RESUMO
UNLABELLED: The role of cellular immune response in pathogenesis of liver cell injury and course of chronic hepatitis C have been previously confirmed. The aim of this study was to determine the modification of T-lymphocyte subsets during pegylated interferon alpha (PegIFN) and ribavirin treatment and its correlation with response to the treatment. MATERIAL AND METHODS: The assessment of subsets of intrahepatic lymphocytes and peripheral blood lymphocytes was done in 62 patients with chronic hepatitis C using flow cytometry and immunohistochemical method. RESULTS: Significant increase in peripheral blood CD4+ cells, was observed in week 12 of treatment in patients with both complete and partial response to therapy. There were no significant modifications in nonspecific CD8+ subsets, but after 12 week of treatment in patients with response to therapy, decrease or lack of HCV-specific CD8+ cells were observed. The assessment of subsets of intrahepatic lymphocytes revealed a significantly higher percentage of CD8+ cells in pretreatment liver biopsies from patients with sustained viral response. CONCLUSIONS: The results confirmed the impact of interferon alpha and ribavirin treatment on cellular response. Some immunological host factors should be considered in the early prognosis of successful treatment.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/imunologia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Subpopulações de Linfócitos T/efeitos dos fármacos , Adulto , Biópsia , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/efeitos dos fármacos , Feminino , Citometria de Fluxo , Hepatite C Crônica/sangue , Hepatite C Crônica/patologia , Humanos , Imunidade Celular , Imuno-Histoquímica , Interferon alfa-2 , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Recombinantes , Ribavirina/uso terapêutico , Subpopulações de Linfócitos T/patologia , Adulto JovemRESUMO
The use of pegylated interferon (PEG-IFN) and ribavirin is considered standard therapy for patients with chronic hepatitis C. Many adverse effects of IFN appear to be of autoimmune origin. Vitiligo is a hypomelanotic disease, whose cause, despite many investigations, remains unknown, although some evidence points to an autoimmune pathogenesis. This report describes a case of vitiligo that occurred during the third month of treatment with PEG-IFN and ribavirin. The sustained virologic response was the result of a 52-week regimen; however, hypomelanotic cutaneous patches persisted. Autoimmune adverse effects of IFN therapy, which may include vitiligo, should be carefully monitored. The decision about whether to discontinue treatment should be discussed with the patient, who must be informed that the lesions may persist.
Assuntos
Antivirais/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Polietilenoglicóis/efeitos adversos , Ribavirina/efeitos adversos , Vitiligo/induzido quimicamente , Adulto , Antivirais/administração & dosagem , Quimioterapia Combinada , Humanos , Interferon alfa-2 , Proteínas Recombinantes , Ribavirina/administração & dosagemRESUMO
UNLABELLED: We evaluated the efficacy and safety of peginterferon alfa-2a [40KD] (Peg-IFNalpha-2a) plus ribavirin in patients with chronic hepatitis C in an open-label programme in a routine clinical setting in Poland. Patients received Peg-IFNalpha-2a 180mg/week plus ribavirin 800-1200 mg/d for 48 weeks. Sustained virological response (SVR) was defined as undetectable HCV RNA (<50IU/mL) at the end of follow-up (week 72). 466 adults were enrolled. Most patients (87.3%) had genotype 1 infection. 440 subjects (94,4%) completed treatment. The overall SVR rate was 55.7%. A higher SVR rate was obtained in treatment-naïve patients (58.7%) than in relapsers (47.8%; p=0,048). SVR rates in genotype 1 and non-1 patients were 51.1% and 88.5%, respectively (p<0.001). There were significant higher SVR rates in patients with lower baseline fibrosis (p=0,01). There were no differences in SVRs by gender or viral load. Hemoglobin, leukocyte and neutrophil levels decreased significantly during treatment, but returned to baseline after the end of treatment. ALT levels decreased significantly during treatment in patients with and without an SVR. 38.4% of patients experienced adverse events like neutropenia, anemia, thrombocytopenia, and other. There was one death (severe thrombocytopenia). CONCLUSIONS: The overall SVR achieved in this predominantly genotype 1 population was 55.7%. SVR rates were significantly higher in treatment-naïve patients, those with non-1 genotypes, and in patients with lower baseline fibrosis scores.
Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Relação Dose-Resposta a Droga , Portadores de Fármacos/administração & dosagem , Quimioterapia Combinada , Feminino , Hepacivirus/efeitos dos fármacos , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis , Proteínas Recombinantes , Resultado do TratamentoRESUMO
150 adult patients were assigned pegylated interferon alpha-2b (once weekly 1.5 microg/kg) plus ribavirin (800-1200 mg depending on bodyweight). The treatment lasted 52 weeks and was completed by 139 persons (92.7%). Because of adverse events the treatment was interrupted in 7 persons, 4 other persons resigned. Periodical reduction of pegylated interferon doses was necessary in 19% and the reduction of ribavirin in 21% of patients. Six months after the completion of treatment HCV-RNA was negative in 82 (59%) patients. Neither hepatitis C virus genotype, nor viremia was marked in the study. The negative correlation between the degree of fibrosis in the liver tissue and the results of sustained virological response was stated. Degree of inflammation at liver tissue, sex, age over and less than 40 years did not correlate with the final virological results. The recurrence of infection happened at 7% of the treated persons (negative HCV-RNA directly after the treatment--positive 6 months after the completion). During the treatment period, and comparison with the results obtained before its implementation, statistically significantly decreased: hemoglobin concentration, the number of leukocytes, granulocytes and thrombocytes. They returned to the referential values half a year after the completion of treatment. The activity of enzymes (AIAT, AspAT, GGTP) was decreasing statistically significantly since the first weeks of the treatment till the end and remained significantly lower after 6 months. In both sexes statistically significant reduction of bodyweight was stated, while it increased during the six months after the completion of treatment. Adverse events, which mostly were mild and were not the cause of interruption of treatment, were numerous and occurred at different frequency, in the range from over 50% (flu-like) to 0.7%.