title: Procalcitonin Identifies Cell Injury, Not Bacterial Infection, in Acute Liver Failure.
abstract: BACKGROUND
  Because acute liver failure (ALF) patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection clinically in ALF patients is challenging. Procalcitonin (PCT) has proven to be a useful marker in detecting bacterial infection. We sought to determine whether PCT discriminated between presence and absence of infection in patients with ALF.
  
  
  METHODS
  Retrospective analysis of data and samples of 115 ALF patients from the United States Acute Liver Failure Study Group randomly selected from 1863 patients were classified for disease severity and ALF etiology. Twenty uninfected chronic liver disease (CLD) subjects served as controls.
  
  
  RESULTS
  Procalcitonin concentrations in most samples were elevated, with median values for all ALF groups near or above a 2.0 ng/mL cut-off that generally indicates severe sepsis. While PCT concentrations increased somewhat with apparent liver injury severity, there were no differences in PCT levels between the pre-defined severity groups-non-SIRS and SIRS groups with no documented infections and Severe Sepsis and Septic Shock groups with documented infections, (p = 0.169). PCT values from CLD patients differed from all ALF groups (median CLD PCT value 0.104 ng/mL, (p ≤0.001)). Subjects with acetaminophen (APAP) toxicity, many without evidence of infection, demonstrated median PCT >2.0 ng/mL, regardless of SIRS features, while some culture positive subjects had PCT values <2.0 ng/mL.
  
  
  CONCLUSIONS
  While PCT appears to be a robust assay for detecting bacterial infection in the general population, there was poor discrimination between ALF patients with or without bacterial infection presumably because of the massive inflammation observed. Severe hepatocyte necrosis with inflammation results in elevated PCT levels, rendering this biomarker unreliable in the ALF setting.
authors.affiliation: Department of Internal Medicine, Division of Digestive Diseases, UT Southwestern Medical Center, Dallas, Texas, United States of America; Department of Clinical Laboratory Sciences, School of Allied Health, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Jody A
authors.initials: JA
authors.lastname: Rule
authors.affiliation: Department of Clinical Sciences and Department of Psychiatry, Division of Biostatistics, UT Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Hynan
authors.affiliation: Department of Internal Medicine, Division of Digestive Diseases, UT Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Nahid
authors.initials: N
authors.lastname: Attar
authors.affiliation: Department of Internal Medicine, Division of Digestive Diseases, UT Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Corron
authors.initials: C
authors.lastname: Sanders
authors.affiliation: Department of Clinical Laboratory Sciences, School of Allied Health, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: William J
authors.initials: WJ
authors.lastname: Korzun
authors.affiliation: Department of Internal Medicine, Division of Digestive Diseases, UT Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001424:Bacterial Infections / Q000175:diagnosis* / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002116:Calcitonin / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide; D005260:Female; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000378:metabolism; D017114:Liver Failure, Acute / Q000175:diagnosis* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011498:Protein Precursors / Q000378:metabolism*; D012189:Retrospective Studies; D018805:Sepsis / Q000175:diagnosis / Q000378:metabolism; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000175:diagnosis / Q000378:metabolism; D018746:Systemic Inflammatory Response Syndrome / Q000175:diagnosis / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide