RESUMEN
Treatment of chronic hepatitis C with type I interferons and ribavirin can be associated with exacerbation of hepatitis and sometimes liver decompensation. We report two patients with chronic hepatitis C virus infection who experienced a severe increase of bilirubin levels of up to 17 times upper the limit of normal value in the absence of deterioration of hepatic function during therapy with pegylated-interferon and ribavirin. A genetic disposition for Gilbert's syndrome explained the adverse events and permitted a continuation of therapy leading to a sustained clearance of chronic hepatitis C infection. Since one patient jaundiced already during a lead-in treatment period with ribavirin monotherapy we suggest that hyperbilirubinaemia during combination therapy is primarily caused by ribavirin rather than by effects of interferon alpha on UDP-glucuronosyltransferase activities. Of note, both patients recovered from their initial unconjugated hyperbilirubinemia despite continuation of ribavirin therapy, which indicates that compensatory mechanisms leading to a normalization of UGT1A1 activity are likely.
Asunto(s)
Antivirales/efectos adversos , Antivirales/uso terapéutico , Enfermedad de Gilbert/inducido químicamente , Hepatitis C Crónica/tratamiento farmacológico , Hiperbilirrubinemia/inducido químicamente , Quimioterapia Combinada , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Enfermedad de Gilbert/diagnóstico , Enfermedad de Gilbert/genética , Humanos , Hiperbilirrubinemia/diagnóstico , Hiperbilirrubinemia/genética , Interferón alfa-2 , Interferón-alfa/efectos adversos , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes , Ribavirina/efectos adversos , Ribavirina/uso terapéutico , Adulto JovenRESUMEN
Autoimmune regulator gene mutations were identified in 3 children with type 2 autoimmune hepatitis and extrahepatic immune diseases, including 1 child with immune hepatitis recurrence after liver transplantation. These findings suggest that autoimmune regulator gene variants might predispose children to systemic autoimmune disease, a recurrence of immune disease, or both.