Immunometabolic drivers of metabolic dysfunction-associated steatotic liver disease in non-obese people living with human immunodeficiency virus

doi:10.3748/wjg.120036

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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

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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 7, 2026; 32(41): 120036
Published online Nov 7, 2026. doi: 10.3748/wjg.120036

Immunometabolic drivers of metabolic dysfunction-associated steatotic liver disease in non-obese people living with human immunodeficiency virus

Fei Ji, Li-Fan Zhang, Yang Gui, Zhen-Hong Qi, Yang Han, Na Su, Qing Zhang, Yan-Ling Li, Wei Zhao, Wei Lyu, Meng Yang

Fei Ji, Yang Gui, Zhen-Hong Qi, Na Su, Wei Zhao, Meng Yang, Department of Ultrasonography, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China

Li-Fan Zhang, Yang Han, Qing Zhang, Wei Lyu, Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China

Co-first authors: Fei Ji and Li-Fan Zhang.

Co-corresponding authors: Wei Lyu and Meng Yang.

Author contributions: Ji F and Zhang LF contributed equally to study design, data collection, statistical analysis, data interpretation, and manuscript preparation (including drafting and critical revision), and they are co-first authors; Lyu W and Yang M contributed equally to study design, data interpretation, and critical revision of the manuscript, they are co-corresponding authors; Ji F, Zhang LF, Gui Y, Qi ZH, Han Y, Su N, Zhang Q, Li YL, Zhao W, Lyu W, and Yang M designed the research study; Ji F, Zhang LF, Gui Y, Han Y, Zhang Q, Li YL, and Zhao W collected the data; Ji F and Zhang LF performed the statistical analysis; Ji F, Zhang LF, Yang M, Lyu W, and Qi ZH analyzed and interpreted the data; Ji F drafted the manuscript; Ji F, Zhang LF, Yang M, Lyu W, and Su N critically revised the manuscript for important intellectual content; all authors have read and approved the final manuscript.

Supported by the National Key RD Program of China, No. 2023YFC2411705; National Natural Science Foundation of China, No. U22A2023 and No. 62325112; CAMS Innovation Fund for Medical Sciences, No. 2025-I2M-XHJC-003; PUMCH Talent Development Support Program, No. ULJ04684; and National High-Level Hospital Clinical Research Funding, No. 2025-PUMCH-C-052 and No. 2022-PUMCH-D-008.

Institutional review board statement: The study complied with the Declaration of Helsinki and the 2018 Declaration of Istanbul, and was approved by the Ethics Committee of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (approval No. HS-3401D).

Informed consent statement: Written informed consent was obtained from all the participants.

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

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

Data sharing statement: Data available on request due to privacy restrictions.

Corresponding author: Meng Yang, MD, PhD, Professor, Department of Ultrasonography, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China. yangmeng_pumch@126.com

Received: February 14, 2026
Revised: April 22, 2026
Accepted: May 9, 2026
Published online: November 7, 2026
Processing time: 213 Days and 0.6 Hours

Abstract

BACKGROUND

Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in people living with human immunodeficiency virus (PLWH), but its drivers in non-obese individuals are unclear. A low cluster of differentiation (CD) 4/CD8 ratio marks immune senescence, yet the role of a normalized ratio in MASLD risk in non-obese PLWH remains unexplored.

AIM

To investigate MASLD prevalence, risk factors, and short-term integrase strand transfer inhibitors (INSTIs) impact on steatosis in non-obese PLWH.

METHODS

This prospective study enrolled virologically suppressed PLWH who had received antiretroviral therapy for ≥ 6 months. All participants underwent clinical assessments, biochemical tests, and vibration-controlled transient elastography. Multivariate logistic regression identified independent risk factors for MASLD. Changes in parameters across the INSTIs-based, non-INSTIs-based, and switching to the INSTIs-based regime groups in non-obese PLWH were compared using mixed-effects models from baseline to month 12.

RESULTS

Among 181 enrolled participants [median age, 40 years (interquartile range: 35-48); 5.0% female], the overall prevalence of MASLD was 46.4%. Notably, among all patients with MASLD (n = 84), 28.6% (24/84) were non-obese. In the non-obese subgroup, higher body mass index [odds ratio (OR) = 2.14, 95% confidence interval (CI): 1.32-3.47], alanine aminotransferase (ALT) (OR = 1.04, 95%CI: 1.003-1.069), triglyceride-glucose index (OR = 3.29, 95%CI: 1.04-10.40), CD4/CD8 ratio (OR = 8.55, 95%CI: 1.57-46.66) and lower high-density lipoprotein level (OR = 0.029, 95%CI: 0.001-0.688) were independently associated with increased MASLD risk. 12-month longitudinal analysis revealed no significant group-by-time interaction effects for ultrasound attenuation parameter, liver stiffness measurement, and ALT.

CONCLUSION

MASLD is prevalent in non-obese PLWH. Higher CD4/CD8 ratio associates with MASLD, indicating that immune reconstitution does not ensure metabolic health. INSTIs were not associated with short-term hepatic steatosis progression.

Keywords: Human immunodeficiency virus; Metabolic dysfunction-associated steatotic liver disease; Integrase strand transfer inhibitors; Antiretroviral therapy; Transient elastography

Core Tip: In virologically suppressed people living with human immunodeficiency virus (PLWH), metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent even in non-obese individuals. We report a paradoxical finding: A higher cluster of differentiation (CD) 4/CD8 ratio, a marker of favorable immune recovery, was independently associated with increased MASLD risk in non-obese PLWH (odds ratio = 8.55). This challenges the view that immune reconstitution is the sole therapeutic endpoint. Instead, metabolic risk stratification including routine steatosis assessment is warranted even in immunologically favorable, non-obese individuals. Integrase strand transfer inhibitors-based antiretroviral therapy demonstrated short-term hepatic safety.