What are the indications and outcomes of Molecular Adsorbent Recirculating System (MARS) in patients with liver failure?

MARS Indications and Outcomes in Liver Failure

Primary Indication

MARS should be used primarily as a bridge to liver transplantation in patients with acute-on-chronic liver failure (ACLF) or acute liver failure, not as a definitive treatment, as it improves hepatic encephalopathy and laboratory parameters but does not improve overall survival. 1, 2

Specific Clinical Indications

Bridge to Transplantation (Primary Role)

• MARS is indicated for patients with fulminant hepatic failure awaiting liver transplantation to stabilize neurological status and delay the need for urgent transplantation. 2
• The American Association for the Study of Liver Diseases recommends MARS as a bridge to liver transplantation in patients with acute liver failure, with post-transplant survival rates of 79-87% at 1 year regardless of MARS use. 2
• Short-term survival improvement (14-day and 28-day) has been demonstrated in patients with ACLF and multiple organ failure, potentially allowing these patients to access liver transplantation. 1

Specific Patient Populations

• Patients with acute decompensation of cirrhosis with progressive hyperbilirubinemia (>20 mg/dL) and hepatic encephalopathy grade ≥2. 3
• Patients with acute liver failure due to Wilson disease, where MARS can stabilize patients and delay transplantation while the ultrafiltration device potentially protects kidneys from copper-mediated tubular damage. 2
• Patients with MELD scores between 20-29 show the best clinical response to MARS therapy. 4

Clinical Outcomes

Symptomatic Improvements (Proven Benefits)

• Significant improvement in hepatic encephalopathy: Post-hoc analysis of randomized European studies demonstrated significant improvement when using albumin dialysis with MARS versus standard medical therapy (OR 3.0; 95% CI 1.9-5.0; p<0.001). 1, 5
• Significant reduction in total bilirubin levels: Net decrease of -7.0 mg/dL (95% CI -10.4, -3.7; p<0.001). 5
• Improvement in hepatorenal syndrome, which frequently coexists with hepatic encephalopathy in advanced liver disease. 1, 2
• Improvement in renal function parameters, daily urine output, and MELD score. 4, 6

Survival Outcomes (Critical Limitation)

• Two large multicentre randomized European studies comparing MARS or Prometheus with standard medical treatment did NOT demonstrate any benefit on survival at 28 and 90 days. 1
• Meta-analysis confirms no beneficial effect on mortality (OR 0.91; 95% CI 0.64,1.31; p=0.62). 5
• However, observational studies and meta-analyses suggest improved short-term survival (14-day and 28-day) specifically in patients with ACLF and multiple organ failure. 1

Treatment Protocol Considerations

Patient Selection Criteria

• Refer patients to an expert center at an early stage after decompensation of their cirrhosis, as the "transplantation window" is often narrow and requires rapid decision-making by a multidisciplinary specialized team. 1, 2
• Inclusion criteria typically include: total bilirubin ≥10 mg/dL AND at least one of the following: hepatic encephalopathy ≥grade II, hepatorenal syndrome, OR total bilirubin ≥5 mg/dL with hepatic encephalopathy ≥grade I for acute patients. 4

Treatment Duration

• Mean treatment cycles range from 2.2 sessions, with individual sessions typically lasting 8 hours. 3, 6
• Treatment should continue until liver transplantation becomes available or liver function recovers. 6, 7

Important Clinical Caveats

Limitations and Contraindications

• The 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. 2
• MARS without liver transplantation does not improve survival in most patients—only 18.2% of patients survived without transplantation in one series. 6
• The original European studies included heterogeneous populations (ACLF grade 0 to grade 3) with markedly different prognoses (mortality ranging from 4% to 80%), which may have diluted treatment effects. 1

Safety Profile

• MARS has been confirmed as safe in multiple studies with no significant adverse events reported. 4, 7
• The treatment removes both hydrosoluble and small- to medium-sized lipophilic toxins, including bilirubin, bile acids, aromatic amino acids, and copper. 7

Clinical Algorithm for MARS Use

1. Identify eligible patients: Acute liver failure or ACLF with progressive hyperbilirubinemia (>20 mg/dL) and hepatic encephalopathy ≥grade 2. 3, 4

2. Immediately contact liver transplant center if patient meets criteria, as MARS is a bridge therapy, not definitive treatment. 1, 2

3. Initiate MARS therapy while awaiting transplantation to improve neurological status and stabilize organ function. 2, 3

4. Monitor response: Expect improvement in bilirubin, encephalopathy grade, and renal function, but do not expect survival benefit without transplantation. 5, 6

5. Proceed to transplantation as soon as donor becomes available—this remains the essential therapy for end-stage liver disease. 1