Clinical Pathology Department, University of Alexandria, Alexandria, Egypt.
Scand J Clin Lab Invest. 2011 Dec;71(8):641-6. doi: 10.3109/00365513.2011.624196. Epub 2011 Oct 24.
This work was carried out to study the level of pretreatment hepatic expression of Toll like receptor 3 (TLR3) among chronic HCV patients, aiming to determine if there are consistent differences in gene expression, between those who show complete early virological response (cEVR) at week-12 of Pegylated-Interferon α-2a plus ribavirin treatment and others who are not responding to this combination, also if this could be used to predict treatment outcomes.
A total of 61 chronic hepatitis C patients were enrolled in the study. For all of them, baseline hepatitis C virus (HCV) viral load was determined and TLR3 gene expression was examined in their hepatic percutaneous needle biopsy specimens using a real time-polymerase chain reaction technique. Hepatic TLR3 was also traced using immunohistochemistry. All patients followed a 12-week regimen of Pegylated-Interferon α-2a plus ribavirin then post-treatment viral load was assayed.
Hepatic expression of TLR3 was significantly increased in the non-responder group as compared to those who showed complete early virological response to the used treatment regimen. Using receiver operator characteristic (ROC) curve analysis, a cutoff level of 1.5 was set for TLR3 expression to distinguish responders from non-responders to the 12-week treatment regimen used.
In conclusion, measuring the hepatic expression of the interferon stimulated gene, TLR3 could provide a new molecular marker for pre-treatment prediction of complete early viral clearance, thus helping in patients' selection and optimizing treatment outcomes.
本研究旨在探讨慢性丙型肝炎患者预处理肝组织 Toll 样受体 3(TLR3)的表达水平,旨在确定在聚乙二醇干扰素 α-2a 联合利巴韦林治疗 12 周时表现出完全早期病毒学应答(cEVR)和未应答的患者之间,基因表达是否存在一致差异,以及这是否可用于预测治疗结局。
共纳入 61 例慢性丙型肝炎患者。对所有患者均检测基线丙型肝炎病毒(HCV)病毒载量,并采用实时聚合酶链反应技术检测其肝穿活检组织中 TLR3 基因表达。采用免疫组织化学法检测肝 TLR3。所有患者均接受 12 周聚乙二醇干扰素 α-2a 联合利巴韦林治疗,然后检测治疗后病毒载量。
与对所用治疗方案表现出完全早期病毒学应答的患者相比,无应答组的肝 TLR3 表达显著增加。采用受试者工作特征(ROC)曲线分析,设定 TLR3 表达的截断值为 1.5,以区分对 12 周治疗方案有应答和无应答的患者。
总之,测量干扰素刺激基因 TLR3 的肝表达水平可能为预测完全早期病毒清除提供新的分子标志物,从而有助于患者选择和优化治疗结局。