title: Recurrent hepatitis C in liver allografts: prospective assessment of diagnostic accuracy, identification of pitfalls, and observations about pathogenesis.
abstract: METHODS
  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 database 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.
authors.affiliation: Department of Pathology, Division of Transplantation, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. demetrisaj@upmc.edu
authors.forename: A J
authors.initials: AJ
authors.lastname: Demetris
authors.forename: B
authors.initials: B
authors.lastname: Eghtesad
authors.forename: A
authors.initials: A
authors.lastname: Marcos
authors.forename: K
authors.initials: K
authors.lastname: Ruppert
authors.forename: M A
authors.initials: MA
authors.lastname: Nalesnik
authors.forename: P
authors.initials: P
authors.lastname: Randhawa
authors.forename: T
authors.initials: T
authors.lastname: Wu
authors.forename: A
authors.initials: A
authors.lastname: Krasinskas
authors.forename: P
authors.initials: P
authors.lastname: Fontes
authors.forename: T
authors.initials: T
authors.lastname: Cacciarelli
authors.forename: A O
authors.initials: AO
authors.lastname: Shakil
authors.forename: N
authors.initials: N
authors.lastname: Murase
authors.forename: J J
authors.initials: JJ
authors.lastname: Fung
authors.forename: T E
authors.initials: TE
authors.lastname: Starzl
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D001706:Biopsy; D002908:Chronic Disease; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000517:prevention & control; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D006526:Hepatitis C / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000032:analysis; D012008:Recurrence; D015203:Reproducibility of Results; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D012367:RNA, Viral