title: The significance of parenchymal changes of acute cellular rejection in predicting chronic liver graft rejection.
abstract: BACKGROUND
  Chronic rejection (CR) in liver allografts shows a rapid onset and progressive course, leading to graft failure within the first year after transplantation. Most cases are preceded by episodes of acute cellular rejection (AR), but histological features predictive for the transition toward CR are not well documented.
  
  
  METHODS
  We assessed the predictive value of centrilobular necrosis, central vein endothelialitis (CVE), central vein fibrosis, and lobular inflammation in the development of CR. One-week and one-month biopsy specimens of 12 patients with CR were compared with those of a control group consisting of 17 patients, who experienced AR without developing CR. The progress of the histological changes was further evaluated in follow-up biopsy specimens of the CR group taken at 2 months and beyond 3 months after transplantation.
  
  
  RESULTS
  Centrilobular necrosis, CVE, central vein fibrosis, and lobular inflammation were common features in both groups at 1 week. At 1 month, the incidence declined in the control group. The CR group showed an increased incidence and persistence of these features in the follow-up biopsy specimens. The incidence and median grade of severity of CVE was significantly higher in the CR group (P=0.04 and P<0.001). The severity of portal and lobular inflammation was also more pronounced in the CR group (P=0.01 and 0.068). Conversely, in the control group, the incidence of the lobular features decreased and the severity of CVE declined significantly (P=0.03).
  
  
  CONCLUSIONS
  The shift from a predominantly portal-based process toward lobular graft damage represents the early transition of AR to CR, for which a modification of immunosuppression might be necessary to prevent graft loss.
authors.affiliation: Department of Pathology and Laboratory Medicine, University Hospital, Groningen, The Netherlands. a.s.h.gouw@path.azg.nl
authors.forename: Annette S H
authors.initials: AS
authors.lastname: Gouw
authors.forename: Marius C
authors.initials: MC
authors.lastname: van den Heuvel
authors.forename: Aad P
authors.initials: AP
authors.lastname: van den Berg
authors.forename: Maarten J H
authors.initials: MJ
authors.lastname: Slooff
authors.forename: Koert P
authors.initials: KP
authors.lastname: de Jong
authors.forename: Sibrand
authors.initials: S
authors.lastname: Poppema
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000473:pathology*; D006801:Humans; D007223:Infant; D008099:Liver / Q000473:pathology*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged