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Alanine aminotransferase, HCV RNA levels and pro-inflammatory and pro-fibrogenic cytokines/chemokines during acute hepatitis C virus infection

BACKGROUND: This study assessed the association of alanine-aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels with pro-inflammatory and pro-fibrogenic cytokines and chemokines during acute HCV infection to provide further insight into the potential HCV immunopathogenesis. METHODS: Partici...

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Autores principales: Hajarizadeh, Behzad, Lamoury, François MJ, Feld, Jordan J., Amin, Janaki, Keoshkerian, Elizabeth, Matthews, Gail V., Hellard, Margaret, Dore, Gregory J., Lloyd, Andrew R., Grebely, Jason, Applegate, Tanya L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765111/
https://www.ncbi.nlm.nih.gov/pubmed/26911712
http://dx.doi.org/10.1186/s12985-016-0482-x
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author Hajarizadeh, Behzad
Lamoury, François MJ
Feld, Jordan J.
Amin, Janaki
Keoshkerian, Elizabeth
Matthews, Gail V.
Hellard, Margaret
Dore, Gregory J.
Lloyd, Andrew R.
Grebely, Jason
Applegate, Tanya L.
author_facet Hajarizadeh, Behzad
Lamoury, François MJ
Feld, Jordan J.
Amin, Janaki
Keoshkerian, Elizabeth
Matthews, Gail V.
Hellard, Margaret
Dore, Gregory J.
Lloyd, Andrew R.
Grebely, Jason
Applegate, Tanya L.
author_sort Hajarizadeh, Behzad
collection PubMed
description BACKGROUND: This study assessed the association of alanine-aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels with pro-inflammatory and pro-fibrogenic cytokines and chemokines during acute HCV infection to provide further insight into the potential HCV immunopathogenesis. METHODS: Participants in the ATAHC study, a prospective study of recent HCV infection, with detectable HCV RNA at the time of HCV detection were included. Plasma levels of 27 cytokines and chemokines were measured and their correlation with ALT and HCV RNA levels were assessed. Log(10) transformed cytokines and ALT values were used in the analysis. RESULTS: Among 117 individuals, the plasma levels of interferon-gamma inducible protein-10 (IP-10) and macrophage inflammatory protein-1beta (MIP-1β) were positively correlated with ALT levels (IP-10: r = 0.42, P < 0.001; MIP-1β: r = 0.29, P = 0.001) and HCV RNA levels (IP-10: rs = 0.44, P < 0.001; MIP-1β: rs = 0.43, P < 0.001). Using linear regression, after adjusting for sex, age, infection duration, symptomatic infection, HIV co-infection, interferon-lambda rs12979860 genotype, HCV genotype, and assay run, higher ALT levels (β = 0.20; 95 % CI: 0.07, 0.32; P = 0.002) and HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; β = 0.16; 95 % CI: 0.03, 0.28; P = 0.014) were independently associated with higher IP-10 levels. HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; β = 0.16; 95 % CI: 0.01, 0.31; P = 0.036) were associated with higher MIP-1β levels. CONCLUSIONS: During acute HCV infection, high ALT and HCV RNA levels were associated with increased IP-10 levels, while high HCV RNA levels were also associated with increased MIP-1β levels. These data suggest that IP-10 and MIP-1β may have a role in HCV immuno-pathogenesis starting early in acute HCV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0482-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-47651112016-02-25 Alanine aminotransferase, HCV RNA levels and pro-inflammatory and pro-fibrogenic cytokines/chemokines during acute hepatitis C virus infection Hajarizadeh, Behzad Lamoury, François MJ Feld, Jordan J. Amin, Janaki Keoshkerian, Elizabeth Matthews, Gail V. Hellard, Margaret Dore, Gregory J. Lloyd, Andrew R. Grebely, Jason Applegate, Tanya L. Virol J Research BACKGROUND: This study assessed the association of alanine-aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels with pro-inflammatory and pro-fibrogenic cytokines and chemokines during acute HCV infection to provide further insight into the potential HCV immunopathogenesis. METHODS: Participants in the ATAHC study, a prospective study of recent HCV infection, with detectable HCV RNA at the time of HCV detection were included. Plasma levels of 27 cytokines and chemokines were measured and their correlation with ALT and HCV RNA levels were assessed. Log(10) transformed cytokines and ALT values were used in the analysis. RESULTS: Among 117 individuals, the plasma levels of interferon-gamma inducible protein-10 (IP-10) and macrophage inflammatory protein-1beta (MIP-1β) were positively correlated with ALT levels (IP-10: r = 0.42, P < 0.001; MIP-1β: r = 0.29, P = 0.001) and HCV RNA levels (IP-10: rs = 0.44, P < 0.001; MIP-1β: rs = 0.43, P < 0.001). Using linear regression, after adjusting for sex, age, infection duration, symptomatic infection, HIV co-infection, interferon-lambda rs12979860 genotype, HCV genotype, and assay run, higher ALT levels (β = 0.20; 95 % CI: 0.07, 0.32; P = 0.002) and HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; β = 0.16; 95 % CI: 0.03, 0.28; P = 0.014) were independently associated with higher IP-10 levels. HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; β = 0.16; 95 % CI: 0.01, 0.31; P = 0.036) were associated with higher MIP-1β levels. CONCLUSIONS: During acute HCV infection, high ALT and HCV RNA levels were associated with increased IP-10 levels, while high HCV RNA levels were also associated with increased MIP-1β levels. These data suggest that IP-10 and MIP-1β may have a role in HCV immuno-pathogenesis starting early in acute HCV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0482-x) contains supplementary material, which is available to authorized users. BioMed Central 2016-02-24 /pmc/articles/PMC4765111/ /pubmed/26911712 http://dx.doi.org/10.1186/s12985-016-0482-x Text en © Hajarizadeh et al. 2016 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. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Hajarizadeh, Behzad
Lamoury, François MJ
Feld, Jordan J.
Amin, Janaki
Keoshkerian, Elizabeth
Matthews, Gail V.
Hellard, Margaret
Dore, Gregory J.
Lloyd, Andrew R.
Grebely, Jason
Applegate, Tanya L.
Alanine aminotransferase, HCV RNA levels and pro-inflammatory and pro-fibrogenic cytokines/chemokines during acute hepatitis C virus infection
title Alanine aminotransferase, HCV RNA levels and pro-inflammatory and pro-fibrogenic cytokines/chemokines during acute hepatitis C virus infection
title_full Alanine aminotransferase, HCV RNA levels and pro-inflammatory and pro-fibrogenic cytokines/chemokines during acute hepatitis C virus infection
title_fullStr Alanine aminotransferase, HCV RNA levels and pro-inflammatory and pro-fibrogenic cytokines/chemokines during acute hepatitis C virus infection
title_full_unstemmed Alanine aminotransferase, HCV RNA levels and pro-inflammatory and pro-fibrogenic cytokines/chemokines during acute hepatitis C virus infection
title_short Alanine aminotransferase, HCV RNA levels and pro-inflammatory and pro-fibrogenic cytokines/chemokines during acute hepatitis C virus infection
title_sort alanine aminotransferase, hcv rna levels and pro-inflammatory and pro-fibrogenic cytokines/chemokines during acute hepatitis c virus infection
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765111/
https://www.ncbi.nlm.nih.gov/pubmed/26911712
http://dx.doi.org/10.1186/s12985-016-0482-x
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