Table_1_Multifaceted Interaction Between Hepatitis B Virus Infection and Lipid Metabolism in Hepatocytes: A Potential Target of Antiviral Therapy for Chronic Hepatitis B.DOCX

Hepatitis B virus (HBV) is considered a “metabolic virus” and affects many hepatic metabolic pathways. However, how HBV affects lipid metabolism in hepatocytes remains uncertain yet. Accumulating clinical studies suggested that compared to non-HBV-infected controls, chronic HBV infection was associated with lower levels of serum total cholesterol and triglycerides and a lower prevalence of hepatic steatosis. In patients with chronic HBV infection, high ALT level, high body mass index, male gender, or old age was found to be positively correlated with hepatic steatosis. Furthermore, mechanisms of how HBV infection affected hepatic lipid metabolism had also been explored in a number of studies based on cell lines and mouse models. These results demonstrated that HBV replication or expression induced extensive and diverse changes in hepatic lipid metabolism, by not only activating expression of some critical lipogenesis and cholesterolgenesis-related proteins but also upregulating fatty acid oxidation and bile acid synthesis. Moreover, increasing studies found some potential targets to inhibit HBV replication or expression by decreasing or enhancing certain lipid metabolism-related proteins or metabolites. Therefore, in this article, we comprehensively reviewed these publications and revealed the connections between clinical observations and experimental findings to better understand the interaction between hepatic lipid metabolism and HBV infection. However, the available data are far from conclusive, and there is still a long way to go before clarifying the complex interaction between HBV infection and hepatic lipid metabolism.

乙型肝炎病毒（Hepatitis B virus, HBV）被归类为“代谢性病毒”，可影响多条肝脏代谢通路。然而，HBV究竟如何调控肝细胞内的脂质代谢，目前仍未明确。现有大量临床研究显示，与未感染HBV的对照个体相比，慢性HBV感染者的血清总胆固醇、甘油三酯水平更低，且肝脂肪变的患病率也更低。在慢性HBV感染者群体中，高丙氨酸氨基转移酶（alanine aminotransferase, ALT）水平、高体质量指数、男性性别以及高龄均与肝脂肪变呈正相关。此外，诸多基于细胞系与小鼠模型的研究也对HBV感染影响肝脏脂质代谢的潜在机制展开了探索。相关研究结果证实，HBV的复制或表达可引发肝脏脂质代谢发生广泛且多样的改变：不仅能够激活部分关键的脂肪生成、胆固醇合成相关蛋白的表达，还可上调脂肪酸氧化与胆汁酸合成通路。与此同时，越来越多的研究发现了若干潜在靶点，可通过调控特定脂质代谢相关蛋白或代谢物的表达水平（上调或下调），从而抑制HBV的复制与表达。有鉴于此，本文全面梳理了上述相关研究文献，整合临床观察结果与实验发现，以期更深入地阐明肝脏脂质代谢与HBV感染之间的相互作用。不过，现有研究数据仍缺乏足够的定论，要彻底厘清HBV感染与肝脏脂质代谢间的复杂相互作用，仍有漫长的探索之路。