Chinese Hepatolgy ›› 2025, Vol. 30 ›› Issue (11): 1521-1524.

• Viral Hepatitis • Previous Articles     Next Articles

Role of Akt signaling pathway in immune regulation and therapeutic potential in chronic hepatitis B and HBV-related acute-on-chronic liver failure

WU Hang1, LIN Yi-ping1, LI Jia-xuan2, CHEN Ai-ping3, ZHENG Rui-dan3   

  1. 1. Department of Clinical Laboratory, Zhengxing Hospital, Zhangzhou 363000, China;
    2. Department of Clinical Medicine, Fujian Medical University, Fuzhou 350122, China;
    3. Diagnosis and Treatment Center for Liver Diseases, Zhangzhou Zhengxing Hospital, Zhangzhou 363000, China
  • Received:2025-02-26 Online:2025-11-30 Published:2026-02-09
  • Contact: ZHENG Rui-dan,Email:zhengruidan175@sina.cn

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Abstract: Objective Chronic hepatitis B (CHB) and hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) are major health issues worldwide, leading to immune dysregulation and T cell dysfunction. This study aimed to reveal the immune mechanisms of the Akt signaling pathway in HBV-related diseases and its potential therapeutic value. Methods A total of 6 subjects each were enrolled from Zhangzhou Zhengxing Hospital between January 2020 and March 2024, comprising healthy controls (NC), patients with chronic hepatitis B (CHB), and patients with HBV-related acute-on-chronic liver failure (HBV-ACLF). Flow cytometry was utilized to measure the expression of the apoptosis marker (Annexin V) and activation molecules (CD25, CD38, and CD69) in CD4+ and CD8+ T lymphocytes treated with DMSO and an Akt inhibitor, as well as the levels of IFN-γ, IL-2, and TNF-α secreted by CD4+ T lymphocytes. Results Compared to the DMSO group (NC: 9.418 ± 1.539%; CHB: 8.455 ± 0.693%; HBV-ACLF: 13.233 ± 2.652%), the proportion of Annexin V-positive CD4+ T cells was significantly increased in the Akt inhibitor group for CHB (15.132 ± 1.073%) and HBV-ACLF (18.767 ± 6.998%) patients, while no significant increase was observed in the NC group (8.820 ± 1.388%). Additionally, the Akt inhibitor did not affect CD8+ T cell apoptosis. Compared to the DMSO group, treatment with the Akt inhibitor significantly reduced the expression of CD25, CD38, and CD69 on CD4+ T and CD8+ T cells in CHB and HBV-ACLF patients, but did not reduce the expression of activation markers on CD4+ T and CD8+ T cells in the NC group. After treatment with the Akt inhibitor, the proportions of CD4+ IFN-γ+, CD4+ IL-2+, and CD4+TNF-α+ T cells in the NC, CHB, and HBV-ACLF groups were similar to those in the DMSO group. Conclusion The Akt signaling pathway plays a significant role in regulating T cell function in HBV infection, which could open up new possibilities for immunotherapy in HBV-related diseases.

Key words: Chronic hepatitis B virus infection, Acute-on-chronic liver failure, T-cell function, Akt signaling pathways, Immune checkpoints