Presentation on theme: "Hepatitis B: Epidemiology and Public Health Issues"— Presentation transcript:
1Hepatitis B: Epidemiology and Public Health Issues Perinatal Hepatitis B Prevention Program2nd Bi-Annual State ConferenceMay 11, 2010Austin, TexasGary Heseltine MD MPHEpidemiologist - Infectious Disease Control UnitChronic Illnesses Demand Chronic Attention
2Topics Hepatitis what is it? Hepatitis B acute Hepatitis B chronic Basic epidemiology, risks, transmissionHepatitis B chronicDisease burden and sequelaeA health disparityGlobal burden of hepatitis BModes of transmission, including injection safetyPerinatal hepatitis BEfficacy of prevention strategiesPatient safety culture and process improvement
3Liver Located upper right side abdomen Largest gland in body; kgReceives most nutrients absorbed by GI tractEssential role in metabolism of fats, sugars, and proteinsProduces bile, clotting substances, proteins, stores sugarDetoxifies compoundsProcesses old erythrocytes
4Hepatitis: Inflammation of the Liver Disease process characterized bydiffuse inflammatory infiltratewith or without necrosis and local fibrosis.Clinical formsAcuteChronic - persistent infection/inflamation > 6 monthsEtiologyUsually a virus sometimes a toxic or chemical substance, immunologic processOrigin: [hepat- + -itis]G. hēpar- (liver) + G. -itis (f. form -ites)-itis: usage now denotes inflammation
5Agents of Viral Hepatitis Enteric transmissionHepatitis A and EAcute diseases with no chronic phaseBloodborne transmissionHepatitis B, C and DAll may produce chronic infectionsAgents not associated with disease?GBV-C (HGV), TTV, SenV
6Acute Viral Hepatitis Signs and Symptoms fatigue mild fever (Elevated ALT almost always found)Signs and Symptomsfatiguemild feverloss of appetiteflu-like illness (prodromal)muscle/joint achesabdominal painnausea and vomitingdark urine - light-colored stoolyellow eyes and skin (jaundice)Aversion to alcohol and cigarettes
11Reported Cases of Acute Hepatitis B in Texas 1980-2005 Hepatitis B recombinant vaccinelicensedUniversal infantvaccinationUniversal adolescentvaccination
12Reported Risk Characteristics Among Adults HBV Recent (<8 yr ago)Injection Drug UseOther*MSMUnknownHeterosexualHCV Recent (<15 yr ago)Injection Drug UseSexualTransfusionUnknownOther*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, CDC12
13Acute Hepatitis B Incidence By Age and Sex: United States, 2005 0.00.0FemaleMale0.00.00.00.00.60.51.72.44.33.02.94.220.127.116.11.18.104.22.168.01.32.20.61.1Rate per 100,000Source: National Notifiable Diseases Surveillance System, CDC
14Acute Hepatitis B Cases by Age Group: Texas, 2005
15Concentration of HBV in Various Body Fluids Low/NotHighModerateDetectableurinefecessweattearsbloodwound exudatessemenserumvaginal fluidsalivabreast milk111
16No Evidence of HBV (or HCV) Transmission BreastmilkMosquitoesKissingFoodWaterCasual contact
17Chronic Hepatitis: A Syndrome Chronicity – continuing disease, no improvementgreater than 6 months durationHepatitis - inflammation of the liverCausesViral, drug, toxin, autoimmune, idiopathicCharacterized by necrosis and inflammationCirrhosis – end stage liver disease, fibrosis, diffuse parenchymal damage, nodular regenerationSequelae - 10 to 20 yearsCirrhosis and hepatocellular carcinoma
18Progression of Liver Disease Time frame: years to decadesFibrosisCancerCirrhosisBC Hepatitis Services, 2003
19Zeus’s punishment of Prometheus Prometheus was a Titan. The Centaur Chiron agreed to die because he was suffering from the poison arrow of Hercules. Hercules who helped the underdog killed the vulture or eagle with a poison arrow. The poison was from the blood of the dying hydra.The Golden Fleece and the Heroes Who Lived before AchillesPrometheus BoundFor 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
20Chronic Hepatitis Burden U.S. HBV estimated 1.2M persons50-70% of these persons born outside U.S.2,000-4,000 deaths per yearHCV estimated M persons70% of these persons age years8,000-10,000 deaths per yearElevated ALT, history IDU, and history blood transfusion identified 85% persons yearsChronic liver disease and cirrhosis 12th leading cause of death nationally, 6th for HispanicsWhat proportion of these persons know their sero-status?Sorrell et al, Ann Int Med, (2):104, Armstrong et al , Ann Int Med 2006;144(10):705,
21Chronic Viral Hepatitis Disease Burden = 409,400 cases Hepatitis BHepatitis CPrevalence in General Population5% or 1,115,0001.6% or 368,000% Chronic Hepatitis10% or 115,00080% or 294,400Texas 2006 population est. 23 million
22Chronic Hepatitis B Three Clinical Forms HBeAg Positive Chronic Hepatitis Braised ALTDNA 107 to 1011 copies per mlchronic hepatitis on biopsyHBeAg Negative Chronic Hepatitis BDNA 104 to 108 copies per mlHBsAg Carrier StateAnti-HBe positivenormal ALTDNA < 101 to 104 copies per mlminimal nonspecific changes on biopsy
23Chronic Hepatitis B con’t HBV causes 85% of primary liver cancer worldwide20% will develop cirrhosis5% will develop hepatocellular cancerHBeAg10% / yr lose HBeAg - become less (non)infectious40% - 50% in 5 years70% - 80% in 10 yearsMore frequent in older carriers, associated ALT flare20% who clear HBeAg have one or more reversionsHBsAg0.5-2% / yr lose HBsAg - become non-carriersLok ASF, McMahon BJ, Hepatology, 2001;34:McMahon BJ, et al, Ann Intern Med, 2001;135:
24Monitoring 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.
27Hepatitis B: Treatment Costs DrugMonthlyAnnualInterferon-alfa$2,084$26,267Lamivudine$449$4,305Adefovir$900$10,705Entecavir$811$9,578Prevent 500 chronic HBV cases - save $5M annually in RxAverages based on 2009 wholesale costs, Hepatitis B Foundation, HepB.org
28HBV: 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.
29HIV HBV Co-infection Multicentre AIDS Cohort Study (MACS) 5293 men followedLiver-related mortality:HBV / 1000HIV / 1000HIV+HBV / 1000 (p0.001)Highest mortality rates with lower CD4 nadir countsThio et al, NEJM 2002;360:1921
302-6% of individuals infected with HBV adults progress to chronic infection. Immunizing adults and older adolescents at risk for HBV infection has been recommended since Despite these facts, infections among adults at risk for infection continue to occur, and the majority of chronic hepatitis B cases in the U.S. are the result of infections acquired in adulthood.
31Alcohol 25% Cause of Newly Diagnosed Chronic Liver Disease HBV 4.4% Hepatitis C 57%Alcohol 25%Hepatitis BOtherNASH 10%HBV 4.4%National Cancer Institute – Surveillance Epidemiology and End ResultsBell et al 2001
32HBV Prevalence and Genotype Distribution 1998 FDACA, C, B, DDB, CBFEGeographic Distribution of Chronic HBV InfectionThe world can be divided into areas of high, intermediate, and low endemicity based on the prevalence of HBsAg in the population. Areas of high endemicity are those in which the prevalence of HBsAg >8%. Southeast Asia, East Asia, many of the Pacific Islands, and parts of South America and Africa are areas of high endemicity. Areas of intermediate endemicity are those in which the prevalence of HBsAg is 2%-7%, and include Eastern Europe, the Middle East, and central Asia. Areas of low endemicity, in which <2% of the population is HBsAg positive, include Australia, North America, and Western Europe.DFAA, B,C,D8% and above = High2% - 8% = IntermediateG, H not determinedBelow 2% = Low
33Global Burden of Hepatitis B Disease 2 billion with markers of current or past infection350 million chronic carriers130 million Chinese (1 in 10) have chronic HBV15%-25% will die from cirrhosis or liver cancer10th leading cause of death600,000 to 1 million preventable deaths / yearSecond only to tobacco in cause of cancer deathsRisk of dying from liver cancer 100 greater for carriers than non-carriersLavanchy D., J Viral Hepat Mar;11(2):WHO.
