Hepatic Graft Versus Host Disease: A Study of the Predictive Value of Liver Biopsy in Diagnosis

Authors

  • Dale C. Snover,

    Corresponding author
    1. Bone Marrow Transplantation Unit, Departments of Laboratory Medicine and Pathology, Pediatrics and Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455
    • Dale C. Snover, M.D., Department of Laboratory Medicine and Pathology, Box 609 Mayo, University of Minnesota, 420 Delaware Street S.E., Minneapolis, Minnesota 55455.
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    • Dr. Snover is a Junior Faculty Clinical Fellow of the American Cancer Society

  • Sally A. Weisdorf,

    1. Bone Marrow Transplantation Unit, Departments of Laboratory Medicine and Pathology, Pediatrics and Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455
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  • Norma K. Ramsay,

    1. Bone Marrow Transplantation Unit, Departments of Laboratory Medicine and Pathology, Pediatrics and Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455
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  • Philip Mcglave,

    1. Bone Marrow Transplantation Unit, Departments of Laboratory Medicine and Pathology, Pediatrics and Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455
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  • John H. Kersey

    1. Bone Marrow Transplantation Unit, Departments of Laboratory Medicine and Pathology, Pediatrics and Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455
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Abstract

Ninety-six liver biopsies [32 bone marrow transplant (BMT), 7 pre-BMT, and 57 non-BMT] are reviewed for histological evidence of graft versus host disease (GVHD), based on bile duct atypia and related inflammatory changes. In addition, the presence of cholestasis, piecemeal necrosis, and attachment of lymphocytes to vascular endothelium (endothelialitis) are evaluated. The 57 non-BMT biopsies include examples of viral hepatitis (acute and chronic), nonviral chronic hepatitis, extrahepatic biliary obstruction, cytomegalovirus hepatitis, primary biliary cirrhosis, and orthotopic liver transplant rejection. Although the sensitivity of bile duct damage as an indicator of GVHD appears high (only one probable false negative was noted), there is considerable overlap between the changes of GVHD and occasional cases of acute and chronic hepatitis and extrahepatic biliary obstruction. Nine of the 57 non-BMT biopsies (15%) were felt to be consistent with GVHD and represent “false positives”. Despite this relative lack of specificity, analysis of several features in combination provided clues to improve accuracy of diagnosis. The findings of extensive bile duct damage with minimal inflammatory changes is characteristic of GVHD. Possibly more predictive is the presence of endothelialitis of portal or central veins, which was seen in only three non-BMT biopsies, being present in eight cases of GVHD.

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