Clinical Classification of MAFLD Based Liver Biopsy

NCT ID: NCT06795646

Last Updated: 2025-02-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

2000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-02-08

Study Completion Date

2038-12-31

Brief Summary

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Metabolic dysfunction-associated Fatty Liver Disease (MAFLD), also known as Non-Alcoholic Fatty Liver Disease (NAFLD), is the most common chronic progressive liver disease in China. It is closely related to the high incidence of cardiovascular-renal-metabolic syndrome and both liver and non-liver malignancies, posing a serious threat to public health. However, the diagnostic criteria for MAFLD are not unified globally, and the classification and staging still rely on liver biopsy for pathological assessment. The characteristics, mechanisms, and predictive indicators of liver and extrahepatic disease outcomes in MAFLD patients are not yet clear.

The severe form of MAFLD, metabolic dysfunction-associated steatohepatitis (MASH), has been a hot and challenging area of research for non-invasive tests (NITs). However, serum markers, imaging examinations, and novel markers under development cannot replace liver biopsy for the diagnosis of MASH. Clinically, the disease outcomes of MAFLD mainly depend on metabolic cardiovascular risk factors and fibrosis staging. Both liver biopsy and NIT-diagnosed advanced fibrosis and cirrhosis can predict liver-related events and all-cause mortality risks in MAFLD patients. Artificial intelligence and machine learning methods can improve the consistency of pathologists in diagnosing MASH and fibrosis. The Agile score, which combines gender, T2DM status, AST/ALT ratio, platelet count, and liver stiffness measurement (LSM), can improve the diagnostic efficacy of advanced fibrosis and cirrhosis in MAFLD patients and the efficiency of predicting liver-related events. However, the predictive effect of fibrosis staging and its changes on liver cancer needs to be improved. There is a lack of high-quality research on early warning indicators for the incidence of CVD, chronic kidney disease, and non-liver malignancies in MAFLD patients. It is necessary to explore the role of conventional indicators such as low-density lipoprotein cholesterol, lipoprotein(a), uric acid, and high-sensitivity C-reactive protein, as well as multi-omics parameters, in the classification, staging, and risk prediction of MAFLD.

MAFLD is an increasingly serious public health issue associated with a higher risk of liver-related events, cardiovascular-renal-metabolic syndrome, and malignancies. The prevalence of MAFLD in China is high, but the rate of standardized management is low. Even patients with the same classification and staging often have different clinical characteristics and outcomes. There is currently a lack of a clinical classification and early warning system for MAFLD that combines metabolic cardiovascular risk factors and NITs for different outcome risks.

Detailed Description

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1. Recruitment and Data Collection:

On the basis of an existing cohort of 1,500 liver biopsy cases, recruit an additional 500 cases from a national multicenter liver biopsy follow-up cohort (totaling 2,000 cases). Collect demographic, anthropometric, laboratory, imaging, and liver biopsy results for these patients.

Concurrently, biological samples, including blood, urine, feces, and liver biopsy tissues, will be collected. Utilize these samples to perform quantitative metabolite information based on database matching. Employ techniques such as genomics, epigenomics, proteomics, metabolomics, immunomics, and microbiome metagenomics to screen for differential biomarkers across different subgroups.

Combine these findings with clinical and imaging parameters of MAFLD patients to analyze and explore key parameters and molecules at different stages and outcomes of MAFLD disease progression.
2. Development and Validation of a Diagnostic and Prognostic System:

Based on key molecules identified through multi-omics, in conjunction with characteristic parameters from clinical and imaging data of MAFLD patients, use machine learning methods (such as random forests neural networks) combined with logistic regression to establish a novel non-invasive diagnostic and prognostic assessment system for adverse outcomes (cardiovascular events, non-liver malignancies, and liver-related events).

Validate this new assessment system to ensure its reliability and accuracy in predicting disease outcomes.

Conditions

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Metabolic Dysfunction Associated Steatotic Liver Disease Metabolic Dysfunction-associated Steatohepatitis (MASH)

Study Design

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Observational Model Type

COHORT

Study Time Perspective

OTHER

Study Groups

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MAFLD diagnosed by liver-biopsy

retrospective and prospective cohort about MAFLD diagnosed by liver-biopsy

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Ultrasound confirmation of fatty liver and the presence of at least one of the following metabolic cardiovascular risk factors:

1. BMI ≥ 24 kg/m² or waist circumference ≥ 90 cm (men) and 85 cm (women) or excessive body fat content and body fat percentage.
2. Fasting blood glucose ≥ 6.1 mmol/L or 2-hour post-load blood glucose ≥ 7.8 mmol/L or HbA1c ≥ 5.7% or history of Type 2 Diabetes Mellitus (T2DM) or Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) ≥ 2.5.
3. Fasting serum triglycerides ≥ 1.70 mmol/L or currently receiving lipid-lowering drug therapy.
4. Serum high-density lipoprotein cholesterol (HDL-C) ≤ 1.0 mmol/L (men) and 1.3 mmol/L (women) or currently receiving lipid-lowering drug therapy.
5. Blood pressure ≥ 130/85 mmHg or currently receiving antihypertensive drug therapy.
* histology of liver-biopsy

Exclusion Criteria

* Excessive Alcohol Consumption: Individuals who consume alcohol equivalent to ≥30 grams of ethanol per day for males, or ≥20 grams of ethanol per day for females, or those with missing alcohol consumption information.
* Viral Hepatitis Markers: Individuals who are positive for hepatitis B surface antigen (HBsAg), positive for hepatitis C virus (HCV) antibodies, or have missing information regarding these markers.
* History of Serious Medical Conditions: Individuals with a history of malignant tumors, cardiovascular diseases, chronic kidney disease, decompensated liver cirrhosis (manifested by ascites, gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome, etc.), or those who have undergone liver transplantation.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fudan University

OTHER

Sponsor Role collaborator

Tianjin Second People's Hospital

OTHER

Sponsor Role collaborator

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role collaborator

The Affiliated Hospital of Hangzhou Normal University

OTHER

Sponsor Role collaborator

Ruijin Hospital

OTHER

Sponsor Role collaborator

Beijing Friendship Hospital

OTHER

Sponsor Role lead

Responsible Party

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Hong You

Vice-President

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hong You, PhD. / M.D.

Role: PRINCIPAL_INVESTIGATOR

Beijing Friendship Hospital

Locations

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Beijing Friendship Hospital, Capital Medical University

Beijing, Xicheng, China

Site Status

Hangzhou Normal University Affiliated Hospital

Hangzhou, Xicheng, China

Site Status

Zhongshan Hospital, Fudan University

Shanghai, Xicheng, China

Site Status

Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, , China

Site Status

Xinhua Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, , China

Site Status

Tianjin Second People's Hospital

Tianjin, , China

Site Status

Countries

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China

Central Contacts

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Jingjie Zhao, M.D.

Role: CONTACT

01063138328

Facility Contacts

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Jingjie Zhao

Role: primary

01063138328

Chunlan Liu

Role: primary

+8618325321386

Xinyu Yang

Role: primary

+8618800332829

Xiaolin Wang

Role: primary

+8613916785394

Ruixu Yang

Role: primary

+8615000600658

Huan Liu

Role: primary

+8613622105240

Other Identifiers

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2023ZD0508702

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2023ZD0508702

Identifier Type: -

Identifier Source: org_study_id

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