Hepatitis in Swaziland
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An overview of Hepatitis B infection with a Swaziland touch.
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Hepatitis in Swaziland
- 1. 11 02/08/1802/08/18 Viral Hepatitis Department of Internal MedicineDepartment of Internal Medicine Presenter: Dr Nicholas KamaraPresenter: Dr Nicholas Kamara
- 2. 22 02/08/1802/08/18 Viral Hepatitis 5 types:5 types: AA:: fecal-oral transmissionfecal-oral transmission BB:: sexual fluids & blood to bloodsexual fluids & blood to blood CC:: blood to bloodblood to blood DD:: travels with Btravels with B EE:: fecal–oralfecal–oral transmissiontransmission VaccineVaccine PreventablePreventable Adapted from Corneil, 2003Adapted from Corneil, 2003
- 3. 33 02/08/1802/08/18 Structure Cultured in cells Epidemiology Transmission Incubation period Symptoms Jaundice Onset Vaccine Diagnostic tests RNA yes endemic & epidemic oral/fecal, water & food 2-7 weeks fever, G-I tract disorder 1 case in 10 acute/short not available yes DNA no endemic blood/serum, close contact 1-6 months fever, rash, arthritis common gradual/chronic yes yes HBV no endemic blood/serum, intimate contact 2-8 weeks similar to HBV common acute/chronic not available yes Hepatitis A HAV Hepatitis B HBV Hepatitis C HCV
- 6. 66 02/08/1802/08/18 Hepatitis A Epidemiology Prevalence of antibody to hepatitis A virus, 2010Prevalence of antibody to hepatitis A virus, 2010 Source: CDC YellowBookSource: CDC YellowBook
- 7. 77 02/08/1802/08/18 Hepatitis A Hepatitis A has an incubation period ofHepatitis A has an incubation period of approximately 28 days (range: 15–50 days)approximately 28 days (range: 15–50 days) HAV replicates in the liver and is shed in highHAV replicates in the liver and is shed in high concentrations in feces from 2 weeks before to 1concentrations in feces from 2 weeks before to 1 week after the onset of clinical illnessweek after the onset of clinical illness HAV infection produces a self-limited disease thatHAV infection produces a self-limited disease that does not result in chronic infection or chronic liverdoes not result in chronic infection or chronic liver diseasedisease Humans are the only natural hostHumans are the only natural host
- 8. 88 02/08/1802/08/18 Hepatitis A Host Defenses antibodies develop late in incubationantibodies develop late in incubation periodperiod IgMIgM within a week of dark urinewithin a week of dark urine peaks a week laterpeaks a week later lasts 40-60 dayslasts 40-60 days IgGIgG after IgMafter IgM peaks 60-80 dayspeaks 60-80 days
- 9. 99 02/08/1802/08/18 Hepatitis A Diagnosis Clinical manifestionsClinical manifestions Viral antigensViral antigens Immunoelectron microscopyImmunoelectron microscopy RIARIA ELISAELISA Immune Adherence hemagglutination (oldImmune Adherence hemagglutination (old method)method) Viral antibodiesViral antibodies
- 10. 1010 02/08/1802/08/18 Hepatitis A Prevention Hepatitis A vaccine is the best protection.Hepatitis A vaccine is the best protection. Good sanitation measures are essential forGood sanitation measures are essential for preventing environmental contamination.preventing environmental contamination. Good personal hygiene is also essential forGood personal hygiene is also essential for prevention and control including:prevention and control including: Hand washing with soap:Hand washing with soap: After using the bathroomAfter using the bathroom After changing a diaperAfter changing a diaper Before preparing and eating foodBefore preparing and eating food
- 13. 1313 02/08/1802/08/18 Hepatitis C Prevalence of chronic infection with hepatitis C virus Source: CDC YellowBook 2012Source: CDC YellowBook 2012
- 15. 1515 02/08/1802/08/18 Hepatitis C Epidemiology Source: CDC DVHSource: CDC DVH
- 16. 1616 02/08/1802/08/18 Hepatitis C Natural History of Infection
- 17. 1717 02/08/1802/08/18 85% 15% Chronically infected Clear the infection HEPATITIS C
- 18. 1818 02/08/1802/08/18 Hepatitis C Diagnosis Sixty to 70% of persons newly infected with HCVSixty to 70% of persons newly infected with HCV typically are usually asymptomatic or have a mildtypically are usually asymptomatic or have a mild clinical illness.clinical illness. HCV RNA can be detected in blood within 1–3HCV RNA can be detected in blood within 1–3 weeks after exposure.weeks after exposure. The average time from exposure to antibody toThe average time from exposure to antibody to HCV (anti-HCV) seroconversion is 8–9 weeks,HCV (anti-HCV) seroconversion is 8–9 weeks, and anti-HCV can be detected in >97% of personsand anti-HCV can be detected in >97% of persons by 6 months after exposure.by 6 months after exposure.
