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在病毒载量得到抑制的患者中,人类免疫缺陷病毒合并感染根据乙型肝炎 e 抗原状态对乙型肝炎病毒病毒标志物产生不同影响。

Human immunodeficiency virus coinfection differentially impacts hepatitis B virus viral markers based on hepatitis Be antigen status in patients with suppressed viremia.

机构信息

Division of Gastroenterology, Washington University School of Medicine and John Cochran VA Medical Center, St. Louis, Missouri, USA.

School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

出版信息

J Viral Hepat. 2023 Aug;30(8):700-709. doi: 10.1111/jvh.13857. Epub 2023 Jun 6.

DOI:10.1111/jvh.13857
PMID:37278302
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10524380/
Abstract

Hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg), reflecting transcriptional activity of covalently closed circular DNA, are gaining traction as important markers to assess viral activity. Whether their expression differs under viral suppression by HIV co-infection status is unknown. Among adults with chronic HBV on antiviral therapy, we sought to determine if the expression of HBV markers (specialized and well-established) differs between HBV-HIV co-infection vs. HBV mono-infection. We compared HBV marker levels among 105 participants in the Hepatitis B Research Network (HBRN) HBV-HIV Ancillary Study and 105 participants in the HBRN mono-infected Cohort Study, matched for HBeAg status and HBV DNA suppression on therapy. Among HBeAg+ participants (N = 58 per group), after adjusting for age, sex, race, ALT and HBV DNA, viral markers were higher (p < .05) in the HBV-HIV versus the HBV-only sample (HBeAg: 1.05 vs. 0.51 log IU/mL; HBsAg: 3.85 vs. 3.17 log IU/mL; HBV RNA: 5.60 vs. 3.70 log U/mL; HBcrAg: 6.59 vs. 5.51 log U/mL). Conversely, among HBeAg(-) participants (N = 47 per group), HBsAg (2.00 vs. 3.04 log10 IU/mL) and HBV RNA (1.87 vs. 2.66 log U/mL) were lower (p < .05) in HBV-HIV vs. HBV-only; HBcrAg levels were similar (4.14 vs. 3.64 log U/mL; p = .27). Among adults with chronic HBV with suppressed viremia on antiviral therapy, viral markers tracked with HIV co-infection status and associations differed inversely by HBeAg status. The greater sensitivity and specificity of HBV RNA compared to HBcrAg allows for better discrimination of transcriptional activity regardless of HBeAg status.

摘要

乙型肝炎病毒 (HBV) RNA 和乙型肝炎核心相关抗原 (HBcrAg),反映共价闭合环状 DNA 的转录活性,作为评估病毒活性的重要标志物逐渐受到重视。在 HIV 合并感染状态下抑制病毒的情况下,它们的表达是否不同尚不清楚。在接受抗病毒治疗的慢性乙型肝炎成人中,我们试图确定 HBV 标志物(专业且成熟的标志物)在 HBV-HIV 合并感染与 HBV 单感染之间的表达是否不同。我们比较了乙型肝炎病毒研究网络 (HBRN) HBV-HIV 辅助研究中的 105 名参与者和 HBRN 单感染队列研究中的 105 名参与者的 HBV 标志物水平,这些参与者按 HBeAg 状态和治疗期间 HBV DNA 抑制情况进行匹配。在 HBeAg+参与者中(每组 58 名),在校正年龄、性别、种族、ALT 和 HBV DNA 后,HBV-HIV 组的病毒标志物高于 HBV 单感染组(p<0.05)(HBeAg:1.05 与 0.51 log IU/mL;HBsAg:3.85 与 3.17 log IU/mL;HBV RNA:5.60 与 3.70 log U/mL;HBcrAg:6.59 与 5.51 log U/mL)。相反,在 HBeAg(-)参与者中(每组 47 名),HBV-HIV 组的 HBsAg(2.00 与 3.04 log10 IU/mL)和 HBV RNA(1.87 与 2.66 log U/mL)低于 HBV 单感染组(p<0.05);HBcrAg 水平相似(4.14 与 3.64 log U/mL;p=0.27)。在接受抗病毒治疗且病毒血症抑制的慢性 HBV 成人中,病毒标志物与 HIV 合并感染状态相关,且相关性根据 HBeAg 状态呈相反方向变化。HBV RNA 比 HBcrAg 具有更高的灵敏度和特异性,无论 HBeAg 状态如何,都能更好地区分转录活性。

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本文引用的文献

1
HBV transcription and translation persist despite viral suppression in HBV-HIV co-infected patients on antiretroviral therapy.尽管接受抗逆转录病毒治疗的 HBV-HIV 合并感染患者的病毒得到抑制,但 HBV 的转录和翻译仍持续存在。
Hepatology. 2023 Feb 1;77(2):594-605. doi: 10.1002/hep.32634. Epub 2022 Jul 21.
2
A Prospective Cohort Study of Novel Markers of Hepatitis B Virus Replication in Human Immunodeficiency Virus Coinfection.一项关于人类免疫缺陷病毒合并感染中乙型肝炎病毒复制新型标志物的前瞻性队列研究。
Clin Gastroenterol Hepatol. 2023 Jan;21(1):125-135.e8. doi: 10.1016/j.cgh.2021.12.038. Epub 2021 Dec 29.
3
Comparison of HBV RNA and Hepatitis B Core Related Antigen With Conventional HBV Markers Among Untreated Adults With Chronic Hepatitis B in North America.
北美未经治疗的慢性乙型肝炎成年患者中 HBV RNA 和乙型肝炎核心相关抗原与常规 HBV 标志物的比较。
Hepatology. 2021 Nov;74(5):2395-2409. doi: 10.1002/hep.32018. Epub 2021 Sep 9.
4
Spectrum of Liver Disease in Hepatitis B Virus (HBV) Patients Co-infected with Human Immunodeficiency Virus (HIV): Results of the HBV-HIV Cohort Study.乙型肝炎病毒(HBV)与人类免疫缺陷病毒(HIV)合并感染患者的肝脏疾病谱:HBV-HIV 队列研究结果。
Am J Gastroenterol. 2019 May;114(5):746-757. doi: 10.1038/s41395-018-0409-9.
5
Hepatitis B Virus Serum DNA andRNA Levels in Nucleos(t)ide Analog-Treated or Untreated Patients During Chronic and Acute Infection.慢性和急性感染期间核苷(酸)类似物治疗或未治疗患者的乙型肝炎病毒血清 DNA 和 RNA 水平。
Hepatology. 2018 Dec;68(6):2106-2117. doi: 10.1002/hep.30082. Epub 2018 Sep 22.
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Hepatitis B core-related antigen: a strong indicator for cessation of nucleos(t)ide analog therapy in patients with chronic hepatitis B.乙型肝炎核心相关抗原:慢性乙型肝炎患者停止核苷(酸)类似物治疗的有力指标。
J Gastroenterol. 2017 Jan;52(1):127-128. doi: 10.1007/s00535-016-1259-0. Epub 2016 Sep 24.
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J Hepatol. 2016 Oct;65(4):700-710. doi: 10.1016/j.jhep.2016.05.029. Epub 2016 May 28.
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Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors.血清乙型肝炎病毒 RNA 水平作为治疗期间乙型肝炎表面抗原血清学转换的早期预测指标。
Hepatology. 2015 Jan;61(1):66-76. doi: 10.1002/hep.27381. Epub 2014 Nov 25.