Multiomics Study of Fibrosis Factors After Liver Transplantation and Exploration of Fibrosis Methylation Biomarkers
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Specificity
研究概览
简要总结
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.
详细描述
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.
- 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.
- 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.
- 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.
- Based on the GM-seq and Tcr-Seq data, a novel diagnostic model including DNA-methylation and TCR-Seq biomarkers will be established.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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;
- •Oral tacrolimus immunosuppressive therapy;
- •Received liver transplantation in our hospital for the first time and did not receive liver transplantation again;
- •Patients need to be admitted to hospital for programmed liver biopsy or receive liver biopsy due to abnormal liver function;
- •Complete clinical data and samples (including liver puncture biopsy specimens, plasma, and PBMC of the same period);
- •The subjects or their guardians voluntarily join the study, sign the informed consent, comply well, and cooperate with follow-up.
排除标准
- •Combined multi-organ transplantation;
- •Pregnancy or lactation;
- •Severe systemic infection;
- •Contraindications of liver biopsy with multiple organ failure or coagulation dysfunction;
- •Previous history of allergy to narcotic or sedative drugs;
- •In the stage of acute rejection hormone shock therapy;
- •Incomplete clinical data and samples;
- •Situations considered unsuitable for inclusion by other researchers.
结局指标
主要结局
Specificity
时间窗: 7 Days
Specificity is the true negative rate of the novel diagnostic model \[Liver fibrosis is determined by histological examination of liver biopsy (LAFSc)\].
AUROC
时间窗: 7 Days
AUROC is the area under the receiver operating characteristic curve \[Liver fibrosis is determined by histological examination of liver biopsy (LAFSc)\].
Sensivity
时间窗: 7 Days
Sensivity is the true positive rate of the novel diagnostic model \[Liver fibrosis is determined by histological examination of liver biopsy (LAFSc)\].
次要结局
- Heterogeneity of the TCR-Seq biomarkers in allograft liver fibrosis cohort(7 Days)
- Heterogeneity of the DNA-methylation biomarkers in allograft liver fibrosis cohort(7 Days)