This document summarizes the characteristics and epidemiology of viral hepatitis. It describes the different hepatitis viruses (A-E), their worldwide prevalence, at-risk populations, modes of transmission, clinical outcomes, and treatments. Key points include:
- Hepatitis B is the most common, with over 350 million chronic carriers worldwide and 1 million deaths annually. Perinatal and sexual transmission are major routes.
- Hepatitis C affects over 170 million people globally. Past exposure through blood transfusions or injection drug use are primary risk factors.
- Different hepatitis viruses have varying rates of progression to chronic liver disease and fulminant hepatic failure. Vaccines exist for hepatitis A and B but not C.
This document summarizes the characteristics and epidemiology of viral hepatitis. It describes the different hepatitis viruses (A-E), their worldwide prevalence, at-risk populations, modes of transmission, clinical outcomes, and treatments. Key points include:
- Hepatitis B is the most common, with over 350 million chronic carriers worldwide and 1 million deaths annually. Perinatal and sexual transmission are major routes.
- Hepatitis C affects over 170 million people globally. Past exposure through blood transfusions or injection drug use are primary risk factors.
- Different hepatitis viruses have varying rates of progression to chronic liver disease and fulminant hepatic failure. Vaccines exist for hepatitis A and B but not C.
This document summarizes the characteristics and epidemiology of viral hepatitis. It describes the different hepatitis viruses (A-E), their worldwide prevalence, at-risk populations, modes of transmission, clinical outcomes, and treatments. Key points include:
- Hepatitis B is the most common, with over 350 million chronic carriers worldwide and 1 million deaths annually. Perinatal and sexual transmission are major routes.
- Hepatitis C affects over 170 million people globally. Past exposure through blood transfusions or injection drug use are primary risk factors.
- Different hepatitis viruses have varying rates of progression to chronic liver disease and fulminant hepatic failure. Vaccines exist for hepatitis A and B but not C.
Caracteristicas y Epidemiologia de las Hepatitis Virales
Virus Family Type Worldwide Prevalence A Picornavirus ssRNA Varies by Geography High prevalence areas: nearly all adults exposed Low prevalence areas: 33% of populations exposed B Hepadnaviridae dsDNA 300 million worldwide High prevalence (China and SoutheastAsia): 10-20% of population Medium prevalence (Africa and Eastern Europe): 3-5% of population Low prevalence (North America and Western Europe):<2% of population C Flaviviridae ssRNA 100 million worldwide 1-2% of population D Deltaviridae ssRNA 15 million persons worldwide (-5% with patients with chronic HBV; most commonly Eastern Europe) E Calciviridae ssRNA Varies by Geography High prevalence (India): 40-70% of population Low prevalence (North America and Europe): 1-5% of population Virus Age Group Most Commonly Infected Modes of Infection A Infants and children
Adults Person-person via fecal oral spread and contaminated food
Same as for children, homosexual activity B Infants
Children and adults Perinatal exposure
Sexual activity, intravenous drug use, contaminated instruments , and other parenteral expsorues
C All patients Vertical and sexual transmission rare but increased in setting of HIV coinfection
Drug use, other parenteral exposures D All patients Sexual activity, durg use, other parenteral exposures E All persons Person-person via fecal-oral spread and contaminated food Caracteristicas y Epidemiologia de las Hepatitis Virales Fulminant Hepatic Failure and chronicity rates for Hepatitis viruses Virus Fulminant Hepatic Failure Chronicity rates A 0.1% mostly adults
