The molecular diagnosis of rejection in liver transplant biopsies: First results of the INTERLIVER study

The molecular diagnosis of rejection in liver transplant biopsies: First results of the INTERLIVER study.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1111/ajt.15828
Journal or Publication Title: American Journal of Transplantation
Volume: 20
Number: 8
Page Range: pp. 2156-2172
Date: 2020
Divisions: Liver Injury and Cancer
Depositing User: General Admin
Identification Number: 10.1111/ajt.15828
ISSN: 1600-6135
Date Deposited: 04 Jan 2021 02:40
Abstract:

Molecular diagnosis of rejection is emerging in kidney, heart, and lung transplant biopsies and could offer insights for liver transplant biopsies. We measured gene expression by microarrays in 235 liver transplant biopsies from 10 centers. Unsupervised archetypal analysis based on expression of previously annotated rejection‐related transcripts identified 4 groups: normal “R1normal” (N = 129), T cell–mediated rejection (TCMR) “R2TCMR” (N = 37), early injury “R3injury” (N = 61), and fibrosis “R4late” (N = 8). Groups differed in median time posttransplant, for example, R3injury 99 days vs R4late 3117 days. R2TCMR biopsies expressed typical TCMR‐related transcripts, for example, intense IFNG‐induced effects. R3injury displayed increased expression of parenchymal injury transcripts (eg, hypoxia‐inducible factor EGLN1). R4late biopsies showed immunoglobulin transcripts and injury‐related transcripts. R2TCMR correlated with histologic rejection although with many discrepancies, and R4late with fibrosis. R2TCMR, R3injury, and R4late correlated with liver function abnormalities. Supervised classifiers trained on histologic rejection showed less agreement with histology than unsupervised R2TCMR scores. No confirmed cases of clinical antibody‐mediated rejection (ABMR) were present in the population, and strategies that previously revealed ABMR in kidney and heart transplants failed to reveal a liver ABMR phenotype. In conclusion, molecular analysis of liver transplant biopsies detects rejection, has the potential to resolve ambiguities, and could assist with immunosuppressive management.

Creators:
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Madill‐Thomsen, Katelynn
UNSPECIFIED
Abouljoud, Marwan
UNSPECIFIED
Bhati, Chandra
UNSPECIFIED
Ciszek, Michał
UNSPECIFIED
Durlik, Magdalena
UNSPECIFIED
Feng, Sandy
UNSPECIFIED
Foroncewicz, Bartosz
UNSPECIFIED
Francis, Iman
UNSPECIFIED
Grąt, Michał
UNSPECIFIED
Jurczyk, Krzysztof
UNSPECIFIED
Klintmalm, Goran
UNSPECIFIED
Krasnodębski, Maciej
UNSPECIFIED
McCaughan, Geoff
UNSPECIFIED
Miquel, Rosa
UNSPECIFIED
Montano‐Loza, Aldo
UNSPECIFIED
Moonka, Dilip
UNSPECIFIED
Mucha, Krzysztof
UNSPECIFIED
Myślak, Marek
UNSPECIFIED
Pączek, Leszek
UNSPECIFIED
Perkowska‐Ptasińska, Agnieszka
UNSPECIFIED
Piecha, Grzegorz
UNSPECIFIED
Reichman, Trevor
UNSPECIFIED
Sanchez‐Fueyo, Alberto
UNSPECIFIED
Tronina, Olga
UNSPECIFIED
Wawrzynowicz‐Syczewska, Marta
UNSPECIFIED
Więcek, Andrzej
UNSPECIFIED
Zieniewicz, Krzysztof
UNSPECIFIED
Halloran, Philip F.
UNSPECIFIED
Last Modified: 04 Jan 2021 02:40
URI: https://eprints.centenary.org.au/id/eprint/770

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