Intrahepatic innate immune response pathways are downregulated in untreated chronic hepatitis B
Intrahepatic innate immune response pathways are downregulated in untreated chronic hepatitis B
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DOI：
10.1016/j.jhep.2016.12.024
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发表时间：
2017-05-01
影响因子：
25.7
通讯作者：
Zoulim, Fabien
中科院分区：
文献类型：
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作者：
Lebosse, Fanny;Testoni, Barbara;Zoulim, Fabien
背景和目标：B型肝炎病毒（HBV）的持续存在和慢性HBV（CH B）感染的病理学是病毒复制和宿主免疫应答之间相互作用的结果。我们的目的是全面分析肝内宿主基因的表达，以及血清和肝脏HBV标志物在一个大的队列未经治疗的CHB patients.Methods：105例未经治疗的CHB患者在肝活检（34 HBeAg[+]和71 HBeAg[-]）的肝内表达谱67个基因属于多个先天免疫途径进行了分析。结果与血清学（HBsAg [qHBsAg]和HBV DNA定量）和肝内病毒标志物（总HBV DNA、前基因组RNA和共价闭合环状HBV DNA）。肝内基因表达谱显示，与未感染对照组相比，CHB患者的抗病毒效应子、干扰素刺激基因、Toll样和病原体识别受体途径强烈下调，与HBV复制无直接关系。与HBeAg（+）患者相比，HBeAg（-）患者中的一个基因子集[CXCL 10、GBP 1、IFITM 1、IFNB 1、IL 10、IL 6、ISG 15、TLR 3、SOCS 1、SOCS 3]受到更多抑制（血清HBV DNA中位数分别为7.9 x 10（3）和7.9 x 10（7）IU/ml）。值得注意的是，HBeAg（-）患者qHBsAg（
Background & Aims: Hepatitis B virus (HBV) persistence and the pathobiology of chronic HBV (CHB) infections result from the interplay between viral replication and host immune responses. We aimed to comprehensively analyse the expression of intrahepatic host genes as well as serum and liver HBV markers in a large cohort of untreated CHB patients.Methods: One-hundred and five CHB patients untreated at the time of liver biopsy (34 HBeAg[+] and 71 HBeAg[-]) were analysed for the intrahepatic expression profile of 67 genes belonging to multiple innate immunity pathways. Results were correlated to serological (quantification of HBsAg [qHBsAg] and HBV DNA) and intrahepatic viral markers (total HBV DNA, pre-genomic RNA and covalently closed circular HBV DNA).Results: Intrahepatic gene expression profiling revealed a strong downregulation of antiviral effectors, interferon stimulated genes, Toll-like and pathogen recognition receptor pathways in CHB patients as compared to non-infected controls, which was not directly correlated to HBV replication. A subset of genes [CXCL10, GBP1, IFITM1, IFNB1, IL10, IL6, ISG15, TLR3, SOCS1, SOCS3] was more repressed in HBeAg(-) respect to HBeAg(+) patients (median of serum HBV DNA 7.9 x 10(3) vs. 7.9 x 10(7) IU/ml, respectively). Notably, HBeAg(-) patients with lower qHBsAg (