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The association between FABP7 serum levels with survival and neurological complications in acetaminophen-induced acute liver failure: a nested case–control study

BACKGROUND: Acetaminophen (APAP)-induced acute liver failure (ALF) is associated with significant mortality due to intracranial hypertension (ICH), a result of cerebral edema (CE) and astrocyte swelling. Brain-type fatty acid-binding protein (FABP7) is a small (15 kDa) cytoplasmic protein abundantly...

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Autores principales: Karvellas, Constantine J., Speiser, Jaime L., Tremblay, Mélanie, Lee, William M., Rose, Christopher F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629189/
https://www.ncbi.nlm.nih.gov/pubmed/28983815
http://dx.doi.org/10.1186/s13613-017-0323-0
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author Karvellas, Constantine J.
Speiser, Jaime L.
Tremblay, Mélanie
Lee, William M.
Rose, Christopher F.
author_facet Karvellas, Constantine J.
Speiser, Jaime L.
Tremblay, Mélanie
Lee, William M.
Rose, Christopher F.
author_sort Karvellas, Constantine J.
collection PubMed
description BACKGROUND: Acetaminophen (APAP)-induced acute liver failure (ALF) is associated with significant mortality due to intracranial hypertension (ICH), a result of cerebral edema (CE) and astrocyte swelling. Brain-type fatty acid-binding protein (FABP7) is a small (15 kDa) cytoplasmic protein abundantly expressed in astrocytes. The aim of this study was to determine whether serum FABP7 levels early (day 1) or late (days 3–5) level were associated with 21-day mortality and/or the presence of ICH/CE in APAP-ALF patients. METHODS: Serum samples from 198 APAP-ALF patients (nested case–control study with 99 survivors and 99 non-survivors) were analyzed by ELISA methods and assessed with clinical data from the US Acute Liver Failure Study Group (ALFSG) Registry (1998–2014). RESULTS: APAP-ALF survivors had significantly lower serum FABP7 levels on admission (147.9 vs. 316.5 ng/ml, p = 0.0002) and late (87.3 vs. 286.2 ng/ml, p < 0.0001) compared with non-survivors. However, a significant association between 21-day mortality and increased serum FABP7 early [log FABP7 odds ratio (OR) 1.16, p = 0.32] and late (log FABP7 ~ OR 1.34, p = 0.21) was not detected after adjusting for significant covariates (MELD, vasopressor use). Areas under the receiver-operating curve for early and late multivariable models were 0.760 and 0.892, respectively. In a second analysis, patients were grouped based on the presence (n = 46) or absence (n = 104) of ICH/CE. A significant difference in FABP7 levels between patients with or without ICH/CE at early (259.7 vs. 228.2 ng/ml, p = 0.61) and late (223.8 vs. 192.0 ng/ml, p = 0.19) time points was not identified. CONCLUSION: Serum FABP7 levels were significantly elevated at early and late time points in APAP-ALF non-survivors compared to survivors. However, significant differences in FABP7 levels by 21-day mortality were not ascertained after adjusting for significant covariates (reflecting severity of illness). Our study suggests that FABP7 may not discriminate between patients with or without intracranial complications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13613-017-0323-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-56291892017-10-23 The association between FABP7 serum levels with survival and neurological complications in acetaminophen-induced acute liver failure: a nested case–control study Karvellas, Constantine J. Speiser, Jaime L. Tremblay, Mélanie Lee, William M. Rose, Christopher F. Ann Intensive Care Research BACKGROUND: Acetaminophen (APAP)-induced acute liver failure (ALF) is associated with significant mortality due to intracranial hypertension (ICH), a result of cerebral edema (CE) and astrocyte swelling. Brain-type fatty acid-binding protein (FABP7) is a small (15 kDa) cytoplasmic protein abundantly expressed in astrocytes. The aim of this study was to determine whether serum FABP7 levels early (day 1) or late (days 3–5) level were associated with 21-day mortality and/or the presence of ICH/CE in APAP-ALF patients. METHODS: Serum samples from 198 APAP-ALF patients (nested case–control study with 99 survivors and 99 non-survivors) were analyzed by ELISA methods and assessed with clinical data from the US Acute Liver Failure Study Group (ALFSG) Registry (1998–2014). RESULTS: APAP-ALF survivors had significantly lower serum FABP7 levels on admission (147.9 vs. 316.5 ng/ml, p = 0.0002) and late (87.3 vs. 286.2 ng/ml, p < 0.0001) compared with non-survivors. However, a significant association between 21-day mortality and increased serum FABP7 early [log FABP7 odds ratio (OR) 1.16, p = 0.32] and late (log FABP7 ~ OR 1.34, p = 0.21) was not detected after adjusting for significant covariates (MELD, vasopressor use). Areas under the receiver-operating curve for early and late multivariable models were 0.760 and 0.892, respectively. In a second analysis, patients were grouped based on the presence (n = 46) or absence (n = 104) of ICH/CE. A significant difference in FABP7 levels between patients with or without ICH/CE at early (259.7 vs. 228.2 ng/ml, p = 0.61) and late (223.8 vs. 192.0 ng/ml, p = 0.19) time points was not identified. CONCLUSION: Serum FABP7 levels were significantly elevated at early and late time points in APAP-ALF non-survivors compared to survivors. However, significant differences in FABP7 levels by 21-day mortality were not ascertained after adjusting for significant covariates (reflecting severity of illness). Our study suggests that FABP7 may not discriminate between patients with or without intracranial complications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13613-017-0323-0) contains supplementary material, which is available to authorized users. Springer International Publishing 2017-10-05 /pmc/articles/PMC5629189/ /pubmed/28983815 http://dx.doi.org/10.1186/s13613-017-0323-0 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Research
Karvellas, Constantine J.
Speiser, Jaime L.
Tremblay, Mélanie
Lee, William M.
Rose, Christopher F.
The association between FABP7 serum levels with survival and neurological complications in acetaminophen-induced acute liver failure: a nested case–control study
title The association between FABP7 serum levels with survival and neurological complications in acetaminophen-induced acute liver failure: a nested case–control study
title_full The association between FABP7 serum levels with survival and neurological complications in acetaminophen-induced acute liver failure: a nested case–control study
title_fullStr The association between FABP7 serum levels with survival and neurological complications in acetaminophen-induced acute liver failure: a nested case–control study
title_full_unstemmed The association between FABP7 serum levels with survival and neurological complications in acetaminophen-induced acute liver failure: a nested case–control study
title_short The association between FABP7 serum levels with survival and neurological complications in acetaminophen-induced acute liver failure: a nested case–control study
title_sort association between fabp7 serum levels with survival and neurological complications in acetaminophen-induced acute liver failure: a nested case–control study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629189/
https://www.ncbi.nlm.nih.gov/pubmed/28983815
http://dx.doi.org/10.1186/s13613-017-0323-0
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