MASLDMASLDNCT07640880
Lipidomic and Multi-Omics Profiling of Fatty Liver Disease in People With and Without HIV
An observational study of MASLD and HIV (Human Immunodeficiency Virus), run by Yinzhong Shen at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- MASLD, HIV (Human Immunodeficiency Virus)
- How many people
- 120 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2026to 1 Sep 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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)
- Diagnosis of MASLD per the 2024 Chinese Guidelines: hepatic steatosis confirmed by imaging or histology (≥5% macrovesicular steatosis), exclusion of excessive alcohol consumption (>210 g/week for men, >140 g/week for women), and at least one metabolic cardiovascular risk factor
- For Group 2 (HIV-negative individuals with MASLD):
Show all 12Show fewer
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Shanghai Public Health Clinical Center
Shanghai, Shanghai Municipality, 201508
Yinzhong Shen, PhD, +86 18916113951, shenyinzhong@shphc.org.cn
Wei Xu, PhD, +86 13660308971, 24111300008@m.fudan.edu.cn
About this study
Official title: Multi-Omics Characterization of Lipid Metabolic Reprogramming in People With HIV Versus HIV-Negative Metabolic Dysfunction-Associated Steatotic Liver Disease
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.
Read the detailed description
MASLD is characterized by hepatic lipid accumulation driven by metabolic dysfunction, and its pathophysiology involves extensive lipid metabolic reprogramming - including dysregulation of triglycerides, diacylglycerols, ceramides, and phosphatidylcholines. In people living with HIV (PWH), the metabolic burden imposed by chronic immune activation and long-term antiretroviral therapy (ART) further disrupts circulating lipid homeostasis, potentially creating a distinct pathophysiological profile compared to HIV-negative individuals with MASLD. However, the molecular differences between HIV-associated and HIV-negative MASLD have not been systematically characterized.
This prospective, observational, cross-sectional study enrolls three groups: (1) PWH with MASLD, (2) HIV-negative individuals with MASLD, and (3) healthy controls matched for age, sex, and BMI. All participants are recruited from Shanghai Public Health Clinical Center and affiliated health examination centers. A single fasting peripheral blood sample (10 mL) is collected from each participant, from which plasma is isolated and stored at -80°C until analysis.
Plasma samples will undergo multi-omics profiling including:
Targeted lipidomics: quantitative analysis of core lipid classes (free fatty acids, ceramides, sphingomyelins, triglycerides, diacylglycerols, phosphatidylcholines) using UPLC-MS/MS in multiple reaction monitoring (MRM) mode Proteomics: plasma protein profiling to identify disease-associated protein expression changes Transcriptomics: gene expression analysis to characterize transcriptional alterations associated with MASLD in the context of HIV infection Differential lipid features will be identified using multivariate analysis (PCA, OPLS-DA) and univariate filtering (VIP > 1, |FC| > 1.5, FDR < 0.05). KEGG and LipidMaps pathway enrichment analyses will reveal key metabolic pathways involved in lipid reprogramming. Correlations between lipid signatures and clinical parameters will be examined using Spearman correlation analysis. ROC curve analysis and logistic regression will be used to evaluate the diagnostic performance of candidate biomarkers.
This study aims to: (1) establish a comprehensive plasma lipidomic and multi-omics atlas of MASLD in PWH versus HIV-negative individuals; (2) identify HIV-specific lipid dysregulation patterns; and (3) discover novel, non-invasive biomarkers for MASLD diagnosis applicable to the HIV-infected population.
- Conditions
- MASLD, HIV (Human Immunodeficiency Virus)
- Keywords
- HIV, MASLD, lipidomics
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At enrollment (single time point, cross-sectional)
Secondary outcomes (2)
Number of differentially abundant plasma proteins identified by quantitative proteomics
Number of plasma proteins showing statistically significant differential abundance among the three groups (treatment-naïve people with HIV and MASLD, HIV-negative people with MASLD, and healthy controls), quantified by mass spectrometry-based (DIA) proteomics. A protein is counted as differentially abundant if it meets |log2 fold change| >1 and adjusted p <0.05.
Measured: At enrollment
Number of differentially expressed genes in PBMCs identified by RNA sequencing
Number of genes showing statistically significant differential expression in peripheral blood mononuclear cells (PBMCs) among the three groups (treatment-naïve people with HIV and MASLD, HIV-negative people with MASLD, and healthy controls), quantified by RNA sequencing. A gene is counted as differentially expressed if it meets |log2 fold change| >1 and FDR <0.05.
Measured: At enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2026
- Study start1 Jun 2026 (estimated)
- Primary completion1 Sep 2026 (estimated)
- Study completion1 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for MASLDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yinzhong Shen
- Sponsor type
- Other government
- Responsible party
- Sponsor-investigator, Yinzhong Shen, Shanghai Public Health Clinical Center
- Investigators
- Yinzhong Shen, Principal investigator, Shanghai Public Health Clinical Center, Shanghai, Shanghai 201508
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07640880
- Sponsor's protocol ID
- GKT1341
- Acronym
- MASLD
- Status last verified
- Jun 2026
- First submitted
- 31 May 2026
- Last updated
- 11 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared publicly to protect the privacy and confidentiality of people living with HIV, given the sensitive nature of HIV status and the potential risk of participant re-identification in this population. De-identified data may be made available from the corresponding author upon reasonable request and with appropriate ethical approval.
