Clinicopathologic Research Of Acute Cellular Rejection And Cytomegalovirus Infection Post Liver Transplantation

Liver transplantation (LT) is widely accepted as a most effective therapeutic modality for a variety of irreversible acute and chronic liver disease. With the developed surgical technique and new effective immunosuppressant, diagnosis and treatment of complications are becoming the keypoints for long-term outcome. Acute cellular rejection (ACR) is the most common complication post-LT , and its pathologic diagnosis and differential diagnosis are difficult and important. Because the therapeutic method for cytomegalovirus (CMV) infection, the most common opportunistic infection, is opposed to ACR, and the CMV disease is delitescence, not specific and lack of effective method of virus detection, the differential diagnosis between CMV disease and ACR is important and difficult.In this study, the clinicopathologic analysis of 234 patients suffered LT have been performed. The pathologic features of ACR and the relationships between histological features in"time-zero"biopsies and the incurrence of complications post-LT have been studied. To discriminate between late-onset acute rejection (LAR) and recurrence of HBV hepatitis, the biopsies obtained more than six months post-LT were immunohistochemically stained for HBsAg and HBcAg. To analyze the immunophenotype of infiltrating lymphocytes and the expression of cytotoxic proteins, 108 Biopsies were immunohistochemically stained for CD8,CD4,CD3,CD20,CD45RO,CD45RA,Perforin,GranzymeB and TIA-1. Meanwhile, 25 biopsies with CMV infection and 25 without have been observed double-blindly, and the pathologic features of CMV hepatitis have been studied. CMV has been detected with monoclonal antibody and polymerase chain reaction (PCR), and their specificity and sensitivity have been analyzed. The main results and conclusions are as follows:1. 44% (40/91) of"time-zero"biopsies have shown histological evidence of ischemic-reperfusion injury (IRI). The coincidence of ACR and BC in grafts with IRI is higher than in grafts without. The grafts with IRI were more easily to have late or persistent preservation injury (PI) than the grafts without IRI. The incidence of ACR and BC are higher in grafts with severer centrilobular necrosis and apoptosis. The severity of inflammation in port tract grafts is associated with late or persistent PI. In conclusion, the histological features in time-zero biopsies are related with the incurrence of ACR, BC and PI post-LT.2. Within six months post-LT, 89 patients (38.0 %) have one or more episodes of ACR, and the incidences of ACR in patients with primary hepatic carcinoma and severe hepatitis are higher than patients with other primary diseases. 76.2% patients (16/21) who suffered BC which not associated with surgical technique have one or more episode of ACR, showing correlation between BC and ACR. In biopsies diagnosed as ACR, the detection rates of mixed inflammatory cell infiltrating, eosinaphils, inflammatory injury of bile ducts, endothelial inflammation of portal veins and endothelial inflammation of central veins are 87.4%,65.8%,73.0%,69.4%and38.7% relatively,significantly higher than those in biopsies diagnosed as not ACR, showing these histological features are sensitive and specific to ACR.3. CD3+ cells,CD8+ cells and CD20+ cells in portal tract in biopsies of ACR group are significantly more than those in biopsies of non-ACR group, but not different in lobule between the two groups. In ACR group, CD3+cell and CD8+ cells are more than CD20+cell and CD4+ cells relatively in both portal tract and lobule. CD8+ cells and CD45RO+ cells infiltrate ducts or veins in ACR Group more easily than those in non-ACR group. The amount of CD8+ cells and CD45RO+ cells is related to the degree of ACR. In conclusion, the increase of CD8+ cytotoxic cell and bile duct or veins infiltration of CD8+ cell and CD45RO+ T cell in biopsies are useful predicator of ACR. The amounts of positive cells of Perforin and GranzymeB in ACR group are significantly more than in non-ACR group in both portal tracts and lobules, and correlate with the severity of ACR and the heightened degree of AST and GGT. TIA-1 positive cells of ACR group are more than that of non-ACR group in port tract, but less in lobule. The frequencies of these three kinds of positive cells infiltrating ducts or veins are significantly different between the two groups.4. The frequencies of microabscess, aggregation of monocyte and macrophage and cytomegalic change in biopsies with CMV infection are higher than that without. The positive rates of IHC and PCR detecting CMV virus in biopsies of CMV group are 20% and 72%. The sensitivity and specificity of this two methods are 72% and 84%,20% and 100%, showing that PCR is the sensitive and specific way to detect CMV in biopsies.