34Un homme enceinte s’accouche dans son tombeau* *A pregnant man delivers in his grave
36Indonesia: 80–90% home births Vaccinate all babies within 7 days of birth70,000 midwivesUNIJECT
37Hepatitis B Carrier Prevalence Before and After Immunization
38Safe 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 infectionsEstimated 1 billion injections for childhood immunizationsLittle change until Global Alliance for Vaccine and Immunizations (GAVI) and SIGN were formedEligible countries get auto-disable syringes for 3 years. 200 million already distributedCountries responsible for national plan, training, waste managementKane A, et al, Bulletin of WHO, 1999, 77:
42HBV Childhood Exposure Routes In Asia, HBV infection is vertical, mother-to-child30-40% mothers HBeAg+In Africa, horizontal transmission is predominantAbout 10% mothers HBeAg+, mothers may be HBsAg-Studies in two Gambian villages have showninfection uncommon first year of life50% of the children infected by age of 5By the age of 10, almost everybody infected, 15 to 20% chronic carriers.Significant associations, but no predominant route of exposureNumber of siblingsTropical ulcer scarsE antigen positive household memberGHIS Site Review Report 2004
43Estimated Births to HBsAg-Positive Mothers United States, 2002
44Perinatal HBV Transmission Efficacy If mother positive for HBsAg and HBeAg70%-90% of infants infected90% of infected infants become chronic carriersIf positive for HBsAg only20-30% of infants infectedIn utero transmission rare - accounts for <5% of perinatal infections
45HBV Vaccine and HBIG HBIG only ~ 75% effective in preventing carriage Protection wanesHBIG & Vaccine ~ 85 – 95% effectiveHBV Vaccine only ~ 80 – 90% effectiveBirth dose (3-7 days)HBIG not cost effective developing countriesLittle value added
46Are Three Doses Needed? Unapparent exposures as “boosters”? “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:Unapparent exposures as “boosters”?
48Biologic Processes and Bureaucratic Processes Success
49Hepatitis B 9 serotypes, 8 genotypes worldwide “serum hepatitis”Hepatitis B virus (1970 Dane particle) - HepadnaviridaeEnveloped, spherical 42 nmPartial ds circular DNA genome, about 3.2 kbPartial + strand, full length - strand, 5’ RTFour overlapping open reading frames9 serotypes, 8 genotypes worldwideGenotype B milder disease than CResistant to environmental stress44º C for 7 days, room temperature 6 months, years at -20 º C
50HBV: 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 diseasePre-core mutants lack HBeAg production, 20%-30% US patientsP 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-HBsAgNo evidence to date that variants spread in immunized populationsX gene - X protein (regulates gene transcription)Associated with hepatocellular carcinoma
51HBV S-gene mutantsEmergence 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
52Hepatitis D Virus Tiny single stranded RNA virus A “defective” virus that requires HBVsAg for replication.Coinfection produces severe diseaseSperinfection often produces chronic diseaseExposure risks same as HBVPreventing HBV infection prevents HDV infection, why?
53Hepatitis B Vaccines Twinrix 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 year olds (Merk)Protection ~50% dose 1; 85% - 2; 96% - 3TwinrixCombination adult A and B vaccineSchedule: 0, 1, 6-12 monthsApproved for persons >18 yearsVaccine advisory groups that have endorsed this strategy include the Immunization Practices Advisory Committee to the U.S. Public Health Service (ACIP), the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the American College of Physicians (ACP).
54Recommended for Hepatitis B Vaccination (Adults) High-risk heterosexual men and womenMSMInjection drug usersInmates of correctional facilitiesHealth care workersHousehold and sex partners of persons with chronic infectionHemodialysis patientsRecipients of blood productsClients and employees of institution for developmentally disabledFamilies of adoptees from endemic countriesPersons with chronic liver diseasePersons who are immunocompromised - HIVRoutine vaccine for all children
55Missed Opportunities for Adult Hepatitis B Vaccination Of all persons with reported acute hepatitis B:37% reported prior treatment for an STD29% reported prior incarceration56% had been treated for an STD and/or incarcerated in a prison or jail prior to their illnessSource:Goldstein ST et.al., JID 2002;185:713-9
56Perinatal HBV infections are healthcare-associated infections. Improving Hospital ComplianceProblem:Failure to screen motherFailure to give birth doseFailure to give prophylaxisRoot Cause:Too much to doToo many people involvedToo complex a processToo few resources???Solutions:Put into delivery check-list (simplify)Put into publicly reported quality measuresPut development of patient safety culture firstPerinatal HBV infections are healthcare-associated infections.
57Resources Texas Liver Coalition 800-72-LIVER Hepatitis Affiliated St. Luke’s Episcopal Health System, HoustonHepatitisHIV and Hepatitis
58HBV, HCV and HIV Viruses Commonalities Differences Infection through blood and body fluids containing virusTransmission from mother to child at birthProduce chronic infectionsDifferencesInfectivity after sharps injuryHBV 30%, HCV 3%, HIV 0.3%Level of chronicityHBV 10% (variable), HCV 75-85%, HIV 100%
59Other Viruses Associated with Acute Hepatitis Common in U.S.*CytomegalovirusEpstein-BarrHerpes simplexVaricella zosterMeaslesRubellaCoxsackieExotic**Yellow feverArgentinean hemorrhagic feverBolivian hemorrhagic feverLassa feverRift Valley feverMarburgEbola* Each causes less than 1% of acute hepatitis ** Not usually seen in the U.S.