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Hepatitis Virales

Hepatitis Virales. Jose A Lavergne, M.D., F.A.C.P. Caracteristicas y Epidemiologia de las Hepatitis Virales. Caracteristicas y Epidemiologia de las Hepatitis Virales. Fulminant Hepatic Failure and chronicity rates for Hepatitis viruses. Acute Hepatitis Treatment.

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Hepatitis Virales

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  1. Hepatitis Virales Jose A Lavergne, M.D., F.A.C.P.

  2. Caracteristicas y Epidemiologia de las Hepatitis Virales

  3. Caracteristicas y Epidemiologia de las Hepatitis Virales

  4. Fulminant Hepatic Failure and chronicity rates for Hepatitis viruses

  5. Acute Hepatitis Treatment • Acute Hepatitis A and E – never develop chronic disease • Only 5% of adults with Acute Hepatitis B develop Chronic infection • A, B, and E – treatment is supportive and to monitor for signs of acute fulminant hepatic failure • HBV-HDV coinfection and pregnant females with HEV • 80% of Acute Hepatitis C progress to Chronic liver disease • 90% HCVRNA undetectable if treated with IFN alfa. • Active treatment for acute hepatitis is only recommended for Acute HCV

  6. Hepatitis A Prevention: Vaccine vs. Immunoglobulin Victor J et al. NEJM 2007;157:1685-1694

  7. MMR. March 2008

  8. Coinfection with HAV NEJM 29;338(5):286-90

  9. MMR. October 19, 2007 / 56(41);1080-1084

  10. Hepatitis B • Infeccion cronica --- Cirrosis y Cancer de Higado • 2 billones de infectados mundialmente (30%) • 350 millones con infeccion cronica • 1 millon de muertes mundialmente

  11. Hepatitis B • Transmision • Perinatal • Contacto percutaneo o permucoso con sangre u otros fluidos corporales (semen y fluidos vaginales) • No por contacto casual

  12. Risk of chronic infection Risk of Chronic Infection 100 80 60 % Risk 40 20 0 Neonates Infants Children Adults Age at Infection HBV - Epidemiology

  13. Hepatitis B • 25% de infectados al nacer mueren de cancer hepatico o cirrosis • Vacuna (1982) • 95% efectiva • Segura y efectiva

  14. Hepatitis B - Vacunacion

  15. Hepatitis B • 50-100 veces mas infeccioso que el HIV • Importante riesgo ocupacional para los trabajadores de la salud. • Vacunacion universal – segura y efectiva

  16. Lok AS. Hepatology 2007

  17. Lok AS. Hepatology 2007

  18. Serological Markers of Acute HBV Infection Acute Infection HBV DNA HBeAg Anti-HBe Anti-HBs Anti-HBc HBsAg Anti-HBc IgM 0 2 4 6 Months Years HBV - Diagnosis

  19. Serological Markers of Chronic HBV Infection HBV DNA HBeAg Anti-HBe HBsAg Anti-HBc IgG Anti-HBc IgM Months Years HBV - Diagnosis Chronic Infection

  20. Serology associated with the different phases of HBV and common hepatitis B mutants

  21. HBV DNA -- Incidencia de Cirrosis 36% 5% Illoeje UH, et al. Gastroenterology 2006;130-678-686

  22. Riesgo de HCC y nivel de HBVDNA CJ Chen et al. JAMA 2006; 295:65-73

  23. HBV Genotipos • A-G • Correlacion con etnicidad y pais de origen • Asiaticos –Genotipo B y C • C > B Reactivacion, severidad, y HCC • Europa Oriental – Genotipo D • USA (caucasicos y africo-americanos) – Genotipo A • Genotipo A es un fuerte predictor de respuesta a tratamiento con PEG Interferon.

  24. HBV Tratamiento – Metas “Convertir una infeccion activa a una inactiva” HBeAg (+) HBeAg (-) • Perdida del HBeAg • Aparicion de AntiHBe • Conversion a status inactivo • Normalizacion de Aminotransferasas hepaticas • Perdida de HBVDNA detectable • Mejoria de la histologia hepatica • Reducir el riesgo de Carcinoma Hepatocelular • Perdida de HBsAg

  25. EB Keefe, et al. Clin Gastroenterol Hepatol 2008;6:1315-1341

  26. EB Keefe, et al. Clin Gastroenterol Hepatol 2008;6:1315-1341

  27. TerapiasAntivirales for HBeAg+ JL Dienstag. NEJM 2008; 359:1486-1500

  28. HBV PEG IFN alfa • PEG IFN alfa semanal por 6-12 meses • Genotype A - 50% seroconversion (EAg to Anti-E) • HBVDNA, EAg y AntiE al finalizar , 3 meses y 6 meses post tratamiento • No ventaja a combinacion con antivirales orales • No iniciar antivirales orales hasta 6 meses post tratamiento.

