The Third People's Hospital of Shenzhen (National Clinical Research Center for Infectious Diseases) and The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China.
Clinical Research Center, The Fifth People's Hospital of Wuxi, Jiangnan University, Wuxi, Jiangsu, China.
Front Immunol. 2024 Jul 18;15:1414594. doi: 10.3389/fimmu.2024.1414594. eCollection 2024.
Hepatitis B Virus (HBV) is a stealthy and insidious pathogen capable of inducing chronic necro-inflammatory liver disease and hepatocellular carcinoma (HCC), resulting in over one million deaths worldwide per year. The traditional understanding of Chronic Hepatitis B (CHB) progression has focused on the complex interplay among ongoing virus replication, aberrant immune responses, and liver pathogenesis. However, the dynamic progression and crucial factors involved in the transition from HBV infection to immune activation and intrahepatic inflammation remain elusive. Recent insights have illuminated HBV's exploitation of the sodium taurocholate co-transporting polypeptide (NTCP) and manipulation of the cholesterol transport system shared between macrophages and hepatocytes for viral entry. These discoveries deepen our understanding of HBV as a virus that hijacks hepatocyte metabolism. Moreover, hepatic niche macrophages exhibit significant phenotypic and functional diversity, zonal characteristics, and play essential roles, either in maintaining liver homeostasis or contributing to the pathogenesis of chronic liver diseases. Therefore, we underscore recent revelations concerning the importance of hepatic niche macrophages in the context of viral hepatitis. This review particularly emphasizes the significant role of HBV-induced metabolic changes in hepatic macrophages as a key factor in the transition from viral infection to immune activation, ultimately culminating in liver inflammation. These metabolic alterations in hepatic macrophages offer promising targets for therapeutic interventions and serve as valuable early warning indicators, shedding light on the disease progression.
乙型肝炎病毒（HBV）是一种隐匿且阴险的病原体，能够引起慢性坏死性炎症性肝病和肝细胞癌（HCC），每年导致全球超过 100 万人死亡。传统上认为慢性乙型肝炎（CHB）的进展是由病毒持续复制、异常免疫反应和肝脏发病机制之间的复杂相互作用引起的。然而，HBV 感染向免疫激活和肝内炎症转变的动态进展以及关键因素仍然难以捉摸。最近的研究结果揭示了 HBV 利用牛磺胆酸钠共转运多肽（NTCP）以及操纵巨噬细胞和肝细胞之间共同的胆固醇转运系统进行病毒进入的机制。这些发现加深了我们对 HBV 作为一种劫持肝细胞代谢的病毒的理解。此外，肝内龛位巨噬细胞表现出显著的表型和功能多样性、区域特征，并发挥着重要作用，无论是在维持肝脏内稳态还是在慢性肝病的发病机制中。因此，我们强调了最近关于病毒肝炎背景下肝龛位巨噬细胞重要性的发现。本综述特别强调了 HBV 诱导的肝巨噬细胞代谢变化在病毒感染向免疫激活转变过程中的关键作用，最终导致肝脏炎症。肝巨噬细胞的这些代谢改变为治疗干预提供了有前途的靶点，并作为有价值的早期预警指标，揭示了疾病的进展。