Approximately 30% in patients with chronic liver disease Never, regardless of age B 1% mostly in adults
Approximately 25% in patients with chronic liver disease 90% when exposed perinatally
50% when exposed as a child
5% when exposed as adult C Not reported 80%, regardless of age D Coinfection: 20-25%
Superinfection: uncommon Coinfection 2%
Superinfection > 90% E 0.5 4% overall
15-30% if exposure during pregnancy None regardless of age 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 Hepatitis A Prevention: Vaccine vs. Immunoglobulin Victor J et al. NEJM 2007;157:1685-1694 MMR. March 2008 Coinfection with HAV NEJM 29;338(5):286-90 MMR. October 19, 2007 / 56(41);1080-1084 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
Hepatitis B Transmision Perinatal Contacto percutaneo o permucoso con sangre u otros fluidos corporales (semen y fluidos vaginales) No por contacto casual HBV - Epidemiology Risk of chronic infection Age at Infection 0 20 40 60 80 100 Neonates Infants Children Adults % Risk Risk of Chronic Infection Hepatitis B 25% de infectados al nacer mueren de cancer hepatico o cirrosis Vacuna (1982) 95% efectiva Segura y efectiva
Hepatitis B - Vacunacion Hepatitis B 50-100 veces mas infeccioso que el HIV Importante riesgo ocupacional para los trabajadores de la salud. Vacunacion universal segura y efectiva Lok AS. Hepatology 2007 Lok AS. Hepatology 2007 HBV - Diagnosis Acute Infection 0 2 4 6 HBsAg Anti-HBs Anti- HBc Anti-HBc IgM Months Years HBeAg HBV DNA Anti-HBe Serological Markers of Acute HBV Infection Chronic Infection HBV - Diagnosis HBV DNA HBeAg Months Years Anti-HBc IgM Anti-HBc IgG Anti-HBe HBsAg Serological Markers of Chronic HBV Infection Serology associated with the different phases of HBV and common hepatitis B mutants Serology testing sAg Anticore eAg Anti-E Antisurface HBV DNA (copies/ml) Resolved Infection X X X Wild type infection X X X > 1 000 000 Inactive infection X X X < 100 000 Vaccination X Mutants forms of HBV: Pre core X X +/- > 100 000 Surface X X +/- Variable Core X +/- +/- Variable HBV DNA -- Incidencia de Cirrosis Illoeje UH, et al. Gastroenterology 2006;130-678-686 36% 5% Riesgo de HCC y nivel de HBVDNA CJ Chen et al. JAMA 2006; 295:65-73 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.
HBV Tratamiento Metas 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 Convertir una infeccion activa a una inactiva EB Keefe, et al. Clin Gastroenterol Hepatol 2008;6:1315-1341 EB Keefe, et al. Clin Gastroenterol Hepatol 2008;6:1315-1341 JL Dienstag. NEJM 2008; 359:1486-1500
Terapias Antivirales for HBeAg+ 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. JL Dienstag. NEJM 2008; 359:1486-1500 Oral Antivirales HBeAg+ EAg a AntiE (seroconversion) depende de HBVDNA no detectable META = Supresion completa de HBVDNA HBV DNA no detectable a 6-12 meses Continuar 6-12 meses post seroconversion HBVDNA detectable a 6-12 meses = Agregar otro antiviral con diferente sitio de accion Site 1 Site 2 Site 3 Lamivudine
Adefovir
Tenofovir Telbivudine Emtricitabine Entevavir 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 EB Keefe, et al. Clin Gastroenterol Hepatol 2008;6:1315-1341 Terapias Antivirales para HBeAg- EB Keefe, et al. Clin Gastroenterol Hepatol 2008;6:1315-1341 EB Keefe, et al. Clin Gastroenterol Hepatol 2008;6:1315-1341 EB Keefe, et al. Clin Gastroenterol Hepatol 2008;6:1315-1341 Liaw Y. NEJM 2004;351:1521-1531 Disease progression Increase in Child-Pugh Score Diagnosis de HCC Efecto de Lamivudine en Progresion de Cirrosis y HCC 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.
