Editor's Note: In the field of viral hepatitis, while most chronic hepatitis B (CHB) patients receiving tenofovir alafenamide (TMF) antiviral therapy experience a rapid decline in HBV DNA levels, only a subset achieves a significant reduction in HBsAg levels. The underlying immunological mechanisms behind this response remain unclear. To address this, a prospective, single-center clinical study was conducted by Dr. Xin Zheng and Dr. Jia Liu from the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. The study aimed to dynamically observe changes in immune function during the early phase of TMF therapy and their correlation with clinical indicators. The findings were presented at the 75th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) and earned the prestigious "Poster of Distinction" award.Key Findings from the Study
The research, conducted by a team including Dr. Jia Liu, Dr. Shue Xiong, Dr. Hang Jia, and Master’s student Xufeng Quan, involved 37 treatment-naïve CHB patients meeting antiviral therapy guidelines. These patients, 18 HBeAg-positive and 19 HBeAg-negative, were monitored during routine clinical follow-ups over a 48-week TMF treatment period. Peripheral blood samples were collected to isolate peripheral blood mononuclear cells (PBMCs) for dynamic evaluation of B cells, dendritic cells (DCs), monocytes, T cell phenotypes, and HBV-specific T cell functions.
Clinical Observations
• TMF therapy resulted in a rapid and significant decline in HBV DNA and HBV RNA levels in all patients.
• While baseline levels of HBsAg, HBV DNA, and HBV RNA were higher in the HBeAg-positive group compared to the HBeAg-negative group, the HBeAg-positive patients exhibited a more pronounced decline in HBsAg, particularly within the first 12 weeks of treatment.
• Among the HBeAg-positive patients, those with significantly abnormal ALT levels at baseline showed greater reductions in HBsAg during treatment.
Immune Function Dynamics
Over the 48-week follow-up, distinct differences in immune cell functionality were observed between the HBeAg-positive and HBeAg-negative groups:
HBeAg-Positive Group
- Higher baseline and follow-up frequencies of B cells and CD8+ T cells compared to the HBeAg-negative group.
- Significant decline in monocyte frequencies at weeks 40 and 48
HBeAg-Negative Group
- Increased frequencies of DCs, particularly with a noticeable rise at week 20.
- Marked decrease in T cell frequencies post-treatment, primarily due to reductions in CD4+ T cells.
Immune Cell Activation
- Short-term increases in immune markers on B cells at weeks 4–8, with elevated CD80 and PD-L1 expression in the HBeAg-negative group peaking at week 20. CD72 expression on B cells declined significantly at week 28.
- Monocytes exhibited rising trends in CD80 and PD-L1 expression, with significant increases in CD80 at week 20 in the HBeAg-negative group. Conversely, CD86 expression showed a declining trend, with the most notable decrease in the HBeAg-positive group at week 12.
T Cell Phenotype and Function
- In the HBeAg-positive group, CD4+ T cells exhibited sustained high Foxp3 expression during the first 12 weeks, which began to decline after week 8.
- CD8+ T cells in the HBeAg-positive group demonstrated relatively low expression of HLA-DR, PD-1, and CD95 throughout the follow-up period, with significant reductions in HLA-DR and CD95 expression at week 20.
HBV-Specific T Cell Responses
- The HBeAg-negative group showed stronger HBcAg-specific T cell responses.
- The HBeAg-positive group exhibited robust CD4+ T cell responses targeting the HBsAg peptide pool.
Subgroup Analysis of HBeAg-Positive Patients
Among HBeAg-positive patients, those with an HBsAg decline of over 0.5 log after 12 weeks of treatment showed:
- Increased expression of CD80 and CD72 on B cells, and CD86, CD80, and PD-L1 on monocytes.
- A transient rise in CD86 expression on monocytes within the first 8 weeks, followed by a decline.
- Sustained high expression of CD25 on CD4+ T cells and HLA-DR on CD8+ T cells.
