Multiomics Study of Fibrosis Factors After Liver Transplantation and Exploration of Fibrosis Methylation Biomarkers

This is a retrospective observational study in liver transplantation recipients with or without allograft liver fibrosis. Based on the GM-seq and Tcr-Seq data, a novel diagnostic model including DNA-methylation and TCR-Seq biomarkers will be established.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Fibrosis
• Intervention / Treatment: Other: Liver allograft fibrosis

Detailed Description

This is a retrospective study on 60 patients who had previously received liver transplantation in our hospital. The patients will be stratified according to age, including 20 children and 20 adults with allograft liver fibrosis after liver transplantation, while 10 children and 10 adults with fibrosis, respectively.

1. The differential analysis of DNA-methylation will be performed between the allograft liver fibrosis cohort and the control cohort based on the GM-seq sequencing data. And the fibrosis-specific DNA-methylation CpG sites or regions in liver and peripheral blood will be explored in the liver transplantation recipients.
2. The abundance and diversity of TCR between the allograft liver fibrosis cohort and the control cohort will be analyzed. And the fibrosis-specific TCR sequence of allograft liver fibrosis will be screened based on TCR-Seq sequencing and tNGS.
3. The characteristics of DNA-methylation and TCR-Seq biomarkers in allograft liver fibrosis population will be defined. And the similarities and differences of the characteristics between children and adults will be explored.
4. Based on the GM-seq and Tcr-Seq data, a novel diagnostic model including DNA-methylation and TCR-Seq biomarkers will be established.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Hao Feng, MD., Ph.D.; Phone Number: 008615000901110; Email: surgeonfeng@live.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
      • Contact: Hao Feng, MD., Ph.D.; Phone Number: 15000901110; Email: surgeonfeng@live.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult or pediatric recipients who underwent liver transplantation

Description

Inclusion Criteria:

1. Living donor liver transplantation of left outer lobe or left half liver for biliary atresia in children (≤18 years old), or orthotopic liver transplantation for hepatitis B cirrhosis in adults (> 18 years old), regardless of gender;
2. Oral tacrolimus immunosuppressive therapy;
3. Received liver transplantation in our hospital for the first time and did not receive liver transplantation again;
4. Patients need to be admitted to hospital for programmed liver biopsy or receive liver biopsy due to abnormal liver function;
5. Complete clinical data and samples (including liver puncture biopsy specimens, plasma, and PBMC of the same period);
6. The subjects or their guardians voluntarily join the study, sign the informed consent, comply well, and cooperate with follow-up.

Exclusion Criteria:

1. Combined multi-organ transplantation;
2. Pregnancy or lactation;
3. Severe systemic infection;
4. Contraindications of liver biopsy with multiple organ failure or coagulation dysfunction;
5. Previous history of allergy to narcotic or sedative drugs;
6. In the stage of acute rejection hormone shock therapy;
7. Incomplete clinical data and samples;
8. Situations considered unsuitable for inclusion by other researchers.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Fibrosis Cohort; Adult(10 patients) and pediatric(10 patients) liver transplant recipients with fibrosis determined by histological examination of liver biopsy	Other: Liver allograft fibrosis; Observational studies without intervention
Control Cohort; Adult(20 patients) and pediatric(20 patients) liver transplant recipients without fibrosis determined by histological examination of liver biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensivity	Sensivity is the true positive rate of the novel diagnostic model [Liver fibrosis is determined by histological examination of liver biopsy (LAFSc)].	7 Days
Specificity	Specificity is the true negative rate of the novel diagnostic model [Liver fibrosis is determined by histological examination of liver biopsy (LAFSc)].	7 Days
AUROC	AUROC is the area under the receiver operating characteristic curve [Liver fibrosis is determined by histological examination of liver biopsy (LAFSc)].	7 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heterogeneity of the DNA-methylation biomarkers in allograft liver fibrosis cohort	The similarities and differences of the characteristics of DNA-methylation and TCR-Seq biomarkers between children and adults in the allograft liver fibrosis cohort.	7 Days
Heterogeneity of the TCR-Seq biomarkers in allograft liver fibrosis cohort	The similarities and differences of the characteristics of TCR-Seq biomarkers between children and adults in the allograft liver fibrosis cohort.	7 Days

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Study Chair: Qiang Xia, Prof. MD, Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU; Principal Investigator: Hao Feng, MD., Ph.D., Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): October 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: June 6, 2023
• First Submitted That Met QC Criteria: June 22, 2023
• First Posted (Actual): July 3, 2023

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 22, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Biomarkers; DNA methylation; Liver Transplantation; Liver Fibrosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: Renji-LY2023-075-B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No