[Structural analysis of the PKR-binding region of HCV 1b samples from patients with chronic hepatitis C and the correlation with IFN-sensitivity].
Gervain J., Czibula A., Simon J., Kalmár T.
INTRODUCTION: 91.5% of all chronic HCV infections are of 1b-type in Hungary. Japanese researchers found a correlation between the outcome of interferon (IFN) therapy and the structure of the PKR-Binding Region (aa: 2209-2274) of the viral NS5A domain, especially a particular subsection of the PKR-BR, the Interferon Sensitivity Determining Region (ISDR: aa 2209-2248). Several international studies could not confirm these findings. AIMS: The objectives of this study were 1. to determine the Hungarian prototype of HCV 1b based on the nucleotide sequence analysis of the PKR-BR of HCV 1b samples from patients with chronic hepatitis C; and 2. to investigate the relationship between the phenotypically expressed mutations of ISDR and the response to IFN therapy. PATIENTS: Pre-treatment serum samples of 21 chronic hepatitis C patients (13 women, 8 men), infected with HCV 1b and treated with IFN-alpha (3 sustained responders, 18 non-responders), were analysed retrospectively. METHODS: Nested reverse transcriptase-polymerase chain reaction (RT-PCR) and direct nucleotide sequencing were applied. RESULTS: 1. The dominant Hungarian quasispecies of HCV 1b differs from the Japan HCV 1b-J, the internationally accepted prototype. 2. The results showed significant correlation between the type of ISDR and the interferon response. Mutant type ISDRs (4 > or = amino acid substitutions) have predictive value for sustained response (p = 0.012). 3. The types and locations of substitutions are not characteristic, except that arginine in position 2218 has predictive value for therapy resistance. CONCLUSIONS: The authors' study results are in accordance with the earlier Japanese findings and confirm the predictive value of pre-treatment nucleotide sequencing in Hungary. Full adaptation of international research results to a Hungarian context should be treated with caution due to the between-countries virus prototype differences.