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Unit 4 Part 4 Hepatitis A-E Viruses

Unit 4 Part 4 Hepatitis A-E Viruses. An Overview Terry Kotrla, MS, MT(ASCP)BB. Background. Viral hepatitis caused by infection by any of at least five distinct viruses. Hepatitis A, B and C most common ones identified in US. Produce acute illness characterized by: Nausea Malaise

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Unit 4 Part 4 Hepatitis A-E Viruses

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  1. Unit 4Part 4 Hepatitis A-E Viruses An Overview Terry Kotrla, MS, MT(ASCP)BB

  2. Background • Viral hepatitis caused by infection by any of at least five distinct viruses. • Hepatitis A, B and C most common ones identified in US. • Produce acute illness characterized by: • Nausea • Malaise • Abdominal pain • Dark urine • Jaundice • HBV and HCV can become chronic, associated with increased risk of chronic liver disease and hepatocellular carcinoma.

  3. Viral Hepatitis - Historical Perspectives Enterically transmitted “Infectious” A E Viral hepatitis NANB Parenterally transmitted B D C “Serum” F, G, TTV ? other

  4. Summary of Viral Hepatitis A B C D E Source of feces blood/ blood/ blood/ feces virus blood-derived blood-derived blood-derived body fluids body fluids body fluids percutaneous Route of fecal-oral percutaneous percutaneous fecal-oral transmission permucosal permucosal permucosal Chronic no yes yes yes no infection Prevention pre/post- pre/post- blood donor pre/post- ensure safe exposure exposure screening; exposure drinking immunization immunization risk behavior immunization; water modification risk behavior modification

  5. Hepatitis A Virus

  6. Hepatitis A Virus • RNA virus • Humans only natural host • Can be stable in environment for months. • Children younger than 6 years of age may have asymptomatic infection (70%). • Older children and adults usually symptomatic, jaundice occurring in 70%.

  7. Hepatitis A Virus Transmission • Transmitted by close personal contact(e.g., household contact, sex contact, child day care centers) • Contaminated food, water(e.g., infected food handlers, raw shellfish) • Blood exposure (rare)(e.g., injecting drug use, transfusion)

  8. Hepatitis A - Clinical Features • Incubation period: Average 28 days Range 15-50 days • Jaundice by age group: <6 yrs, <10% 6-14 yrs, 40%-50% >14 yrs, 70%-80% • Complications: Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis • Chronic sequelae: None

  9. Hepatitis A Infection Typical Serological Course Total anti-HAV Symptoms Titer ALT Fecal HAV IgM anti-HAV 4 5 6 12 24 0 1 2 3 Months after exposure

  10. Global Patterns of Hepatitis A Virus Transmission Disease Peak Age Endemicity Rate of Infection Transmission Patterns High Low to Early Person to person; High childhood outbreaks uncommon Moderate High Late Person to person; childhood/ food and waterborne young adults outbreaks Low Low Young adults Person to person; food and waterborne outbreaks Very low Very low Adults Travelers; outbreaks uncommon

  11. Prevalence of Antibody to HAV 2006

  12. Laboratory Diagnosis • Acute infection is diagnosed by the detection of IgM anti-HAV in serum by EIA. • Generally detectable 5-10 days before onset of symtpoms. • May persist for up to 6 months. • Past infection is determined by the detection of IgG anti-HAV by EIA. • Appears during convalescence. • Present in serum forever, confers lifelong immunity. • PCR helpful during outbreaks to determine common source.

  13. Hepatitis A Vaccination Strategies Epidemiologic Considerations • Many cases occur in community-wide outbreaks • No risk factor identified for most cases • Highest attack rates in 5-14 year olds • Asymptomatic children serve as source of infection • Persons at increased risk of infection • Travelers • Homosexual men • Injecting drug users

  14. Hepatitis A Prevention - Immune Globulin • Pre-exposure • Travelers to intermediate and high HAV-endemic regions • Post-exposure (within 14 days) Routine • Household and other intimate contacts Selected situations • Institutions (e.g., day care centers) • Common source exposure (e.g., food prepared by infected food handler)

  15. Hepatitis B Virus

  16. Hepatitis B - Clinical Features • Incubation period: Average 60-90 days Range 45-180 days • Clinical illness (jaundice): <5 yrs, <10% 5 yrs, 30%-50% • Acute case-fatality rate: 0.5%-1% • Chronic infection: <5 yrs, 30%-90% 5 yrs, 2%-10% • Premature mortality fromchronic liver disease: 15%-25%

  17. Hepatitis B Diseases • DNA virus • May cause: • Chronic Persistent Hepatitis – asymptomatic • Chronic Active Hepatitis – symptomatic exacerbations of disease • Cirrhosis of liver • Hepatocellular Carcinoma • Liver failure • Death

  18. Acute HBV Infection with Recovery Typical Serologic Course Symptoms anti-HBe HBeAg Total anti-HBc Titer anti-HBs IgM anti-HBc HBsAg 0 4 8 12 16 24 28 32 52 100 20 36 Weeks after Exposure

  19. Progression to Chronic HBV Infection - Serology Acute (6 months) Chronic (Years) HBeAg anti-HBe HBsAg Total anti-HBc Titer IgM anti-HBc Years 0 4 8 16 20 24 28 36 12 32 52 Weeks after Exposure

  20. Outcome of Hepatitis B Virus Infection by Age at Infection 100 100 80 80 Chronic Infection (%) 60 60 Chronic Infection Symptomatic Infection (%) 40 40 Chronic Infection (%) 20 20 Symptomatic Infection 0 0 1-6 months 7-12 months Older Children and Adults Birth 1-4 years Age at Infection

  21. Global Patterns of Chronic HBV Infection • High (>8%): 45% of global population • lifetime risk of infection >60% • early childhood infections common • Intermediate (2%-7%): 43% of global population • lifetime risk of infection 20%-60% • infections occur in all age groups • Low (<2%): 12% of global population • lifetime risk of infection <20% • most infections occur in adult risk groups

  22. Prevalence of Chronic HBV 2006

  23. Concentration of Hepatitis B Virus in Various Body Fluids Low/Not High Moderate Detectable blood semen urine serum vaginal fluid feces wound exudates saliva sweat tears breastmilk

  24. Hepatitis B Virus Modes of Transmission • Sexual - sex workers and homosexuals are particular at risk. • Parenteral - IVDA, Health Workers are at increased risk. • Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations.

