title: Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure.
abstract: OBJECTIVE
  N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen-related acute liver failure.
  
  
  METHODS
  In a prospective, double-blind trial, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned randomly to groups that were given NAC or placebo (dextrose) infusion for 72 hours. The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation.
  
  
  RESULTS
  A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70% for patients given NAC and 66% for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40%) than for those given placebo (27%; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52% compared with 30% for placebo; 1-sided P = .010); transplant-free survival for the 59 patients with coma grades III-IV was 9% in those given NAC and 22% in those given placebo (1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32% vs 45%; P = .093). Intravenous NAC generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14% vs 4%; P = .031).
  
  
  CONCLUSIONS
  Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation.
authors.affiliation: Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8887, USA. William.Lee@utsouthwestern.edu
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.forename: Linda S
authors.initials: LS
authors.lastname: Hynan
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Rossaro
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.forename: R Todd
authors.initials: RT
authors.lastname: Stravitz
authors.forename: Anne M
authors.initials: AM
authors.lastname: Larson
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Davern
authors.forename: Natalie G
authors.initials: NG
authors.lastname: Murray
authors.forename: Timothy
authors.initials: T
authors.lastname: McCashland
authors.forename: Joan S
authors.initials: JS
authors.lastname: Reisch
authors.forename: Patricia R
authors.initials: PR
authors.lastname: Robuck
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D000111:Acetylcysteine / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000506:poisoning*; D004311:Double-Blind Method; D005260:Female; D006501:Hepatic Encephalopathy / Q000188:drug therapy; D006801:Humans; D007262:Infusions, Intravenous; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D000111:Acetylcysteine