Center for the Study of Hepatitis C and Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY, USA.
Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, USA.
J Hepatol. 2011 Sep;55(3):545-553. doi: 10.1016/j.jhep.2010.12.033. Epub 2011 Jan 21.
BACKGROUND & AIMS: Characterization of inflammatory mediators, such as chemokines, during acute hepatitis C virus (HCV) infection might shed some light on viral clearance mechanisms.
Plasma levels of CXCR3 (CXCL9-11)- and CCR5 (CCL3-4)-associated chemokines, ALT, and HCV RNA were measured in nine injection drug users (median 26 samples/patient) before and during 10 acute (eight primary and two secondary) HCV infections. Using functional data analysis, we estimated smooth long-term trends in chemokine expression levels to obtain the magnitude and timing of overall changes. Residuals were analyzed to characterize short-term fluctuations.
CXCL9-11 induction began 38-53days and peaked 72-83days after virus acquisition. Increases in ALT levels followed a similar pattern. Substantial negative auto-correlations of chemokine levels at 1 week lags suggested substantial week-to-week oscillations. Significant correlations were observed between CXCL10 and HCV RNA as well as ALT and CXCR3-associated chemokines measured in the preceding week, CCL3-4 expression levels did not change appreciably during acute HCV infection.
Elevation of CXCR3-associated chemokines late during acute HCV infection suggests a role for cellular immune responses in chemokine induction. Week-to-week oscillations of HCV RNA, chemokines, and ALT suggest frequent, repeated cycles of gain and loss of immune control during acute hepatitis C.
在急性丙型肝炎病毒（HCV）感染期间，对趋化因子等炎症介质进行特征描述，可能有助于阐明病毒清除机制。
对 9 名注射吸毒者（每位患者中位数 26 个样本）在 10 次急性（8 次原发性和 2 次继发性）HCV 感染之前和期间，测量血浆中 CXCR3（CXCL9-11）和 CCR5（CCL3-4）相关趋化因子、丙氨酸氨基转移酶（ALT）和 HCV RNA 的水平。我们使用功能数据分析来估计趋化因子表达水平的平滑长期趋势，以获得整体变化的幅度和时间。分析残差以描述短期波动。
CXCL9-11 的诱导始于病毒获得后 38-53 天，在 72-83 天达到峰值。ALT 水平的升高也呈现类似的模式。趋化因子水平在 1 周滞后时存在显著的负自相关，表明存在显著的周间波动。在 HCV RNA 以及 ALT 和 CXCR3 相关趋化因子的前一周测量中，观察到 CXCL10 与 HCV RNA 之间以及 ALT 和 CXCR3 相关趋化因子之间存在显著相关性，而 CCL3-4 表达水平在急性 HCV 感染期间没有明显变化。
在急性 HCV 感染后期 CXCR3 相关趋化因子的升高提示细胞免疫反应在趋化因子诱导中起作用。HCV RNA、趋化因子和 ALT 的周间波动表明在急性丙型肝炎期间，免疫控制经常发生反复的得失循环。
