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

Liver Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05926778
• Other study ID #: Renji-LY2023-075-B
• Status: Not yet recruiting
• Start date: July 1, 2023
• Est. completion date: December 31, 2023

Study information

• Verified date: June 2023
• Source: RenJi Hospital
• Contact: Hao Feng, MD., Ph.D.
• Phone: 008615000901110
• Email: surgeonfeng[@]live.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 31, 2023
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Fibrosis
• Liver Cirrhosis
• Liver Fibrosis

Intervention

Other:
• Liver allograft fibrosis
Observational studies without intervention

Locations

Country	Name	City	State
China	Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
RenJi Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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