title: Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Liver Unit, Hospital General Universitario Gregorio Marañón, IiSGM, Medical School, Universidad Complutense, Madrid, Spain. rbanares.hgugm@salud.madrid.org
authors.forename: Rafael
authors.initials: R
authors.lastname: Bañares
authors.forename: Frederik
authors.initials: F
authors.lastname: Nevens
authors.forename: Fin Stolze
authors.initials: FS
authors.lastname: Larsen
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
authors.forename: Agustín
authors.initials: A
authors.lastname: Albillos
authors.forename: Matthias
authors.initials: M
authors.lastname: Dollinger
authors.forename: Faouzi
authors.initials: F
authors.lastname: Saliba
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: Sebastian
authors.initials: S
authors.lastname: Klammt
authors.forename: Johann
authors.initials: J
authors.lastname: Ockenga
authors.forename: Albert
authors.initials: A
authors.lastname: Pares
authors.forename: Julia
authors.initials: J
authors.lastname: Wendon
authors.forename: Tanja
authors.initials: T
authors.lastname: Brünnler
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kramer
authors.forename: Philippe
authors.initials: P
authors.lastname: Mathurin
authors.forename: Manuel
authors.initials: M
authors.lastname: de la Mata
authors.forename: Antonio
authors.initials: A
authors.lastname: Gasbarrini
authors.forename: Beat
authors.initials: B
authors.lastname: Müllhaupt
authors.forename: Alexander
authors.initials: A
authors.lastname: Wilmer
authors.forename: Wim
authors.initials: W
authors.lastname: Laleman
authors.forename: Martin
authors.initials: M
authors.lastname: Eefsen
authors.forename: Sambit
authors.initials: S
authors.lastname: Sen
authors.forename: Alexander
authors.initials: A
authors.lastname: Zipprich
authors.forename: Teresa
authors.initials: T
authors.lastname: Tenorio
authors.forename: Marco
authors.initials: M
authors.lastname: Pavesi
authors.forename: Hartmut H-J
authors.initials: HH
authors.lastname: Schmidt
authors.forename: Steffen
authors.initials: S
authors.lastname: Mitzner
authors.forename: Roger
authors.initials: R
authors.lastname: Williams
authors.forename: Vicente
authors.initials: V
authors.lastname: Arroyo
mesh_terms: D000328:Adult; D058625:End Stage Liver Disease / Q000401:mortality / Q000628:therapy*; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008103:Liver Cirrhosis / Q000401:mortality / Q000628:therapy; D017114:Liver Failure, Acute / Q000401:mortality / Q000628:therapy*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000401:mortality / Q000628:therapy; D015999:Multivariate Analysis; D010538:Peritonitis / Q000401:mortality / Q000628:therapy; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects / Q000379:methods; D012709:Serum Albumin / Q000378:metabolism*; D016060:Sorption Detoxification / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D012709:Serum Albumin