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High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
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High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes

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Liver interleukin-8 messenger RNA expression and interferon sensitivity-determining region mutations relate to

Chuan-Mo Lee1, Yi-Hao Yen, Chao-Hung Hung

  • 1Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. chmolee@ms15.hinet.net

Antiviral Therapy
|September 9, 2011
PubMed
Abstract

Insights

Hepatitis C patients achieving sustained virological response (SVR) with combination therapy showed lower interleukin-8 (IL-8) mRNA expression and more non-structural 5A protein mutations in the interferon sensitivity-determining region (ISDR). These factors independently predicted SVR success.

Area of Science:

  • Hepatology
  • Virology
  • Immunology

Background:

  • Interferon (IFN)-α antiviral action can be inhibited by non-structural 5A protein through interactions with IFN-induced RNA-dependent protein kinase and interleukin (IL)-8 expression.
  • Mutations in the non-structural 5A protein's IFN sensitivity-determining region (ISDR) have been linked to sustained virological response (SVR).
  • IL-8 is implicated in the inhibition of IFN-α's antiviral effects.

Purpose of the Study:

  • To investigate the impact of pretreatment ISDR mutations and hepatic IL-8 mRNA expression on SVR rates in Hepatitis C virus (HCV) genotype 1b patients receiving combination therapy.
  • To determine if IL-8 expression and ISDR mutations are predictive biomarkers for treatment outcome.

Main Methods:

  • A cohort of 53 HCV-1b patients who completed 24 weeks of pegylated-IFN-α2b plus ribavirin therapy and follow-up were analyzed.
  • Liver biopsies were obtained within 6 months prior to therapy for analysis.
  • Hepatic IL-8 mRNA expression was quantified using real-time reverse transcriptase PCR.

Main Results:

  • 30 out of 53 patients achieved SVR.
  • Multivariate analysis identified hepatic IL-8 mRNA expression <1.5×10(-4) (OR 6.66) and ISDR mutations ≥4 (OR 12.20) as independent predictors of SVR.
  • Fibrosis scores and alanine aminotransferase levels predicted hepatic IL-8 mRNA expression (r(2)=0.204).

Conclusions:

  • Down-regulated hepatic IL-8 mRNA expression and the presence of ISDR mutations are associated with successful SVR to combination therapy in Hepatitis C 1b patients.
  • Hepatic IL-8 mRNA expression levels are influenced by fibrosis scores and alanine aminotransferase levels.

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