Predictive values of amino acid sequences of the core and NS5A regions in antiviral therapy for hepatitis C: A Japanese multi-center study

Hepatology Center, Saiseikai Suita Hospital, 1-2 Kawazonocho, Suita, 564-0013, Japan.
Journal of Gastroenterology (Impact Factor: 4.52). 07/2009; 44(9):952-63. DOI: 10.1007/s00535-009-0087-x
Source: PubMed


Chronic hepatitis C (CHC) genotype 1b patients with high viral load are resistant to peginterferon (PEG-IFN) and ribavirin (RBV) combination therapy, especially older and female patients.
To elucidate the factors affecting early and sustained viral responses (EVR and SVR), 409 genotype 1b patients CHC with high viral loads who had received 48 weeks of PEG-IFN/RBV therapy were enrolled. The amino acid (aa) sequences of the HCV core at positions 70 and 91 and of the interferon sensitivity determining region (ISDR) were analyzed. Host factors, viral factors, and treatment-related factors were subjected to multivariate analysis.
Male gender, low HCV RNA load, high platelet count, two or more aa mutations of ISDR, and wild type of core aa 70 were independent predictive factors for SVR. In patients with over 80% adherences to both PEG-IFN and RBV, male gender, mild fibrosis stage, and wild type of core aa 70 were independent predictors for SVR.
Independent predictive factors for SVR were: no aa substitution at core aa 70, two or more aa mutations in the ISDR, low viral load, high values of platelet count, mild liver fibrosis and male gender.

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    • "Enomoto and Maekawa reported that mutations both in NS5A-ISDR (interferon sensitivity-determining region) and core 70Q substitution are associated with no early viral response during PEGIFN and RBV combination therapy [25]. Association of core aa70 substitution and mutations in NS5A region is confirmed to be associated with viral response by PEGIFN and RBV combination therapy in a Japanese multicenter cooperative study [26]. The number of mutations in the interferon sensitivity-determining region was shown to be associated with the viral response to PEGIFN and RBV combination treatment not only in Japan [27], but also in Tunisia [28]. "
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