Decreased IP-10 and elevated TGFß1 levels are associated with viral clearance following therapy in patients with hepatitis C virus

The role of pro-fibrogenic cytokines in the outcome of infections with hepatitis C virus (HCV) and the response to treatment with pegylated interferon-alpha (pegIFNa) and ribavirin remains unclear. To address this issue, we assessed hepatic fibrosis and plasma markers pertinent to T-cell mediated fi...

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Main Authors: Lee, S., Varano, J., Flexman, J., Cheng, W., Watson, M., Rossi, E., Adams, L., Bulsara, M., Price, Patricia
Format: Journal Article
Published: Hindawi Publishing Corporation 2010
Online Access:http://hdl.handle.net/20.500.11937/41097
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author Lee, S.
Varano, J.
Flexman, J.
Cheng, W.
Watson, M.
Rossi, E.
Adams, L.
Bulsara, M.
Price, Patricia
author_facet Lee, S.
Varano, J.
Flexman, J.
Cheng, W.
Watson, M.
Rossi, E.
Adams, L.
Bulsara, M.
Price, Patricia
author_sort Lee, S.
building Curtin Institutional Repository
collection Online Access
description The role of pro-fibrogenic cytokines in the outcome of infections with hepatitis C virus (HCV) and the response to treatment with pegylated interferon-alpha (pegIFNa) and ribavirin remains unclear. To address this issue, we assessed hepatic fibrosis and plasma markers pertinent to T-cell mediated fibrogenesis and inflammation at the start of treatment. Levels of soluble (s)CD30, interleukin-13 receptor alpha 2 (IL-13Ra2), total and active transforming growth factor-beta 1 (TGFß1), interleukin-18 (IL-18) and interferon-gamma inducible protein-10 (IP-10, CXCL10) were correlated with the severity of fibrosis and with treatment outcome using multiple logistic regression modelling. The Hepascore algorithm was confirmed as a marker of fibrosis, but was a poor predictor of treatment outcome. Inclusion of all immunological markers improved prediction based on Hepascore alone (p=0.045), but optimal prediction was achieved with an algorithm ("TIPscore") based on TGFß1 (total), IP-10, age, sex and HCV genotype (p=0.003 relative to Hepascore). Whilst this was only marginally more effective than predictions based on HCV genotype age and sex (p=0.07), it associates high TGFß1 and low IP-10 levels with a failure of therapy. © 2010 - IOS Press and the authors. All rights reserved.
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spelling curtin-20.500.11937-410972017-09-13T14:28:47Z Decreased IP-10 and elevated TGFß1 levels are associated with viral clearance following therapy in patients with hepatitis C virus Lee, S. Varano, J. Flexman, J. Cheng, W. Watson, M. Rossi, E. Adams, L. Bulsara, M. Price, Patricia The role of pro-fibrogenic cytokines in the outcome of infections with hepatitis C virus (HCV) and the response to treatment with pegylated interferon-alpha (pegIFNa) and ribavirin remains unclear. To address this issue, we assessed hepatic fibrosis and plasma markers pertinent to T-cell mediated fibrogenesis and inflammation at the start of treatment. Levels of soluble (s)CD30, interleukin-13 receptor alpha 2 (IL-13Ra2), total and active transforming growth factor-beta 1 (TGFß1), interleukin-18 (IL-18) and interferon-gamma inducible protein-10 (IP-10, CXCL10) were correlated with the severity of fibrosis and with treatment outcome using multiple logistic regression modelling. The Hepascore algorithm was confirmed as a marker of fibrosis, but was a poor predictor of treatment outcome. Inclusion of all immunological markers improved prediction based on Hepascore alone (p=0.045), but optimal prediction was achieved with an algorithm ("TIPscore") based on TGFß1 (total), IP-10, age, sex and HCV genotype (p=0.003 relative to Hepascore). Whilst this was only marginally more effective than predictions based on HCV genotype age and sex (p=0.07), it associates high TGFß1 and low IP-10 levels with a failure of therapy. © 2010 - IOS Press and the authors. All rights reserved. 2010 Journal Article http://hdl.handle.net/20.500.11937/41097 10.3233/DMA-2010-0699 Hindawi Publishing Corporation restricted
spellingShingle Lee, S.
Varano, J.
Flexman, J.
Cheng, W.
Watson, M.
Rossi, E.
Adams, L.
Bulsara, M.
Price, Patricia
Decreased IP-10 and elevated TGFß1 levels are associated with viral clearance following therapy in patients with hepatitis C virus
title Decreased IP-10 and elevated TGFß1 levels are associated with viral clearance following therapy in patients with hepatitis C virus
title_full Decreased IP-10 and elevated TGFß1 levels are associated with viral clearance following therapy in patients with hepatitis C virus
title_fullStr Decreased IP-10 and elevated TGFß1 levels are associated with viral clearance following therapy in patients with hepatitis C virus
title_full_unstemmed Decreased IP-10 and elevated TGFß1 levels are associated with viral clearance following therapy in patients with hepatitis C virus
title_short Decreased IP-10 and elevated TGFß1 levels are associated with viral clearance following therapy in patients with hepatitis C virus
title_sort decreased ip-10 and elevated tgfß1 levels are associated with viral clearance following therapy in patients with hepatitis c virus
url http://hdl.handle.net/20.500.11937/41097