title: Improvements in hepatic serological biomarkers are associated with clinical benefit of intravenous N-acetylcysteine in early stage non-acetaminophen acute liver failure.
abstract: BACKGROUND
  N-acetylcysteine (NAC) improves transplant-free survival in early coma grade (I-II) patients with non-acetaminophen induced acute liver failure (ALF). We determined whether the clinical benefit was associated with improvements in hepatic function.
  
  
  METHODS
  In a prospective, double blind trial, 173 ALF patients without evidence of acetaminophen overdose were stratified by coma grade (I-II vs. III-IV) and randomly assigned to receive either intravenous NAC or dextrose (placebo) for 72 h, resulting in four patient groups. INR, ALT, bilirubin, creatinine, and AST obtained on admission (day 1) and subsequent days (days 2-4) were used for secondary analysis performed by fitting longitudinal logistic regression models to predict death or transplantation or transplantation alone.
  
  
  RESULTS
  Treatment group and day of study in models including bilirubin or ALT were predictors of transplantation or death (maximum p < 0.03). Those patients with early coma grade who were treated with NAC showed significant improvement in bilirubin and ALT levels when compared to the other three groups (maximum p < 0.02 for NAC 1-2 vs. the 3 other treatments) when predicting death or transplantation. Treatment group, day of study, and bilirubin were predictors of transplantation (maximum p < 0.03) in ALF patients.
  
  
  CONCLUSIONS
  The decreased risk of transplantation or death or of transplantation alone with intravenous NAC in early coma grade patients with non-acetaminophen induced ALF was reflected in improvement in parameters related to hepatocyte necrosis and bile excretion including ALT and bilirubin, but not in INR, creatinine, or AST. Hepatic recovery appears hastened by NAC as measured by several important lab values.
authors: Division of Gastroenterology and Hepatology, Stanford University, 300 Pasteur Drive, Stanford, CA 94305-5187, USA. sundeeps@stanford.edu
authors: Sundeep
authors: S
authors: Singh
authors: Linda S
authors: LS
authors: Hynan
authors: William M
authors: WM
authors: Lee
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D003128:Coma / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000628:therapy; D004311:Double-Blind Method; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D017114:Liver Failure, Acute / Q000097:blood* / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D016166:Free Radical Scavengers; D000111:Acetylcysteine