联合治疗前后与肝内和循环病毒标志物相关的乙型肝炎核心

StephenW

联合治疗前后与肝内和循环病毒标志物相关的乙型肝炎核心相关抗原
Robin Erken 1、Hans L Zaaijer 2、Sophie B Willemse 3、Ed Bakker 4、Bart B Takkenberg 5、Henk W Reesink 6、Neeltje A Kootstra 7
隶属关系
隶属关系

    1
    胃肠病学和肝病学系，阿姆斯特丹胃肠病学内分泌代谢；实验免疫学系，阿姆斯特丹 UMC，阿姆斯特丹感染与免疫研究所，阿姆斯特丹大学，阿姆斯特丹，荷兰.. 电子地址：[email protected]。
    2
    医学微生物学，学术医学中心，阿姆斯特丹，荷兰。电子地址：[email protected]。
    3
    胃肠病学和肝病学系，阿姆斯特丹胃肠病学内分泌代谢。电子地址：[email protected]。
    4
    Sanquin Blood Supply Foundation, Plesmanlaan 125, Amsterdam, the Netherlands.. 电子地址：[email protected]。
    5
    胃肠病学和肝病学系，阿姆斯特丹胃肠病学内分泌代谢。电子地址：[email protected]。
    6
    阿姆斯特丹 UMC，地点 AMC，Meibergdreef 9，阿姆斯特丹，荷兰。电子地址：[email protected]。
    7
    实验免疫学系，阿姆斯特丹 UMC，阿姆斯特丹感染与免疫研究所，阿姆斯特丹大学，阿姆斯特丹，荷兰.. 电子地址：[email protected]。

    PMID：34583061 DOI：10.1016/j.aohep.2021.100540

抽象的

介绍和目标：共价闭合环状 (ccc) DNA 作为慢性乙型肝炎 (CHB) 感染患者肝脏中的病毒库，只能在肝脏活检中量化。血浆/血清中的乙型肝炎核心相关抗原 (HBcrAg) 水平已被提议反映肝内 cccDNA 水平，因此可以监测治疗效果。本研究旨在验证高病毒载量 CHB 患者在联合治疗前后 HBcrAg 与其他肝内和循环病毒标志物之间的关系。

材料和方法：在 89 名 HBV-DNA 水平为>100,000 拷贝/mL (17,182 IU/mL)。在一项前瞻性研究 (ISRCTN77073364) 中，在使用聚乙二醇化干扰素 alfa-2a 和阿德福韦治疗 48 周之前和之后进行了测量。

结果：基线 HBcrAg 值与肝内 cccDNA (ρ 0.77, p<0.001)、肝内 HBV-DNA (ρ 0.73, p<0.001) 和血浆/血清 HBV-DNA (ρ 0.80, p<0.001)、HBV- pgRNA (ρ 0.80, p<0.001) 和 HBsAg 的延伸程度较小 (ρ 0.56, p<0.001)。基线 HBcrAg 水平无法预测功能性治愈 (FC)，但在发展为 FC 或 HBeAg 消失的患者中，HBcrAg 水平下降得更厉害。此外，大多数相关性在治疗和随访结束时仍然存在。

结论：HBcrAg 比 HBsAg 更准确地反映 cccDNA 转录活性，并且可能在未来的治疗方案中取代 HBV-DNA 作为标志物，尤其是当靶向 cccDNA 转录或在治疗方案中包含核苷酸类似物时。

关键词：HBcrAg，HBV pgRNA；乙型肝炎病毒;阿德福韦，聚乙二醇干扰素；病毒标记。

版权所有 © 2021。由 Elsevier España, S.L.U. 出版。

StephenW

Hepatitis B core related antigen in relation to intrahepatic and circulating viral markers, before and after combination therapy
Robin Erken  1 , Hans L Zaaijer  2 , Sophie B Willemse  3 , Ed Bakker  4 , Bart B Takkenberg  5 , Henk W Reesink  6 , Neeltje A Kootstra  7
Affiliations
Affiliations

    1
    Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism; Department of Experimental Immunology, Amsterdam UMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, Netherlands.. Electronic address: [email protected].
    2
    Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: [email protected].
    3
    Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism. Electronic address: [email protected].
    4
    Sanquin Blood Supply Foundation, Plesmanlaan 125, Amsterdam, the Netherlands.. Electronic address: [email protected].
    5
    Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism. Electronic address: [email protected].
    6
    Amsterdam UMC, location AMC, Meibergdreef 9, Amsterdam, the Netherlands. Electronic address: [email protected].
    7
    Department of Experimental Immunology, Amsterdam UMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, Netherlands.. Electronic address: [email protected].

    PMID: 34583061 DOI: 10.1016/j.aohep.2021.100540

Abstract

Introduction & objectives: Covalently closed circular (ccc)DNA acts as a viral reservoir in the liver of patients with a chronic hepatitis B (CHB) infection and can only be quantified in liver biopsies. Hepatitis B core-related antigen (HBcrAg) levels in plasma/serum have been proposed to reflect intrahepatic cccDNA-levels and may therefore monitor treatment efficacy. This study aimed to validate the relationship between HBcrAg and other intrahepatic and circulating viral markers in CHB patients with high viral load, before and after combination treatment.

Materials & methods: Plasma/serum levels of HBcrAg, HBsAg, HBV-DNA, and HBV pregenomic RNA (HBV-pgRNA), and intrahepatic cccDNA and HBV-DNA levels and fibrosis scores were measured in 89 CHB patients with HBV-DNA levels of >100,000 copies/mL (17,182 IU/mL). Measurements were done before and after a 48-week treatment with pegylated interferon alfa-2a and adefovir in a prospective study (ISRCTN77073364).

Results: Baseline HBcrAg-values correlated strongly with intrahepatic cccDNA (ρ 0.77, p<0.001), intrahepatic HBV-DNA (ρ 0.73, p<0.001) and plasma/serum HBV-DNA (ρ 0.80, p<0.001), HBV-pgRNA (ρ 0.80, p<0.001), and to lesser extend HBsAg (ρ 0.56, p<0.001). Baseline HBcrAg-levels could not predict functional cure (FC) but HBcrAg-levels declined more strongly in patients who developed FC or HBeAg-loss. Furthermore, most correlations persisted at the end of treatment and follow-up.

Conclusions: HBcrAg reflects cccDNA transcription activity more accurately than HBsAg and may replace HBV-DNA as a marker during future treatment regimens, especially when cccDNA transcription is targeted or nucleot(s)ide analogues are included in the treatment regime.

Keywords: HBcrAg, HBV pgRNA; Hepatitis B Virus; adefovir, pegylated interferon; viral markers.

Copyright © 2021. Published by Elsevier España, S.L.U.

StephenW

https://www.sciencedirect.com/sc ... 21002398?via%3Dihub