Single-Cell and Spatial Transcriptomics Analysis of Steatotic Donor Liver Susceptibility to Post-Transplant Injury
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Differential Expression of Post-Transplant Injury-Related Genes
研究概览
简要总结
The goal of this observational study is to understand why liver transplants from donors with fatty liver disease (steatotic donor livers) are more vulnerable to post-transplant injury, analyzing historical clinical data and collected tissue samples using advanced genetic techniques.
The main questions it aims to answer are:
- Which specific cell types and their spatial interactions contribute to increased post-transplant injury susceptibility in steatotic donor livers?
- What are the key molecular differences in gene expression between steatotic and normal donor livers following transplantation?
Researchers will compare 300 historical liver transplant cases from 2015-2025, including 50 cases with archived tissue samples available for molecular analysis, and 250 cases with clinical data only. Donor liver steatosis was assessed by histopathology when tissue was available, or by donor clinical data when tissue was not available. The two groups (steatotic donor liver recipients vs. normal donor liver recipients) will be matched based on donor age, ischemia time, recipient scores, and other key clinical parameters to control for potential confounding variables.
This is a retrospective analysis of existing data and archived biospecimens; no prospective participant enrollment or additional sample collection will occur.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Recipient Criteria:
- •Participant (or legal representative if unable to read/sign) provides written informed consent
- •Age 18-80 years (inclusive) at time of enrollment
- •Clinical diagnosis of liver failure requiring liver transplantation
- •Stable vital signs and deemed medically fit to tolerate liver transplantation surgery
- •Donor Criteria:
- •Fatty degeneration range: Macrovesicular steatosis 0-30%
- •Donor age: ≤60 years
- •Cold ischemia time (CIT): ≤12 hours for deceased donors
- •Liver function: ALT/AST <5 times upper limit of normal
排除标准
- •Recipient Criteria:
- •Pregnant or lactating women
- •Prior history of non-autologous (allogeneic) bone marrow or stem cell transplantation
- •Blood transfusion within 7 days prior to tissue sampling
- •Radical cancer treatment within 3 years prior to enrollment
- •Use of anti-tumor medications within 30 days prior to enrollment
- •Known bleeding diathesis or coagulation disorder
- •Active autoimmune disease
- •Concurrent malignancy or multiple primary tumors
- •Donor Criteria:
- •Fibrosis: Any degree of hepatic fibrosis
- •Steatohepatitis: Presence of lobular inflammation or hepatocyte ballooning
- •Active infection: HBV, HCV, or HIV positive
- •Severe fatty liver-related comorbidities: Uncontrolled diabetes (HbA1c>8%), severe hyperlipidemia
研究组 & 干预措施
Steatotic Donor Liver Recipients
Liver transplant recipients receiving donor livers with macrovesicular steatosis ≥5% (steatotic donor liver). Participants undergo standard liver transplantation with two small liver tissue samples collected during surgery (during graft preparation and before abdominal closure) followed by postoperative monitoring.
Normal Donor Liver Recipients
Liver transplant recipients receiving donor livers with <5% steatosis (normal donor liver). Participants undergo standard liver transplantation with two small liver tissue samples collected during surgery (during graft preparation and before abdominal closure) followed by postoperative monitoring.
结局指标
主要结局
Differential Expression of Post-Transplant Injury-Related Genes
时间窗: Tissue collection at two intraoperative time points (during graft preparation and before abdominal closure); sequencing and data analysis completed within 1 year of data collection
Quantification of injury-related gene expression changes associated with post-transplant liver injury in liver tissue samples analyzed by single-cell RNA sequencing. Expression levels will be compared between recipients of steatotic donor livers (≥5% macrovesicular steatosis) and recipients of normal donor livers (\<5% steatosis) to identify molecular mechanisms underlying increased injury susceptibility.
Postoperative Liver Function Recovery and Clinical Outcomes
时间窗: Up to 10 years post-transplantation, determined by retrospective data availability
Comparison of post-transplant clinical parameters between recipients of steatotic versus normal donor livers, including serial measurements of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and other standard liver function tests, as well as vital signs and clinical assessment data collected during postoperative follow-up.
次要结局
未报告次要终点
研究者
Wang Lin
Professor
Xijing Hospital