a recommended treatment 3

Practical Considerations for MARS Implementation

• Proper patient selection is critical for clinical success with MARS therapy 2
• Aggressive treatment of infections and sepsis is a decisive pre-requisite for safe and efficient use 2
• Cautious anticoagulation with heparin is the common standard, while citrate use is recommended for patients prone to bleeding 2

Conclusion

• Despite showing improvements in laboratory parameters and certain clinical symptoms, MARS therapy has not demonstrated consistent survival benefits in chronic liver disease 5
• Current guidelines do not support the routine use of MARS in chronic liver disease management 3
• Future well-conducted randomized trials are needed to better define the role of MARS in specific patient populations with liver failure 5