title: Glycodeoxycholic acid levels as prognostic biomarker in acetaminophen-induced acute liver failure patients.
abstract: Acetaminophen (APAP)-induced acute liver failure (ALF) remains a major clinical problem. Although a majority of patients recovers after severe liver injury, a subpopulation of patients proceeds to ALF. Bile acids are generated in the liver and accumulate in blood during liver injury, and as such, have been proposed as biomarkers for liver injury and dysfunction. The goal of this study was to determine whether individual bile acid levels could determine outcome in patients with APAP-induced ALF (AALF). Serum bile acid levels were measured in AALF patients using mass spectrometry. Bile acid levels were elevated 5-80-fold above control values in injured patients on day 1 after the overdose and decreased over the course of hospital stay. Interestingly, glycodeoxycholic acid (GDCA) was significantly increased in non-surviving AALF patients compared with survivors. GDCA values obtained at peak alanine aminotransferase (ALT) and from day 1 of admission indicated GDCA could predict survival in these patients by receiver-operating characteristic analysis (AUC = 0.70 for day 1, AUC = 0.68 for peak ALT). Of note, AALF patients also had significantly higher levels of serum bile acids than patients with active cholestatic liver injury. These data suggest measurements of GDCA in this patient cohort modestly predicted outcome and may serve as a prognostic biomarker. Furthermore, accumulation of bile acids in serum or plasma may be a result of liver cell dysfunction and not cholestasis, suggesting elevation of circulating bile acid levels may be a consequence and not a cause of liver injury.
authors.affiliation: *Department of Pharmacology, Toxicology and Therapeutics, Department of Biostatistics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, Department of Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, Arizona 85006, Department of Medicine, and Center for Toxicology and Pharmacology Education and Research, University of Arizona College of Medicine, Phoenix, Arizona 85006 and Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Woolbright
authors.affiliation: *Department of Pharmacology, Toxicology and Therapeutics, Department of Biostatistics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, Department of Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, Arizona 85006, Department of Medicine, and Center for Toxicology and Pharmacology Education and Research, University of Arizona College of Medicine, Phoenix, Arizona 85006 and Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: McGill
authors.affiliation: *Department of Pharmacology, Toxicology and Therapeutics, Department of Biostatistics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, Department of Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, Arizona 85006, Department of Medicine, and Center for Toxicology and Pharmacology Education and Research, University of Arizona College of Medicine, Phoenix, Arizona 85006 and Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Vincent S
authors.initials: VS
authors.lastname: Staggs
authors.affiliation: *Department of Pharmacology, Toxicology and Therapeutics, Department of Biostatistics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, Department of Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, Arizona 85006, Department of Medicine, and Center for Toxicology and Pharmacology Education and Research, University of Arizona College of Medicine, Phoenix, Arizona 85006 and Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Winefield
authors.affiliation: *Department of Pharmacology, Toxicology and Therapeutics, Department of Biostatistics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, Department of Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, Arizona 85006, Department of Medicine, and Center for Toxicology and Pharmacology Education and Research, University of Arizona College of Medicine, Phoenix, Arizona 85006 and Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Parviz
authors.initials: P
authors.lastname: Gholami
authors.affiliation: *Department of Pharmacology, Toxicology and Therapeutics, Department of Biostatistics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, Department of Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, Arizona 85006, Department of Medicine, and Center for Toxicology and Pharmacology Education and Research, University of Arizona College of Medicine, Phoenix, Arizona 85006 and Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Olyaee
authors.affiliation: *Department of Pharmacology, Toxicology and Therapeutics, Department of Biostatistics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, Department of Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, Arizona 85006, Department of Medicine, and Center for Toxicology and Pharmacology Education and Research, University of Arizona College of Medicine, Phoenix, Arizona 85006 and Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Sharpe
authors.affiliation: *Department of Pharmacology, Toxicology and Therapeutics, Department of Biostatistics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, Department of Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, Arizona 85006, Department of Medicine, and Center for Toxicology and Pharmacology Education and Research, University of Arizona College of Medicine, Phoenix, Arizona 85006 and Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 *Department of Pharmacology, Toxicology and Therapeutics, Department of Biostatistics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, Department of Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, Arizona 85006, Department of Medicine, and Center for Toxicology and Pharmacology Education and Research, University of Arizona College of Medicine, Phoenix, Arizona 85006 and Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Curry
authors.affiliation: *Department of Pharmacology, Toxicology and Therapeutics, Department of Biostatistics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, Department of Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, Arizona 85006, Department of Medicine, and Center for Toxicology and Pharmacology Education and Research, University of Arizona College of Medicine, Phoenix, Arizona 85006 and Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 *Department of Pharmacology, Toxicology and Therapeutics, Department of Biostatistics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, Department of Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, Arizona 85006, Department of Medicine, and Center for Toxicology and Pharmacology Education and Research, University of Arizona College of Medicine, Phoenix, Arizona 85006 and Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.affiliation: *Department of Pharmacology, Toxicology and Therapeutics, Department of Biostatistics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, Department of Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, Arizona 85006, Department of Medicine, and Center for Toxicology and Pharmacology Education and Research, University of Arizona College of Medicine, Phoenix, Arizona 85006 and Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 hjaeschke@kumc.edu.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Jaeschke
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000209:etiology; D002779:Cholestasis / Q000097:blood*; D062787:Drug Overdose; D005260:Female; D006002:Glycodeoxycholic Acid / Q000097:blood*; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006002:Glycodeoxycholic Acid; D000082:Acetaminophen
keywords: acetaminophen; acute liver failure; bile acid; cholestasis; hepatotoxicity; serum biomarker