Standardizing the histological assessment of late posttransplantation biopsies from pediatric liver allograft recipients
Corresponding Author
Stefan G. Hübscher
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Correspondence
Stefan G. Hübscher, Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Level 1, Queen Elizabeth Hospital, Birmingham, B15 2WB, UK.
Email: [email protected]
Search for more papers by this authorSandy Feng
Division of Transplantation, Department of Surgery, University of California, San Francisco, California, USA
Search for more papers by this authorAnnette S. H. Gouw
Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, the Netherlands
Search for more papers by this authorHironori Haga
Department of Diagnostic Pathology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorHyo Jeong Kang
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Search for more papers by this authorDeirdre A. Kelly
Liver Unit, Birmingham Women's & Children's NHS Trust and University of Birmingham, Birmingham, UK
Search for more papers by this authorMina Komuta
Department of Pathology, Keio University, Tokyo, Japan
Search for more papers by this authorAndrew Lesniak
Division of Liver and Transplantation Pathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Search for more papers by this authorBenjamin A. Popp
Division of Liver and Transplantation Pathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Search for more papers by this authorHenkjan J. Verkade
Pediatric Gastroenterology/Hepatology, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
Search for more papers by this authorEunsil Yu
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Search for more papers by this authorAnthony J. Demetris
Division of Liver and Transplantation Pathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Search for more papers by this authorCorresponding Author
Stefan G. Hübscher
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Correspondence
Stefan G. Hübscher, Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Level 1, Queen Elizabeth Hospital, Birmingham, B15 2WB, UK.
Email: [email protected]
Search for more papers by this authorSandy Feng
Division of Transplantation, Department of Surgery, University of California, San Francisco, California, USA
Search for more papers by this authorAnnette S. H. Gouw
Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, the Netherlands
Search for more papers by this authorHironori Haga
Department of Diagnostic Pathology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorHyo Jeong Kang
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Search for more papers by this authorDeirdre A. Kelly
Liver Unit, Birmingham Women's & Children's NHS Trust and University of Birmingham, Birmingham, UK
Search for more papers by this authorMina Komuta
Department of Pathology, Keio University, Tokyo, Japan
Search for more papers by this authorAndrew Lesniak
Division of Liver and Transplantation Pathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Search for more papers by this authorBenjamin A. Popp
Division of Liver and Transplantation Pathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Search for more papers by this authorHenkjan J. Verkade
Pediatric Gastroenterology/Hepatology, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
Search for more papers by this authorEunsil Yu
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Search for more papers by this authorAnthony J. Demetris
Division of Liver and Transplantation Pathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Search for more papers by this authorFunding information
The Graft Injury Group has received project funding from the European Association for the Study of the Liver (EASL) and from the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN).
Abstract
Excellent short-term survival after pediatric liver transplantation (LT) has shifted attention toward the optimization of long-term outcomes. Despite considerable progress in imaging and other noninvasive 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 standardized manner. Whole-slide digital images from 31 biopsies obtained ≥4 years after transplantation 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 semiquantitatively by six pathologists to determine inter- and intraobserver 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 interobserver kappa statistics showed a high level of agreement for various parameters of inflammation, interface activity, fibrosis, and microvascular injury. Intraobserver 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 LT.
CONFLICT OF INTEREST
Nothing to report.
Supporting Information
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Appendix S1 Supporting information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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