Mutations in the core and NS5A region of hepatitis C virus genotype 1b and correlation with response to pegylated-interferon-alpha 2b and ribavirin combination therapy.

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J Viral Hepat. 2010 Mar 28. [Epub ahead of print]

Mutations in the core and NS5A region of hepatitis C virus genotype 1b and

correlation with response to pegylated-interferon-alpha 2b and ribavirin

combination therapy.

Hayashi K, Katano Y, Ishigami M, Itoh A, Hirooka Y, Nakano I, Urano F, Yoshioka

K, Toyoda H, Kumada T, Goto H.

Department of Gastroenterology, Nagoya University Graduate School of Medicine,

Tsuruma-cho, Showa-ku, Nagoya, Japan.

Abstract

Summary. Mutations in two regions of hepatitis C virus (HCV) have been

implicated in influencing response to interferon (IFN) therapy. Substitutions in

the NS5A region of HCV have been associated with response to IFN therapy, and

this region has been known as the IFN sensitivity-determining region (ISDR). The

mutations in the core region of HCV have also been reported to predict IFN

response. The aim of this study was to investigate whether amino acid

substitutions in the core region and ISDR among patients with HCV genotype 1b

affect the response to IFN therapy. A total of 213 patients who completed IFN

treatment were randomly selected. All patients received pegylated-IFN-alpha 2b

once each week, plus oral ribavirin daily for 48 weeks. Of the 213 patients, 117

(54.9%) showed early virologic response (EVR), with HCV-negativity, at 12 weeks.

Factors related to EVR on multivariate analysis were non-Gln70 and Leu91 in the

core region, and ISDR mutant-type. One hundred and two (47.9%) showed a

sustained virologic response (SVR). SVR occurred more frequently in patients

without Gln70 (55.4%) than in those with Gln70 (21.3%) (P < 0.0001). SVR was

achieved in 43.6% of patients with wild-type ISDR and 62.5% of patients with

mutant-type (P = 0.0227). Of the 34 patients who simultaneously had non-Gln70

and mutant-type ISDR, 26 (76.5%) achieved SVR. Factors related to SVR on

multivariate analysis were non-Gln70 and ISDR mutant-type. In conclusion, amino

acid substitutions in the core region and ISDR were useful for predicting the

response to IFN in patients with HCV genotype 1b.

PMID: 20367792 [PubMed - as supplied by publisher]