Procalcitonin identifies cell injury, not bacterial infection, in acute liver failure

Jody A. Rule, Linda S. Hynan, Nahid Attar, Corron Sanders, William J. Korzun, William M. Lee, Anne M. Larson, Iris Liou, Timothy Davern, Oren Fix, Michael Schilsky, Timothy McCashland, J. Eileen Hay, Natalie Murray, A. Obaid S. Shaikh, Andres Blei, Daniel R Ganger, Atif Zaman, Steven H.B. Han, Robert Fontana & 13 others Brendan McGuire, Raymond T. Chung, Alastair Smith, Robert Brown, Jeffrey Crippin, Edwyn Harrison, Adrian Reuben, Santiago Munoz, Rajender Reddy, R. Todd Stravitz, Lorenzo Rossaro, Raj Satyanarayana, Tarek Hassanein

Research output: Contribution to journalArticle

17 Citations (Scopus)

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. Method. 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. Summary/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.

Original languageEnglish (US)
Article numbere0138566
JournalPloS one
Volume10
Issue number9
DOIs
StatePublished - Sep 22 2015

Fingerprint

liver failure
Acute Liver Failure
Calcitonin
bacterial infections
Bacterial Infections
Liver
Wounds and Injuries
cells
liver diseases
septic shock
sepsis (infection)
Liver Diseases
Sepsis
Chronic Disease
infection
Acetaminophen
Septic Shock
Infection
inflammation
acetaminophen

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Rule, J. A., Hynan, L. S., Attar, N., Sanders, C., Korzun, W. J., Lee, W. M., ... Hassanein, T. (2015). Procalcitonin identifies cell injury, not bacterial infection, in acute liver failure. PloS one, 10(9), [e0138566]. https://doi.org/10.1371/journal.pone.0138566
Rule, Jody A. ; Hynan, Linda S. ; Attar, Nahid ; Sanders, Corron ; Korzun, William J. ; Lee, William M. ; Larson, Anne M. ; Liou, Iris ; Davern, Timothy ; Fix, Oren ; Schilsky, Michael ; McCashland, Timothy ; Hay, J. Eileen ; Murray, Natalie ; Shaikh, A. Obaid S. ; Blei, Andres ; Ganger, Daniel R ; Zaman, Atif ; Han, Steven H.B. ; Fontana, Robert ; McGuire, Brendan ; Chung, Raymond T. ; Smith, Alastair ; Brown, Robert ; Crippin, Jeffrey ; Harrison, Edwyn ; Reuben, Adrian ; Munoz, Santiago ; Reddy, Rajender ; Stravitz, R. Todd ; Rossaro, Lorenzo ; Satyanarayana, Raj ; Hassanein, Tarek. / Procalcitonin identifies cell injury, not bacterial infection, in acute liver failure. In: PloS one. 2015 ; Vol. 10, No. 9.
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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. Method. 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. Summary/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.",
author = "Rule, {Jody A.} and Hynan, {Linda S.} and Nahid Attar and Corron Sanders and Korzun, {William J.} and Lee, {William M.} and Larson, {Anne M.} and Iris Liou and Timothy Davern and Oren Fix and Michael Schilsky and Timothy McCashland and Hay, {J. Eileen} and Natalie Murray and Shaikh, {A. Obaid S.} and Andres Blei and Ganger, {Daniel R} and Atif Zaman and Han, {Steven H.B.} and Robert Fontana and Brendan McGuire and Chung, {Raymond T.} and Alastair Smith and Robert Brown and Jeffrey Crippin and Edwyn Harrison and Adrian Reuben and Santiago Munoz and Rajender Reddy and Stravitz, {R. Todd} and Lorenzo Rossaro and Raj Satyanarayana and Tarek Hassanein",
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Rule, JA, Hynan, LS, Attar, N, Sanders, C, Korzun, WJ, Lee, WM, Larson, AM, Liou, I, Davern, T, Fix, O, Schilsky, M, McCashland, T, Hay, JE, Murray, N, Shaikh, AOS, Blei, A, Ganger, DR, Zaman, A, Han, SHB, Fontana, R, McGuire, B, Chung, RT, Smith, A, Brown, R, Crippin, J, Harrison, E, Reuben, A, Munoz, S, Reddy, R, Stravitz, RT, Rossaro, L, Satyanarayana, R & Hassanein, T 2015, 'Procalcitonin identifies cell injury, not bacterial infection, in acute liver failure', PloS one, vol. 10, no. 9, e0138566. https://doi.org/10.1371/journal.pone.0138566

Procalcitonin identifies cell injury, not bacterial infection, in acute liver failure. / Rule, Jody A.; Hynan, Linda S.; Attar, Nahid; Sanders, Corron; Korzun, William J.; Lee, William M.; Larson, Anne M.; Liou, Iris; Davern, Timothy; Fix, Oren; Schilsky, Michael; McCashland, Timothy; Hay, J. Eileen; Murray, Natalie; Shaikh, A. Obaid S.; Blei, Andres; Ganger, Daniel R; Zaman, Atif; Han, Steven H.B.; Fontana, Robert; McGuire, Brendan; Chung, Raymond T.; Smith, Alastair; Brown, Robert; Crippin, Jeffrey; Harrison, Edwyn; Reuben, Adrian; Munoz, Santiago; Reddy, Rajender; Stravitz, R. Todd; Rossaro, Lorenzo; Satyanarayana, Raj; Hassanein, Tarek.

In: PloS one, Vol. 10, No. 9, e0138566, 22.09.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Procalcitonin identifies cell injury, not bacterial infection, in acute liver failure

AU - Rule, Jody A.

AU - Hynan, Linda S.

AU - Attar, Nahid

AU - Sanders, Corron

AU - Korzun, William J.

AU - Lee, William M.

AU - Larson, Anne M.

AU - Liou, Iris

AU - Davern, Timothy

AU - Fix, Oren

AU - Schilsky, Michael

AU - McCashland, Timothy

AU - Hay, J. Eileen

AU - Murray, Natalie

AU - Shaikh, A. Obaid S.

AU - Blei, Andres

AU - Ganger, Daniel R

AU - Zaman, Atif

AU - Han, Steven H.B.

AU - Fontana, Robert

AU - McGuire, Brendan

AU - Chung, Raymond T.

AU - Smith, Alastair

AU - Brown, Robert

AU - Crippin, Jeffrey

AU - Harrison, Edwyn

AU - Reuben, Adrian

AU - Munoz, Santiago

AU - Reddy, Rajender

AU - Stravitz, R. Todd

AU - Rossaro, Lorenzo

AU - Satyanarayana, Raj

AU - Hassanein, Tarek

PY - 2015/9/22

Y1 - 2015/9/22

N2 - 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. Method. 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. Summary/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.

AB - 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. Method. 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. Summary/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.

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Rule JA, Hynan LS, Attar N, Sanders C, Korzun WJ, Lee WM et al. Procalcitonin identifies cell injury, not bacterial infection, in acute liver failure. PloS one. 2015 Sep 22;10(9). e0138566. https://doi.org/10.1371/journal.pone.0138566