  25. Diagnosis • A battery of serological tests are used for the diagnosis of acute and chronic hepatitis B infection. • HBsAg - used as a general marker of infection. • HBsAb - used to document recovery and/or immunity to HBV infection. • anti-HBc IgM - marker of acute infection. • anti-HBcIgG - past or chronic infection. • HBeAg - indicates active replication of virus and therefore infectiveness. • Anti-Hbe - virus no longer replicating. However, the patient can still be positive for HBsAg which is made by integrated HBV. • HBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy.

  26. Treatment • Interferon - for HBeAg positive carriers with chronic active hepatitis. Response rate is 30 to 40%. • Lamivudine - a nucleoside analogue reverse transcriptase inhibitor. Well tolerated, most patients will respond favorably. However, tendency to relapse on cessation of treatment. Another problem is the rapid emergence of drug resistance. • Successful response to treatment will result in the disappearance of HBsAg, HBV-DNA, and seroconversion to HBeAg.

  27. Prevention • Vaccination - highly effective recombinant vaccines are now available. Vaccine can be given to those who are at increased risk of HBV infection such as health care workers. It is also given routinely to neonates as universal vaccination in many countries. • Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B. It is particular efficacious within 48 hours of the incident. It may also be given to neonates who are at increased risk of contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg positive. • Other measures - screening of blood donors, blood and body fluid precautions.

  28. Hepatitis C Virus capsid envelope protein protease/helicase RNA-dependent RNA polymerase c22 c-100 33c 5’ 3’ NS3 NS5 core E1 E2 NS2 NS4 hypervariable region

  29. Hepatitis C - Clinical Features Incubation period: Average 6-7 wks Range 2-26 wks Clinical illness (jaundice): 30-40% (20-30%) Chronic hepatitis: 70% Persistent infection: 85-100% Immunity: No protective antibody response identified.

  30. Chronic Hepatitis C Infection • RNA virus • The spectrum of chronic hepatitis C infection is essentially the same as chronic hepatitis B infection. • All the manifestations of chronic hepatitis B infection may be seen, albeit with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma.

  31. Hepatitis C Virus Infection Typical Serologic Course anti-HCV Symptoms Titer ALT Normal 6 1 2 3 4 0 1 2 3 4 5 Months Years Time after Exposure

  32. Risk Factors Associated with Transmission of HCV • Transfusion or transplant from infected donor • Injecting drug use • Hemodialysis (years on treatment) • Accidental injuries with needles/sharps • Sexual/household exposure to anti-HCV-positive contact • Multiple sex partners • Birth to HCV-infected mother

  33. Prevalence of Hepatitis C Infection

  34. Laboratory Diagnosis • HCV antibody - generally used to diagnose hepatitis C infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears. • HCV-RNA- various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy. • HCV-antigen - an EIA for HCV antigen is available. It is used in the same capacity as HCV-RNA tests but is much easier to carry out.

  35. Viral Load • Done by PCR • Negative defined as less than 100 copies/mL • 200,000 to 1,000,000 low • 1,000,000 to 5,000,000 medium • 5,000,000 to 25,000,000 high • above 25,000,000 very high

  36. Treatment for HCV • Treatment based on HCV viral load. • Interferon • May be considered for patients with chronic active hepatitis. • Response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment. • Ribavirin • Less experience than with interferon. • Recent studies suggest combination of interferon and ribavirin.

  37. Prevention of Hepatitis C • Screening of blood, organ and tissue donors. • High-risk behavior modification. • Blood and body fluid precautions.

  38. Hepatitis D (Delta) Virus antigen HBsAg RNA

  39. Hepatitis D Clinical Features • RNA virus • Coinfection with Hepatitis B required • Severe, acute disease • Low risk of chronic infection • Super infection • Usually develop chronic HDV infection • High risk of severe chronic liver disease • May present as an acute hepatitis.

  40. Heptaitis D Virus Modes Transmission • Percutaneous exposure • Injecting (IV) drug use. • Permucosal exposure • Sexual contact

  41. HBV - HDV Coinfection Serology Symptoms ALT Elevated Titer anti-HBs IgM anti-HDV HDV RNA HBsAg Total anti-HDV Time after Exposure

  42. HBV - HDV Superinfection Typical Serologic Course Jaundice Symptoms Total anti-HDV ALT Titer HDV RNA HBsAg IgM anti-HDV Time after Exposure

  43. Hepatitis D Prevention • Because HDV requires HBV for replication pre- or postexposure prophylaxis to prevent HBV infection. • No product exists to prevent HDV superinfection in persone with chronic HBV infection. • Educate to reduce risk behaviors among persons with chronic HBV infecion.

  44. Hepatitis E Virus

  45. Hepatitis E - Clinical Features • Incubation period: Average 40 days • Range 15-60 days • Case-fatality rate: Overall, 1%-3%Pregnant women, 15%-25% • Illness severity: Increased with age • Chronic sequelae: None identified

  46. Typical Serologic Course of HEV Infection Symptoms IgG anti-HEV ALT Titer IgM anti-HEV Virus in stool 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Weeks after Exposure

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