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Expanding the pool of Transplantable Livers using Molecular profiling and Histopathological Analysis

Srivastava A PhD, Manchel A BS, Waters J BS, Ambelil M MD, Barnhart B. K PhD, Hoek J. B PhD, Shah A.P MD, Vadigepalli R PhD

Poster # 52

Introduction: Liver transplantation is the solution for acute or chronic liver failure. There is an unmet demand for liver transplantation, as not all donated organs are transplanted. The clinical selection criteria for the use of donated livers depends on histopathological evaluation and liver function tests. A molecular characterization of the donor livers, if available, could reduce the variability in the application of the current clinical criteria. We applied an integrated transcriptomics and histopathological approach to characterize the donor livers evaluated for transplantation. Methods: We obtained liver biopsies from deceased donors during organ collection (n=10 accepted and n= 21 rejected for transplantation). We performed RNA sequencing to characterize the global gene expression profiles. We assessed steatosis, fibrosis, and necrosis via manual histopathological evaluation and a custom artificial intelligence-based image analysis. Results: Our results identified two transcriptomically distinct subsets in the rejected donor liver group (termed rejected-1 and rejected-2), where the rejected-2 subset had a near complete transcriptomic overlap with the accepted livers, suggesting the potential for acceptability from a molecular standpoint. The liver metabolic functional genes were similarly upregulated in the accepted and rejected-2 groups compared to the rejected-1 subset. Expression levels of several extracellular matrix genes were similarly low in the accepted and rejected-2 groups. Filtering the rejected-2 subset based on histopathological evaluation identified the cases with borderline scores and extensive molecular overlap with the accepted group. Conclusions: Our integrated approach identified a subset of rejected donor livers that may be suitable for transplantation, thereby expanding the pool of transplantable livers. Funding: National Institute of Alcoholism and Alcohol Abuse: R01 AA018873; Gift of Life Foundation.

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