What are the indications and treatment guidelines for using the Molecular Adsorbent Recirculating System (MARS) in patients with liver failure?

Molecular Adsorbent Recirculating System (MARS) in Liver Failure

Primary Indication and Role

MARS should be used primarily as a bridge to liver transplantation in patients with acute liver failure, not as a definitive treatment, as it improves hepatic encephalopathy and biochemical parameters but does not improve overall survival. 1

Specific Clinical Indications

Acute Liver Failure

• MARS is indicated for patients with fulminant hepatic failure awaiting liver transplantation to stabilize neurological status and delay (but not eliminate) the need for urgent transplantation 2, 3
• Use MARS when bilirubin >15 mg/dL, ammonia >160 μg/dL, and Glasgow Coma Score between 6-11 4
• MARS effectively reduces severe cerebral edema and raised intracranial pressure in fulminant hepatic failure, possibly through reduction of toxic metabolites like ammonia and bilirubin 3

Wilson Disease with Acute Liver Failure

• MARS can stabilize patients with acute liver failure due to Wilson disease and delay transplantation, though transplantation remains necessary 2
• The ultrafiltration device may be efficacious in protecting kidneys from copper-mediated tubular damage while awaiting transplantation 2

Hepatic Encephalopathy

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

Acute-on-Chronic Liver Failure (ACLF)

• MARS shows short-term survival improvement in patients with ACLF and multiple organ failure, potentially allowing access to transplantation 1
• MARS improves hepatorenal syndrome, which frequently coexists with hepatic encephalopathy in advanced liver disease 1

Treatment Protocol and Technical Considerations

Session Parameters

• Median treatment duration is approximately 7-8 hours per session 5, 4
• Median number of sessions is 4 (range 3-5 sessions) 6
• Treatment can be repeated for extended periods with high tolerance 4

Biochemical Effects

• MARS significantly reduces serum bilirubin levels in the short term across all etiologies 6, 4
• In acute liver injury, bilirubin reduction is sustained even after MARS therapy ends 6
• Ammonia levels decrease during treatment 5, 4
• INR changes are not significant and may actually increase during MARS therapy 5, 4

Patient Selection and Referral

Refer patients to specialized centers with experience in liver support systems at an early stage after decompensation of cirrhosis for optimal outcomes 1

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

Critical Limitations and Caveats

Survival Impact

• MARS does not improve 28-day mortality in acute liver injury (5.3% MARS vs 3.3% standard medical therapy, p=0.754) or graft dysfunction (20.0% MARS vs 11.1% standard medical therapy, p=0.478) 6
• Post-transplant survival rates remain 79-87% at 1 year regardless of MARS use 2

Bleeding Risk

• In patients with activated clotting systems, MARS can precipitate disseminated intravascular coagulation with clinically significant bleeding 7
• Use MARS very cautiously in patients with coagulopathy and avoid routine correction of coagulation abnormalities unless active bleeding occurs 7

Comparative Efficacy

• Combined plasma exchange and hemodialysis (PE/HD) shows superior efficacy compared to intermittent MARS therapy in children with acute liver failure 5
• PE/HD reduced bilirubin by 37±11% versus 2±22% increase with MARS (p<0.001) 5
• PE/HD decreased ammonia by 39±23% versus 18±27% with MARS (p<0.05) 5
• PE/HD decreased INR by 37±20% while MARS increased INR by 26±41% (p<0.01) 5

Clinical Algorithm for MARS Implementation

1. Confirm indication: Acute liver failure with PT <50%, bilirubin >15 mg/dL, ammonia >160 μg/dL, Glasgow Coma Score 6-11 4, 8

2. Contact transplant center immediately if PT <50% to establish patient as transplant candidate 9

3. Assess bleeding risk: Check for activated clotting system or active coagulopathy before initiating MARS 7

4. Initiate MARS as bridge therapy: Begin 6-8 hour sessions while awaiting transplantation 4

5. Monitor response: Track bilirubin, ammonia, encephalopathy grade, and coagulation parameters before and after each session 4

6. Consider alternative: If MARS unavailable or contraindicated due to bleeding risk, use combined plasma exchange and hemodialysis which shows superior biochemical efficacy 5

7. Proceed to transplantation: MARS is temporizing only; definitive treatment requires liver transplantation 1, 9

Unresolved Clinical Questions

The optimal timing of MARS initiation, intensity of therapy (continuous versus intermittent), and comparison with bio-artificial liver devices remain areas requiring further investigation through large multi-center randomized controlled trials 3