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Dig Dis. 2013;31(5-6):426-33. doi: 10.1159/000355381. Epub 2013 Nov 21.

Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotypes 2a and 2b and high viral load.

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1
Department of Gastroenterology, Kobe Asahi Hospital, Kobe, Japan.

Abstract

OBJECTIVE:

We investigated the impact of host genetics represented by the single nucleotide polymorphism (SNP) of the IL28B gene and viral genetic variations within the nonstructural protein 5A (NS5A) [including the interferon (IFN)/ribavirin (RBV) resistance-determining region (IRRDR) and the IFN sensitivity-determining region (ISDR)] on the outcome of pegylated IFN and RBV (PEG-IFN/RBV) treatment.

METHODS:

Sixty-six patients infected with hepatitis C virus (HCV)-2a or HCV-2b who received PEG-IFN/RBV for 24 weeks were examined.

RESULTS:

In HCV-2a, the major genotype of IL28B SNP showed a tendency toward association with sustained virological response (SVR) and rapid virological response (RVR), and four or more mutations in IRRDR (IRRDR[2a] ≥4) and one or more mutations in ISDR plus its carboxyl-flanking region (ISDR/+C[2a] ≥1) were significantly associated with SVR and RVR. In HCV-2b, one or more mutations in the N-terminal part of IRRDR (IRRDR/N[2b] ≥1) were significantly associated with RVR. Multivariate analysis identified the major genotype of IL28B SNP and IRRDR[2a] ≥4 as independent predictive factors of SVR in HCV-2a, with IRRDR[2a] ≥4 being more powerful than the IL28B SNP. Also, IRRDR[2a] ≥4 in HCV-2a and IRRDR/N[2b] ≥1 in HCV-2b were significant determiners of RVR.

CONCLUSION:

The NS5A sequence heterogeneity and IL28B SNP are useful factors to predict the sensitivity to PEG-IFN/RBV therapy in HCV-2a and HCV-2b infections.

PMID:
24281016
DOI:
10.1159/000355381
[Indexed for MEDLINE]
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