细胞衰老与乙肝相关的肝细胞癌：一个有趣的链接

StephenW

Cellular senescence and hepatitis b related hepatocellular carcinoma: an intriguing link
Nikolaos D Karakousis  1   2 , Alkistis Papatheodoridi  2   3 , Antonios Chatzigeorgiou  2   4 , George Papatheodoridis  1
Affiliations
Affiliations

    1
    Department of Gastroenterology, Medical School of National, Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece.
    2
    Department of Physiology, Medical School of National, Kapodistrian University of Athens, Athens, Greece.
    3
    Department of Clinical Therapeutics, Medical School of National, Kapodistrian University of Athens, "Alexandra" General Hospital of Athens, Athens, Greece.
    4
    Institute for Clinical Chemistry and Laboratory Medicine, University Clinic Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

    PMID: 32890439 DOI: 10.1111/liv.14659

Abstract

Chronic hepatitis B is mainly responsible for the morbidity and mortality from hepatitis B virus (HBV) related complications, including hepatocellular carcinoma and decompensated cirrhosis. Hepatocellular carcinoma remains the main challenge in the management of not only undiagnosed and/or untreated but also diagnosed and treated patients with chronic HBV infection, as its incidence decreases but is not eliminated even after many years of effective anti-HBV therapy. The exact mechanisms used by HBV to cause malignant transformation remain uncertain, although much of the available data are in favor of a pathogenetic role of HBx protein. Senescence is a cellular state, in which cells lose their ability to proliferate. This biological mechanism may function in a dual mode, namely being both cancer-protective due to reduced cellular proliferation, but also cancer-enhancing due to modulation of the tissular microenvironment by immune cells during persistent accumulation of senescent cells. Protein X of HBV protein exhibits many similarities in terms of the implemented mechanisms of action and pathways related to the biological process of cellular senescence. Concurrently, insufficient clearance of both senescent and pre-cancerous hepatocytes combined with inadequate immune surveillance due to immunosenescence caused by chronic HBV infection may lead to hepatocarcinogenesis. Thus, the effect of HBV seems to be critical as a connecting link between cellular senescence and development of hepatocellular carcinoma. An ongoing research is underway towards identifying and validating markers of hepatocyte senescence, which could improve the landscape for evaluation of chronic liver disease, thereby providing valuable information in terms of HBV related carcinogenesis.

Keywords: hepatitis B virus; hepatocellular carcinoma; hepatocyte senescence; immunosenescence; protein X.

This article is protected by copyright. All rights reserved.

StephenW

细胞衰老与乙肝相关的肝细胞癌：一个有趣的链接
Nikolaos D Karakousis 1 2，Alkistis Papatheodoridi 2 3，Antonios Chatzigeorgiou 2 4，George Papatheodoridis 1
隶属关系
隶属关系

    1个
    雅典卡普迪斯安大学国立医学院胃肠病学系，希腊雅典“莱科”总医院。
    2
    希腊雅典卡波迪斯安大学国立医学院生理学系。
    3
    雅典卡普迪斯安大学国立医学院临床治疗学系，希腊雅典“亚历山大”综合医院。
    4
    德国德累斯顿工业大学，University Clinical Carl Gustav Carus临床化学和检验医学研究所。

    PMID：32890439 DOI：10.1111 / liv.14659

抽象

慢性乙型肝炎主要负责与乙型肝炎病毒（HBV）相关的并发症（包括肝细胞癌和代偿性肝硬化）的发病率和死亡率。肝细胞癌不仅在未诊断和/或未治疗的患者中而且在已诊断和治疗的慢性HBV感染患者的治疗中仍然是主要挑战，因为其发病率降低但即使经过多年有效的抗HBV治疗也无法消除。 HBV引起恶性转化的确切机制仍不确定，尽管许多可用数据都支持HBx蛋白的致病作用。衰老是一种细胞状态，其中细胞丧失了增殖能力。这种生物学机制可能以双重模式起作用，即既由于减少的细胞增殖而具有癌症保护性，又由于在衰老细胞持续积累期间免疫细胞对组织微环境的调节而使癌症增强。 HBV蛋白的蛋白X在与细胞衰老的生物学过程相关的作用机制和途径方面表现出许多相似之处。同时，由于慢性HBV感染引起的免疫衰老导致衰老和癌前肝细胞清除能力不足，以及免疫监测不足，可能导致肝癌发生。因此，HBV的作用作为细胞衰老与肝细胞癌发展之间的联系至关重要。正在进行一项有关鉴定和验证肝细胞衰老标记的研究，这可以改善评估慢性肝病的前景，从而提供有关HBV相关癌变的有价值的信息。

关键词：乙型肝炎病毒；肝细胞癌；肝细胞衰老免疫衰老蛋白质X。

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StephenW

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/liv.14659