- 19. 1919 02/08/1802/08/18 Hepatitis C Treatment Interferon-based therapy is currently theInterferon-based therapy is currently the standard of care for patients with chronicstandard of care for patients with chronic HCV, and has been proven to be effectiveHCV, and has been proven to be effective in eliminating HCV.in eliminating HCV. Both conventional and pegylated interferonBoth conventional and pegylated interferon (IFN) therapy have been used widely, with(IFN) therapy have been used widely, with the aim of achieving a sustained virologicalthe aim of achieving a sustained virological response (SVR).response (SVR).
- 20. 2020 02/08/1802/08/18 Hepatitis C Prevention Unlike HBV, there is currently no vaccineUnlike HBV, there is currently no vaccine for HCV.for HCV. However, with the screening of HCV inHowever, with the screening of HCV in blood transfusion services, transfusion-blood transfusion services, transfusion- related HCV infection has been lowered torelated HCV infection has been lowered to almost zero.almost zero.
- 22. 2222 02/08/1802/08/18 Newer drugs- Interferon free. HARVONI (ledipasvir/sofosbuvirHARVONI (ledipasvir/sofosbuvir simeprevir (OLYSIOsimeprevir (OLYSIO VIEKIRA PAKVIEKIRA PAK (ombitasvir/paritaprevir/ritonavir(ombitasvir/paritaprevir/ritonavir tablets; dasabuvir tablets)tablets; dasabuvir tablets) EPCLUSA (sofosbuvirEPCLUSA (sofosbuvir 400mg/velpatasvir 100 mg)- All400mg/velpatasvir 100 mg)- All genotypes.genotypes.
- 23. 2323 02/08/1802/08/18 Hepatitis C Prevention It may be possible to develop a preventive vaccineIt may be possible to develop a preventive vaccine for HCV:for HCV: 30% of persons clear the virus spontaneously30% of persons clear the virus spontaneously The genome of HCV is not integrated into the hostThe genome of HCV is not integrated into the host genomegenome After HCV infection, CD-8 CTL responses andAfter HCV infection, CD-8 CTL responses and antibodies appear, but the “protective immuneantibodies appear, but the “protective immune response” or critical epitopes are not knownresponse” or critical epitopes are not known Persons who clear HCV and become re-infected havePersons who clear HCV and become re-infected have low viral loads and are more likely to clear HCVlow viral loads and are more likely to clear HCV
- 24. 2424 02/08/1802/08/18 Hepatitis C and HIV 30 - 40% of HIV+ people in US also30 - 40% of HIV+ people in US also infected with Hep Cinfected with Hep C More rapid progression of Hep C (twice asMore rapid progression of Hep C (twice as fast)fast) Little to no affect on HIV progression (stillLittle to no affect on HIV progression (still inconclusive)inconclusive) Complications of medication regimensComplications of medication regimens Increases risk of perinatal transmissionIncreases risk of perinatal transmission
- 27. 2727 02/08/1802/08/18 Hepatitis D Dependovirus,Dependovirus, it is defective and cannotit is defective and cannot produce infection unless the cell is alsoproduce infection unless the cell is also infected with HBV.infected with HBV. ViroidViroid - a naked strand of RNA that enters- a naked strand of RNA that enters the cell in piggy-back fashion.the cell in piggy-back fashion.
