Viral clearance is associated with improved insulin resistance in genotype 1 chronic hepatitis C but not genotype 2/3

Alexander J. Thompson, Keyur Patel, Wan Long Chuang, Eric J. Lawitz, Maribel Rodriguez-Torres, Vinod Rustgi, Robert Flisiak, Stephen Pianko, Moises Diago, Sanjeev Arora, Graham R. Foster, Michael Torbenson, Yves Benhamou, David R. Nelson, Mark S. Sulkowski, Stefan Zeuzem, Erik Pulkstenis, G. Mani Subramanian, John G. McHutchison

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Abstract

Objectives: Genotype-specific associations between hepatitis C virus (HCV) and insulin resistance (IR) have been described, but a causal relationship remains unclear. This study investigated the association between a sustained virological response (SVR) and IR after chronic HCV therapy. Methods: 2255 treatment-naive patients with chronic HCV genotype 1 or 2/3 were enrolled in two phase 3 trials of albinterferon alpha-2b versus pegylated interferon alpha-2a for 48 or 24 weeks, respectively. IR was measured before treatment and 12 weeks after treatment using homeostasis model assessment (HOMA)-IR. Results: Paired HOMA-IR measurements were available in 1038 non-diabetic patients (497 with genotype 1; 541 with genotype 2/3). At baseline the prevalence of HOMA-IR >3 was greater in patients with genotype 1 than 2/3 (33% vs 27%; p=0.048). There was a significant reduction in the prevalence of IR in patients with genotype 1 achieving SVR (δ 10%; p<0.001), but not in genotype 1 non-responders or those with genotype 2/3. Multivariate analysis indicated that SVR was associated with a significant reduction in mean HOMA-IR in patients with genotype 1 (p=0.004), but not in those with genotype 2/3, which was independent of body mass index, alanine transaminase, γ-glutamyl transpeptidase and lipid level changes. Conclusions: SVR is associated with a reduction in HOMA-IR in patients with HCV genotype 1 but not in those with genotype 2/3. Genotype 1 may have a direct effect on the development of IR, independent of host metabolic factors, and may be partially reversed by viral eradication.

Original languageEnglish (US)
Pages (from-to)128-134
Number of pages7
JournalGut
Volume61
Issue number1
DOIs
StatePublished - Jan 1 2012

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Chronic Hepatitis C
Insulin Resistance
Genotype
Homeostasis
Hepacivirus
gamma-Glutamyltransferase
Therapeutics
Alanine Transaminase
Body Mass Index
Multivariate Analysis

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Thompson, A. J., Patel, K., Chuang, W. L., Lawitz, E. J., Rodriguez-Torres, M., Rustgi, V., ... McHutchison, J. G. (2012). Viral clearance is associated with improved insulin resistance in genotype 1 chronic hepatitis C but not genotype 2/3. Gut, 61(1), 128-134. https://doi.org/10.1136/gut.2010.236158
Thompson, Alexander J. ; Patel, Keyur ; Chuang, Wan Long ; Lawitz, Eric J. ; Rodriguez-Torres, Maribel ; Rustgi, Vinod ; Flisiak, Robert ; Pianko, Stephen ; Diago, Moises ; Arora, Sanjeev ; Foster, Graham R. ; Torbenson, Michael ; Benhamou, Yves ; Nelson, David R. ; Sulkowski, Mark S. ; Zeuzem, Stefan ; Pulkstenis, Erik ; Subramanian, G. Mani ; McHutchison, John G. / Viral clearance is associated with improved insulin resistance in genotype 1 chronic hepatitis C but not genotype 2/3. In: Gut. 2012 ; Vol. 61, No. 1. pp. 128-134.
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abstract = "Objectives: Genotype-specific associations between hepatitis C virus (HCV) and insulin resistance (IR) have been described, but a causal relationship remains unclear. This study investigated the association between a sustained virological response (SVR) and IR after chronic HCV therapy. Methods: 2255 treatment-naive patients with chronic HCV genotype 1 or 2/3 were enrolled in two phase 3 trials of albinterferon alpha-2b versus pegylated interferon alpha-2a for 48 or 24 weeks, respectively. IR was measured before treatment and 12 weeks after treatment using homeostasis model assessment (HOMA)-IR. Results: Paired HOMA-IR measurements were available in 1038 non-diabetic patients (497 with genotype 1; 541 with genotype 2/3). At baseline the prevalence of HOMA-IR >3 was greater in patients with genotype 1 than 2/3 (33{\%} vs 27{\%}; p=0.048). There was a significant reduction in the prevalence of IR in patients with genotype 1 achieving SVR (δ 10{\%}; p<0.001), but not in genotype 1 non-responders or those with genotype 2/3. Multivariate analysis indicated that SVR was associated with a significant reduction in mean HOMA-IR in patients with genotype 1 (p=0.004), but not in those with genotype 2/3, which was independent of body mass index, alanine transaminase, γ-glutamyl transpeptidase and lipid level changes. Conclusions: SVR is associated with a reduction in HOMA-IR in patients with HCV genotype 1 but not in those with genotype 2/3. Genotype 1 may have a direct effect on the development of IR, independent of host metabolic factors, and may be partially reversed by viral eradication.",
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Thompson, AJ, Patel, K, Chuang, WL, Lawitz, EJ, Rodriguez-Torres, M, Rustgi, V, Flisiak, R, Pianko, S, Diago, M, Arora, S, Foster, GR, Torbenson, M, Benhamou, Y, Nelson, DR, Sulkowski, MS, Zeuzem, S, Pulkstenis, E, Subramanian, GM & McHutchison, JG 2012, 'Viral clearance is associated with improved insulin resistance in genotype 1 chronic hepatitis C but not genotype 2/3', Gut, vol. 61, no. 1, pp. 128-134. https://doi.org/10.1136/gut.2010.236158

