We found that these diversities were primarily found in E1, p7 and NS5A. In systemic searching for single amino acid positions or consecutive amino acid regions in the HCV ORF associated with the treatment outcome, several regions were extracted in E2, p7, NS2, NS5A and NS5B. Among those identified regions, E2 aa 723–770, NS2 aa 879– 893, NS5A aa2224–2242, and NS5A aa2379–2405 were correlated with the final outcome in an incremental manner according to the number of amino acid substitutions. Specifically, the sequences of those regions in non-SVR patients were almost homogeneous, while the sequences of the region in SVR patients were significantly diverse and multiple amino acid substitutions were found compared to the consensus sequence. Interestingly, among those regions, aa 2224– 2242 was completely included in the ISDR, in which the number of amino acid substitutions is known to show significant correlation with the treatment response to IFN-based therapy in genotype 1b, and also in genotype 2. In Temozolomide molecular weight recent studies of genotype 1b infection, amino acid variation of residues 70 and 91 in the Core were reported to be associated with the treatment response to IFN-based therapy. The correlation of amino acid variation in the Core with the response to PEG-IFN/RBV therapy was also identified in genotype 2a infection. In genotype 2b infection, however, we could not find such associations between amino acid variation in the core region and the response to PEG-IFN/RBV therapy. Amino acid residues of aa 70 and 91 were conserved irrespective of differences in the PEG-IFN/RBV responses. On the other hand, although amino acid variations were also sometimes found at residues 4 and 110 in genotype 2b HCV, their frequency was low, and no evident association between the variation and the treatment response was found. Although the reason of the lack of association between the Core and the PEG-IFN/RBV treatment response in genotype-2b HCV infection is unknown, it suggests that a different mechanism affecting the treatment response might exist, depending on genotype-specific viral features. In genotype 1 HCV, variations within the PKR-binding region of NS5A, including those within the ISDR, were reported to disrupt the NS5A-PKR interaction, possibly rendering HCV sensitive to the antiviral effects of interferon. Clinically, the number of substitutions within the ISDR has been reported to correlate with the serum HCV RNA level in genotype 1 and 2a infections. In addition, a recent study reported that mutations in the ISDR also show the correlation with the relapse in the PEGIFN/RBV therapy in genotype 1b infection. Because NS5A aa2224–2242, part of ISDR, was extracted as one of those regions related to the treatment response in genotype 2b infection, we undertook further analysis to investigate the correlation between amino acid variation numbers and serum HCV RNA level. Though the reason is unknown, we could not find evidence of a relationship between variation in the NS5A aa 2224–2242 and HCV RNA titer in genotype 2b infection, unlike genotypes 1 and 2a.