Standardising the histological assessment of late post-transplant biopsies from paediatric liver allograft recipients

Stefan G Hübscher*, Sandy Feng, Annette Sh Gouw, Hironori Haga, Hyo Jeong Kang, Deirdre A Kelly, Mina Komuta, Andrew Lesniak, Benjamin A Popp, Henkjan J Verkade, Eunsil Yu, Anthony J Demetris

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Excellent short-term survival after paediatric liver transplantation has shifted attention toward the optimization of long-term outcomes. Despite considerable progress in imaging and other non-invasive modalities, liver biopsies continue to be required to monitor allograft health and to titrate immunosuppression. However, a standardized approach to the detailed assessment of long-term graft histology is currently lacking. The aim of this study was to formulate a list of histopathological features relevant for the assessment of long-surviving liver allograft health and to develop an approach for assessing the presence and severity of these features in a standardised manner. Whole slide digital images from 31 biopsies obtained ≥ 4 years post-transplant to determine eligibility for an immunosuppression withdrawal trial were selected to illustrate a range of typical histopathological findings seen in children with clinically stable grafts, including those associated with alloantibodies. Fifty histological features were independently assessed and, where appropriate, scored semi-quantitatively by 6 pathologists to determine inter- and intra-observer reproducibility of the histopathological features using unweighted and weighted kappa statistics; the latter metric enabled distinction between minor and major disagreements in parameter severity scoring. Weighted inter-observer kappa statistics showed a high level of agreement for various parameters of inflammation, interface activity, fibrosis, and microvascular injury. Intra-observer agreement for these features was even more substantial. The results of this study will help to standardize the assessment of biopsies from long-surviving liver allografts, aid the recognition of important histological features and facilitate international comparisons and clinical trials aiming to improve outcomes for children undergoing liver transplantation.

Original languageEnglish
Pages (from-to)1475-1489
Number of pages15
JournalLiver Transplantation
Issue number9
Early online date16-Apr-2022
Publication statusPublished - Sept-2022

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