What is the role of MARS (Molecular Adsorbent Recirculating System) in patients with cirrhosis and HRS (Hepatorenal Syndrome) or AKI (Acute Kidney Injury)?

Role of MARS and Other Extracorporeal Liver Support Systems in Cirrhosis with HRS/AKI

MARS and Prometheus systems show promising effects in improving hepatic encephalopathy and hepatorenal syndrome but should not be used routinely outside of specialized centers as a bridge to liver transplantation, as they have not demonstrated survival benefit in randomized controlled trials. 1

Current Guideline Recommendations

Limited Role in Standard Practice

The most recent 2022 AGA guidelines do not recommend extracorporeal liver support systems like MARS as standard therapy for HRS-AKI. 1 These systems are notably absent from the primary treatment algorithm, which focuses on:

• Volume expansion with albumin
• Vasoconstrictor therapy (terlipressin, or midodrine/octreotide)
• Renal replacement therapy (RRT) as bridge to transplant
• Liver transplantation as definitive treatment 1

Evidence from European Guidelines

The 2018 EASL guidelines provide more specific guidance on artificial liver support systems:

• Two controlled studies showed promising beneficial effects of both MARS and Prometheus in patients with type 1 HRS, but these systems require further investigation before routine use. 1
• The systems demonstrated significant improvement in hepatic encephalopathy and hepatorenal syndrome in post-hoc analyses. 1
• However, no survival benefit at 28 or 90 days was demonstrated in multicentre randomized European trials comparing MARS or Prometheus with standard medical treatment. 1

When to Consider MARS: Bridge to Transplant Only

Appropriate Clinical Context

MARS should only be considered in highly selected patients at specialized transplant centers as a bridge to liver transplantation, not as a standalone therapy or for non-transplant candidates. 1

The French Society of Anesthesia and Intensive Care (2020) suggests potential benefit in specific scenarios:

• Patients with ACLF (acute-on-chronic liver failure) and multiple organ failure awaiting transplantation 1
• Short-term survival improvement (14-day and 28-day) has been observed in observational studies and meta-analyses in ACLF patients with multiple organ failure. 1
• This short-term stabilization may allow patients to reach transplantation, which remains the essential therapy. 1

Critical Limitation of Prior Studies

A major flaw in the negative randomized trials was heterogeneous patient selection—studies included patients with acute decompensation without organ failure (ACLF grade 0) through those with multiple organ failures (ACLF grade 3), whose mortality ranged from 4% to 80%. 1 This heterogeneity likely obscured potential benefits in specific subgroups.

Mechanism and Depurative Efficiency

MARS is a modified dialysis method using albumin-containing dialysate recirculated through charcoal and anion-exchanger columns, enabling selective removal of albumin-bound substances. 2

What MARS Removes

• Total bilirubin reduction rate per session: 23% (range 17-29%) 3
• Ammonia reduction: 34% (range 12-86%) 3
• Conjugated bile acids: 58% reduction for cholic acid 3
• Cytokines and inflammatory mediators 3

Clinical Improvements Observed

In the original 2000 prospective randomized trial in type I HRS:

• Significant decrease in bilirubin and creatinine levels (P <0.01) 2
• Increase in serum sodium and prothrombin activity (P <0.01) 2
• Mortality at day 7: 62.5% in MARS group vs 100% in control group (P <0.01) 2
• However, by day 30, mortality was still 75% in the MARS group 2

Practical Algorithm for Decision-Making

Step 1: Establish Transplant Candidacy First

• If patient is NOT a transplant candidate: Do not initiate MARS therapy. Focus on standard RRT for metabolic derangements and consider palliative care consultation. 4
• If patient IS a transplant candidate: Proceed to Step 2

Step 2: Optimize Medical Management

Before considering MARS, ensure the following have been attempted:

• Albumin 1 g/kg for 2 days, then 20-40 g/day 4, 5
• Vasoconstrictor therapy (terlipressin preferred, or midodrine/octreotide) for 3-7 days 4, 5
• Infection treatment and withdrawal of nephrotoxic agents 5, 6

Step 3: Consider MARS Only If

• Patient has failed vasoconstrictor therapy after adequate trial (3-7 days) 4
• Patient has ACLF with multiple organ failure 1
• Transplant is anticipated within days to weeks (narrow "transplantation window") 1
• Patient is at a specialized center with MARS capability and expertise 1

Step 4: Initiate Standard RRT Concurrently

MARS does not replace conventional RRT—it supplements it. 2

• Use continuous RRT (CRRT) with bicarbonate-buffered solutions 4
• Regional citrate anticoagulation when possible 4
• Target effluent volume 20-25 mL/kg/hour 4

Critical Caveats and Pitfalls

Cost and Resource Considerations

MARS is extremely expensive and requires specialized equipment and trained personnel. 7 The cost-effectiveness has not been established, particularly given the lack of survival benefit in randomized trials. 1

Patient Selection Errors

Common mistake: Using MARS in non-transplant candidates or patients with irreversible multi-organ failure. This represents futile care given the poor prognosis and lack of survival benefit. 1, 4

Timing Issues

• Duration of RRT >14 days pretransplant predicts poor renal recovery post-transplant. 1
• Each additional day on dialysis increases risk of renal non-recovery by 3.6-6%. 1
• Therefore, MARS should be considered early in the course if used at all, not as a last-ditch effort after prolonged conventional RRT. 1

Monitoring During MARS

• Hepatocyte growth factor (HGF) levels increase during MARS and may predict better outcomes. 3
• Age, male gender, and SOFA score predict mortality, while number of MARS sessions and change in HGF are protective factors. 3
• Patients require hemodynamic stability during treatment—MARS is not appropriate for profoundly unstable patients. 3

Bottom Line for Clinical Practice

In 2024, MARS and similar extracorporeal liver support systems remain investigational therapies that should be restricted to specialized transplant centers for highly selected patients with HRS-AKI or ACLF who are awaiting liver transplantation and have failed standard medical therapy. 1 The primary treatment pathway remains albumin plus vasoconstrictors, followed by conventional CRRT if needed, with liver transplantation as the definitive treatment. 1, 4

For the vast majority of patients with cirrhosis and HRS/AKI, standard RRT (preferably CRRT) is the appropriate extracorporeal therapy, not MARS. 1, 4