Krónikus C-hepatitises betegekból izolált hepatitis C-vírus 1b protein kináz kötó régiójának szerkezeti analízise és ennek összefüggése az interferon kezelés eredményességével.

Translated title of the contribution: Structural analysis of the PKR-binding region of HCV 1b samples from patients with chronic hepatitis C and the correlation with IFN-sensitivity

Judit Gervain, A. Czibula, Judit Simon, Tibor Kalmár

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageHungarian
Pages (from-to)1179-1184
Number of pages6
JournalOrvosi Hetilap
Volume144
Issue number24
Publication statusPublished - Jun 15 2003

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Chronic Hepatitis C
Interferons
Hungary
Nucleotides
Therapeutics
Amino Acid Substitution
Reverse Transcriptase Polymerase Chain Reaction
Interferon-alpha
Sequence Analysis
Arginine
Japan
Research Personnel
Viruses
Mutation
Infection
Serum
Research

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Krónikus C-hepatitises betegekból izolált hepatitis C-vírus 1b protein kináz kötó régiójának szerkezeti analízise és ennek összefüggése az interferon kezelés eredményességével. / Gervain, Judit; Czibula, A.; Simon, Judit; Kalmár, Tibor.

In: Orvosi Hetilap, Vol. 144, No. 24, 15.06.2003, p. 1179-1184.

Research output: Contribution to journalArticle

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title = "Kr{\'o}nikus C-hepatitises betegekb{\'o}l izol{\'a}lt hepatitis C-v{\'i}rus 1b protein kin{\'a}z k{\"o}t{\'o} r{\'e}gi{\'o}j{\'a}nak szerkezeti anal{\'i}zise {\'e}s ennek {\"o}sszef{\"u}gg{\'e}se az interferon kezel{\'e}s eredm{\'e}nyess{\'e}g{\'e}vel.",
abstract = "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.",
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