- 28. 2828 02/08/1802/08/18 Hepatitis D Clinical Manifestations Dual infection is more severe than HBVDual infection is more severe than HBV fulminating hepatitisfulminating hepatitis severe rapidly progressive hepatitissevere rapidly progressive hepatitis severe exacerbationssevere exacerbations
- 29. 2929 02/08/1802/08/18 Hepatitis D Epidemiology hemophiliacs and IV drug usershemophiliacs and IV drug users Contaminated blood and blood productsContaminated blood and blood products
- 30. 3030 02/08/1802/08/18 Hepatitis D Diagnosis Clinical manifestationsClinical manifestations Delta antigenDelta antigen ImmunofluorescenceImmunofluorescence RIARIA ELISAELISA Anti delta antigenAnti delta antigen same as abovesame as above
- 31. 3131 02/08/1802/08/18 Hepatitis E Levels of Endemicity, 2010 Source: CDC DVHSource: CDC DVH
- 32. 3232 02/08/1802/08/18 Hepatitis E The highest attack rate is seen among persons aged 15-40The highest attack rate is seen among persons aged 15-40 years.years. In most hepatitis E outbreaks, the highest rates of clinicallyIn most hepatitis E outbreaks, the highest rates of clinically evident disease have been in young to middle-age adults; lowerevident disease have been in young to middle-age adults; lower disease rates in younger age groups may be the result of an ictericdisease rates in younger age groups may be the result of an icteric and/or subclinical HEV infection.and/or subclinical HEV infection. The case fatality rate overall is 1%-3%.The case fatality rate overall is 1%-3%. In pregnant women, the case fatality rate can be as high as 15%-In pregnant women, the case fatality rate can be as high as 15%- 25%.25%. HEV is found in the stool (feces) of persons and animalsHEV is found in the stool (feces) of persons and animals with hepatitis E.with hepatitis E. HEV is spread by eating or drinking contaminated food orHEV is spread by eating or drinking contaminated food or water.water. Transmission from person to person occurs less commonlyTransmission from person to person occurs less commonly than with hepatitis A virus.than with hepatitis A virus.
- 33. 3333 02/08/1802/08/18 Hepatitis B 2 billion2 billion people worldwide (1/3 world population)people worldwide (1/3 world population) have been infected with HBV (WHO)have been infected with HBV (WHO) 350 million350 million people worldwide have chronicpeople worldwide have chronic (lifelong) HBV (CDC)(lifelong) HBV (CDC) 1 million1 million people die each year from liver diseasepeople die each year from liver disease and liver cancer (CDC)and liver cancer (CDC) Every 30–45 seconds, one person dies from theEvery 30–45 seconds, one person dies from the vaccine-preventable HBVvaccine-preventable HBV
- 36. 3636 02/08/1802/08/18 Swaziland(2009-2011) Retrospective chart review among 1282Retrospective chart review among 1282 HIV ptsHIV pts Overall 3.7%Overall 3.7% Children 1.5%Children 1.5% Adults 5.1% ( Men 9.8%Vs 4.2%)Adults 5.1% ( Men 9.8%Vs 4.2%) Prevalence under 5 was 0.4%Prevalence under 5 was 0.4%
- 41. 4141 02/08/1802/08/18 Hepatitis B Source: J Viral Hepat. 2010 Apr;17(4):229-35. Hepatitis B virus: origin and evolution.Source: J Viral Hepat. 2010 Apr;17(4):229-35. Hepatitis B virus: origin and evolution.
- 43. 4343 02/08/1802/08/18 Transmission Parenterally ie via blood, saliva, menstrualParenterally ie via blood, saliva, menstrual and vaginal discharges, semen and breastand vaginal discharges, semen and breast milkmilk infected blood and blood productsinfected blood and blood products sexual contactsexual contact perinatally from mother to childperinatally from mother to child
- 48. 4848 02/08/1802/08/18 Incubation period The incubation period from the time of exposureThe incubation period from the time of exposure to onset of symptoms is 6 weeks to 6 months.to onset of symptoms is 6 weeks to 6 months. HBV is found in highest concentrations in bloodHBV is found in highest concentrations in blood and in lower concentrations in other body fluidsand in lower concentrations in other body fluids (e.g., semen, vaginal secretions, and wound(e.g., semen, vaginal secretions, and wound exudates).exudates). Communicability highest 1-2 months beforeCommunicability highest 1-2 months before symptoms and after.symptoms and after. Reservoir is human.Reservoir is human.
