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

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 Overview

• Status: Completed
• Conditions: End Stage Liver Disease; Liver Failure; Postoperative Complications; Fatty Liver; Liver Transplant; Complications; Ischaemia Reperfusion Injury of Liver

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This retrospective, single-center observational cohort study will enroll 300 adult liver transplant recipients at the First Affiliated Hospital of Air Force Medical University. The study population consists of patients aged 18-80 years with end-stage liver disease requiring orthotopic liver transplantation. Participants will be naturally grouped based on donor liver characteristics into: (1) steatotic donor liver recipients (donor livers with macrovesicular steatosis ≥5%), and (2) normal donor liver recipients (donor livers with steatosis <5%). All participants must have stable vital signs and be medically fit to tolerate liver transplantation surgery. 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Up to 10 years post-transplantation, determined by retrospective data availability

Collaborators and Investigators

• Sponsor: Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): January 1, 2026
• Study Completion (Actual): January 1, 2026

Study Registration Dates

• First Submitted: January 6, 2026
• First Submitted That Met QC Criteria: January 14, 2026
• First Posted (Actual): January 23, 2026

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Hepatic Insufficiency; Pathological Conditions, Signs and Symptoms; Fatty Liver; End Stage Liver Disease; Liver Failure; Postoperative Complications
• Other Study ID Numbers: KY20252571-C-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

**Plan to Share IPD (Individual Participant Data): No**

**Rationale:** This study involves highly sensitive personal data including genomic/transcriptomic information (single-cell and spatial transcriptomics) and detailed clinical records from human transplant recipients. Due to privacy protection requirements, Chinese regulations on human genetic data, and the need for explicit participant consent for data sharing beyond the original research purpose, individual participant data will not be shared publicly. Aggregated, de-identified results will be published in scientific reports.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No