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Out line • • • • • • • • Overview of viral hepatitis Structure of HBV Distribution Transmission Possible out come of Hepatitis infection Serological course of acute and chronic infection Laboratory Diagnosis/interpretation Treatment \Prevention 2 Introduction • Hepatitis = 'inflammation of the liver'. • Five medically important viruses are commonly described as “hepatitis viruses”: HAV,HBV,HCV,HDV,HEV. 3 Overview of Viral hepatitis 4 Hepatitis B Virus 5 HBV : Structure 6 Hepatitis B In the World • An estimated 240 million people are chronically infected with hepatitis B. • More than 780 000 people die every year due to complications of hepatitis B, including cirrhosis and liver cancer 7 8 3、HBV: Modes of Transmission Parenteral - IV drug abusers, health workers are at increased risk. Sexual - sex workers and homosexuals are particular at risk. Perinatal(Vertical) - mother(HBeAg+) →infant. 9 High-risk groups for HBV infection • • • • • People from endemic regions Babies of mothers with chronic HBV Intravenous drug abusers People with multiple sex partners patients requiting blood and blood product treatments • Health care personnel who have contact with blood 10 6、Clinical Features Incubation period: Average 60-90 days Range 45-180 days Insidious onset of symptoms. Tends to cause a more severe disease than Hepatitis A. Clinical illness (jaundice): <5 yrs, <10% ≥ 5 yrs, 30%-50% 1/3 adults-no symptoms Clinical Illness at presentation 10 - 15% Acute case-fatality rate: Chronic infection: infections Premature mortality from chronic liver disease: 0.5%-1% < 5 yrs, 30%-90% ≥ 5 yrs, 2%-10% More likely in ansymptomatic 15%-25% 11 Possible Outcomes of HBV Infection Acute hepatitis B infection 3-5% of adultacquired infections 95% of infantacquired infections Chronic HBV infection Chronic hepatitis 12-25% in 5 years 6-15% in 5 years Cirrhosis Hepatocellular carcinoma Death 20-23% in 5 years Liver failure Liver transplant Death 12 Typical Serological Markers for Acute Hepatitis B Infection Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Titer 0 4 8 12 16 20 24 28 32 36 52 100 Weeks after Exposure 14 Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Titer HBsAg 0 4 8 12 16 20 24 28 32 36 52 100 Weeks after Exposure 15 Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course HBeAg Titer HBsAg 0 4 8 12 16 20 24 28 32 36 52 100 Weeks after Exposure 16 Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course HBeAg anti-HBe Titer HBsAg 0 4 8 12 16 20 24 28 32 36 52 100 Weeks after Exposure 17 Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Symptoms HBeAg anti-HBe Titer HBsAg 0 4 8 12 16 20 24 28 32 36 52 100 Weeks after Exposure 18 Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Symptoms HBeAg anti-HBe Titer IgM anti-HBc HBsAg 0 4 8 12 16 20 24 28 32 36 52 100 Weeks after Exposure 19 Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Symptoms HBeAg Titer anti-HBe IgG anti-HBc IgM anti-HBc HBsAg 0 4 8 12 16 20 24 28 32 36 52 100 Weeks after Exposure 20 Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Symptoms HBeAg Titer anti-HBe IgG anti-HBc IgM anti-HBc anti-HBs HBsAg 0 4 8 12 16 20 24 28 32 36 52 100 Weeks after Exposure 21 Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Symptoms HBeAg Titer anti-HBe IgG anti-HBc IgM anti-HBc anti-HBs HBsAg Window Period 0 4 8 12 16 20 24 28 32 36 52 100 Weeks after Exposure 22 Typical Serological Markers for Chronic Hepatitis B Infection Chronic Hepatitis B Virus Infection Typical Serologic Course Titer HBsAg 0 1 2 3 4 5 6 7 8 9 10 Years After Exposure 24 Chronic Hepatitis B Virus Infection Typical Serologic Course Titer HBsAg IgM, anti-HBc 0 1 2 3 4 5 6 7 8 9 10 Years After Exposure 25 Chronic Hepatitis B Virus Infection Typical Serologic Course