RESUMO
Antecedentes: menos de la mitad de los pacientes con hepatitis C logra eliminar el virus de manera sostenida después de la terapia con peginterferón alfa y ribavirina (Peg-IFN/RBV). Objetivos: la talidomida posee propiedades antiinflamatorias e inmunomoduladoras a través de la inhibición del TNF-α y al efecto estimulador sobre las células T CD8+. Métodos: se inició un estudio prospectivo y abierto de re-tratamiento de pacientes con hepatitis crónica C genotipo 1, no respondedores al tratamiento con Peg-IFN/RBV, mediante triple terapia añadiendo a los mismos antivirales 200 mg/día de talidomida. Resultados: ninguno de los once pacientes que fueron incluidos en el ensayo consiguió respuesta viral completa en la semana 12 ni respuesta viral sostenida. La dinámica viral en las 12 primeras semanas de tratamiento no difirió de la dinámica viral durante el primer curso de tratamiento. La triple terapia fue bien tolerada y solo un paciente desarrolló neuropatía bilateral autolimitada. Conclusiones: añadir talidomida al tratamiento estándar fue bien tolerado pero no incrementó la tasa de respuesta viral sostenida en pacientes con hepatitis C genotipo 1 no respondedores previos(AU)
Background: fewer than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after peginterferon alfa/ribavirin (Peg-IFN/RBV) therapy. Aims: thalidomide posses anti-inflammatory and immunomodulatory properties through inhibition of tumor necrosis factor and costimulatory effect on human CD8+ T cells. Methods: we started a prospective, open label trial of retreatment of very-difficult-to-treat genotype 1 chronic hepatitis C patients (CHC) patients, who had failed to respond to the (Peg-IFN/RBV), with a triple therapy consisting in these same antivirals plus thalidomide 200 mg/day (the TRITAL study). Results: none of the eleven patients fulfilling the inclusion criteria and included in the trial reached complete early virological response or sustained virological response. Viral load decline after 12 weeks of triple therapy thalidomide-based retreatment did not differ from viral dynamics during the first course. The triple therapy was well tolerated and only one patient developed mild bilateral neuropathy. Conclusions: thalidomide addition to standard therapy is tolerated and did not increase the SVR rate in very-difficult-to-treat genotype 1 CHC patients. Different schedules are warranted to improve attempting retreatment of non responder CHC patients(AU)
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Talidomida/uso terapêutico , Ribavirina/uso terapêutico , Hepatite Crônica/tratamento farmacológico , Fatores Hospedeiros de Integração/uso terapêutico , gama-Glutamiltransferase/uso terapêutico , Hepatite Crônica/metabolismo , Hepatite Crônica/fisiopatologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/complicações , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Projetos Piloto , Estudos Prospectivos , Análise Multivariada , Modelos LogísticosRESUMO
BACKGROUND: fewer than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after peginterferon alfa/ribavirin (Peg-IFN/RBV) therapy. AIMS: thalidomide posses anti-inflammatory and immunomodulatory properties through inhibition of tumor necrosis factor and costimulatory effect on human CD8+ T cells. METHODS: we started a prospective, open label trial of retreatment of very-difficult-to-treat genotype 1 chronic hepatitis C patients (CHC) patients, who had failed to respond to the (Peg-IFN/RBV), with a triple therapy consisting in these same antivirals plus thalidomide 200 mg/day (the TRITAL study). RESULTS: none of the eleven patients fulfilling the inclusion criteria and included in the trial reached complete early virological response or sustained virological response. Viral load decline after 12 weeks of triple therapy thalidomide-based retreatment did not differ from viral dynamics during the first course. The triple therapy was well tolerated and only one patient developed mild bilateral neuropathy. CONCLUSIONS: thalidomide addition to standard therapy is tolerated and did not increase the SVR rate in very-difficult-to-treat genotype 1 CHC patients. Different schedules are warranted to improve attempting retreatment of non responder CHC patients.
