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

Hepatology. 2013 Mar;57(3):1153-62. doi: 10.1002/hep.26185. Epub 2013 Feb 15.

Abstract

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=95) or to standard therapy (SMT) (n=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=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=0.02) and bilirubin (P=0.001) and a more frequent improvement in HE (from grade II-IV to grade 0-I; 62.5% versus 38.2%; P=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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • End Stage Liver Disease / mortality
  • End Stage Liver Disease / therapy*
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Liver Cirrhosis / mortality
  • Liver Cirrhosis / therapy
  • Liver Failure, Acute / mortality
  • Liver Failure, Acute / therapy*
  • Logistic Models
  • Male
  • Middle Aged
  • Multiple Organ Failure / mortality
  • Multiple Organ Failure / therapy
  • Multivariate Analysis
  • Peritonitis / mortality
  • Peritonitis / therapy
  • Prospective Studies
  • Renal Dialysis / adverse effects
  • Renal Dialysis / methods
  • Serum Albumin / metabolism*
  • Sorption Detoxification / adverse effects
  • Sorption Detoxification / methods*
  • Sorption Detoxification / mortality
  • Treatment Outcome

Substances

  • Serum Albumin