Procalcitonin Identifies Cell Injury, Not Bacterial Infection, in Acute Liver Failure
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 whethe...
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Published in | PloS one Vol. 10; no. 9; p. e0138566 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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United States
Public Library of Science
22.09.2015
Public Library of Science (PLoS) |
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Abstract | 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.
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.
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.
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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AbstractList | 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. 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. 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 [less than or equal to]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. 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. 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 [less than or equal to]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. 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. 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. 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. 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. 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. BACKGROUNDBecause 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.METHODRetrospective 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.RESULTSProcalcitonin 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/CONCLUSIONSWhile 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. 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. 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.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.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.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. |
Audience | Academic |
Author | Hynan, Linda S. Rule, Jody A. Korzun, William J. Sanders, Corron Attar, Nahid Lee, William M. |
AuthorAffiliation | 2 Department of Clinical Sciences and Department of Psychiatry, Division of Biostatistics, UT Southwestern Medical Center, Dallas, Texas, United States of America University Hospital Oldenburg, GERMANY 3 Department of Clinical Laboratory Sciences, School of Allied Health, Virginia Commonwealth University, Richmond, Virginia, United States of America 1 Department of Internal Medicine, Division of Digestive Diseases, UT Southwestern Medical Center, Dallas, Texas, United States of America |
AuthorAffiliation_xml | – name: 2 Department of Clinical Sciences and Department of Psychiatry, Division of Biostatistics, UT Southwestern Medical Center, Dallas, Texas, United States of America – name: University Hospital Oldenburg, GERMANY – name: 1 Department of Internal Medicine, Division of Digestive Diseases, UT Southwestern Medical Center, Dallas, Texas, United States of America – name: 3 Department of Clinical Laboratory Sciences, School of Allied Health, Virginia Commonwealth University, Richmond, Virginia, United States of America |
Author_xml | – sequence: 1 givenname: Jody A. surname: Rule fullname: Rule, Jody A. – sequence: 2 givenname: Linda S. surname: Hynan fullname: Hynan, Linda S. – sequence: 3 givenname: Nahid surname: Attar fullname: Attar, Nahid – sequence: 4 givenname: Corron surname: Sanders fullname: Sanders, Corron – sequence: 5 givenname: William J. surname: Korzun fullname: Korzun, William J. – sequence: 6 givenname: William M. surname: Lee fullname: Lee, William M. |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26393924$$D View this record in MEDLINE/PubMed |
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ContentType | Journal Article |
Contributor | Murray, Natalie Stravitz, R Todd Harrison, Edwyn Samuel, Grace Zaman, Atif Rossaro, Lorenzo Reddy, Rajender Lalani, Ezmina Sanders, Corron Ganger, Daniel Hassanein, Tarek Reuben, Adrian Fontana, Robert McGuire, Brendan Munoz, Santiago Schilsky, Michael Pezzia, Carla Murry, Mechelle Satyanarayana, Raj Balko, Jody A Liou, Iris Smith, Janet P Han, Steven H B Crippin, Jeffrey Larson, Anne M Brown, Robert Dillon, Catherine McCashland, Timothy Chung, Raymond T Smith, Alastair Hynan, Linda Lee, William M Fix, Oren Webster, Joe W Goddard, Tomoko Durkalski, Valerie Hay, J Eileen Attar, Nahid Davern, Timothy Battenhouse, Holly Blei, Andres Zhao, Wenle Reisch, Joan Shaikh, A Obaid S |
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Copyright | COPYRIGHT 2015 Public Library of Science 2015 Rule et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2015 Rule et al 2015 Rule et al |
Copyright_xml | – notice: COPYRIGHT 2015 Public Library of Science – notice: 2015 Rule et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: 2015 Rule et al 2015 Rule et al |
CorporateAuthor | Acute Liver Failure Study Group |
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DOI | 10.1371/journal.pone.0138566 |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: Siemens Healthcare Diagnostics provided instrumentation and reagents only for this study. The authors have no other relevant declarations relating to Siemens Healthcare Diagnostics. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. These authors also contributed equally to this work. Conceived and designed the experiments: JAR LSH WJK WML. Performed the experiments: JAR. Analyzed the data: JAR LSH WML. Contributed reagents/materials/analysis tools: JAR LSH. Wrote the paper: JAR LSH. Sample and data selection and procurement: NA CS. Membership of the Acute Liver Failure Study Group is listed in the Acknowledgments. |
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article-title: Clinical significance of serum procalcitonin levels in patients with acute or chronic liver disease publication-title: Eur J Gastroenterol Hepatol doi: 10.1097/00042737-200605000-00012 – volume: 253 start-page: 170 year: 2011 ident: ref21 article-title: Macrophage activation by factors released from acetaminophen-injured hepatocytes: Potential role of HMGB-1 publication-title: Toxicol Appl Pharmacol doi: 10.1016/j.taap.2011.04.003 – volume: 40 start-page: 336 year: 2007 ident: ref23 article-title: Evaluation of serum procalcitonin and interleukin-6 levels as markers of liver metastasis publication-title: Clin Biochem doi: 10.1016/j.clinbiochem.2006.10.027 – volume: 43 start-page: 341 issue: 3 year: 2010 ident: ref31 article-title: Long-term stability of procalcitonin in frozen samples and comparison of kryptor and VIDAS automated immunoassays publication-title: Clin Biochem doi: 10.1016/j.clinbiochem.2009.08.029 |
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Snippet | Because acute liver failure (ALF) patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection clinically in ALF... Background Because acute liver failure (ALF) patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection... BACKGROUNDBecause acute liver failure (ALF) patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection... Background Because acute liver failure (ALF) patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection... |
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SubjectTerms | Acetaminophen Adolescent Adult Aged Aged, 80 and over Analgesics Analysis Bacteria Bacterial diseases Bacterial infections Bacterial Infections - diagnosis Bacterial Infections - metabolism Bioindicators Biomarkers Biomarkers - metabolism Calcitonin - metabolism Calcitonin Gene-Related Peptide Cell culture Cell injury Data processing Disease control Etiology Failure Female Health aspects Humans Infection Infections Inflammation - diagnosis Inflammation - metabolism Internal medicine Laboratories Liver Liver diseases Liver failure Liver Failure, Acute - diagnosis Liver Failure, Acute - metabolism Male Medical research Medicine Middle Aged Patients Procalcitonin Prospective Studies Protein Precursors - metabolism Retrospective Studies Review boards Sepsis Sepsis - diagnosis Sepsis - metabolism Septic shock Severity of Illness Index Shock, Septic - diagnosis Shock, Septic - metabolism Studies Systemic Inflammatory Response Syndrome - diagnosis Systemic Inflammatory Response Syndrome - metabolism Thyroid gland Toxicity Young Adult |
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Title | Procalcitonin Identifies Cell Injury, Not Bacterial Infection, in Acute Liver Failure |
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