Departments of Gastroenterology and Hepatology and.
Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
J Infect Dis. 2017 May 1;215(9):1421-1429. doi: 10.1093/infdis/jix140.
Hepatitis B virus (HBV) modulates microRNA (miRNA) expression to support viral replication. The aim of this study was to identify miRNAs associated with hepatitis B e antigen (HBeAg) status and response to antiviral therapy in patients with chronic hepatitis B (CHB) , and to assess if these miRNAs are actively secreted by hepatoma cells.
Plasma miRNA levels were measured by reverse-transcription quantitative polymerase chain reaction in healthy controls (n = 10) and pretreatment samples of an identification cohort (n = 24) and a confirmation cohort (n = 64) of CHB patients treated with peginterferon/nucleotide analogue combination therapy. Levels of HBV-associated miRNAs were measured in cells, extracellular vesicles, and hepatitis B surface antigen (HBsAg) particles of hepatoma cell lines.
HBeAg-positive patients had higher plasma levels of miR-122-5p, miR-125b-5p, miR-192-5p, miR-193b-3p, and miR-194-5p compared to HBeAg-negative patients, and levels of these miRNAs were associated with HBV DNA and HBsAg levels. Pretreatment plasma levels of miR-301a-3p and miR-145-5p were higher in responders (combined response or HBsAg loss) compared to nonresponders. miR-192-5p, miR-193b-3p, and miR-194-5p were present in extracellular vesicles and HBsAg particles derived from hepatoma cells.
We identified miRNAs that are associated with HBeAg status, levels of HBV DNA and HBsAg, and treatment response in CHB patients. We demonstrated that several of these miRNAs are present in extracellular vesicles and HBsAg particles secreted by hepatoma cells.
乙型肝炎病毒（HBV）通过调节 microRNA（miRNA）的表达来支持病毒复制。本研究旨在鉴定与乙型肝炎 e 抗原（HBeAg）状态和慢性乙型肝炎（CHB）患者抗病毒治疗反应相关的 miRNA，并评估这些 miRNA 是否由肝癌细胞主动分泌。
采用逆转录定量聚合酶链反应（qRT-PCR）检测健康对照者（n=10）和接受聚乙二醇干扰素/核苷酸类似物联合治疗的 CHB 患者鉴定队列（n=24）和确认队列（n=64）治疗前血浆 miRNA 水平。测量肝癌细胞系细胞、细胞外囊泡和乙型肝炎表面抗原（HBsAg）颗粒中的 HBV 相关 miRNA 水平。
与 HBeAg 阴性患者相比，HBeAg 阳性患者的血浆 miR-122-5p、miR-125b-5p、miR-192-5p、miR-193b-3p 和 miR-194-5p 水平更高，这些 miRNA 水平与 HBV DNA 和 HBsAg 水平相关。与无应答者相比，应答者（联合应答或 HBsAg 丢失）的预处理血浆 miR-301a-3p 和 miR-145-5p 水平更高。miR-192-5p、miR-193b-3p 和 miR-194-5p 存在于肝癌细胞衍生的细胞外囊泡和 HBsAg 颗粒中。
我们鉴定了与 CHB 患者 HBeAg 状态、HBV DNA 和 HBsAg 水平以及治疗反应相关的 miRNA。我们证明了其中一些 miRNA 存在于肝癌细胞分泌的细胞外囊泡和 HBsAg 颗粒中。
