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25 Hepatitis Virus Viral Hepatitis - Historical Perspective Enterically E transmitted “Infectious” A Viral hepatitis “Serum” NANB Parenterally C transmitted B D F, G, ? other Viral Hepatitis - Overview Type of Hepatitis A Source of virus feces Route of transmission Chronic infection Prevention B C D blood/ blood/ blood/ blood-derived blood-derived blood-derived body fluids body fluids body fluids E feces fecal-oral percutaneous percutaneous percutaneous fecal-oral permucosal permucosal permucosal no pre/postexposure immunization yes yes yes no pre/post- blood donor pre/post- ensure safe exposure screening; exposure drinking immunization risk behavior immunization; water risk behavior modification modification HEPATITIS A VIRUS HEPATITIS A VIRUS • RNA Picornavirus Single serotype worldwide Acute disease and asymptomatic infection • No chronic infection Protective antibodies develop in response to infection - confers lifelong immunity HEPATITIS A - CLINICAL FEATURES •Jaundice by age group: <6 yrs 6-14 yrs >14 yrs <10% 40%-50% 70%-80% •Rare complications: Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis •Incubation period: Average 30 days Range 15-50 days •Chronic sequelae: None EVENTS IN HEPATITIS A VIRUS INFECTION Clinical illness Infection ALT Response IgM IgG Viremia HAV in stool 0 1 2 3 4 5 6 Week 7 8 9 10 11 12 13 CONCENTRATION OF HEPATITIS A VIRUS IN VARIOUS BODY FLUIDS Body Fluids Feces Serum Saliva Urine 100 102 104 106 Infectious Doses per mL 108 1010 HEPATITIS A VIRUS TRANSMISSION • Close personal contact (e.g., household contact, sex contact, child day-care centers) • Contaminated food, water (e.g., infected food handlers) • Blood exposure (rare) (e.g., injection drug use, rarely by transfusion) PREVENTING HEPATITIS A • Hygiene (e.g., hand washing) • Sanitation (e.g., clean water sources) • Hepatitis A vaccine (pre-exposure) attenuated virus or inactivated virus • Immune globulin (pre- and post-exposure) Hepatitis E Virus •HEV is a 30-32nm non-enveloped particle containing a s/s (+)sense RNA genome of ~7.5Kb. •Genetic organization similar (not identical) to Caliciviruses: Hepatitis E - Clinical Features • Incubation period: • Case-fatality rate: Average 40 days Range 15-60 days Overall, 1%-3% Pregnant women, 5%25% • Illness severity: Increased with age • Chronic sequelae: None identified Hepatitis E Virus Infection Typical Serologic Course Symptoms ALT IgG anti-HEV Titer IgM anti-HEV Virus in stool 0 1 2 3 4 5 6 Weeks after Exposure 7 8 9 1 0 1 1 1 2 1 3 Hepatitis E Epidemiologic Features • Most outbreaks associated with fecally contaminated drinking water • Minimal person-to-person transmission Prevention and Control Measures for Travelers to HEV-Endemic Regions • Avoid drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruit/vegetables not peeled or prepared by traveler • IG prepared from donors in Western countries does not prevent infection • Unknown efficacy of IG prepared from donors in endemic areas • Vaccine? Hepatitis B - Clinical Features • Incubation period: Average 60-90 days Range 45-180 days • Clinical illness (jaundice): <5 yrs, <10% ³5 yrs, 30%-50% • Acute case-fatality rate: • Chronic infection: 0.5%-1% <5 yrs, 30%-90% ³5 yrs, 2%-10% (350m ) carrier state • Premature mortality from chronic liver disease: 15%-25% Acute Viral Hepatitis Source: CDC Hepatitis B Virus secreted sphere hepatitis B virion secreted filament • Baruch Blumberg, 1963: ‘Australian antigen - Au'. • 1967: Au was a viral antigen = HBsAg (surface antigen) • Dane, 1970: Discovered 42nm 'Dane particles‘ HBcAg (core antigen). • 1973: HBeAg discovered (endogenous antigen = a truncated version of HBcAg). • spherical, • enveloped (? lipid-containing, detergent disrupted ?) • 42-47nm diameter • d/s DNA • an RNA-dependent DNA polymerase (i.e. reverse transcriptase) • family Hepadnaviridae HBV genome organization two uneven strands of DNA: (-)sense strand: 3.0 - 3.3kb (+)sense strand: 1.7 - 2.8kb The HBV infectious cycle Reverse transcription P protein Capsid protein ER/IC e Golgi cap RNA pregenome RNA ccc-DNA Precore, L, M, S + X proteins four open reading frames (ORFs) : S,C,P,X • S – HBsAg • C – HBcAg C + preC – HBeAg • P – polymerase • X – HBxAg (a transcriptional transactivator) HBsAg & anti-HBs • HBsAg is an envelope protein & an poor immunogen -------- replication • recovery of acute HBV infection is characterized by HBsAg/anti-HBs seroconversion • passively acquired anti-HBs protects individuals from infection with HBV • Anti-HBs is not strictly a ‘neutralizing’ antibody HBcAg & anti-HBc • HBcAg is not detectable in the sera of some patients. • immunogen • IgM anti-HBc – virus replication, acute infection, transient response • IgG anti-HBc – do not protect individuals, chronic infections, alst for a long time HBeAg & anti-HBe • HBeAg is produced when virus is replicating. • HBeAg is correlated strongly with the detection of viral DNA, virons and the viral DNA polymerase in the serum. • The disappearace of HBeAg and replacement with anti-Hbe indicates that the patient is responding to the infection and will clear HBsAg. Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Symptoms anti-HBe HBeAg Total anti-HBc Titer HBsAg 0 4 8 anti-HBs IgM anti-HBc 12 16 20 24 28 32 36 Weeks after 52 100 Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course Acute (6 months) Chronic (Years) HBeAg anti-HBe HBsAg Total antiHBc Titer IgM anti-HBc 0 4 8 12 16 20 24 28 32 36 Weeks after Exposure 52 Years Summary Hepatitis B Lab Tests (1) • HBV: Hepatitis B virus. • HBsAg: Hepatitis B surface antigen. Marker of infectivity when found in serum. • anti-HBs: Antibody to HBsAg. Marker of immunity when found in serum. • HBcAg: Hepatitis B core antigen. No commercial test available for this. • anti-HBc: Antibody HBcAg. Marker of past or current infection. Hepatitis B Lab Tests (2) • IgM anti-HBc: IgM is an antibody subclass of anti-HBc. Indicates recent infection with HBV (<4-6 mos.). • IgG anti-HBc: IgG is a subclass of anti-HBc. Indicates “older” infection with HBV. • HBeAg: Hepatitis B “e” antigen. Can only be present if HBsAg is positive. Marker of high degree of infectivity. • Anti-HBe: Antibody to “e” antigen. May be present in infected or immune person. Interpretation of Hepatitis B Panel HBsAg antiHBc antiHBs negative negative negative susceptible HBsAg antiHBc antiHBs negative positive positive immune due to natural infection HBsAg antiHBc antiHBs negative negative positive immune due to vaccine HBsAg antiHBc IgM antiHBc antiHBs positive positive positive negative HBsAg antiHBc IgM antiHBc antiHBs positive positive negative negative HBsAg antiHBc antiHBs negative positive negative acutely infected chronically infected four possible interpretations (see next slide) Four possible interpretations of isolated antiHBc positive 1. May be recovering from acute HBV infection. 2. May be distantly immune and test not sensitive enough to detect very low level of anti-HBs in serum. 3. May be susceptible with a false positive anti-HBc. 4. May be undetectable level of HBsAg present in the serum and the person is actually a carrier. Concentration of Hepatitis B Virus in Various Body Fluids High Moderate blood semen serum vaginal fluid wound exudates saliva Low/Not Detectable urine feces sweat tears breastmilk Main Ways to Get Hepatitis B Having sex without condoms with someone who has hepatitis B Sexual Being born to a mother who has hepatitis B Perinatal Sharing needles and syringes Parenteral You can pass hepatitis B to others if you have just gotten the virus (acute hepatitis) or if you are a carrier of the virus (chronic hepatitis). How does a baby get hepatitis B from mother? • If you have hepatitis B and a tiny bit of your blood gets inside your baby at birth. CONTROL Passive immunization • Hyperimmune hepatitis B immunoglobulin HBIG Active immunization • Vaccine HBsAg Hepatitis B can be prevented! If you have never had hepatitis B, you can get 3 shots . . . 1 2 3 . . . and get long lasting protection. Baby Shots for Hepatitis B if the mother has Hepatitis B 1 - 2 months old Birth Hepatitis B Vaccine + Hepatitis B Vaccine H-BIG 6 months old Hepatitis B Vaccine Hepatitis D (Delta) Virus d antigen HBsAg RNA Hepatitis D - Clinical Features • Coinfection –severe acute disease –low risk of chronic infection • Superinfection –usually develop chronic HDV infection –high risk of severe chronic liver disease Hepatitis D Virus Modes of Transmission • Percutanous exposures –injecting drug use • Permucosal exposures –sex contact Hepatitis D - Prevention • HBV-HDV Coinfection Pre or postexposure prophylaxis to prevent HBV infection • HBV-HDV Superinfection Education to reduce risk behaviors among persons with chronic HBV infection Hepatitis C Flaviviridae a positive-sense RNA molecule 9.5kb in length Features of Hepatitis C Virus Infection Incubation period Acute illness (jaundice) Case fatality rate Chronic infection Chronic hepatitis Agerelated Cirrhosis Mortality from CLD Average 6-7 weeks Range 2-26 weeks Mild (<20%) Low 60%-85% 10%-70% <5%-20% 1%-5% Serologic Pattern of Acute HCV Infection with Recovery antiHCV Symptoms +/- Titer HCV RNA ALT Normal 0 1 2 3 4 Months 5 6 1 2 3 Years Time after Exposure 4 Serologic Pattern of Acute HCV Infection with Progression to Chronic Infection antiHCV Symptoms +/- Titer HCV RNA ALT Normal 0 1 2 3 4 Months 5 6 1 2 3 Years Time after Exposure 4 HCV Prevention and Control Reduce or Eliminate Risks for Acquiring HCV Infection • Screen and test donors • Virus inactivation of plasma-derived products • Risk-reduction counseling and services – Obtain history of high-risk drug and sex behaviors – Provide information on minimizing risky behavior, including referral to other services – Vaccinate against hepatitis A and/or hepatitis B • Safe injection and infection control practices Preventing HCV Transmission to Others Avoid Direct Exposure to Blood • Do not donate blood, body organs, other tissue or semen • Do not share items that might have blood on them – personal care (e.g., razor, toothbrush) – home therapy (e.g., needles) • Cover cuts and sores on the skin HCV Counseling Other Transmission Issues • HCV not spread by kissing, hugging, sneezing, coughing, food or water, sharing eating utensils or drinking glasses, or casual contact • Do not exclude from work, school, play, child-care or other settings based on HCV infection status