Ribavirin improves early responses to peginterferon through improved interferon signaling.
Ribavirin improves early responses to peginterferon through improved interferon signaling.
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DOI：
10.1053/j.gastro.2010.03.037
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发表时间：
2010-07
期刊：
影响因子：
29.4
通讯作者：
Hoofnagle JH
中科院分区：
文献类型：
--
作者：
Feld JJ;Lutchman GA;Heller T;Hara K;Pfeiffer JK;Leff RD;Meek C;Rivera M;Ko M;Koh C;Rotman Y;Ghany MG;Haynes-Williams V;Neumann AU;Liang TJ;Hoofnagle JH
The therapeutic mechanisms of ribavirin for hepatitis C are unclear. Microarray analyses have shown that ribavirin increases induction of interferon-stimulated genes (ISGs). We evaluated viral kinetics, serum cytokine expression, and viral mutagenesis during early stages of peginterferon therapy with and without ribavirin. Fifty patients with chronic hepatitis C virus (HCV) infection genotype 1 were randomly assigned to groups that were given peginterferon alfa-2a, with or without ribavirin, for 4 weeks; all patients then received an additional 44 weeks of combination therapy. First- and second-phase viral kinetics were evaluated. Serum levels of IP10, MIG, and MCP1 were quantified as measures of the ISG response. NS5A and NS5B were partially sequenced and mutation rates were calculated. The first-phase decrease in HCV RNA was similar between groups. Patients that received ribavirin had a more rapid second-phase decrease, compared with patients that did not receive ribavirin—particularly those with an adequate first-phase decrease (0.61 vs. 0.35 log10 IU/mL/week, p=0.018). At 12 hrs, fold induction of serum IP10 was higher in patients given the combination therapy than those given only peginterferon (7.6- vs. 3.8-fold, p=0.01); however, the difference was greatest in patients with an adequate first-phase decrease in HCV RNA. IP10-induction correlated with first- and second-phase kinetics and with ribavirin serum concentrations on day 3. HCV mutation rates were similar between groups. Ribavirin improves the kinetics of the early response to therapy in patients with an adequate initial response to peginterferon. Induction of interferon-stimulated cytokines correlates with viral kinetics following ribavirin therapy, suggesting that ribavirin promotes interferon signaling.
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影响因子：
64.8
作者：
Dixit, NM;Layden-Almer, JE;Perelson, AS
通讯作者：
Perelson, AS
影响因子：
158.5
作者：
McHutchison, JG;Gordon, SC;Albrecht, JK
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Albrecht, JK
影响因子：
13.5
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Perelson, Alan S.
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Belle, Steven H.
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作者：
Neumann, AU;Lam, NP;Perelson, AS
通讯作者：
Perelson, AS