Viral clearance is associated with improved insulin resistance in genotype 1 chronic hepatitis C but not genotype 2/3. / Thompson, Alexander J.; Patel, Keyur; Chuang, Wan Long; Lawitz, Eric J.; Rodriguez-Torres, Maribel; Rustgi, Vinod; Flisiak, Robert; Pianko, Stephen; Diago, Moises; Arora, Sanjeev; Foster, Graham R.; Torbenson, Michael; Benhamou, Yves; Nelson, David R.; Sulkowski, Mark S.; Zeuzem, Stefan; Pulkstenis, Erik; Subramanian, G. Mani; McHutchison, John G.

In: Gut, Vol. 61, No. 1, 01.01.2012, p. 128-134.

Research output: Contribution to journalArticle

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T1 - Viral clearance is associated with improved insulin resistance in genotype 1 chronic hepatitis C but not genotype 2/3

AU - Thompson, Alexander J.

AU - Patel, Keyur

AU - Chuang, Wan Long

AU - Lawitz, Eric J.

AU - Rodriguez-Torres, Maribel

AU - Rustgi, Vinod

AU - Flisiak, Robert

AU - Pianko, Stephen

AU - Diago, Moises

AU - Arora, Sanjeev

AU - Foster, Graham R.

AU - Torbenson, Michael

AU - Benhamou, Yves

AU - Nelson, David R.

AU - Sulkowski, Mark S.

AU - Zeuzem, Stefan

AU - Pulkstenis, Erik

AU - Subramanian, G. Mani

AU - McHutchison, John G.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Objectives: Genotype-specific associations between hepatitis C virus (HCV) and insulin resistance (IR) have been described, but a causal relationship remains unclear. This study investigated the association between a sustained virological response (SVR) and IR after chronic HCV therapy. Methods: 2255 treatment-naive patients with chronic HCV genotype 1 or 2/3 were enrolled in two phase 3 trials of albinterferon alpha-2b versus pegylated interferon alpha-2a for 48 or 24 weeks, respectively. IR was measured before treatment and 12 weeks after treatment using homeostasis model assessment (HOMA)-IR. Results: Paired HOMA-IR measurements were available in 1038 non-diabetic patients (497 with genotype 1; 541 with genotype 2/3). At baseline the prevalence of HOMA-IR >3 was greater in patients with genotype 1 than 2/3 (33% vs 27%; p=0.048). There was a significant reduction in the prevalence of IR in patients with genotype 1 achieving SVR (δ 10%; p<0.001), but not in genotype 1 non-responders or those with genotype 2/3. Multivariate analysis indicated that SVR was associated with a significant reduction in mean HOMA-IR in patients with genotype 1 (p=0.004), but not in those with genotype 2/3, which was independent of body mass index, alanine transaminase, γ-glutamyl transpeptidase and lipid level changes. Conclusions: SVR is associated with a reduction in HOMA-IR in patients with HCV genotype 1 but not in those with genotype 2/3. Genotype 1 may have a direct effect on the development of IR, independent of host metabolic factors, and may be partially reversed by viral eradication.

AB - Objectives: Genotype-specific associations between hepatitis C virus (HCV) and insulin resistance (IR) have been described, but a causal relationship remains unclear. This study investigated the association between a sustained virological response (SVR) and IR after chronic HCV therapy. Methods: 2255 treatment-naive patients with chronic HCV genotype 1 or 2/3 were enrolled in two phase 3 trials of albinterferon alpha-2b versus pegylated interferon alpha-2a for 48 or 24 weeks, respectively. IR was measured before treatment and 12 weeks after treatment using homeostasis model assessment (HOMA)-IR. Results: Paired HOMA-IR measurements were available in 1038 non-diabetic patients (497 with genotype 1; 541 with genotype 2/3). At baseline the prevalence of HOMA-IR >3 was greater in patients with genotype 1 than 2/3 (33% vs 27%; p=0.048). There was a significant reduction in the prevalence of IR in patients with genotype 1 achieving SVR (δ 10%; p<0.001), but not in genotype 1 non-responders or those with genotype 2/3. Multivariate analysis indicated that SVR was associated with a significant reduction in mean HOMA-IR in patients with genotype 1 (p=0.004), but not in those with genotype 2/3, which was independent of body mass index, alanine transaminase, γ-glutamyl transpeptidase and lipid level changes. Conclusions: SVR is associated with a reduction in HOMA-IR in patients with HCV genotype 1 but not in those with genotype 2/3. Genotype 1 may have a direct effect on the development of IR, independent of host metabolic factors, and may be partially reversed by viral eradication.

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