title: Profiles of miRNAs in serum in severe acute drug induced liver injury and their prognostic significance.
abstract: Drug induced liver injury (DILI) is challenging because of the lack of biomarkers to predict mortality. Our aim was to describe miRNA changes in sera of subjects with acute idiosyncratic DILI and determine if levels of miRNAs were associated with 6 month mortality.
  
  
  
  Clinical data and sera were collected from subjects enrolled in the Drug Induced Liver Injury Network prospective study. miRNAs were isolated from serum obtained from 78 subjects within 2 weeks of acute DILI and followed up for 6 months or longer. miRNAs were compared to 40 normal controls and 6 month survivors vs non-survivors.
  
  
  
  The mean age of the DILI cohort was 48 years, and 55% were female. Eleven (14.1%) subjects died, 10 within 6 months of DILI onset, 5 (45%) liver related. Lower levels of miRNAs-122, -4463 and -4270 were associated with death within 6 months (P<.05). None of the subjects with miRNA-122 greater than the median value died within 6 months for a sensitivity of 100% and specificity of 57%. In subjects with a serum albumin <2.8 g/dL and miR-122<7.89 RFU the sensitivity, specificity, positive and negative predictive values for death within 6 months were 100%, 57%, 38% and 100% respectively.
  
  
  
  Serum miRNA-122 combined with albumin accurately identified subjects who died within 6 months of drug induced liver injury. If confirmed prospectively, miRNA-122 and albumin may be useful in identifying patients at high risk for mortality or liver transplantation.
authors.affiliation: Carolinas Healthcare System, Charlotte, NC, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Russo
authors.affiliation: Carolinas Healthcare System, Charlotte, NC, USA.
authors.forename: Nury
authors.initials: N
authors.lastname: Steuerwald
authors.affiliation: Carolinas Healthcare System, Charlotte, NC, USA.
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Norton
authors.affiliation: Carolinas Healthcare System, Charlotte, NC, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Anderson
authors.affiliation: Carolinas Healthcare System, Charlotte, NC, USA.
authors.forename: David
authors.initials: D
authors.lastname: Foureau
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Naga
authors.initials: N
authors.lastname: Chalasani
authors.affiliation: University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Watkins
authors.affiliation: NIDDK, Bethesda, MD, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Serrano
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000401:mortality*; D005260:Female; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012709:Serum Albumin; D012720:Severity of Illness Index; D014481:United States
chemical_list: D015415:Biomarkers; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D012709:Serum Albumin
keywords: albumin; drugs; hepatotoxicity; herbals; prognosis