Clonorchis sinensis co-infection potentiates polymorphonuclear-myeloid-derived suppressor cells expansion and metabolic reprogramming in chronic hepatitis B patients

doi:10.3748/wjg.122956

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Observational Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Nov 28, 2026; 32(44): 122956
Published online Nov 28, 2026. doi: 10.3748/wjg.122956

Clonorchis sinensis co-infection potentiates polymorphonuclear-myeloid-derived suppressor cells expansion and metabolic reprogramming in chronic hepatitis B patients

Jie-Ru Qiu, Hong-Bin Zhang, Mei Shang, Jue Xu, Yue-Chun Fu, Yuan Liao, Bo Hu, Hui-Min Dong

Jie-Ru Qiu, Hong-Bin Zhang, Mei Shang, Jue Xu, Yue-Chun Fu, Yuan Liao, Bo Hu, Hui-Min Dong, Department of Laboratory Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China

Co-first authors: Jie-Ru Qiu and Hong-Bin Zhang.

Co-corresponding authors: Bo Hu and Hui-Min Dong.

Author contributions: Qiu JR and Zhang HB contributed equally to this work as co-first authors; Hu B, and Dong HM contributed equally to this work as co-corresponding authors; Qiu JR wrote the manuscript; Zhang HB performed the experiments; Shang M contributed to the analysis; Xu J and Fu YC collected clinical information; Liao Y, Hu B, and Dong HM designed and supervised the study. All authors approved the final version.

AI contribution statement: We used DeepSeek R1 and Baidu Scholar only for formatting and organizing the reference list. No AI tools were used for data analysis, interpretation, or any other scientific aspects of the study.

Supported by the National Natural Science Foundation of China, No. 81902082.

Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University (approval No. [2020]02-045-01).

Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at donghmin@mail.sysu.edu.cn.

Corresponding author: Hui-Min Dong, PhD, Researcher, Department of Laboratory Medicine, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Tianhe District, Guangzhou 510630, Guangdong Province, China. donghmin@mail.sysu.edu.cn

Received: May 7, 2026
Revised: August 3, 2026
Accepted: September 10, 2026
Published online: November 28, 2026
Processing time: 149 Days and 17.6 Hours

Abstract

BACKGROUND

Clonorchis sinensis (C. sinensis) co-infection is known to accelerate disease progression and induce immune tolerance in patients with hepatitis B virus (HBV), particularly in regions where both infections are endemic. Metabolic reprogramming has emerged as a key driver of immunosuppression. These metabolic shifts are often orchestrated by myeloid-derived suppressor cells (MDSCs), which expand during chronic infections to promote immune tolerance. However, whether C. sinensis co-infection reprograms metabolism to favor MDSC-linked suppression and how this process relates to normal liver enzyme levels remains unclear.

AIM

To investigate whether C. sinensis co-infection induces MDSC- linked metabolic reprogramming in patients with HBV and normal liver enzyme levels.

METHODS

In this cross-sectional study, a total of 117 participants were enrolled and assigned to four groups: Healthy controls (n = 30), C. sinensis mono-infected participants (n = 29), HBV mono-infected participants (n = 28), and co-infected participants (n = 30). Serum cytokine profiles were measured using chemiluminescence immunoassay, amino acid metabolites using liquid chromatography-tandem mass spectrometry, and MDSC subsets using flow cytometry. Spearman correlation and mediation analyses were performed to explore the relationships among inflammation, metabolism, and immunity.

RESULTS

HBV mono-infected and co-infected patients showed no statistically significant differences in liver enzyme and HBV DNA levels. However, compared with the HBV mono-infected group, the co-infected group had higher levels of the inflammatory cytokine: Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), accompanied by markedly lower interferon-γ (IFN-γ) levels. Flow cytometric assay revealed that polymorphonuclear MDSCs (PMN-MDSCs) showed the greatest expansion in the co-infected group, and their proportion correlated strongly with IL-6 and TNF-α levels. Metabolically, the co-infected group had a significantly higher ornithine-to-arginine ratio. Mediation analysis suggested that PMN-MDSCs accounted for approximately 45% of the total effect of IL-6 on IFN-γ suppression.

CONCLUSION

C. sinensis co-infection was associated with immunosuppression through IL-6/TNF-α-linked PMN-MDSC expansion and elevated ornithine-to-arginine ratio, resulting in suppressed IFN-γ production despite normal liver enzyme levels.

Keywords: Clonorchis sinensis; Chronic hepatitis B; Hepatitis B virus-Clonorchis sinensis co-infection; Polymorphonuclear myeloid-derived suppressor cell; Ornithine-to-arginine ratio; Immunosuppression

Core Tip: Compared with hepatitis B virus mono-infected patients with normal liver enzyme levels, Clonorchis sinensis co-infection expands polymorphonuclear-myeloid-derived suppressor cells. This activates the arginine (Arg)-ornithine (Orn) axis, raising the Orn-to-Arg ratio. Consequently, interferon-γ production is suppressed. The Orn-to-Arg ratio outperforms standard liver enzyme levels for immune assessment. Screening for Clonorchis sinensis is warranted even in patients with well-controlled viremia.