Clinical relevance of the 2′-5′-oligoadenylate synthetase/RNase L system for treatment response in chronic hepatitis C

被引：7
|
作者：
Mihm, Ulrike [1 ]
Ackermann, Oliver [1 ]
Welsch, Christoph [1 ,2 ]
Herrmann, Eva [3 ]
Hofmann, Wolf Peter [1 ]
Grigorian, Natalia [4 ]
Welker, Martin Walter [1 ]
Lengauer, Thomas [2 ]
Zeuzem, Stefan [1 ]
Sarrazin, Christoph [1 ]
机构：
[1] Univ Frankfurt Klinikum, Med Klin 1, D-60590 Frankfurt, Germany
[2] Max Planck Inst Informat & Angew Algorithm, D-66123 Saarbrucken, Germany
[3] Univ Frankfurt, Fachbereich Med, D-60590 Frankfurt, Germany
[4] Uniu Klinikum Saarlandes, Klin Innere Med 2, D-66421 Homburg, Germany
来源：
JOURNAL OF HEPATOLOGY | 2009年 / 50卷 / 01期
关键词：
Treatment response; Genotype; RNase L; RNA secondary structure; PROTEASE INHIBITOR TELAPREVIR; INTERFERON-TREATED CELLS; ALPHA-2B PLUS RIBAVIRIN; AMINO-ACID VARIATIONS; VIRUS TYPE 3A; RNASE-L; COMBINATION THERAPY; PEGYLATED INTERFERON-ALPHA-2B; 2-5A-DEPENDENT RNASE; HCV GENOTYPE-2;
D O I：
10.1016/j.jhep.2008.08.024
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
Background/Aims: Interferon-a induces 2'-5'-oligoadenylate synthetase which activates RNase L. Viral RNA is cleaved by RNase L at UU/-UA dinucleotides. The clinical relevance of RNase L cleavage for response to an interferon-alpha-based therapy in chronic hepatitis C is unknown. Methods: RNase L cleavage sites within pre-treatment sequences coding for structural and non-structural hepatitis C virus proteins were compared between non-responders and responders to an interferon-alpha-based therapy. Furthermore, RNase L cleavage sites were analyzed in full length and partial genome isolates of hepatitis C virus genotype 1b infected non-responders before and during treatment and in different hepatitis C virus genotypes (1b, 2a/b, 3a/b). Results: No differences in RNase L cleavage sites were observed between non-responders and responders within a given hepatitis C genotype. Non-responders with hepatitis C virus genotype 1b infection did not eliminate UA/UU dinucleotides during therapy. Hepatitis C virus genotype 1b isolates showed a lower number of UA/UU dinucleotides than hepatitis C virus genotypes 2/3 (p < 0.001). Conclusions: Response or non-response to an interferon-a-based therapy within a given hepatitis C virus genotype is not explained by differences for RNase L cleavage sites. General differences of interferon sensitivity between hepatitis C virus genotypes correlate significantly with frequencies of RNase L cleavage sites. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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页码：49 / 58
页数：10
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