- 49. 4949 02/08/1802/08/18 There areThere are 10x10x more people with chronicmore people with chronic HBV than HIV/AIDS worldwide (WHO)HBV than HIV/AIDS worldwide (WHO) HBV isHBV is 50-100x50-100x more infectious than HIVmore infectious than HIV (WHO)(WHO) HBV can survive outside the body for atHBV can survive outside the body for at leastleast 7 days7 days (WHO)(WHO) Virulence
- 50. 5050 02/08/1802/08/18 Perinatal Transmission Most infections occur from mother toMost infections occur from mother to childchild OverOver 90%90% of babies infected during theof babies infected during the first year of life develop chronicfirst year of life develop chronic infection (CDC)infection (CDC)
- 52. 5252 02/08/1802/08/18 Hepatitis B Diagnosis Hepatitis B is detected by looking for a number ofHepatitis B is detected by looking for a number of different antigens and antibodies:different antigens and antibodies: Hepatitis B surface antigen (HBsAg):Hepatitis B surface antigen (HBsAg): A protein on the surface of HBV; it can be detected in highA protein on the surface of HBV; it can be detected in high levels in serum during acute or chronic HBV infection.levels in serum during acute or chronic HBV infection. The presence of HBsAg indicates that the person is infectious.The presence of HBsAg indicates that the person is infectious. The body normally produces antibodies to HBsAg as part ofThe body normally produces antibodies to HBsAg as part of the normal immune response to infection.the normal immune response to infection. HBsAg is the antigen used to make Hepatitis B vaccine.HBsAg is the antigen used to make Hepatitis B vaccine.
- 53. 5353 02/08/1802/08/18 Hepatitis B Diagnosis Hepatitis B is detected by looking for a number ofHepatitis B is detected by looking for a number of different antigens and antibodies:different antigens and antibodies: Hepatitis B surface antibody (anti-HBs):Hepatitis B surface antibody (anti-HBs): TThe presence of anti-HBs is generally interpreted as indicatinghe presence of anti-HBs is generally interpreted as indicating recovery and immunity from HBV infection.recovery and immunity from HBV infection. Anti-HBs also develops in a person who has been successfullyAnti-HBs also develops in a person who has been successfully vaccinated against Hepatitis B.vaccinated against Hepatitis B. Total Hepatitis B core antibody (anti-HBc):Total Hepatitis B core antibody (anti-HBc): Appears at the onset of symptoms in acute Hepatitis B andAppears at the onset of symptoms in acute Hepatitis B and persists for life.persists for life. The presence of anti-HBc indicates previous or ongoingThe presence of anti-HBc indicates previous or ongoing infection with HBV in an undefined time frame.infection with HBV in an undefined time frame.
- 54. 5454 02/08/1802/08/18 Hepatitis B Diagnosis Hepatitis B is detected by looking for a number ofHepatitis B is detected by looking for a number of different antigens and antibodies:different antigens and antibodies: IgM antibody to Hepatitis B core antigen (IgM anti-IgM antibody to Hepatitis B core antigen (IgM anti- HBc):HBc): Positivity indicates recent infection with HBV (≤6 months).Positivity indicates recent infection with HBV (≤6 months). Its presence indicates acute infection.Its presence indicates acute infection. Hepatitis B e antigen (HBeAg):Hepatitis B e antigen (HBeAg): A secreted product of the nucleocapsid gene of HBV that isA secreted product of the nucleocapsid gene of HBV that is found in serum during acute and chronic Hepatitis B.found in serum during acute and chronic Hepatitis B. Its presence indicates that the virus is replicating and theIts presence indicates that the virus is replicating and the infected person has high levels of HBV.infected person has high levels of HBV.
- 55. 5555 02/08/1802/08/18 Hepatitis B Diagnosis Hepatitis B is detected by looking for a number ofHepatitis B is detected by looking for a number of different antigens and antibodies:different antigens and antibodies: Hepatitis B e antibody (HBeAb or anti-HBe):Hepatitis B e antibody (HBeAb or anti-HBe): Produced by the immune system temporarily during acuteProduced by the immune system temporarily during acute HBV infection or consistently during or after a burst in viralHBV infection or consistently during or after a burst in viral replication.replication. Spontaneous conversion from e antigen to e antibody (aSpontaneous conversion from e antigen to e antibody (a change known as seroconversion) is a predictor of long-termchange known as seroconversion) is a predictor of long-term clearance of HBV in patients undergoing antiviral therapy andclearance of HBV in patients undergoing antiviral therapy and indicates lower levels of HBV.indicates lower levels of HBV.
