Clinical trial NCT05926778: Multiomics Study of Fibrosis Factors After Liver Transplantation and Exploration of Fibrosis Methylation Biomarkers
Official title: Multiomics Study of Fibrosis Factors After Liver Transplantation and Exploration of Fibrosis Methylation Biomarkers
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Liver Fibrosis
Keywords: Liver Fibrosis
Liver Transplantation
Biomarkers
DNA methylation
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2023-07-03
Enrollment: 60
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult or pediatric recipients who underwent liver transplantation

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Sensivity
timeFrame: 7 Days
measure: Specificity
timeFrame: 7 Days
measure: AUROC
timeFrame: 7 Days
Secondary outcomes:
measure: Heterogeneity of the DNA-methylation biomarkers in allograft liver fibrosis cohort
timeFrame: 7 Days
measure: Heterogeneity of the TCR-Seq biomarkers in allograft liver fibrosis cohort
timeFrame: 7 Days
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
state: Shanghai
Study officials:
affiliation: Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU
name: Qiang Xia, Prof. MD
role: STUDY_CHAIR
affiliation: Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU
name: Hao Feng, MD., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: