RESUMO
BACKGROUND AND METHODS: To investigate the frequency of apoptosis and the expression of Fas/Fas ligand (FasL) in liver allografts, we examined 97 biopsy specimens from 62 patients after orthotopic liver transplantation. The results of the biopsies were as follows: acute allograft rejection (n=32); hepatitis C virus (HCV) reinfection (n=18); cytomegalovirus infection (n=5); acute rejection plus HCV reinfection (n=3); and stable graft function (n=30); and after treatment of acute rejection (n=9). RESULTS: Apoptotic cells were found in all cases examined, and their frequency increased significantly during acute rejection (0.17 vs. 9.0; P<0.05). The immunoreactivity of Fas and FasL antigen was higher in specimens with acute rejection than in those with stable graft function. Increased apoptosis, Fas, and FasL expression, however, were also seen in HCV reinfection. CONCLUSION: We conclude that apoptosis plays an important role in the hepatocellular damage observed in acute rejection and also in HCV reinfection. However, these parameters are, taken by themselves, not useful as indicators of acute rejection or HCV reinfection.
Assuntos
Apoptose/fisiologia , Infecções por Citomegalovirus/etiologia , Rejeição de Enxerto/fisiopatologia , Hepatite C/etiologia , Transplante de Fígado , Glicoproteínas de Membrana/metabolismo , Receptor fas/metabolismo , Biópsia , Proteína Ligante Fas , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/patologia , Humanos , Fígado/patologia , Fígado/virologia , Complicações Pós-Operatórias , Recidiva , Transplante HomólogoAssuntos
Rejeição de Enxerto/patologia , Transplante de Fígado/imunologia , Transplante de Fígado/patologia , Glicoproteínas de Membrana/biossíntese , Receptor fas/biossíntese , Antígenos CD/análise , Antígenos CD/biossíntese , Apoptose , Biópsia por Agulha , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/patologia , Sondas de DNA , Proteína Ligante Fas , Seguimentos , Rejeição de Enxerto/imunologia , Hepatite C/fisiopatologia , Hepatite C/cirurgia , Humanos , Glicoproteínas de Membrana/análise , Variações Dependentes do Observador , Recidiva , Receptor fas/análiseRESUMO
BACKGROUND: The prognosis of patients with curatively resectable hepatocellular carcinoma depends mainly on anatomic extent of the tumour and on the general condition of the patient. Given the growing evidence that proliferation indices may be of prognostic significance in hepatocellular carcinomas, identification and quantitation of proliferative capacity may be of prognostic importance. METHODS: We have compared four different methods to assess proliferation in a series of 193 curatively (R0-) resected hepatocellular carcinomas: Mitotic count, immunohistochemical assessment of the MIB-1- (Ki-67-), Antigen Proliferating Cell Nuclear Antigen (PCNA) and silverstained nucleolar organiser regions (AgNOR). The results obtained were compared with pathohistological stage (according to UICC), Edmondson Grade and with survival rate. RESULTS: In each carcinoma, we could demonstrate mitotic figures, MIB-1, PCNA and AgNOR dots in variable proportions. Significant statistical correlations were seen between Mitotic Index, the rate of nuclear positivity for MIB-1 and PCNA and the number of AgNOR dots. In univariate survival analysis tumour stage and Edmondson Grade, Mitotic Index, MIB-1 and PCNA Index and mean AgNOR-number were significant patients' survival influencing factors. Performing multivariate Cox survival analysis, Mitotic Index, concomitant cirrhosis, Edmondson Grade and patient age were the only significant independent prognostic factors. CONCLUSION: These results indicated that Mitotic Index is an additional prognostic parameter which could provide auxiliary information for patients' outcome.