- 56. 5656 02/08/1802/08/18 Hepatitis B Diagnosis Electron microscopyElectron microscopy Viral DNA polymeraseViral DNA polymerase Viral DNA probesViral DNA probes SerologySerology
- 57. 5757 02/08/1802/08/18 Hepatitis B Characteristics A Hepadnaviridae – partially double-stranded DNAA Hepadnaviridae – partially double-stranded DNA virusvirus HBsAg – stimulates protective antibodies, a markerHBsAg – stimulates protective antibodies, a marker for current infectionfor current infection HBcAg – localized within liver cells, identifies acuteHBcAg – localized within liver cells, identifies acute infection, anti-HBcAg persists for life and is a markerinfection, anti-HBcAg persists for life and is a marker of past infectionof past infection HBeAG – a marker of active replication andHBeAG – a marker of active replication and infectivityinfectivity
- 58. 5858 02/08/1802/08/18 Hepatitis B Host Defenses Cell mediated ImmunityCell mediated Immunity important for recover in acute phaseimportant for recover in acute phase autoimmune liver damage in chronic infectionsautoimmune liver damage in chronic infections Humoral ImmunityHumoral Immunity not always protectivenot always protective HBsAg for VaccinesHBsAg for Vaccines InterferonInterferon not detected during infectionnot detected during infection exogenous application effectiveexogenous application effective
- 61. 6161 02/08/1802/08/18 Hepatitis B Typical interpretation of serologic test results for hepatitis B virus infection Source: MMWR Recomm Rep. 2006; 55(RR-16):1–25.Source: MMWR Recomm Rep. 2006; 55(RR-16):1–25.
- 63. 6363 02/08/1802/08/18 Factors for progression to Chronic Disease Persistently elevated levels of HBV DNA and,Persistently elevated levels of HBV DNA and, ALTALT Male sexMale sex Older ageOlder age Family history of HCCFamily history of HCC Alcohol useAlcohol use Elevated alpha-fetoprotein (AFP)Elevated alpha-fetoprotein (AFP) Coinfection with hepatitis D (delta) virus (HDV),Coinfection with hepatitis D (delta) virus (HDV), hepatitis C virus (HCV), or humanhepatitis C virus (HCV), or human immunodeficiency virus (HIV)immunodeficiency virus (HIV)
- 64. 6464 02/08/1802/08/18 10% 90% Chronically infected Clear the infection HEPATITIS B
- 65. 6565 02/08/1802/08/18 Chronic carriers 10-20% chronic carriers10-20% chronic carriers 12% develop liver cirrhosis annually12% develop liver cirrhosis annually 5% develop hepatocellular carcinoma5% develop hepatocellular carcinoma Absolute lifetime death from HCC or cirrhosisAbsolute lifetime death from HCC or cirrhosis is 15-25%is 15-25% HCC risk is 6% every 5 yearsHCC risk is 6% every 5 years Decompesation risk is 21% every 5 years.Decompesation risk is 21% every 5 years.
