突变的乙型肝炎病毒的慢性乙型肝炎患者增加的促炎细胞因

StephenW

Increased Proinflammatory Cytokine Production by Chronic Hepatitis B Patients With Mutant Hepatitis B Virus: Plausible Mechanisms Underlying Severe Liver Diseases in These Patients
Ruksana Raihan  1 , Sheikh Mohammad Fazle Akbar  2   3 , Mamun Al Mahtab  4 , Md Sakirul Islam Khan  5 , Shahina Tabassum  6 , Kok Keng Tee  7   8 , Rosmawati Binti Mohamed  1
Affiliations
Affiliations

    1
    Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
    2
    Department of Pathology, Ehime University Proteo-Science Center, Ehime University Graduate School of Medicine, Toon City, Japan.
    3
    Miyakawa Memorial Research Foundation, Tokyo, Japan.
    4
    Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.
    5
    Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Matsuyama, Japan.
    6
    Department of Virology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.
    7
    Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
    8
    School of Healthcare and Medical Sciences, Sunway University, Bandar Sunway, Malaysia.

    PMID: 32513066 DOI: 10.1089/vim.2019.0198

Abstract

Hepatitis B virus (HBV) is a noncytopathic virus and billions of HBV-infected patients live uneventful lives and do not suffer from notable liver damage. However, HBV also causes progressive liver diseases characterized by hepatic inflammation, hepatic fibrosis, and liver cancer in millions of HBV-infected patients. The goal of this study was to evaluate the role of mutant HBV in HBV pathogenesis. In a cohort of 360 chronic HBV-infected patients, mutations at T1762/A1764 of HBV genome were detected in most of the patients with HBV-induced liver cirrhosis and hepatocellular carcinoma. To explore if mutations at T1762/A1764 of HBV genome has any role in progressive liver disease, peripheral blood mononuclear cells (PBMCs) and antigen-presenting dendritic cells (DCs) were isolated from five chronic hepatitis B (CHB) patients with mutations at T1762/A1764 and five comparable patients of CHB without mutations at T1762/A1764. DCs were pulsed with hepatitis B surface antigen (HBsAg). The levels of cytokines produced by PBMCs and DCs as well as nitrite production by DCs were evaluated. Significantly higher levels of interleukin-12, tumor necrosis factor-alpha, interferon-gamma, and transforming growth factor-beta were detected in cultures of PBMCs, DCs, and HBsAg-pulsed DCs from CHB patients with mutations at T1762/A1764 compared with those without mutations (p < 0.05). DCs of all CHB patients with mutations produced significantly higher levels of nitrite compared with those without mutation at T1762/A1764 (p < 0.001). This study discusses the inflammatory potential of mutant HBV that may be responsible for diverse levels of pathogenicity of HBV. Further studies involving larger cohorts would provide more insight into these unresolved issues about HBV pathogenesis and these insights may aid in developing immune therapy for CHB patients.

Keywords: chronic hepatitis B; host immunity; viral mutation.

StephenW

突变的乙型肝炎病毒的慢性乙型肝炎患者增加的促炎细胞因子产生：这些患者中严重肝病的潜在机制
Ruksana Raihan 1，Sheikh Mohammad Fazle Akbar 2 3，Mamun Al Mahtab 4，Ms Sakirul Islam Khan 5，Shahina Tabassum 6，Kok Keng Tee 7 8，Rosmawati Binti Mohamed 1
隶属关系
隶属关系

    1个
    马来西亚吉隆坡马来亚大学医学院医学系。
    2
    日本卡通城市爱媛大学医学院研究生院爱媛大学蛋白质科学中心病理学系。
    3
    日本东京都宫川纪念研究基金会。
    4
    孟加拉国达卡，班加班德谢赫穆吉布医科大学肝病系。
    5
    爱媛大学医学研究科解剖学与胚胎学系，日本松山。
    6
    孟加拉国达卡的Bangabandhu Sheikh Mujib医科大学病毒学系。
    7
    马来西亚吉隆坡马来亚大学医学院医学微生物学系。
    8
    马来西亚双威，双威大学医疗与医学学院。

    PMID：32513066 DOI：10.1089 / vim.2019.0198

抽象

乙型肝炎病毒（HBV）是一种非细胞病性病毒，数十亿的HBV感染患者过上平淡无奇的生活，没有明显的肝脏损害。但是，HBV还会在数百万感染HBV的患者中引起以肝脏炎症，肝纤维化和肝癌为特征的进行性肝病。这项研究的目的是评估突变型HBV在HBV发病机理中的作用。在360名慢性HBV感染患者队列中，在大多数HBV诱发的肝硬化和肝细胞癌患者中检测到HBV基因组T1762 / A1764处的突变。为了探讨HBV基因组的T1762 / A1764处的突变是否在进行性肝病中起任何作用，从五名在T1762突变的慢性乙型肝炎（CHB）患者中分离了外周血单核细胞（PBMC）和抗原呈递树突状细胞（DC）。 / A1764和5名在T1762 / A1764无突变的CHB患者。 DC用乙肝表面抗原（HBsAg）脉冲。评估了PBMC和DC产生的细胞因子水平以及DC产生的亚硝酸盐水平。与T1762 / A1764突变相比，CHB患者的PBMC，DC和HBsAg脉冲DC的培养物中检测到的白细胞介素12，肿瘤坏死因子-α，干扰素-γ和转化生长因子-β的水平明显更高。无突变（p <0.05）。与T1762 / A1764处无突变的CHB患者相比，所有具有突变的CHB患者的DC产生的亚硝酸盐水平均显着更高（p <0.001）。这项研究讨论了突变型HBV的炎性潜能，其可能与HBV的多种致病性有关。涉及较大人群的进一步研究将为这些尚未解决的有关HBV发病机制的问题提供更多的见识，这些见解可能有助于开发CHB患者的免疫疗法。

关键词：慢性乙型肝炎；宿主免疫病毒突变。