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Impact of IL28B gene polymorphisms on interferon-?3 plasma levels during pegylated interferon-?/ribavirin therapy for chronic hepatitis C in patients coinfected with HIV.

ABSTRACT: OBJECTIVES:The mechanism explaining the strong association between IL28B rs12979860 polymorphisms and treatment outcome in chronic hepatitis C remains unclear. We explore whether IL28B protein [interferon (IFN)-?3] plasma levels may vary according to IL28B genotype and/or following pegylated IFN-?/ribavirin therapy. PATIENTS AND METHODS:A total of 112 HIV/hepatitis C virus (HCV)-coinfected patients who completed a course of pegylated IFN-?/ribavirin therapy were examined. Sustained virological response (SVR) was achieved by 56% of patients. IL28B rs12979860 alleles were genotyped using the 5' nuclease assay with specific TaqMan probes. A specific enzyme immunoassay was used to measure IFN-?3 plasma levels before initiating anti-HCV therapy and at week 4 of treatment. RESULTS:No significant differences between CC and non-CC IL28B carriers were found at baseline, either in the proportion of patients with detectable IFN-?3 plasma levels or in their median values. In contrast, median IFN-?3 plasma levels at week 4 of therapy significantly increased with respect to baseline in CC carriers [34.3 (16.7-56.3) versus 15.6 (15.6-30.3) pg/mL, respectively; P < 0.0001], but not in CT/TT carriers. Unexpectedly, increases in IFN-?3 at week 4 of therapy did not predict SVR. CONCLUSIONS:The exogenous administration of IFN-? may induce IFN-?3 release in IL28B CC carriers, but not in CT/TT carriers. However, this finding does not account for the link between IL28B polymorphisms and treatment outcome.

SUBMITTER: Rallon NI

PROVIDER: S-EPMC3695611 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Impact of IL28B gene polymorphisms on interferon-λ3 plasma levels during pegylated interferon-α/ribavirin therapy for chronic hepatitis C in patients coinfected with HIV.

Rallón Norma I NI Soriano Vincent V Naggie Susanna S Restrepo Clara C McHutchison John J Vispo Eugenia E Benito José M JM

The Journal of antimicrobial chemotherapy 20120201 5

<h4>Objectives</h4>The mechanism explaining the strong association between IL28B rs12979860 polymorphisms and treatment outcome in chronic hepatitis C remains unclear. We explore whether IL28B protein [interferon (IFN)-λ3] plasma levels may vary according to IL28B genotype and/or following pegylated IFN-α/ribavirin therapy.<h4>Patients and methods</h4>A total of 112 HIV/hepatitis C virus (HCV)-coinfected patients who completed a course of pegylated IFN-α/ribavirin therapy were examined. Sustaine ...[more]

PMID: 22294646

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Project description:Background and aim: Conventional hepatitis C treatment using pegylated interferon (PEG-IFN) and ribavirin is associated with significant side effects. IL28B polymorphism can predict response to treatment, with CC genotype having a better response. ITPA gene deficiency protects against clinically significant anaemia induced by treatment. The purpose of this study was to determine IL28B polymorphism and ITPA variation among hepatitis C genotype 1 patients who have undergone therapy with PEG-IFN and ribavirin and their association with sustained viral response (SVR). Methods: All hepatitis C genotype 1 patients who had been treated with PEG-IFN and ribavirin over the past 10 years were identified by available medical records and were contacted by letter of invitation to participate in the study. Blood samples for IL28B and ITPA genotyping were obtained. Medical records were reviewed for verification of treatment response, development of anaemia and if treatment reduction was required during the treatment. Results: A total of 61 patients with hepatitis C genotype 1 were treated with PEG-IFN and ribavirin, of whom 42 agreed to participate in the study. Mean age was 45.6±12.9 years at time of treatment, and 83.3% of patients were males. Thirty-three (78.6%) had IL28B CC genotype, of whom 25 (75.8%) obtained SVR compared with only 3 of 9 (33.3%) non C/C genotype patients who achieved SVR (P=0.041). Eleven (26.1%) patients had ITPA AC genotype, and 30 (71.4%) had CC genotype. There was no statistically significant difference between ITPA AC and CC genotypes in predicting clinically significant anaemia (45.5% vs 63.3%, P=0.302). Even among patients who developed anaemia, 70.8% still managed to achieve SVR. Treatment reduction also had no impact on SVR. Conclusion: Hepatitis C genotype 1 patients should be informed of the response rate for treatment with PEG-IFN and ribavirin in a population with favourable IL28B genotype before consideration of newer therapeutic options.

Dataset Information

Impact of IL28B gene polymorphisms on interferon-?3 plasma levels during pegylated interferon-?/ribavirin therapy for chronic hepatitis C in patients coinfected with HIV.

Publications

Impact of IL28B gene polymorphisms on interferon-λ3 plasma levels during pegylated interferon-α/ribavirin therapy for chronic hepatitis C in patients coinfected with HIV.

Similar Datasets

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