- 67. 6767 02/08/1802/08/18 Complications Fulminant HepatitisFulminant Hepatitis HospitalizationHospitalization CirrhosisCirrhosis Hepatocellular CarcinomaHepatocellular Carcinoma Systemic vasculitisSystemic vasculitis Polyarteritis nodosaPolyarteritis nodosa GlumerulonephritisGlumerulonephritis
- 68. 6868 02/08/1802/08/18 HCC Worldwide, HBV is the primary cause ofWorldwide, HBV is the primary cause of liver cancerliver cancer For males, it is the third leading cause of cancerFor males, it is the third leading cause of cancer mortalitymortality For females, it is the sixth leading cause ofFor females, it is the sixth leading cause of cancer mortalitycancer mortality
- 69. 6969 02/08/1802/08/18 Hepatitis B Control No specific controlNo specific control Passive ImmunizationPassive Immunization HBV immunoglobulinHBV immunoglobulin 250-500 IU within 48 hours250-500 IU within 48 hours neonates of infected mothers -immediately afterneonates of infected mothers -immediately after birthbirth Active ImmunizationActive Immunization HBsAgHBsAg recombinant DNA in yeastrecombinant DNA in yeast
- 70. 7070 02/08/1802/08/18 Hepatitis B Treatment For acute infection, no medication is available;For acute infection, no medication is available; treatment is supportive.treatment is supportive. For chronic infection, several antiviral drugsFor chronic infection, several antiviral drugs (adefovir dipivoxil, interferon alfa-2b, pegylated(adefovir dipivoxil, interferon alfa-2b, pegylated interferon alfa-2a, lamivudine, entecavir, andinterferon alfa-2a, lamivudine, entecavir, and telbivudine, Tenofovir) are available.telbivudine, Tenofovir) are available. Persons with chronic HBV infection require medicalPersons with chronic HBV infection require medical evaluation and regular monitoring to determine whetherevaluation and regular monitoring to determine whether disease is progressing and to identify liver damage ordisease is progressing and to identify liver damage or hepatocellular carcinoma.hepatocellular carcinoma.
- 71. 7171 02/08/1802/08/18 Hepatitis B Elimination WHO’s national strategy to eliminate transmissionWHO’s national strategy to eliminate transmission of HBV infection includes:of HBV infection includes: Prevention of perinatal infection through routinePrevention of perinatal infection through routine screening of all pregnant women for HBsAg andscreening of all pregnant women for HBsAg and immunoprophylaxis of infants born to HBsAg-positiveimmunoprophylaxis of infants born to HBsAg-positive mothers and infants born to mothers with unknownmothers and infants born to mothers with unknown HBsAg statusHBsAg status Routine infant vaccinationRoutine infant vaccination VaccinationVaccination of previously unvaccinated children andof previously unvaccinated children and adolescents through age 18 yearsadolescents through age 18 years Vaccination of previously unvaccinated adults atVaccination of previously unvaccinated adults at increased risk for infectionincreased risk for infection
- 73. 7373 02/08/1802/08/18 HBV Vaccination Newborns born to infected mothers shouldNewborns born to infected mothers should be vaccinated (1be vaccinated (1stst dose vaccine + HBIG)dose vaccine + HBIG) withinwithin 12 hours12 hours of birthof birth 3 vaccine doses: month3 vaccine doses: month 0, 1, 60, 1, 6
- 76. 7676 02/08/1802/08/18 Swaziland Children – 6, 10,14 weeksChildren – 6, 10,14 weeks Pentavalent Vaccine( DPT-Hib-HepB)Pentavalent Vaccine( DPT-Hib-HepB) Adults- First contact, 4 weeks,4 weeksAdults- First contact, 4 weeks,4 weeks
- 87. 8787 02/08/1802/08/18 Interferon Its better in certain circumstancesIts better in certain circumstances Its use is limited byIts use is limited by Side effectsSide effects ExpenseExpense Presence of decompensated cirrhosisPresence of decompensated cirrhosis Autoimmune diseasesAutoimmune diseases PregnancyPregnancy Infants below one yearInfants below one year
- 92. 9292 02/08/1802/08/18 Complications Fulminant HepatitisFulminant Hepatitis HospitalizationHospitalization CirrhosisCirrhosis Hepatocellular CarcinomaHepatocellular Carcinoma Systemic vasculitisSystemic vasculitis Polyarteritis nodosaPolyarteritis nodosa GlumerulonephritisGlumerulonephritis
- 93. 9393 02/08/1802/08/18 Conclusion Hepatitis Viruses are commonHepatitis Viruses are common Hepatitis B and Hepatitis B are highlyHepatitis B and Hepatitis B are highly infectious and lead to chronic liver diseaseinfectious and lead to chronic liver disease Vaccines exist for HAV and HBVVaccines exist for HAV and HBV HCV is potentially curable with treatment.HCV is potentially curable with treatment.
Editor's Notes
- HBV is transmitted like HIV- by blood or body fluid. 33.4 million people live with HIV/AIDS worldwide, but 350 million people live with chronic HBV.
- On Dec 2006, CDC & ACIP recommended that all adults born in Asia and the Pacific should be tested for HBV