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Recurrent Hepatitis C in Liver Allografts: Prospective Assessment of Diagnostic Accuracy, Identification of Pitfalls, and Observations about Pathogenesis

Demetris, AJ and Eghtesad, B and Marcos, A and Ruppert, K and Nalesnik, MA and Randhawa, P and Wu, T and Krasinskas, A and Fontes, P and Cacciarelli, T and Shakil, AO and Murase, N and Fung, JJ and Starzl, TE (2004) Recurrent Hepatitis C in Liver Allografts: Prospective Assessment of Diagnostic Accuracy, Identification of Pitfalls, and Observations about Pathogenesis. American Journal of Surgical Pathology, 28 (5). 658 - 669. ISSN 0147-5185

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Rationale and Design: The accuracy of a prospective histopathologic diagnosis of rejection and recurrent hepatitis C (HCV) was determined in 48 HCV RNA-positive liver allograft recipients enrolled in an "immunosuppression minimization protocol" between July 29, 2001 and January 24, 2003. Prospective entry of all pertinent treatment, laboratory, and histopathology results into an electronic data-base enabled a retrospective analysis of the accuracy of histopathologic diagnoses and the pathophysiologic relationship between recurrent HCV and rejection. Results: Time to first onset of acute rejection (AR) (mean, 107 days; median, 83 days; range, 7-329 days) overlapped with the time to first onset of recurrent HCV (mean, 115 days; median, 123 days; range, 22-315 days), making distinction between the two difficult. AR and chronic rejection (CR) with and without co-existent HCV showed overlapping but significantly different liver injury test profiles. One major and two minor errors occurred (positive predictive values for AR = 91%; recurrent HCV = 100%) ; all involved an overdiagnosis of AR in the context of recurrent HCV. Retrospective analysis of the mistakes showed that major errors can be avoided altogether and the impact of unavoidable minor errors can be minimized by strict adherence to specific histopathologic criteria, close clinicopathologic correlation including examination of HCV RNA levels, and a conservative approach to the use of additional immunosuppression. In addition, histopathologic diagnoses of moderate and severe AR and CR were associated with relatively low HCV RNA levels, whereas relatively high HCV RNA levels were associated with a histopathologic diagnosis of hepatitis alone, particularly the cholestatic variant of HCV. Conclusions: Liver allograft biopsy interpretation can rapidly and accurately distinguish between recurrent HCV and AR/CR. In addition, the histopathologic observations suggest that the immune mechanism responsible for HCV clearance overlap with those leading to significant rejection.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Demetris, AJ
Eghtesad, B
Marcos, A
Ruppert, Kruppertk@pitt.eduRUPPERTK
Nalesnik, MAnalesnik@pitt.eduNALESNIK
Randhawa, P
Wu, T
Krasinskas, A
Fontes, P
Cacciarelli, T
Shakil, AO
Murase, N
Fung, JJ
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 2004
Date Type: Publication
Journal or Publication Title: American Journal of Surgical Pathology
Volume: 28
Number: 5
Page Range: 658 - 669
DOI or Unique Handle: 10.1097/00000478-200405000-00015
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0147-5185
Other ID: uls-drl:31735062121086, Starzl CV No. 2196
Date Deposited: 08 Apr 2010 17:37
Last Modified: 02 Feb 2019 15:55


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