  29. JL Dienstag. NEJM 2008; 359:1486-1500

  30. Oral Antivirales – HBeAg+ • EAg a AntiE (seroconversion) depende de HBVDNA no detectable • META = Supresioncompleta de HBVDNA • HBV DNA no detectable a 6-12 meses • Continuar 6-12 meses post seroconversion • HBVDNA detectable a 6-12 meses = Agregarotro antiviral con diferentesitio de accion

  31. Oral Antivirales – HBeAg (-) • No pueden seroconvertir (Precore mutant) • Tratamiento es por vida • Oral antivirales • Supresion completa de HBVDNA • Agregar un antiviral adicional si HBVDNA es detectable a 6-12 meses

  32. TerapiasAntiviralesparaHBeAg- EB Keefe, et al. Clin Gastroenterol Hepatol 2008;6:1315-1341

  33. EB Keefe, et al. Clin Gastroenterol Hepatol 2008;6:1315-1341

  34. EB Keefe, et al. Clin Gastroenterol Hepatol 2008;6:1315-1341

  35. EB Keefe, et al. Clin Gastroenterol Hepatol 2008;6:1315-1341

  36. Efecto de Lamivudine en Progresion de Cirrosis y HCC Disease progression Liaw Y. NEJM 2004;351:1521-1531 Increase in Child-Pugh Score Diagnosis de HCC

  37. HBV Profilaxis en Quimioterapia • Reactivacion de HBV 14-50% • HBV cronica que reciben quimioterapia (cytotoxicos) o immunosupresores (Infliximab). • Aumento de ALTs, histologica inflamacion, y (en pocos casos) falla hepatica. • Recomendacion: HBsAg (+)/ AntiHBc –Lamivudine 1 semana antes , y por > 1 yr despues de terminar. Kohrt HE.Aliment Pharmacol Ther 24:1003-1016

  38. Prevalence Worldwide 170 million ( 3%) United States Anti-HCV positive 3.9 million (1.8%) HCV RNA positive 2.7 million (1.4%) HCV - Epidemiology Prevalence Alter MJ et al., New Engl J Med 1999; 341:556 Lavanchy D & McMahon B, In: Liang TJ & Hoofnagle JH (eds.) Hepatitis C. New York: Academic Press, 2000:185

  39. Worldwide Prevalence Worldwide Prevalence HCV Ab pos (%) 10 to 20 5 to 10 2 to 5 1 to 2 0 to 1 HCV - Epidemiology Heintges, T., Hepatology 1997; 26:521

  40. Risk Factors for Hepatitis C Clotting Factor Treatment Prior to 1987 Blood Transfusion or Organ Transplant Prior to 1992 Long-Term Hemodialysis Risk Factors for Hepatitis C Multiple Sexual Partners Injection Drug Use Mass Injections and Traditional Practices Birth from Infected Mother HCV - Epidemiology

  41. Prevalence In Groups at Risk Prevalence In Groups at Risk Recipients of clotting factors before 1987 75 - 90% Injection drug users 70 - 85% Long-term hemodialysis patients 10% Individuals with > 50 sexual partners 10% Recipients of blood prior to 1990 5% Infants born to infected mothers 5% Long-term sexual partners of HCV positive 1 - 5% Health workers after random needlesticks 1 - 2% HCV - Epidemiology CDC, MMWR 1998;47(No. RR-19):1

  42. Incidence of Acute Hepatitis C Has Declined in the U.S. Surrogate tests on donors Anti-HCV test 20 15 Decline among injection drug users Cases per 100,000 10 5 0 ‘82 ‘84 ‘86 ‘88 ‘90 ‘92 ‘94 ‘95 Year HCV - Epidemiology Incidence of Acute Hepatitis C Has Declined in the U.S. CDC, 1995

  43. Outcome Following Hepatitis C Infection Outcome Following Hepatitis C Infection Acute hepatitis C 55 - 85% Chronic infection 70% Chronic hepatitis 1 - 4%/yr HCC 20% Cirrhosis Decompensation 4 - 5%/yr Time (yr) 20 30 10 HCV - Natural History

  44. Factores Claves que influyen en la decision tomar tratamiento • Predictores de la probabilidad de obtener SVR • Stadio de Fibrosis • Severidad de actividadnecroinflamatoria • Presencia de contraindicacionesabsolutas or relativas a tratamiento • Embarazo o intencion de concepcion • EnfermedadAutoinmuneActiva • Enfermedad Cardiovascular significativa • EnfermedadPsiquiatricaactiva • Convulsiones no-controladas • Citopeniasseveras- incluyendonecesidadpor transfusion • Motivacion del paciente a tomartratamiento.

  45. Pretreatment Factors Associated with reduced likelihood of achieving SVR

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