Publications
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.
PubMed 38718757Rui 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.
PubMed 35584814Waters 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.
PubMed 30704819Horn 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.
PubMed 38823393
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-Omics Characterization of Lipid Metabolic Reprogramming in People With HIV Versus HIV-Negative Metabolic Dysfunction-Associated Steatotic Liver Disease
- ClinicalTrials.gov ID
- NCT07640880
- Acronym / sponsor ID
- MASLD / GKT1341
- Conditions
- MASLD, HIV (Human Immunodeficiency Virus)
- Keywords
- HIV, MASLD, lipidomics
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Yinzhong ShenOther government
- Study start
- 1 Jun 2026 (estimated)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 1 Sep 2026 (estimated)
- First posted
- 11 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
MASLD is characterized by hepatic lipid accumulation driven by metabolic dysfunction, and its pathophysiology involves extensive lipid metabolic reprogramming - including dysregulation of triglycerides, diacylglycerols, ceramides, and phosphatidylcholines. In people living with HIV (PWH), the metabolic burden imposed by chronic immune activation and long-term antiretroviral therapy (ART) further disrupts circulating lipid homeostasis, potentially creating a distinct pathophysiological profile compared to HIV-negative individuals with MASLD. However, the molecular differences between HIV-associated and HIV-negative MASLD have not been systematically characterized.
This prospective, observational, cross-sectional study enrolls three groups: (1) PWH with MASLD, (2) HIV-negative individuals with MASLD, and (3) healthy controls matched for age, sex, and BMI. All participants are recruited from Shanghai Public Health Clinical Center and affiliated health examination centers. A single fasting peripheral blood sample (10 mL) is collected from each participant, from which plasma is isolated and stored at -80°C until analysis.
Plasma samples will undergo multi-omics profiling including:
Targeted lipidomics: quantitative analysis of core lipid classes (free fatty acids, ceramides, sphingomyelins, triglycerides, diacylglycerols, phosphatidylcholines) using UPLC-MS/MS in multiple reaction monitoring (MRM) mode Proteomics: plasma protein profiling to identify disease-associated protein expression changes Transcriptomics: gene expression analysis to characterize transcriptional alterations associated with MASLD in the context of HIV infection Differential lipid features will be identified using multivariate analysis (PCA, OPLS-DA) and univariate filtering (VIP > 1, |FC| > 1.5, FDR < 0.05). KEGG and LipidMaps pathway enrichment analyses will reveal key metabolic pathways involved in lipid reprogramming. Correlations between lipid signatures and clinical parameters will be examined using Spearman correlation analysis. ROC curve analysis and logistic regression will be used to evaluate the diagnostic performance of candidate biomarkers.
This study aims to: (1) establish a comprehensive plasma lipidomic and multi-omics atlas of MASLD in PWH versus HIV-negative individuals; (2) identify HIV-specific lipid dysregulation patterns; and (3) discover novel, non-invasive biomarkers for MASLD diagnosis applicable to the HIV-infected population.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (12 listed)
- Age 18-80 years
- Able to provide written informed consent and cooperate with blood sample collection and clinical data recording
- Confirmed HIV infection with no prior antiretroviral therapy (treatment-naive)
- Diagnosis of MASLD per the 2024 Chinese Guidelines: hepatic steatosis confirmed by imaging or histology (≥5% macrovesicular steatosis), exclusion of excessive alcohol consumption (>210 g/week for men, >140 g/week for women), and at least one metabolic cardiovascular risk factor
- HIV-negative
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Number of differentially abundant plasma lipid species identified by targeted lipidomics (UPLC-MS/MS)
Time frame: At enrollment (single time point, cross-sectional)
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.
2 secondary outcomes
Number of differentially abundant plasma proteins identified by quantitative proteomics
Time frame: At enrollment
Number of differentially expressed genes in PBMCs identified by RNA sequencing
Time frame: At enrollment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2026.
- Results publication: PubMed 38718757Bo 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.
- Results publication: PubMed 35584814Rui 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.
- Results publication: PubMed 30704819Waters 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.
- Results publication: PubMed 38823393Horn 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.
- Individual participant dataSharing planned: No. Individual participant data will not be shared publicly to protect the privacy and confidentiality of people living with HIV, given the sensitive nature of HIV status and the potential risk of participant re-identification in this population. De-identified data may be made available from the corresponding author upon reasonable request and with appropriate ethical approval.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yinzhong Shen principal investigator
Shanghai Public Health Clinical Center, Shanghai, Shanghai 201508
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of MASLD and HIV (Human Immunodeficiency Virus), run by Yinzhong Shen at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yinzhong Shen, PhD (+8618916113951, shenyinzhong@shphc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of differentially abundant plasma lipid species identified by targeted lipidomics (UPLC-MS/MS) (time frame: At enrollment (single time point, cross-sectional)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07640880, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.