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Hepatitis A-E Viruses

Hepatitis A-E Viruses. Enock Anassi MD, PharmD. Viral Hepatitis - Historical Perspectives. Enterically transmitted. “ Infectious”. A. E. Viral hepatitis. NANB. Parenterally transmitted. B. D. C. “ Serum”. F, G, TTV ? other. Type of Hepatitis. A. B. C. D. E. Source of.

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Hepatitis A-E Viruses

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  1. Hepatitis A-E Viruses Enock Anassi MD, PharmD

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

  3. Type of 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 Route of fecal-oral percutaneous 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

  4. Hepatitis A Virus

  5. HEPATITIS A: signs and symptoms • Nausea and vomiting, anorexia, jaundice • Self limited • No chronic disease • Stool excretion 2 weeks before and 1 week after appearance

  6. Hepatitis A - Clinical Features • Incubation period: Average 30 days Range 15-50 days • Jaundice by <6 yrs, <10%age group: 6-14 yrs, 40%-50% >14 yrs, 70%-80% • Complications: Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis • Chronic sequelae: None

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

  8. 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, raw shellfish) • Blood exposure (rare)(e.g., injecting drug use, transfusion)

  9. 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

  10. Laboratory Diagnosis • Acute infection is diagnosed by the detection of HAV-IgM in serum by EIA. • Past Infection i.e. immunity is determined by the detection of HAV-IgG by EIA.

  11. 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 • children serve as reservoir of infection • Persons at increased risk of infection • travelers • homosexual men • injecting drug users

  12. 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)

  13. VIRAL HEPATITIS HEPATITIS B

  14. Hepatitis B Virus

  15. 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%immunocompetent 5 yrs, 1%-5% • Premature mortality fromchronic liver disease: 15%-25%

  16. Spectrum of Chronic Hepatitis B Diseases 1Chronic Persistent Hepatitis - asymptomatic 2. Chronic Active Hepatitis - symptomatic exacerbations of hepatitis 3. Cirrhosis of Liver 4. Hepatocellular Carcinoma

  17. Hepatitis B ACUTE CHRONIC- 5-10% <6 months (infection >6months) • Every year 1 to 2 million people die due to an infection by this virus complications of chronic hepatitis

  18. Endemicity

  19. 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

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

  21. Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course Acute (< 6 months) Chronic (>6 months) HBeAg anti-HBe HBsAg Total anti-HBc Titre IgM anti-HBc Years 0 4 8 16 20 24 28 36 12 32 52 Weeks after Exposure

  22. 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

  23. Interpretation of Serologic Tests in Hepatitis B +

  24. Viral Hepatitis and Serology

  25. Serological Marker Hep B • 1) HBsAg (Hepatitis B surface antigen): • if positive, person is infectious • Sensitivity = 0.15 ng/ml • Specificity = 99.5% • 2) Anti-HBs (Antibody to HBV surface antigen): • indicates immunity to HBV and protection from disease • Protective level is >10 IU/ml

  26. Serological Markers Hep B • 3) Anti - HBc (Antibody to HBV core antigen): • Total - indicates past or active infection; present whether person is immune or chronic carrier • Specificity = 99.8% to 99.9% • IgM - early indicator of acute infection • No antigen test

  27. Serological Marker Hep B • 4) HBeAg (Hepatitis Be antigen): • indicates person is highly infectious • Selecting patients for therapy • 5) Anti-HBe (Antibody to HBVe antigen): • prognostic for resolution of infection; less infectious; spontaneous seroconversion in 10 to 20% of healthy adults per year

  28. Serologic markers – caveats: • Precore or HBeAg negative mutants: • Due to mutation in precore (abolishes HBeAg production) or core promoter region (down-regulates HBeAg production) • No effect on viral replication (may be enhanced) • More difficult to treat; greater risk of cirrhosis • Co-infection with HCV may suppress both HBeAg and HBsAg

  29. Serologic markers – caveats: • Persistent HBsAg for >6 mos = chronic infection • HBsAg and anti-HBs may co-exist in up to 24% of chronically infected individuals; likely due to mutations in the “a” determinant of the S gene • Surface antigen escape mutants described in infants infected with HBV after HBIG + vaccination and in Liver transplants after prolonged HBIG • Anti-HBc IgM may persist for up to 2 years in 20%; chronically infected individuals may have low titres which rise during acute flares

  30. Hepatitis B – Laboratory Tests Serologic markers – caveats: • Isolated HBcAb may be due to: • Remote infection (immune or chronic carrier) • “Window” period between HBsAg and HBsAb • Co-infection with HCV • False positive test result – HBcAb is marker most prone to false positives • HBV DNA may help sort this out

  31. 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

  32. 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.

  33. 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.

  34. Treatment • Interferon (PEGinterferon-2α) , - for HBeAg +ve 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. • Entecavir and Adefovir • Successful response to treatment will result in the disappearance of HBsAg, HBV-DNA, and seroconversion to HBeAg.

  35. 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.

  36. Complications • Arthritis • Glomerulonephritis • Polyarteritis nodosa • Hepatocellular carcinoma

  37. Hepatitis D • Subviral satellite because it can propagate only in the presence of hepatitis B coinfection superinfection • Transmission: parenteral (intravenous drug use mostly) • > 60% develop cirrhosis

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

  39. Hepatitis D • Anti-HDV Total (IgG & IgM) available • Incubation time – similar to Hepatitis B • High titires of HDV antibodies indicate ongoing chronic infection • Treatment same as HBV • If acquired as superainfection in chronic HBV there is in severity of infection i.e fulminant hepatitis, chronic hepatitis with rapid progression to cirhosis

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

  41. 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.

  42. Hepatitis C • Affects each person differently • No vaccine available • Many people have the virus and do not even know it • By blood transfusion and IV drug abuse • Intranasal cocaine use, piercing • Type 1 (most resistant) type II and III

  43. 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

  44. Chronic Hepatitis C Infection • 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. • Waxing and waning aminotransferases (ALT/AST)

  45. Hepatitis C Virus Infection Waxing and Waning ALT/AST anti-HCV Symptoms Titre ALT Normal 6 1 2 3 4 0 1 2 3 4 5 Months Years Time after Exposure

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

  47. Hepatitis C Dispelling Myths • Hepatitis C is not spread by: • Casual contact • Hugging/kissing • Sharing eating utensils and drinking glasses • Sneezing/coughing • Shaking hands • Sitting on a toilet seat

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