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Hepatitis B: Epidemiology and Public Health Issues

Hepatitis B: Epidemiology and Public Health Issues. Perinatal Hepatitis B Prevention Program 2 nd Bi-Annual State Conference May 11, 2010 Austin, Texas Gary Heseltine MD MPH Epidemiologist - Infectious Disease Control Unit. Chronic Illnesses Demand Chronic Attention. Topics.

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Hepatitis B: Epidemiology and Public Health Issues

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  1. Hepatitis B: Epidemiology and Public Health Issues Perinatal Hepatitis B Prevention Program 2nd Bi-Annual State Conference May 11, 2010 Austin, Texas Gary Heseltine MD MPH Epidemiologist - Infectious Disease Control Unit Chronic Illnesses Demand Chronic Attention

  2. Topics • Hepatitis what is it? • Hepatitis B acute • Basic epidemiology, risks, transmission • Hepatitis B chronic • Disease burden and sequelae • A health disparity • Global burden of hepatitis B • Modes of transmission, including injection safety • Perinatal hepatitis B • Efficacy of prevention strategies • Patient safety culture and process improvement

  3. Liver • Located upper right side abdomen • Largest gland in body; 1.3 - 1.6kg • Receives most nutrients absorbed by GI tract • Essential role in metabolism of fats, sugars, and proteins • Produces bile, clotting substances, proteins, stores sugar • Detoxifies compounds • Processes old erythrocytes

  4. Hepatitis: Inflammation of the Liver • Disease process characterized by • diffuse inflammatory infiltrate • with or without necrosis and local fibrosis. • Clinical forms • Acute • Chronic - persistent infection/inflamation> 6 months • Etiology • Usually a virus sometimes a toxic or chemical substance, immunologic process • Origin: [hepat- + -itis] • G. hēpar- (liver) + G. -itis(f. form -ites) • -itis: usage now denotes inflammation

  5. Agents of Viral Hepatitis • Enteric transmission • Hepatitis A and E • Acute diseases with no chronic phase • Bloodborne transmission • Hepatitis B, C and D • All may produce chronic infections • Agents not associated with disease? • GBV-C (HGV), TTV, SenV

  6. Acute Viral Hepatitis (Elevated ALT almost always found) Signs andSymptoms • fatigue • mild fever • loss of appetite • flu-like illness (prodromal) • muscle/joint aches • abdominal pain • nausea and vomiting • dark urine - light-colored stool • yellow eyes and skin (jaundice) Aversion to alcohol and cigarettes

  7. Fulminant Viral HepatitisAcute hepatic failure • Massive hepatic necrosis within 8 weeks of onset • Signs Neurologic - Hepatic Encephalopathy Acute Pancreatitis, jaundice, ascites Coagulopathy - gastrointestinal bleeding Acute Renal Failure - Hepatorenal Syndrome Cardiopulmonary collapse

  8. Hepatitis B – Clinical Features • Incubation period: Average 60-90 days • Range 45-180 days • Clinical illness (jaundice): <5 yrs, <10%>5 yrs, 30%-50% • Acute case-fatality rate: 0.5%-1% • Chronic infection: <5 yrs, 30%-90%>5 yrs, 2%-10%

  9. 2006 HBV: 4,700 Reported Cases46,000 estimated www.cdc.gov/hepatitis/statistics.htm MMWR March 21, 2008 / Vol. 57 / No. SS-2 Chronicity 5% adults

  10. Reported Cases of Acute Hepatitis B in Texas 1980-2005 Hepatitis B recombinant vaccine licensed Universal infant vaccination Universal adolescent vaccination

  11. Reported Risk Characteristics Among Adults HCV Recent (<15 yr ago) HBV Recent (<8 yr ago) Injection Drug Use Injection Drug Use Unknown Sexual Other* MSM Transfusion Unknown Other* Heterosexual With shared risk behaviors integrated testing and prevention makes sense. *Other: Household contact, institutionalization, hemodialysis, occupational exposure etc. Modified from Sentinel Counties Study of Viral Hepatitis, CDC

  12. Acute Hepatitis B Incidence By Age and Sex: United States, 2005 0.0 0.0 Female Male 0.0 0.0 0.0 0.0 0.5 0.6 1.7 2.4 4.3 3.0 2.9 4.2 2.9 4.5 2.3 4.5 2.2 3.4 1.7 3.0 1.3 2.2 0.6 1.1 Rate per 100,000 Source: National Notifiable Diseases Surveillance System, CDC

  13. Acute Hepatitis B Cases by Age Group: Texas, 2005

  14. blood urine feces wound exudates sweat tears Concentration of HBV in Various Body Fluids Low/Not High Moderate Detectable semen serum vaginal fluid saliva breast milk

