Lipidomic and Multi-Omics Profiling of Fatty Liver Disease in People With and Without HIV

NCT07640880 | Not Yet Recruiting DMC

• 1 other identifier: GKT1341
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Metabolic dysfunction-associated steatotic liver disease (MASLD), commonly known as fatty liver disease, is increasingly prevalent worldwide. People living with HIV (PWH) face a higher risk of developing MASLD due to chronic immune activation and long-term antiretroviral therapy, yet whether the underlying biological changes differ from those in HIV-negative individuals with MASLD remains unknown. This prospective observational study will enroll three groups: PWH with MASLD, HIV-negative individuals with MASLD, and healthy controls without liver disease. A single fasting blood sample will be collected from each participant. Using targeted lipidomics, proteomics, and transcriptomics platforms, researchers will compare plasma molecular profiles across the three groups to identify MASLD-specific lipid signatures, characterize metabolic pathway dysregulation, and discover potential blood-based biomarkers for non-invasive diagnosis of MASLD. Findings from this study may help explain how HIV infection alters lipid metabolism in the context of MASLD and support the development of HIV-specific diagnostic tools for fatty liver disease.

Conditions

MASLD; HIV (Human Immunodeficiency Virus)

Keywords

HIV; MASLD; lipidomics

Outcome Measures

Primary Outcomes (1)

• Number of differentially abundant plasma lipid species identified by targeted lipidomics (UPLC-MS/MS)

  Number of plasma lipid species showing statistically significant differential abundance among the three groups (treatment-naïve people with HIV and MASLD, HIV-negative people with MASLD, and healthy controls). Lipid species across core lipid classes (free fatty acids, ceramides, sphingomyelins, triglycerides, diacylglycerols, and phosphatidylcholines) are quantified by targeted lipidomics using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in multiple reaction monitoring (MRM) mode, with quality-control samples and internal standards (e.g., TAG 17:0, Cer d18:1/17:0; RSD \<15%). A lipid species is counted as differentially abundant if it meets fold change ≥1.5 or ≤0.67, and FDR \<0.05.

  At enrollment (single time point, cross-sectional)

Secondary Outcomes (2)

• Number of differentially abundant plasma proteins identified by quantitative proteomics

  At enrollment

• Number of differentially expressed genes in PBMCs identified by RNA sequencing

  At enrollment

Study Arms (3)

PWH with MASLD

People with HIV diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD), enrolled from the outpatient clinic of Shanghai Public Health Clinical Center.

HIV negative with MASLD

HIV-negative individuals diagnosed with MASLD, enrolled from Shanghai Public Health Clinical Center and affiliated health examination centers.

healthy controls

HIV-negative individuals without liver disease, matched to MASLD groups by age, sex, and BMI, enrolled from affiliated health examination centers.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants are recruited from a single tertiary hospital (Shanghai Public Health Clinical Center): (1) treatment-naive people with HIV and MASLD from the outpatient Department of Infection and Immunity; (2) HIV-negative individuals with MASLD identified through the hospital's Health Management Center; and (3) healthy controls without liver disease from the same Health Management Center, matched to MASLD groups by age, sex, and BMI.

You may qualify if:

• Age 18-80 years
• Able to provide written informed consent and cooperate with blood sample collection and clinical data recording
• For Group 1 (Treatment-naive people with HIV and MASLD):
• Confirmed HIV infection with no prior antiretroviral therapy (treatment-naive)
• For Group 2 (HIV-negative individuals with MASLD):
• HIV-negative
• Diagnosis of MASLD as defined above
• For Group 3 (Healthy Controls):
• HIV-negative
• Normal liver morphology on abdominal ultrasonography within the past year, with no evidence of hepatic steatosis
• Matched to MASLD groups by age (within 5 years), sex, and BMI (within 3 kg/m²)

You may not qualify if:

• Chronic liver disease with decompensated cirrhosis, hepatic malignancy, or history of liver transplantation
• Pregnancy or lactation
• Active severe infectious disease (other than HIV for Group 1)
• Severe critical illness or major organ failure

Sponsors & Collaborators

• Yinzhong Shen: lead

Study Sites (1)

Shanghai Public Health Clinical Center

Shanghai, Shanghai Municipality, 201508, China

Location

Related Publications (4)

• Bo T, Gao L, Yao Z, Shao S, Wang X, Proud CG, Zhao J. Hepatic selective insulin resistance at the intersection of insulin signaling and metabolic dysfunction-associated steatotic liver disease. Cell Metab. 2024 May 7;36(5):947-968. doi: 10.1016/j.cmet.2024.04.006.

  PMID: 38718757 RESULT

• Rui L, Lin JD. Reprogramming of Hepatic Metabolism and Microenvironment in Nonalcoholic Steatohepatitis. Annu Rev Nutr. 2022 Aug 22;42:91-113. doi: 10.1146/annurev-nutr-062220-105200. Epub 2022 May 18.

  PMID: 35584814 RESULT

• Waters DD, Hsue PY. Lipid Abnormalities in Persons Living With HIV Infection. Can J Cardiol. 2019 Mar;35(3):249-259. doi: 10.1016/j.cjca.2018.11.005. Epub 2018 Nov 15.

  PMID: 30704819 RESULT

• Horn P, Tacke F. Metabolic reprogramming in liver fibrosis. Cell Metab. 2024 Jul 2;36(7):1439-1455. doi: 10.1016/j.cmet.2024.05.003. Epub 2024 May 31.

  PMID: 38823393 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Fasting peripheral blood (10 mL) is collected from each participant via venipuncture. Blood samples are centrifuged within 30 minutes of collection at 2,000 × g for 10 minutes at 4°C to isolate plasma. Plasma aliquots are stored at -80°C until analysis for targeted lipidomics and proteomics. Peripheral blood mononuclear cells (PBMCs) are simultaneously isolated using density gradient centrifugation, and cell pellets are stored at -80°C for subsequent transcriptomic profiling. All biospecimens are retained for the duration of the study and may be used for additional omics analyses related to the study objectives.

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Yinzhong Shen

  Shanghai Public Health Clinical Center, Shanghai, Shanghai 201508

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yinzhong Shen, PhD

CONTACT

+8618916113951; shenyinzhong@shphc.org.cn

Wei Xu, PhD

CONTACT

+8613660308971; 24111300008@m.fudan.edu.cn

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: May 31, 2026
• First Posted: June 11, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)