Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: The RELIEF trial

Abstract

on behalf of the RELIEF study group Acute-on-chronic liver failure (ACLF) is a frequent cause of death in cirrhosis. Albumin dialysis with the molecular adsorbent recirculating system (MARS) decreases retained substances and improves hemodynamics and hepatic encephalopathy (HE). However, its survival impact is unknown. In all, 189 patients with ACLF were randomized either to MARS (n 5 95) or to standard therapy (SMT) (n 5 94). Ten patients (five per group) were excluded due to protocol violations. In addition, 23 patients (MARS: 19; SMT: 4) were excluded from per-protocol (PP) analysis (PP population n 5 156). Up to 10 6-8-hour MARS sessions were scheduled. The main endpoint was 28-day ITT and PP survival. There were no significant differences at inclusion, although the proportion of patients with Model for Endstage Liver Disease (MELD) score over 20 points and with spontaneous bacterial peritonitis (SBP) as a precipitating event was almost significantly greater in the MARS group. The 28-day survival was similar in the two groups in the ITT and PP populations (60.7% versus 58.9%; 60% versus 59.2% respectively). After adjusting for confounders, a significant beneficial effect of MARS on survival was not observed (odds ratio [OR]: 0.87, 95% confidence interval [CI] 0.44-1.72). MELD score and HE at admission and the increase in serum bilirubin at day 4 were independent predictors of death. At day 4, a greater decrease in serum creatinine (P 5 0.02) and bilirubin (P 5 0.001) and a more frequent improvement in HE (from grade II-IV to grade 0-I; 62.5% versus 38.2%; P 5 0.07) was observed in the MARS group. Severe adverse events were similar. Conclusion: At scheduled doses, a beneficial effect on survival of MARS therapy in patients with ACLF could not be demonstrated. However, MARS has an acceptable safety profile, has significant dialysis effect, and nonsignificantly improves severe HE.

Blood purification in intensive care patients with multiple organ dysfunction syndrome and sepsis after cardiac surgery

“…[26,38] However, the albumin loss during Prometheus-therapy can reach 3 g/L (P = 0.055). [31,39] We observed no significant negative dynamics of serum albumin [oscillations: 32 (30-35) and 30 (26)(27)(28)(29)(30)(31)(32)(33)(34)(35) g/L, P = 0.052, before and after MARS-therapy; 33 (31-34) and 31 (28-36) g/L, P = 0.051, before and after Prometheus-therapy], which is probably due to the adequate routine correction of hypoproteinemia in patients with ALF. [39] Likewise, despite published data on the loss of coagulation factors during Prometheus-therapy, [40] we did not observe clinically significant hemorrhagic complications.…”

“…[29] The beneficial effect of these procedures on clinical and laboratory parameters is explained by the removal of vasoactive substances and toxins, leading to improvements in organ and tissue perfusion, hemodynamic parameters and kidney function and reducing portal hypertension, intracranial pressure and hepatic encephalopathy. [30,31] The experience from implementing this therapy in adults allows the use of extracorporeal liver support to be recommended in pediatric practice. [32][33][34] MARS-therapy is a method of albumin dialysis that uses a filter permeable to substances with a molecular weight of up to 50 kDa.…”

The molecular adsorbent recirculating system in posthepatectomy liver failure: Results from a prospective phase I study

“…Despite potentially positive effects on clinical and laboratory parameters, no study has been able to demonstrate a significant survival benefit in ALF15 or ACLF patients 14. A systematic evaluation of MARS has not been undertaken with respect to PHLF.…”

“…In this context, the Molecular Adsorbent Recirculating System (MARS) has emerged as a promising tool due to its capacity to remove water‐soluble and albumin‐bound toxins and to improve several clinically relevant hemodynamic and biochemical parameters in patients suffering from ALF or ACLF 9, 10, 11, 12, 13. Large, randomized, controlled trials did, however, fail to demonstrate a statistically significant survival benefit 14, 15. In the PHLF situation, only a few single‐center experiences have addressed the use of MARS as a rescue treatment option,16, 17, 18, 19, 20 and all of them suffer from heterogeneous patient groups and a lack of standardized treatment protocols.…”

An Update on Hepatorenal Syndrome

“…Molecular absorbent recirculating system (MARS) removes albumin-bound and water-soluble substances, including NO and TNF, which are involved in pathogenesis of HRS. MARS has been shown to improve neurological function and coagulation parameters although a randomised trial of 189 patients reported no beneficial effect on survival of MARS therapy in patients with acute or chronic liver failure (23).…”