  15. No Evidence of HBV (or HCV) Transmission • Breastmilk • Mosquitoes • Kissing • Food • Water • Casual contact

  16. Chronic Hepatitis: A Syndrome Chronicity – continuing disease, no improvement • greater than 6 months duration Hepatitis - inflammation of the liver • Causes • Viral, drug, toxin, autoimmune, idiopathic • Characterized by necrosis and inflammation • Cirrhosis – end stage liver disease, fibrosis, diffuse parenchymal damage, nodular regeneration Sequelae - 10 to 20 years • Cirrhosis and hepatocellular carcinoma

  17. Progression of Liver Disease Time frame: years to decades Fibrosis Cancer Cirrhosis BC Hepatitis Services, 2003

  18. Zeus’s punishment of Prometheus The Golden Fleece and the HeroesWho Lived before Achilles Prometheus Bound • For Prometheus to be set free: • An Immortal would have to give up his life for Prometheus – Chiron (centaur) • A mortal would have to slay the liver-eating eagle - Hercules

  19. Chronic Hepatitis Burden U.S. • HBV estimated 1.2M persons • 50-70% of these persons born outside U.S. • 2,000-4,000 deaths per year • HCV estimated 3.2-3.7M persons • 70% of these persons age 35-54 years • 8,000-10,000 deaths per year • Elevated ALT, history IDU, and history blood transfusion identified 85% persons 20-59 years • Chronic liver disease and cirrhosis 12th leading cause of death nationally, 6th for Hispanics What proportion of these persons know their sero-status? Sorrell et al, Ann Int Med, 2009 150(2):104, Armstrong et al , Ann Int Med 2006;144(10):705, www.cdc.gov/hepatitis/

  20. Chronic Viral Hepatitis Disease Burden = 409,400 cases

  21. Chronic Hepatitis BThree Clinical Forms • HBeAg Positive Chronic Hepatitis B • raised ALT • DNA 107 to 1011 copies per ml • chronic hepatitis on biopsy • HBeAg Negative Chronic Hepatitis B • raised ALT • DNA 104 to 108 copies per ml • chronic hepatitis on biopsy • HBsAg Carrier State • Anti-HBe positive • normal ALT • DNA < 101 to 104 copies per ml • minimal nonspecific changes on biopsy

  22. Chronic Hepatitis B con’t HBV causes 85% of primary liver cancer worldwide • 20% will develop cirrhosis • 5% will develop hepatocellular cancer HBeAg 10% / yr lose HBeAg - become less (non)infectious • 40% - 50% in 5 years • 70% - 80% in 10 years More frequent in older carriers, associated ALT flare 20% who clear HBeAg have one or more reversions HBsAg 0.5-2% / yr lose HBsAg - become non-carriers Lok ASF, McMahon BJ, Hepatology, 2001;34:1225-1241 McMahon BJ, et al, Ann Intern Med, 2001;135:759-768

  23. Monitoring HBsAg+ Patients • Discuss monitoring with a liver specialist having much experience in managing viral liver diseases. • Annual physical exam. • Blood work every 6-12 mos. • Liver biopsy? • Liver ultrasound or CT scan every 6-12 mos. • fetoprotein (AFP) every 6-12 mos. • Education of patient about disease.

  24. Engardio. San Francisco Chronicle, 2003

  25. Hepatitis B: Treatment • Acute hepatitis B • Supportive care • Chronic hepatitis B - HBV DNA/HBeAg clearance (indicator of viral load) Entecavir 21% Telbivudine 23%-26%

  26. Hepatitis B: Treatment Costs Prevent 500 chronic HBV cases - save $5M annually in Rx Averages based on 2009 wholesale costs, Hepatitis B Foundation, HepB.org

  27. HBV: A Health Disparity • 10% of Asian Americans have chronic HBV versus less than 0.3% of the general population. • Liver cancer second leading cancer for Asian men. • Liver cancer among Asian Americans is 6 to 13 times higher than the general population.

  28. HIV HBV Co-infection Multicentre AIDS Cohort Study (MACS) • 5293 men followed • Liver-related mortality: HBV+ 0.8 / 1000 HIV+ 1.7 / 1000 HIV+HBV+ 14.2 / 1000 (p0.001) • Highest mortality rates with lower CD4 nadir counts Thio et al, NEJM 2002;360:1921

  29. Other Hepatitis B NASH 10% Hepatitis C 57% Alcohol 25% Cause of Newly Diagnosed Chronic Liver Disease HBV 4.4% National Cancer Institute – Surveillance Epidemiology and End Results 2006. http://seer.cancer.gov/resources/ Bell et al 2001

