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Jul 11, 1983 - ORTHOTOPIC LIVER TRANSPLANTATION (OLT) has been performed worldwide in well over 550 pa- tients and has proved to beof value as ...
Histopathology of Serial Graft Biopsies From Liver Transplant Recipients

Departments of Pathology, Medicine, and Surgery, University Hospital and University of Groningen, Groningen, The Netherlands

H. F. EGGINK, MD, N. HOFSTEE, MD, C. H. GIPS, MD, R. A. F. KROM, MD, and H. J. HOUTHOFF, MD, PhD

From the

Serial graft biopsies (n = 78) from 12 liver transplant (followed clinically up to 47 months) were recipients studied with the use of histology, histochemistry, imand electron microscopy. Planned-promunostaining, tocol needle biopsy specimens were taken from the 1 hour after transgraft before removal from the donor, and at yearly intervals. plantation, on the eighth day, Nonprotocol biopsies were taken when deterioration of the clinical condition made a decision on changes in the regimen necessary. The protocol biopsies provided a baseline for graft condition and diagnostic histopathologic features. In these biopsies signs of hyperacute reor the recipient's previous jection, chronic rejection, liver disease were not observed. Mild acute rejection

was regularly present on the eighth day, possibly due to a lag phase in the effect of immunosuppression. The syndromes in the nonprotocol biopsies included "pure" cholestasis, reversible acute rejection parenchymalchronic active hepatitis, viral infection, and resembling acute bacterial cholangitis. Each of these syndromes correlated with a separate histopathologic entity. Therefore, these entities proved to be of diagnostic value. It is concluded that a graft biopsy may substanadd to the pathogenetic interpretation, differentially tial diagnosis, and management of major graft syndromes in orthotopic liver transplant recipients. (Am J Pathol 1984, 114:18-31)

ORTHOTOPIC LIVER TRANSPLANTATION (OLT) has been performed worldwide in well over 550 patients and has proved to be of value as the ultimate treatment in various forms of irreversible liver disease. Most reports on liver graft pathology deal with autopsy findings'-4; pathologic data are still rather scanty in comparison to the literature on graft pathology in other organs such as, for example, the kidney or the skin,5 however. Serial graft biopsies from liver transplant recipients usually have not been included in the screening and follow-up of impaired graft functioning, although incidentally graft biopsies have been performed for the evaluation of major graft

serologic follow-up could be studied longitudinally in a series of graft biopsies per patient. The aim of this study was to evaluate the diagnostic contribution of graft biopsy interpretation in the recognition and separation of histopathologic entities related to the

major graft syndromes.

At the start, no conclusive data could be found in the literature to differentiate between the histopathology of the various graft syndromes, at least not to the extent that the histopathologic diagnosis could reliably be used as a basis for far-reaching changes in the therapeutic regimen. Thus, in comparing the histopathologic features with clinical and serologic parameters and the reaction to changes in the immunosuppressive regimen, circumscribed pathologic features were tentatively linked to clinical syndromes and subsequently used to test this relation in analogous situ-

syndromes.2

When OLT started to be performed in the University Hospital of Groningen, the transplantation team decided that liver biopsy pathology should document and contribute to the clinical diagnosis of the major graft syndromes.6'7 For the pathologic interpretation of the graft biopsies, the morphology in protocol biopsy specimens taken before removal from the donor, 1 hour after OLT, on the eighth day, and at yearly intervals served as a reference.8 Thus, the fluctuations in

Accepted for publication July 11, 1983. Dr. Eggink's present address is Laboratorium voor de Volksgezondheid, Jelsumerstraat 6, 8917 EN Leeuwarden, The Netherlands. Address reprint requests to Prof. Dr. H. J. Houthoff, Department of Pathology, University of Groningen, Oostersingel 63, 9713 EZ Groningen, The Netherlands.

liver disease and their relation to the functional and

18

19

LIVER HOMOGRAFT PATHOLOGY

Vol. 114 * No. 1

ations in the next patients. In giving an overview of the interpretation and differential diagnosis of the pathologic findings in liver graft biopsies, we demonstrate the relevance of these biopsies in the clinical management of patients with OLT.

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after OLT and from the sixth till the tenth postoperative day. Planned protocol needle biopsy specimens were taken from the graft before removal from the donor, 1 hour after OLT, on the eighth day, and at yearly intervals. Further graft biopsy specimens were taken when deterioration of liver function made a decision on changes in the clinical regimen necessary.

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