Digestive Diseases and Sciences

, Volume 58, Issue 5, pp 1397–1402

Improvements in Hepatic Serological Biomarkers Are Associated with Clinical Benefit of Intravenous N-Acetylcysteine in Early Stage Non-Acetaminophen Acute Liver Failure

  • Sundeep Singh
  • Linda S. Hynan
  • William M. Lee
  • The Acute Liver Failure Study Group
Original Article

DOI: 10.1007/s10620-012-2512-x

Cite this article as:
Singh, S., Hynan, L.S., Lee, W.M. et al. Dig Dis Sci (2013) 58: 1397. doi:10.1007/s10620-012-2512-x



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.


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.


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.


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.


Acute liver failure ALF N-acetylcysteine 

Supplementary material

10620_2012_2512_MOESM1_ESM.docx (31 kb)
Supplementary material 1 (DOCX 31 kb)

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Sundeep Singh
    • 1
  • Linda S. Hynan
    • 2
  • William M. Lee
    • 3
  • The Acute Liver Failure Study Group
  1. 1.Division of Gastroenterology and HepatologyStanford UniversityStanfordUSA
  2. 2.Division of BiostatisticsUniversity of Texas Southwestern Medical CenterDallasUSA
  3. 3.Division of Digestive and Liver DiseasesUniversity of Texas Southwestern Medical CenterDallasUSA

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