Despite the fact that both Hepatitis B virus (HBV) infection and excessive alcohol consumption represent health problems worldwide, the mechanism by which alcohol affected the progression of HBV-associated liver disease are not completely understood. Therefore, we studied how alcohol affects the development of HBV infection and the role of T cells and NK cells in the antiviral response. Mononuclear cells (MNCs) derived from HBV-carrier mice and wild type (WT) mice were characterized for phenotype by flow cytometry, HBV antigen and gene expression were detected by Radio Immunoassay (RIA), immunohistochemistry and quantitative real-time (qRT)-PCR. Metabolomics changes were detected in mice liver tissue based on ultra high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOFMS). The mice after ethanol consumption shows higher levels of HBV surface Ag (HBsAg), HBV core antigen (HBcAg) and HBV 3.5 kb RNA expression, and a lower level of CD8⁺ T cells during HBV persistence, with an increased lymphocyte activation gene-3 (LAG-3) expression on CD8⁺ T cell. In addition, the energy metabolism was downregulated and the oxidative stress was upregulated in the liver tissue. Furthermore, NK cells depletion results in a lower levels of HBV surface Ag (HBsAg) and HBV 3.5 kb RNA expression, and a higher level of CD8⁺ T cells with reduced expression of LAG-3. In conclusion, alcohol abuse induces CD8⁺ T cells failure after acute HBV infection, but depletion of NK cells could retore CD8⁺ T cell activity. Moreover, downregulation of energy metabolism and upregulation of oxidative stress may also contribute to CD8⁺ T cell failure.

尽管事实上乙型肝炎病毒（HBV）感染和过量饮酒都代表着世界范围的健康问题，但酒精影响HBV相关肝病进展的机制尚不完全清楚。因此，我们研究了酒精如何影响HBV感染的发展以及T细胞和NK细胞在抗病毒反应中的作用。通过流式细胞术表征源自HBV携带者小鼠和野生型（WT）小鼠的单核细胞（MNC）的表型，并通过放射免疫分析（RIA），免疫组织化学和定量实时（qRT）检测HBV抗原和基因表达。 PCR。基于超高效液相串联色谱四极杆飞行时间质谱（UHPLC-QTOFMS），在小鼠肝脏组织中检测到代谢组学变化。⁺ T细胞在HBV持续存在期间，CD8 ⁺ T细胞上的淋巴细胞激活基因3（LAG-3）表达增加。此外，肝脏组织中的能量代谢被下调，氧化应激被上调。此外，NK细胞的耗竭导致HBV表面Ag（HBsAg）和HBV 3.5 kb RNA表达水平降低，而CD8 ⁺ T细胞水平升高而LAG-3表达降低。总之，滥用酒精可导致急性HBV感染后CD8 ⁺ T细胞衰竭，但NK细胞耗竭可恢复CD8 ⁺ T细胞活性。此外，能量代谢的下调和氧化应激的上调也可能导致CD8 ⁺ T细胞衰竭。