- Declining trends in CD95 expression on CD4+ T cells, and PD-1 and Granzyme B expression on CD8+ T cells.
Conclusions
This study reveals distinct immune functional changes in HBeAg-positive and HBeAg-negative CHB patients during TMF treatment. HBeAg-positive patients with a rapid HBsAg decline in the first 12 weeks showed activation of B cells, monocytes, and T cells. These findings suggest that TMF not only suppresses viral replication but also exerts immunomodulatory effects. This research provides theoretical support for the precise selection of antiviral therapies for treatment-naïve CHB patients, particularly HBeAg-positive individuals with abnormal ALT levels.
Infectious Diseases and Immunology in Global Health: Insights from the Yangtze River Symposium
In the field of global health, research on infectious diseases and immunology remains a cornerstone of scientific advancement. The Department of Infectious Diseases at Union Hospital, Huazhong University of Science and Technology (HUST), led by Dr. Xin Zheng, actively engages in academic exchanges with domestic and international experts to explore the latest findings, clinical practices, and therapeutic strategies in infectious diseases and immunology.
On October 18–19, 2024, Wuhan, Hubei Province, hosted the Yangtze River Symposium on Infectious Diseases and Immunology, a prestigious academic event that brought together experts from around the world. The symposium was co-organized by Union Hospital of Huazhong University of Science and Technology, the Hubei International Science and Technology Cooperation Base for Infection and Immunity, the Joint International Laboratory for Infection and Immunity, the Hubei Center for Tick-borne Disease Control and Prevention, and the Wuhan Immunology Society.
This academic gathering provided a platform for in-depth discussions on topics ranging from basic research to clinical applications and from virology to immunotherapy.
Keynote Presentations by Global and Domestic Experts
Renowned virologists and immunologists presented their latest research on diverse topics, including:
- Dr. Michael Kirschfink (University of Heidelberg, Germany): The role of the complement system in infectious diseases and immunity.
- Dr. Patrick Kennedy (Queen Mary University of London, UK): The impact of hepatitis B virus (HBV) DNA integration on diagnosis, treatment, and prognosis.
- Dr. Mengji Lu (University of Duisburg-Essen, Germany) and Dr. Sebastian Voigt: Insights into microRNA’s role in HBV infection, animal models, and regulation of antiviral immune responses.
- Dr. Jie Yan (National University of Singapore): The micromechanics of DNA and proteins.
- Dr. Nina Le Bert (Duke-NUS Medical School, Singapore): Novel strategies for immunotherapy in HBV.
- Dr. Anna Kosinska (Technical University of Munich, Germany): Mechanisms and strategies for immune response regulation in HBV.
- Dr. Xin Zheng and Dr. Jia Liu (HUST, Union Hospital): Immunological mechanisms in severe fever with thrombocytopenia syndrome (SFTS) and therapeutic strategies.
- Dr. Yuchen Xia (Wuhan University, China): Advances in immunological mechanisms of SFTS and rescue strategies.
Each keynote presentation sparked lively and sustained discussions among the audience, reflecting the symposium’s rich academic atmosphere and the participants’ enthusiasm for the topics.
Contributions from Domestic Experts
Distinguished scholars from HUST, including Dr. Dongliang Yang, Dr. Weimin Wang, Dr.Yueguang Rong, Dr.Xiufang Weng, Dr.Baoju Wang, and Dr.Jun Wu; Peking University’s Dr. Fengmin Lu; Nanfang Hospital University’s Dr. Xiaoyong Zhang; Southern University of Science and Technology’s Dr. Zhenfeng Zhang; and Wuhan University’s Dr. Xiaoming Cheng chaired sessions and participated in discussions.
The collective insights from these experts shed new light on developing immunotherapy strategies for chronic hepatitis B, SFTS, and cytomegalovirus infections—diseases that pose significant threats to human health. Their contributions provided fresh directions for future advancements in combating infectious diseases through immunological innovation.
