Departamento de Gastroenterología y Hepatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zurbirán, Vasco de Quiroga No 15, México, D.F., México.
Arch Med Res. 2011 Jan;42(1):28-33. doi: 10.1016/j.arcmed.2011.01.001.
We undertook this study to determine the baseline gene expression of IFI27, IFIT1, IFI6, ISG15, IRF-1, IRF-3, OAS-2 and CXCL10 and its usefulness as molecular markers of response to antiviral treatment with peg-IFNα 2b/RBV in patients with hepatitis C virus genotype 1 (HCV-1).
Gene expression was analyzed by RT-PCR in baseline liver biopsies from 42 HCV-1 patients who were treated with Peg-IFNα 2b/RBV for 48 weeks. In addition, we investigated gene expression of these genes in a second liver biopsy obtained 24 weeks post-treatment in sustained viral response (SVR) and relapser patients.
Thirteen patients achieved SVR, four were relapsers, four patients with viral response (VR) discontinued the following for 24 weeks post-treatment and 21 patients did not respond to antiviral therapy (NR). All patients with HCV-1 showed gene overexpression in baseline liver tissue, but only IFI27, IFIT1, IFI6, ISG15, and CXCL10 showed differential gene expression, which is inversely related to the response to antiviral therapy. Thus, liver tissue of NR patients showed upregulation of these genes, whereas patients with SVR gene expression level was significantly lower. Furthermore, 24 weeks afterwards treatment, SVR patients showed a significant downregulation of such genes, which was consistent with the RNA-HCV suppression. ISGs (IFI27, IFIT1, IFI6) and chemokine CXCL10 showed the best positive and negative predictive values on SVR to IFN/RBV therapy (range: 70.8-75% and 71.43-82.35%), respectively.
IFI27, IFIT1, IFI6, ISG15, and CXCL10 genes are potential biological markers useful for predicting response to Peg-IFNα 2b/RBV therapy in HCV-1 patients.
本研究旨在确定基线 IFI27、IFIT1、IFI6、ISG15、IRF-1、IRF-3、OAS-2 和 CXCL10 的基因表达情况，并评估其作为聚乙二醇干扰素 α 2b/利巴韦林（Peg-IFNα 2b/RBV）治疗丙型肝炎病毒基因型 1（HCV-1）患者的分子标志物的作用。
采用 RT-PCR 法检测 42 例 HCV-1 患者基线肝组织中上述基因的表达情况。这些患者接受 Peg-IFNα 2b/RBV 治疗 48 周。此外，我们还在持续病毒学应答（SVR）和复发患者治疗 24 周后的第二次肝活检中检测了这些基因的表达情况。
13 例患者获得 SVR，4 例为复发者，4 例病毒学应答（VR）患者在治疗后 24 周时停药，21 例患者对抗病毒治疗无反应（NR）。所有 HCV-1 患者的基线肝组织均显示基因过表达，但只有 IFI27、IFIT1、IFI6、ISG15 和 CXCL10 显示差异表达，且与抗病毒治疗反应呈负相关。因此，NR 患者的肝组织显示这些基因的上调，而 SVR 患者的基因表达水平显著降低。此外，治疗 24 周后，SVR 患者的这些基因表达水平显著下调，与 HCV-RNA 抑制一致。ISGs（IFI27、IFIT1、IFI6）和趋化因子 CXCL10 对 IFN/RBV 治疗 SVR 的阳性和阴性预测值最佳（范围分别为 70.8-75%和 71.43-82.35%）。
IFI27、IFIT1、IFI6、ISG15 和 CXCL10 基因是预测 HCV-1 患者对 Peg-IFNα 2b/RBV 治疗反应的潜在生物学标志物。
