The significance of parenchymal changes of acute cellular rejection in predicting chronic liver graft rejection.
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.
Gouw
Annette S H
AS
Department of Pathology and Laboratory Medicine, University Hospital, Groningen, The Netherlands. a.s.h.gouw@path.azg.nl
van den Heuvel
Marius C
MC
van den Berg
Aad P
AP
Slooff
Maarten J H
MJ
de Jong
Koert P
KP
Poppema
Sibrand
S
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