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Oxidative stress is closely associated with insulin resistance in genotypes 1 and 3 chronic hepatitis C

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Abstract

Background

Chronic hepatitis C (CHC) infection is associated with insulin resistance and with oxidative stress, but the relationship between the two has not been thoroughly examined.

Purpose

To evaluate the association between insulin resistance and oxidative stress in CHC patients.

Method

In 115 CHC patients (68 with genotype 1 and 47 with genotype 3), the relationship between the serum concentration of malondialdehyde (MDA), a marker of oxidative stress and insulin resistance as defined by the homeostasis model (HOMA-IR) was examined.

Results

There was no significant difference in MDA levels between genotype 1- and genotype 3-infected subjects (12.882 vs. 12.426 ng/mL, p = 0.2). By univariate analysis, factors associated with HOMA-IR in both genotypes were oxidative stress as measured by MDA (p = 0.002), body mass index (BMI), portal activity, and fibrosis. Genotype-specific differences in HOMA-IR association were steatosis and triglycerides (TG) for genotype 1, and age and glutathione (GSH) for genotype 3. In a stepwise multiple linear regression analysis in both genotypes, MDA was a significant and independent predictor of HOMA-IR (p = 0.04). As expected, BMI and fibrosis were likewise independently correlated to HOMA-IR. In addition, MDA levels were higher (p < 0.001) and GSH levels were lower (p = 0.023) in insulin-resistant subjects compared to their insulin-sensitive counterparts.

Conclusions

It is concluded that in CHC, oxidative stress is an independent predictor of HOMA-IR, irrespective of virus genotype. Further studies on the role of oxidative stress in the development of insulin resistance in CHC are warranted.

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Abbreviations

CHC:

Chronic hepatitis C

MDA:

Malondialdehyde

GSH:

Glutathione

HOMA-IR:

Homeostasis model assessment of insulin resistance

BMI:

Body mass index

WHR:

Waist/hip ratio

IR:

Insulin resistance

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

IR:

Insulin resistance

ROS:

Reactive oxygen species

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

GGT:

Gamma-glutamyl transpeptidase

T-chol:

Total cholesterol

HDL-C:

High density lipoprotein cholesterol

LDL-C:

Low density lipoprotein cholesterol

TG:

Triglycerides

HIV:

Human immunodeficiency virus

HPLC:

High performance liquid chromatography

SD:

Standard deviation

DNPH:

Dinitrophenylhydrazine

UV:

Ultraviolet

NS3:

Non-structural protein 3

NS5A:

Non-structural protein 5A

SOCS-3:

Suppressor of cytokine signaling-3

NF-κβ:

Nuclear factor-κβ

TNF-α:

Tumor necrosis factor-α

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Conflict of interest

The authors had financial support from Robert W. Storr Bequest to the Sydney Medical Foundation and National Health and Medical Research Council (NHMRC). The authors have no conflict of interest to disclose.

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Authors and Affiliations

  1. Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Darcy Road Westmead, Sydney, NSW 2145, Australia

    Said M. Hashemi, David van der Poorten, Francisco Barrera, Priyanka Bandara & Jacob George

  2. Departamento de Gastroenterología, Pontificia Universidad Católica, Santiago, Chile

    Francisco Barrera

  3. Department of Clinical Chemistry, Prince of Wales Hospital, Sydney, Australia

    Ora Lux

  4. Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, Australia

    James Kench

Authors
  1. Said M. Hashemi
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  2. David van der Poorten
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  3. Francisco Barrera
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  4. Priyanka Bandara
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  5. Ora Lux
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  6. James Kench
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  7. Jacob George
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Correspondence to Jacob George.

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Hashemi, S.M., van der Poorten, D., Barrera, F. et al. Oxidative stress is closely associated with insulin resistance in genotypes 1 and 3 chronic hepatitis C. Hepatol Int 7, 516–523 (2013). https://doi.org/10.1007/s12072-012-9400-5

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  • DOI: https://doi.org/10.1007/s12072-012-9400-5

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