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标题: 乙型肝炎前基因组RNA存在于病毒粒子在等离子，并伴有响应 [打印本页]

作者: StephenW 时间: 2015-8-1 17:31 标题: 乙型肝炎前基因组RNA存在于病毒粒子在等离子，并伴有响应

Hepatitis B Pregenomic RNA is Present in Virions in Plasma and is Associated With Response to Peginterferon and Nucleos(t)ide Analogues

+ Author Affiliations

1Department of Gastroenterology and Hepatology, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, The Netherlands
2Department of Experimental Immunology, AMC, UvA, The Netherlands
3Department of Clinical Virology, AMC, UvA, The Netherlands

Contact information corresponding author: L. Jansen, MD, Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands, Phone: +31 20 56 65 728, Fax: +31 20 56 69 582, E-mail: [email protected]

Abstract

Background. Treatment of chronic hepatitis B (CHB) patients with nucleos(t)ide analogues (NAs) suppresses HBV-DNA production, but does not affect synthesis of the RNA pregenome (HBV-RNA). Whether HBV-RNA containing particles continue to be secreted into the bloodstream remains controversial.

Methods. We developed a sensitive PCR-assay to measure HBV-RNA, which was quantified in supernatant of NA-treated HepG2-2.2.15 cells, plasma of 20 CHB patients on NA-therapy, and 86 patients treated with peginterferon-alfa-2a and adefovir.

Results. Treatment of HepG2-2.2.15 cells with NAs for 9 days reduced HBV-DNA levels (-1.98 log10C/mL), whereas HBV-RNA levels increased (+0.47 log10C/mL, p<0.05). During long-term NA-treatment of CHB patients, HBV-RNA levels remained higher than HBV-DNA. Peginterferon-based treatment induced a stronger HBV-RNA decline than NA-monotherapy, and this decline was more pronounced in responders than in non-responders. In HBeAg-negative patients, a lower baseline plasma HBV-RNA level was independently associated with response to peginterferon and adefovir (OR 0.44, p=0.019). Immunoprecipitation with HBcAg-specific antibodies after removal of the HBsAg envelope demonstrated the association of plasma HBV-RNA with virions.

Conclusions. HBV-RNA is present in virions in plasma of CHB patients. HBV-RNA levels vary significantly from established viral markers during antiviral treatment, which highlights its potential as an independent marker in the evaluation of CHB patients.

作者: StephenW 时间: 2015-8-1 17:32

乙型肝炎前基因组RNA存在于病毒粒子在等离子，并伴有响应聚乙二醇干扰素和核苷（酸）类似物

路易斯Jansen1,2，去往Neeltje A. Kootstra2，卡雷尔面包车A. Dort2，R.巴特Takkenberg1，亨德里克·W·Reesink1,2和Hans L. Zaaijer3

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作者机构

胃肠病学和肝病学术医学中心（AMC），阿姆斯特丹大学（UVA），阿姆斯特丹，荷兰教研室
实验免疫学，AMC，阿姆斯特丹，荷兰教研室
临床病毒学，AMC，阿姆斯特丹，荷兰3Department

联系信息通讯作者：L.詹森博士，胃肠病学和肝病学术医学中心，阿姆斯特丹大学，Meibergdreef 9 1105 AZ阿姆斯特丹，荷兰，电话部：+31 20 56 65 728传真：+31 20 56 69 582，电子信箱：[email protected]

抽象

背景。慢性乙型肝炎（CHB）患者核苷（酸）类似物（NAS）的治疗抑制HBV-DNA的生产，但不影响合成所述RNA前基因组（HBV-RNA）的。是否HBV-RNA的含颗粒继续被分泌到血液中仍存在争议。

方法。我们制定了一个敏感的PCR法来测量HBV-RNA，这是量化NA处理HepG2-2.2.15细胞的上清液中，20例慢性乙型肝炎患者的NA-治疗，86例患者血浆与聚乙二醇干扰素，干扰素α-2a和治疗阿德福韦。

结果。 HepG2-2.2.15细胞的NA 9天的治疗降低的HBV-DNA水平（-1.98 log10C /毫升），而HBV-RNA水平增加（0.47 log10C /毫升，P <0.05）。在长期的NA-治疗慢性乙肝患者，乙肝病毒RNA水平仍比HBV-DNA水平。聚乙二醇化干扰素为基础的治疗诱导更强的HBV-RNA比下降NA-单药治疗，而这种下降明显高于无应答者更明显的反应。在HBeAg阴性患者，较低的基准血浆HBV-RNA水平是独立与回应聚乙二醇干扰素和阿德福韦（OR 0.44，P = 0.019）有关。免疫沉淀并除去的HBsAg包络后的HBcAg特异性抗体证明了等离子体的HBV-RNA与病毒体的关联。

结论。 HBV-RNA存在于慢性乙型肝炎患者血浆病毒粒子。 HBV-RNA水平时，从抗病毒治疗，这凸显其潜在的慢性乙型肝炎患者的评价提供独立的标志建立病毒标志物变化显著。

©该作者发表于2015年由牛津大学出版社代表美国传染病学会的。版权所有。对于权限，请电邮：[email protected]。

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