Diagnostic and Therapeutic Applications of Microarrays in Liver Transplantation

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.

Inclusion Criteria:

- biopsy for clinical indications

Exclusion Criteria:

- no consent, pregnant women