HBsAg Titer IgG anti-HBc 0 1 2 3 4 5 6 7 8 9 10 Years After Exposure 26 Chronic Hepatitis B Virus Infection Typical Serologic Course HBeAg HBsAg Titer IgG anti-HBc 0 1 2 3 4 5 6 7 8 9 10 Years After Exposure 27 Chronic Hepatitis B Virus Infection Typical Serologic Course HBeAg Anti-HBe HBsAg Titer IgG anti-HBc 0 1 2 3 4 5 6 7 8 9 10 Years After Exposure 28 Acute vs. Chronic HBV Infection Acute • HBsAg+ < 6 mos. • IgM anti-HBc + positive • Infection will resolve and person will have lifelong immunity • HBsAb+ and HBcAb+ Chronic • HBsAg + for at least 6 months • Also known as a “carrier” • Infection does not resolve and the person remains infectious • HBsAb- and HBcAB+ 29 Laboratory Tests for HBV • Serology: – Many tests available – most common tests are Enzyme Immunoassays (like ELSA, CLIA) • Molecular: – HBV DNA (quantitative) – HBV resistance testing 30 Hepatitis B – Laboratory Tests Serologic markers: 1) HBsAg (Hepatitis B surface antigen): • if positive, person is infectious 2) Anti-HBs (Antibody to HBV surface antigen): • indicates immunity to HBV and protection from disease 31 Hepatitis B – Laboratory Tests Serologic markers: 3) Anti - HBc (Antibody to HBV core antigen): • Total - indicates past or active infection; present whether person is immune or chronic carrier • IgM - early indicator of acute infection • No antigen test 32 Hepatitis B – Laboratory Tests Serologic markers: 4) HBeAg (Hepatitis Be antigen): • indicates person is highly infectious 5) Anti-HBe (Antibody to HBVe antigen): • prognostic for resolution of infection; less infectious; 33 Interpretation of serological tests 34 Interpretation of Serological Tests Test HBsAg anti-HBc anti-HBs Results Negative Negative Negative Interpretation ??? 35 Interpretation of Serological Tests Test HBsAg anti-HBc anti-HBs Results Negative Negative Negative Interpretation Susceptible (Never infected or vaccinated) 36 Interpretation of Serological Tests Test HBsAg anti-HBc anti-HBs Results Negative Negative Positive Interpretation ??? 37 Interpretation of Serological Tests Test HBsAg anti-HBc anti-HBs Results Negative Negative Positive Interpretation Immune (Due to vaccine) 38 Interpretation of Serological Tests Test HBsAg anti-HBc anti-HBs Results Negative Positive Positive Interpretation ??? 39 Interpretation of Serological Tests Test HBsAg anti-HBc anti-HBs Results Negative Positive Positive Interpretation Immune (Resolved Infection) 40 Interpretation of Serological Tests Test HBsAg anti-HBc IgM anti-HBc anti-HBs Results Positive Positive Positive Negative Interpretation ??? 41 Interpretation of Serological Tests Test HBsAg anti-HBc IgM anti-HBc anti-HBs Results Positive Positive Positive Negative Interpretation Acutely Infected 42 Interpretation of Serological Tests Test HBsAg anti-HBc anti-HBs IgM anti-HBc Results Positive Positive Negative Negative Interpretation ??? 43 Interpretation of Serological Tests Test HBsAg anti-HBc anti-HBs IgM anti-HBc Results Positive Positive Negative Negative Interpretation Chronically Infected 44 Interpretation of Serological Tests Test HBsAg anti-HBc anti-HBs Results Negative Positive Negative Interpretation ??? 45 Interpretation of Serological Tests Test HBsAg anti-HBc anti-HBs Results Negative Positive Negative Interpretation Four Possible Interpretations 1. Resolved infections (most common) 2. False Positive Anti HBc 3. ‘low level’ Chronic infection 4. Resolving Acute infections 46 Treatment • Interferon • Lamivudine (Epivir HBV) (relapse ,drug resistance) • Adefovir dipivoxil (Hepsera) 47 Prevention • Vaccination - highly effective recombinant vaccines • Hepatitis B Immunoglobulin (HBIG) -exposed within 48 hours of the incident/ neonates whose mothers are HBsAg and HBeAg positive. • Other measures -screening of blood donors, blood and body fluid precautions. 48