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Hepatitis B: Epidemiology and Public Health Issues Perinatal Hepatitis B Prevention Program 2 nd Bi-Annual State Conference May 11, 2010 Austin, Texas.

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Presentation on theme: "Hepatitis B: Epidemiology and Public Health Issues Perinatal Hepatitis B Prevention Program 2 nd Bi-Annual State Conference May 11, 2010 Austin, Texas."— Presentation transcript:

1 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

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 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) Signs and Symptoms Aversion to alcohol and cigarettes (Elevated ALT almost always found)


8 Fulminant Viral Hepatitis Acute 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

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

10 2006 HBV: 4,700 Reported Cases 46,000 estimated MMWR March 21, 2008 / Vol. 57 / No. SS-2 Chronicity 5% adults

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

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

13 Acute Hepatitis B Incidence By Age and Sex: United States, 2005 FemaleMale 0.0 0.5 0.6 1.72.4 3.0 4.3 4.2 2.9 4.5 2.3 2.2 3.4 1.73.0 2.21.3 1.1 0.6 Source: National Notifiable Diseases Surveillance System, CDC Rate per 100,000

14 Acute Hepatitis B Cases by Age Group: Texas, 2005

15 Low/Not HighModerateDetectable semen serum vaginal fluid blood wound exudates saliva urine feces sweat tears breast milk Concentration of HBV in Various Body Fluids

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

17 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

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

19 The Golden Fleece an d the Heroes Who 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 Zeuss punishment of Prometheus

20 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 12 th leading cause of death nationally, 6 th for Hispanics Sorrell et al, Ann Int Med, 2009 150(2):104, Armstrong et al, Ann Int Med 2006;144(10):705, What proportion of these persons know their sero-status?

21 Chronic Viral Hepatitis Disease Burden = 409,400 cases Hepatitis BHepatitis C Prevalence in General Population5% or 1,115,0001.6% or 368,000 % Chronic Hepatitis10% or 115,00080% or 294,400 Texas 2006 population est. 23 million

22 Chronic Hepatitis B Three Clinical Forms HBeAg Positive Chronic Hepatitis B raised ALT DNA 10 7 to 10 11 copies per ml chronic hepatitis on biopsy HBeAg Negative Chronic Hepatitis B raised ALT DNA 10 4 to 10 8 copies per ml chronic hepatitis on biopsy HBsAg Carrier State Anti-HBe positive normal ALT l DNA < 10 1 to 10 4 copies per ml minimal nonspecific changes on biopsy

23 Chronic Hepatitis B cont 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 HBV causes 85% of primary liver cancer worldwide

24 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.

25 Engardio. San Francisco Chronicle, 2003

26 Hepatitis B: Treatment Acute hepatitis B – Supportive care Chronic hepatitis B DrugTreated patientsControls Interferon-alfa33%-37%12%-17% Lamivudine16%-18%4%-6% Adefovir12%-14%6% - HBV DNA/HBeAg clearance (indicator of viral load) Entecavir 21% Telbivudine 23%-26%

27 Hepatitis B: Treatment Costs DrugMonthlyAnnual Interferon-alfa$2,084$26,267 Lamivudine$449$4,305 Adefovir$900$10,705 Entecavir$811$9,578 Prevent 500 chronic HBV cases - save $5M annually in Rx Averages based on 2009 wholesale costs, Hepatitis B Foundation,

28 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. HBV: A Health Disparity

29 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


31 Hepatitis C 57% Alcohol 25% Hepatitis B Other NASH 10% National Cancer Institute – Surveillance Epidemiology and End Results 2006. HBV 4.4% Cause of Newly Diagnosed Chronic Liver Disease Bell et al 2001

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

33 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 10 th 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.

34 Un homme enceinte saccouche dans son tombeau* *A pregnant man delivers in his grave

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

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

37 Hepatitis B Carrier Prevalence Before and After Immunization

38 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

39 SIGN Pakistan 2001


41 Coalition for Safe Community Needle Disposal 800-643-1648

42 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

43 Estimated Births to HBsAg-Positive Mothers United States, 2002

44 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

45 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

46 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?


48 Biologic Processes and Bureaucratic Processes Success

49 Hepatitis B 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 serum hepatitis

50 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

51 HBV S-gene mutants Emergence of HBV variant able to escape the vaccine-induced response suggested in Italy 20 years ago (Zanetti et al, Lancet 1988) Evidence indicates that amino acid substitution lead to conformational changes which allows mutated HBV to escape vaccine-induced antibodies (G145R) 44 of 1590 (2.8%) vaccinated people, including babies born to HBsAg mothers, became HBV infected despite immunization. All cases showed co-existence of HBsAg and anti-HBs. At present there is no evidence that S-gene mutants pose a threat to the established PH program of vaccination

52 Hepatitis D Virus Tiny single stranded RNA virus A defective virus that requires HBVsAg for replication. Coinfection produces severe disease Sperinfection often produces chronic disease Exposure risks same as HBV Preventing HBV infection prevents HDV infection, why?

53 Licensed in 1981; currently recombinant (in US) 3 dose series, 0, 1-2, 4-6 months - no maximum time between doses (no need to repeat missed doses or restart) 2 dose series (using adult dose) for 11-15 year olds (Merk) Protection ~50% dose 1; 85% - 2; 96% - 3 Twinrix Combination adult A and B vaccine Schedule: 0, 1, 6-12 months Approved for persons >18 years Hepatitis B Vaccines

54 Recommended for Hepatitis B Vaccination (Adults) High-risk heterosexual men and women MSM Injection drug users Inmates of correctional facilities Health care workers Household and sex partners of persons with chronic infection Hemodialysis patients Recipients of blood products Clients and employees of institution for developmentally disabled Families of adoptees from endemic countries Persons with chronic liver disease Persons who are immunocompromised - HIV Routine vaccine for all children

55 Missed Opportunities for Adult Hepatitis B Vaccination Of all persons with reported acute hepatitis B: 37% reported prior treatment for an STD 29% reported prior incarceration 56% had been treated for an STD and/or incarcerated in a prison or jail prior to their illness Source:Goldstein ST, JID 2002;185:713-9

56 Problem: Failure to screen mother Failure to give birth dose Failure to give prophylaxis Root Cause: Too much to do Too many people involved Too complex a process Too few resources??? Solutions: Put into delivery check-list (simplify) Put into publicly reported quality measures Put development of patient safety culture first Improving Hospital Compliance Perinatal HBV infections are healthcare-associated infections.

57 Resources Texas Liver Coalition800-72-LIVER – – Affiliated St. Lukes Episcopal Health System, Houston Hepatitis – – HIV and Hepatitis – –

58 HBV, HCV and HIV Viruses Commonalities – Infection through blood and body fluids containing virus – Transmission from mother to child at birth – Produce chronic infections Differences – Infectivity after sharps injury HBV 30%, HCV 3%, HIV 0.3% – Level of chronicity HBV 10% (variable), HCV 75-85%, HIV 100%

59 Other Viruses Associated with Acute Hepatitis Common in U.S.* Cytomegalovirus Epstein-Barr Herpes simplex Varicella zoster Measles Rubella Coxsackie Exotic** Yellow fever Argentinean hemorrhagic fever Bolivian hemorrhagic fever Lassa fever Rift Valley fever Marburg Ebola * Each causes less than 1% of acute hepatitis. ** Not usually seen in the U.S.

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