Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan; Research Center for Next Generation Medicine, Shinshu University, Matsumoto, Japan.
Department of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
Cytokine. 2018 Nov;111:357-363. doi: 10.1016/j.cyto.2018.10.004. Epub 2018 Oct 5.
Although serum chemokine levels have been reported to influence the outcome of interferon-based treatment in patients with chronic hepatitis C, their effect on the hepatitis C virus (HCV) response to direct-acting antiviral agents (DAAs), which can achieve high rates of a sustained virological response (SVR), is largely unknown. To clarify this relationship, 9 chemokines (eotaxin, GRO-α, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, RANTES, and SDF-1α) were quantified before, during, and after DAA treatment using serum samples obtained from 57 patients with chronic hepatitis C. All baseline median chemokine levels were significantly higher in patients with chronic hepatitis C than in healthy subjects (P < 0.05). In particular, lower MIP-1β (≤71.5 pg/mL) and higher RANTES (>671.5 pg/mL) levels were significantly associated with patients who failed to clear HCV RNA (P = 0.0039 and 0.013, respectively). Prediction of a clinical response based on a combination of these chemokines demonstrated high sensitivity (82%), specificity (85%), negative predictive value (95%), and area under the curve (0.833). The non-SVR rate (56.3%; 9 of 16) was significantly higher in patients with low MIP-1β and high RANTES compared with other combinations. Moreover, baseline MIP-1β and RANTES were both additive and independent for predicting a non-SVR. Apart from an increase in eotaxin, all chemokines became decreased in patients with a SVR. In conclusion, a combination of serum MIP-1β and RANTES levels may be predictive of a treatment response to DAAs in Japanese patients with chronic hepatitis C.
虽然已有研究报道血清趋化因子水平会影响慢性丙型肝炎患者接受基于干扰素治疗的结局，但它们对直接作用抗病毒药物（DAA）治疗丙型肝炎病毒（HCV）反应的影响（这些药物可以实现高持续病毒学应答率[SVR]）在很大程度上尚不清楚。为了阐明这种关系，我们使用从 57 例慢性丙型肝炎患者中获得的血清样本，在 DAA 治疗前、治疗期间和治疗后定量检测了 9 种趋化因子（嗜伊红细胞趋化因子、GRO-α、白细胞介素 8、干扰素诱导蛋白 10、单核细胞趋化蛋白 1、巨噬细胞炎性蛋白 1α、巨噬细胞炎性蛋白 1β、调节激活正常 T 细胞表达和分泌因子和基质细胞衍生因子 1α）。所有慢性丙型肝炎患者的基线中位趋化因子水平均显著高于健康对照者（P<0.05）。特别是，较低的 MIP-1β（≤71.5pg/mL）和较高的 RANTES（>671.5pg/mL）水平与未能清除 HCV RNA 的患者显著相关（P=0.0039 和 0.013）。基于这些趋化因子的组合对临床应答的预测显示出较高的灵敏度（82%）、特异性（85%）、阴性预测值（95%）和曲线下面积（0.833）。与其他组合相比，低 MIP-1β和高 RANTES 患者的非 SVR 率（56.3%；16 例中有 9 例）显著更高。此外，基线 MIP-1β 和 RANTES 对预测非 SVR 均为相加且独立的。除了嗜伊红细胞趋化因子增加外，所有趋化因子在 SVR 患者中均减少。总之，血清 MIP-1β 和 RANTES 水平的组合可能有助于预测日本慢性丙型肝炎患者对 DAA 的治疗反应。
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