  30. HBV Prevalence and Genotype Distribution 1998 F D A C A, C, B, D D B, C B F E D F A A, B,C,D 8% and above = High 2% - 8% = Intermediate G, H not determined Below 2% = Low

  31. Global Burden of Hepatitis B Disease • 2 billion with markers of current or past infection • 350 million chronic carriers • 130 million Chinese (1 in 10) have chronic HBV • 15%-25% will die from cirrhosis or liver cancer • 10th leading cause of death • 600,000 to 1 million preventable deaths / year • Second only to tobacco in cause of cancer deaths • Risk of dying from liver cancer 100 greater for carriers than non-carriers Lavanchy D., J Viral Hepat. 2004 Mar;11(2):97-107. WHO. www.who.int/csr/disease/hepatitis/en/

  32. Un homme enceinte s’accouche dans son tombeau* *A pregnant man delivers in his grave

  33. Cancer rates, Gambian males 1986-96 Incidence per 100,000 140 120 100 80 all cancer liver cancer 60 40 20 0 0-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 65+ 60-64 Age GHIS Site Review Report 2004

  34. Indonesia: 80–90% home births • Vaccinate all babies within 7 days of birth • 70,000 midwives UNIJECT

  35. Hepatitis B Carrier Prevalence Before and After Immunization

  36. Safe Injection Global Network ~16 billion injections/year / 12 billion syringes sold ~33% unsafe in developing countries ~12 million HBV infections ~3 million HCV infections ~ 120,000 HIV infections Estimated 1 billion injections for childhood immunizations Little change until Global Alliance for Vaccine and Immunizations (GAVI) and SIGN were formed Eligible countries get auto-disable syringes for 3 years. 200 million already distributed Countries responsible for national plan, training, waste management Kane A, et al, Bulletin of WHO, 1999, 77:801-807

  37. SIGN Pakistan 2001

  38. SIGN Pakistan 2001

  39. Coalition for Safe Community Needle Disposal 800-643-1648

  40. HBV Childhood Exposure Routes In Asia, HBV infection is vertical, mother-to-child 30-40% mothers HBeAg+ In Africa, horizontal transmission is predominant About 10% mothers HBeAg+, mothers may be HBsAg- Studies in two Gambian villages have shown infection uncommon first year of life 50% of the children infected by age of 5 By the age of 10, almost everybody infected, 15 to 20% chronic carriers. Significant associations, but no predominant route of exposure Number of siblings Tropical ulcer scars E antigen positive household member GHIS Site Review Report 2004

  41. Estimated Births to HBsAg-Positive Mothers United States, 2002

  42. Perinatal HBV Transmission Efficacy • If mother positive for HBsAg and HBeAg • 70%-90% of infants infected • 90% of infected infants become chronic carriers • If positive for HBsAg only • 20-30% of infants infected • 90% of infected infants become chronic carriers • In utero transmission rare - accounts for <5% of perinatal infections

  43. HBV Vaccine and HBIG • HBIG only ~ 75% effective in preventing carriage • Protection wanes • HBIG & Vaccine ~ 85 – 95% effective • HBV Vaccine only ~ 80 – 90% effective • Birth dose (3-7 days) • HBIG not cost effective developing countries • Little value added

  44. Are Three Doses Needed? “Thus, protection against chronic carriage does not depend on the number of doses received as originally assumed…results from GHIS follow-up of vaccinated subjects, more than 95% of children that received at least one dose are protected against the acquisition of chronic carriage early in life.” Fortuin, M. et al Lancet 1993; 341:1129-31 Unapparent exposures as “boosters”?

  45. Biologic Processes and Bureaucratic Processes Success

  46. Hepatitis B “serum hepatitis” • Hepatitis B virus (1970 Dane particle) - Hepadnaviridae • Enveloped, spherical 42 nm • Partial ds circular DNA genome, about 3.2 kb • Partial + strand, full length - strand, 5’ RT • Four overlapping open reading frames • 9 serotypes, 8 genotypes worldwide • Genotype B milder disease than C • Resistant to environmental stress • 44º C for 7 days, room temperature 6 months, years at -20 º C

  47. HBV: Gene Products and Mutants Genome encodes 4 groups of proteins: • C gene - HBcAg (nucleocapsid protein), HBeAg (soluble protein circulates in serum) • ?Associated fulminant hepatitis and severe liver disease • Pre-core mutants lack HBeAg production, 20%-30% US patients • P gene - Polymerase (DNA synthesis) • Associated with resistance to treatment with nucleoside analogs (e.g., lamivudine) • S gene - HBsAg (surface protein) • Concern that these variants may allow replication in the presence of vaccine-induced anti-HBsAg • No evidence to date that variants spread in immunized populations • X gene - X protein (regulates gene transcription) • Associated with hepatocellular carcinoma

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