Single-Cell and Spatial Transcriptomics Analysis of Steatotic Donor Liver Susceptibility to Post-Transplant Injury

Xijing Hospital300 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

300

Conditions

Fatty Liver Liver Transplant; Complications Ischaemia Reperfusion Injury of Liver End Stage Liver Disease

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 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 Exclusion Criteria: 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

Outcomes

Primary Outcomes

Differential Expression of Post-Transplant Injury-Related Genes

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.

Time frame: 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

Postoperative Liver Function Recovery and Clinical Outcomes

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.

Time frame: Up to 10 years post-transplantation, determined by retrospective data availability