ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Clinical Infectious Diseases
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1653566
Tissue-Resident Memory CD8+T Cells might Enhance HBV DNA Clearance in CHB Patients with MASLD Complication and normal ALT via the CCL-CCR Pathways
Provisionally accepted
Chao Cai1
Wen-Xuan Shang1
Si-Jie Zheng1Chen Chen1Ke Xu1
Lu Chen1Ya-Jie Wang1Yu- Qun Wang1Rui-Cong Chen1
Yi-Jing Cai1
Huifang Zhang1
Chen Huang1
Ji Lin2Bang-Guo Zhou2
Xiu-Li Lin1Lei Zhang1
Ming-Qin Lu1*- 1First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- 2The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
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Background: HBV infection continues to pose a significant global health challenge, particularly in patients with normal alanine aminotransferase (ALT) level. The increasing prevalence of Metabolic dysfunction-associated steatotic liver disease (MASLD) among individuals with chronic hepatitis B (CHB) also presents new complications in management. The study aimed to investigate the relationship between MASLD and HBV DNA clearance in CHB patients with normal ALT. Methods: 403 patients with ALT levels below the normal threshold who underwent liver biopsy at our institution and subsequently received antiviral therapy with NAs were retrospectively examined. Among these, 177 patients were diagnosed with MASLD. Further single cell data analysis was conducted on GSE192740 and GSE182159. Results: CHB patients concurrent with MASLD had a higher probability of achieving HBV DNA clearance. The proportion of CD8+Teff-GZMH cells was increased in the MASLD group. The interactions among CD8+ Trm-CD69 cells and other T cell subtypes were enhanced, especially within the active CCL-CCR pathways. An elevated proportion of Monocyte-THBS1 was also observed. Conclusions: CD8+ Trm-CD69 T cells may be activated by Monocyte-THBS1 cells, thereby stimulating the immune system via the CCL-CCR signaling axis. This activation facilitates the recruitment of immune cells and
Keywords: Chronic hepatits B, Metabolic dysfunction-associated steatotic liver disease, Antiviral therapy, liver biopsy, single-cell RNA sequencing
Received: 25 Jun 2025; Accepted: 29 Aug 2025.
Copyright: © 2025 Cai, Shang, Zheng, Chen, Xu, Chen, Wang, Wang, Chen, Cai, Zhang, Huang, Lin, Zhou, Lin, Zhang and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ming-Qin Lu, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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