A Rat Model of Chronic Allograft Liver Rejection

Abstract

Introduction The aim of this study was to develop a rat model of chronic irreversible rejection, which is a major causes of late graft loss and retransplantation after orthotopic liver allotransplantation. Methods Allogeneic liver transplantation was performed in a rat combination of Dark Agouti (DA) to Brown Norway (BN). Group A was left without treatment, group B received cyclosporine’ (CsA; 1 mg/kg/d) and group C, CsA (4 mg/kg/d). Animals were followed for 6 months. Liver tissue was harvested to construct a time course of histological changes after liver transplantation using histopathological and morphometric techniques. We compared the total histological score of rejection activity index and survival rates. Results In untreated animals, irreversible acute rejection developed, all animals died within 15 days. In the low-dose CsA group, all animals that survived more than 30 days developed moderate to severe manifestations of chronic liver rejection, with graft infiltration, ductular damage or proliferation, obliterative arteriopathy, and liver fibrosis. No apparent histological alterations were observed in group C. Survival analysis showed significant differences between the three groups. Conclusions In the rat strain combination of DA → BN with low-dose immunosuppression, early mild inflammation was followed by the development of chronic rejection.