Lamivudine Placebo Tasa de Hepatitis 9.2% (o-20%) 54% (33-67%) Tasa de HBV reactivacion 8.7% (0-24%) 37% (29-56%) Kohrt HE.Aliment Pharmacol Ther 24:1003-1016 Prevalence HCV - Epidemiology United States Anti-HCV positive 3.9 million (1.8%) HCV RNA positive 2.7 million (1.4%) Worldwide 170 million ( 3%) 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 Prevalence HCV - Epidemiology Heintges, T., Hepatology 1997; 26:521 10 to 20 5 to 10 2 to 5 1 to 2 0 to 1 HCV Ab pos (%) Worldwide Prevalence Worldwide Prevalence HCV - Epidemiology Risk Factors for Hepatitis C Injection Drug Use Multiple Sexual Partners Clotting Factor Treatment Prior to 1987 Long-Term Hemodialysis Blood Transfusion or Organ Transplant Prior to 1992 Birth from Infected Mother Mass Injections and Traditional Practices Risk Factors for Hepatitis C HCV - Epidemiology 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% CDC, MMWR 1998;47(No. RR-19):1 Prevalence In Groups at Risk CDC, 1995 HCV - Epidemiology Incidence of Acute Hepatitis C Has Declined in the U.S. Surrogate tests on donors 0 5 10 15 20 82 84 86 88 90 92 94 95 Year Cases per 100,000 Anti-HCV test Decline among injection drug users Incidence of Acute Hepatitis C Has Declined in the U.S. HCV - Natural History Outcome Following Hepatitis C Infection Acute hepatitis C Chronic infection Chronic hepatitis Cirrhosis Time (yr) 55 - 85% 70% 20% 10 20 30 Decompensation HCC 1 - 4%/yr 4 - 5%/yr Outcome Following Hepatitis C Infection Factores Claves que influyen en la decision tomar tratamiento Predictores de la probabilidad de obtener SVR Stadio de Fibrosis Severidad de actividad necroinflamatoria Presencia de contraindicaciones absolutas or relativas a tratamiento Embarazo o intencion de concepcion Enfermedad Autoinmune Activa Enfermedad Cardiovascular significativa Enfermedad Psiquiatrica activa Convulsiones no-controladas Citopenias severas- incluyendo necesidad por transfusion Motivacion del paciente a tomar tratamiento. Pretreatment Factors Associated with reduced likelihood of achieving SVR Host Viral Disease-specific African American Race Genotype 1 Advanced fibrosis score Latino ethnicity High HCV RNA Steatosis Older age HIV coinfection Male sex Insulin resistance High BMI HCV Genotypes Genotype 1 70% infected patients in USA Lower SVR with current treatment Treated for at least 48 weeks Genotype 2- 3 30% of infected patients in USA More common in Europe (Austrians) and Japanese Higher SVR with current treatment Genotype 4 Egypt and Middle East Genotype 5 Southern Africa Genotype 6 Southeast Asia 4 HCV - Treatment Sustained Virological Response (SVR) 0 24 48 72 0 50 100 150 0 6 12 ALT HCV RNA 200 18 Weeks ALT (IU) HCV RNA (IU/ml) Treatment Sustained virological response (SVR) Peg- IFN (180 ug or 1.5 ug/kg) Weekly + Weight base RBV (13-15 mg/kg) RVR WK 4 WK 12 No RVR 24 wks If baseline VL <400,000 IU/ml and low Fibrosis score Complete EVR HCV RNA < 50 IU/ml Partial EVR 2-log decline No EVR Stop 72 wks 48 wks 48 wks HCV Genotype 1 Genotype 2-3 Peg-IFN 180 ug or 1.5 ug/kg weekly + Ribavirin 800 mg/d
Response Weeks of assessment Interpretation Management implications RVR 4 HCV RNA < 50 IU/ml predicts 90% SVR Duration of treatment of 12-16 weeks can be considered No RVR 4 HCV RNA > 50 IU/ml predicts SVR < 50% Consideration o treatment duration longer than 24 weeks HBV - Therapy Effect of IFN on Survival and HCC Development 0 25 50 75 % Cumulative incidence 100 0 2 4 6 8 10 12 Years of follow-up Treated group Control group Survival p = 0.018 HCC p = 0.013 Lin SM, Hepatology 1999; 29:971 Effect of interferon treatment on survival and hepatocellular carcinoma (HCC) development Conclusiones Las Hepatitis virales son un problema importante de salud mundial. Hepatitis A y E son infecciones agudas que no progresan a cronicidad y cuya propagacion depende de las condiciones de higiene en la comunidad. Hepatitis A es prevenible mas alta mortalidad en adultos y pacientes con enfermedad hepatica cronica Hepatitis B y C son causas importantes de mortalidad y morbilidad por falla hepatica y cancer. Vacunacion es una forma segura y eficaz (y mucho mas economica) de atacar la hepatitis B. Hay opciones de tratamiento para las formas cronicas de hepatitis B y C, las cuales actualmente se encuentran en evolucion. Conclusiones Acute Hepatitis C should be treated with IFN alfa por el alto riesgo de avanzar a cronicidad Los niveles de viremia y genotipos de HBV y HCV son importantes al momento de decidir tratamiento.