INTERLIVER: Diagnostic and Therapeutic Applications of Microarrays in Liver Transplantation
Study Details
Study Description
Brief Summary
INTERLIVER is a prospective observational study of the relationship of the molecular phenotype of 300 liver transplant biopsies to the histologic phenotype and the clinical features and outcomes. A segment of a biopsy performed as standard-of-care for indications, or by center protocol, will be used for gene expression study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
The current standard for biopsy-based diagnoses of dysfunction of liver transplants is histology (the Banff system), an arbitrary international empirical consensus based on lesions and rules, similar in principle to the kidney, heart, and lung histology systems. Recent data-driven approaches using molecular and conventional technologies indicate that such systems frequently produce incorrect diagnoses - perhaps 40-50% in abnormal kidney or heart transplant biopsies and even more in lung biopsies, with great potential for harm to patients due to inappropriate treatment.
To address this unmet need and improve diagnostics in the area of organ transplantation, the Alberta Transplant Applied Genomics Centre (ATAGC, University of Alberta) has developed a new diagnostic system - the Molecular Microscope® Diagnostic System (MMDx) that interprets biopsies in terms of their molecular phenotype, and combines the molecular and histopathological features of transplant biopsies, plus clinical and laboratory parameters, to create the first Integrated Diagnostic System. The MMDx, developed first in kidney transplant biopsies because phenotypes are well established, will now be adapted to liver transplant biopsies. The present study will develop a Reference Set of liver biopsies, adapt the MMDx system to assess and report molecular phenotype of liver biopsies; and validate and refine this system in 300 unselected prospectively collected for clinical indications and a standard of care biopsies from North American and European Centers. In addition to demonstrating the real-time feasibility and potential value of this System in patient care, the study will develop and optimize a transparent and user-friendly reporting format to communicate this information to clinicians and obtain detailed feedback to improve its utility.
Thanks to increasing interest and support from participating centers, INTERLIVER has already processed 798 biopsies from 668 participants and will extend the Reference Set to 900 biopsies.
Study Design
Outcome Measures
Primary Outcome Measures
- Assign molecular scores (probability) of T cell mediated rejection, antibody mediated rejection in liver transplant biopsies, in a reference set of 100 biopsies [two years]
Based on the reference set, create molecular classifier that predicts antibody mediated and T cell mediated rejection for next 200 biopsies
Secondary Outcome Measures
- Assign in real time (two working days upon biopsy receipt) molecular scores (probability) of T cell mediated rejection and antibody mediated rejection. [1 year]
The molecular phenotype of a newly acquired sample predicts the histologic and clinical features of this sample when compared to the reference set.
Eligibility Criteria
Criteria
Inclusion Criteria:
- biopsy for clinical indications
Exclusion Criteria:
- no consent, pregnant women
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California San Francisco, Transplant Research Unit | San Francisco | California | United States | 94143 |
| 2 | Northwestern Memorial Hospital | Chicago | Illinois | United States | 60611 |
| 3 | University of Maryland School of Medicine | Baltimore | Maryland | United States | 21201 |
| 4 | Henry Ford Transplant Institute | Detroit | Michigan | United States | 48202 |
| 5 | Vanderbilt University Medical Center, Vanderbilt Transplant Center | Nashville | Tennessee | United States | 37232 |
| 6 | Baylor University Medical Center, Annette C. and Harold C. Simmons Transplant Institute | Dallas | Texas | United States | 75246 |
| 7 | Transplant Surgery, VCU Medical Center | Richmond | Virginia | United States | 23298 |
| 8 | Division of Transplant Surgery, University of Washington | Seattle | Washington | United States | 98195 |
| 9 | Centenary Institute of Cancer Medicine & Cell Biology, Royal Prince Alfred Hospital | Camperdown | Australia | NSW 2050 | |
| 10 | University of Alberta, Laboratory Medicine and Pathology | Edmonton | Alberta | Canada | T6G 2R7 |
| 11 | Dep. of Nephrology, Transplantation & Internal Med., Samodzielny Publiczny Szpital Kliniczny im. A. Mieleckiego | Katowice | Poland | 40-027 | |
| 12 | Independent Public Composite Regional Hospital | Szczecin | Poland | 71-455 | |
| 13 | Warsaw Medical University, Jesus the Child Clinical Hospital | Warszawa | Poland | 02-005 | |
| 14 | Warsaw Medical University, Independent Public Clinical Hospital | Warszawa | Poland | 02-097 | |
| 15 | Institute for Liver Science, King's College London | London | United Kingdom | SE5 9NU |
Sponsors and Collaborators
- University of Alberta
Investigators
- Principal Investigator: Philip F Halloran, MD, PhD, University of Alberta
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ATAGC04