title: Elevated FABP1 serum levels are associated with poorer survival in acetaminophen-induced acute liver failure.
abstract: Acetaminophen (APAP)-induced acute liver failure (ALF) is associated with significant mortality. Traditional prognostic scores lack sensitivity. Serum liver-type fatty acid binding protein (FABP1) early (day 1) or late (day 3-5) levels are associated with 21-day mortality in the absence of liver transplant. Serum samples from 198 APAP-ALF patients (nested case-control study with 99 survivors, 99 nonsurvivors) were analyzed by enzyme-linked immunosorbent assay with clinical data from the US Acute Liver Failure Study Group registry (1998-2014). APAP-ALF survivors had significantly lower serum FABP1 levels early (238.6 versus 690.8 ng/mL, P < 0.0001) and late (148.4 versus 612.3 ng/mL, P < 0.0001) compared with nonsurvivors. FABP1 > 350 ng/mL was associated with significantly higher risk of death at early (P = 0.0004) and late (P < 0.0001) time points. Increased serum FABP1 early (log FABP1 odds ratio = 1.31, P = 0.027) and late (log FABP1 odds ratio = 1.50, P = 0.005) were associated with significantly increased 21-day mortality after adjusting for significant covariates (Model for End-Stage Liver Disease, vasopressor use). Areas under the receiver operating characteristic curve for early and late multivariable models were 0.778 and 0.907, respectively. The area under the receiver operating characteristic curve of the King's College criteria (early, 0.552 alone, 0.711 with FABP1; late, 0.604 alone, 0.797 with FABP1) and the Acute Liver Failure Study Group prognostic index (early, 0.686 alone, 0.766 with FABP1; late, 0.711 alone, 0.815 with FABP1) significantly improved with the addition of FABP1 (P < 0.002 for all).
  
  
  
  In patients with APAP-ALF, FABP1 may have good potential to discriminate survivors from nonsurvivors and may improve models currently used in clinical practice; validation of FABP1 as a clinical prediction tool in APAP-ALF warrants further investigation. (Hepatology 2017;65:938-949).
authors.affiliation: Division of Gastroenterology and Department of Critical Care Medicine, University of Alberta, Edmonton, Canada.
authors.forename: Constantine J
authors.identifier: 0000-0002-1555-1089
authors.initials: CJ
authors.lastname: Karvellas
authors.affiliation: Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC.
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Speiser
authors.affiliation: Hepato-neuro Laboratory, CRCHUM, Université de Montréal, Montréal, Canada.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Tremblay
authors.affiliation: Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.affiliation: Hepato-neuro Laboratory, CRCHUM, Université de Montréal, Montréal, Canada.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Rose
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects* / Q000627:therapeutic use; D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002423:Cause of Death; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D017114:Liver Failure, Acute / Q000097:blood* / Q000139:chemically induced / Q000401:mortality*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012372:ROC Curve; D012042:Registries; D015203:Reproducibility of Results; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; D000082:Acetaminophen