Hepatitis

• Medically important hepatitis viruses


  • HAV
  • HBV
  • HCV
  • HDV
  • HEV
  • HGV

  
• Other causes of sporadic hepatitis (not exclusively hepatitis viruses)


  • EBV
  • CMV
  • Yellow fever virus

  
• HAV


  Enterovirus 72, picornoviridae family, Naked, genome SS RNA with Icosahedral nucleocapsid

  
• HAV


  • Replication occurs in the cytoplasm of the cell
  • Single serotype
  • Worldwide distribution, humans are the only reservoir
• HAV transmission


  1. Fecal-oral

  2. Contaminated raw seafood (e.g. oysters)

  3. Day-care center outbreaks

  4. Rarely transmitted via blood
• HAV pathogenesis


  • Incubation 4 weeks (2-6wk range)
  • Oral cavity---replicate in the GI tract, then spread to liver via blood
  • Virus in stool 2 weeks after infection, usually shed in stool prior to symptoms
  • Symptoms related to immune response and not direct cytopathic effect of virus
  • No chronicity, no carrier state, nor hepatocellular carcinoma

  
• HAV signs and symptoms

  • Fever
  • Loss of appetite
  • Fatigue
  • Nausea, vomiting
  • Diarrhea
  • Abdominal pain
  • Jaundice, dark urine & pale feces
  • Elevated ALT/AST
• Complete recovery in 99% of HAV cases within 2-4 weeks
• There is no chronic (long-term) HAV infection
• Lifelong immunity after HAV infection - no repeat infections
• HAV diagnosis


  • Hep A IgM antibody (usually present when symptoms occur)
  • Four fold rise in IgG (indicates current infection)
  • IgG (suggests prior infection or vaccination)
  • Virus culture & Isolation (not used)

  
• No antiviral therapy for HAV, only supportive treatment
• HAV prevention


  • Hepatitis A vaccine (formalin inactivated)
  • Two doses (0 and 6-12 months later)
  • Protection begins 4 weeks post vaccine
  • Protection probably at least 20 years (likely lifelong)
  • Twinrix vaccine (for both HAV/HBV)
  • Short-term protection from immune globulin
  • Good hygiene - hand washing

  
• Recommendations for HAV vaccination


  • Travelers to areas with increased rates of hepatitis A
  • Men who have sex with men
  • Injecting and non-injecting drug users
  • Persons with clotting-factor disorders (e.g. hemophilia)
  • Persons with chronic liver disease
  • Children living in areas with increased rates of hepatitis A

  
• HBV


  Member of the Hepadnavirus family, 42-nm Enveloped virion, with Icosahedral nucleocapsid core containing a partially DS circular DNA genome

  
• Forms of HBV


  • 42 nm virions (Dane particle), few in patient serum
  • 22nm spheres and long filaments 22nm width which do not contain DNA; only HBsAg (not infectious)
• HBV genome contains 4 genes


  • Surface protein (HBsAg)
  • Core (nucleoprotein) HBcAg, HBeAg
  • DNA polymerase (RNA dp RT) & (DNA dp activity)
  • X-protein, activator of viral RNA transcription
• HBV transmission


  1. Blood-borne (almost never through transfusion)

  2. Sexual

  3. Perinatal (from mother to newborn)

  
• Persons at risk for HBV infection might also be at risk for infection with hepatitis C virus (HCV) or HIV

  
• HBV epidemiology


  • 100,000 infections per year
  • Higher seroprevalence among Asian-Americans
  • High rates in SE Asia, Alaska, Africa
  • Estimated 1.25 million chronically infected Americans, of whom 20-30% acquired their infection in childhood

  
• HBV pathogenesis


  • Illness is immune mediated
  • 5% chronic carriers (in adults)
  • Higher rate of hepatocellular carcinoma in chronic carriers, especially "e" antigen positive
  • Surface antibody likely confers lifelong immunity
  • Antibody to "e" antigen indicates low transmissibility
  • Incubation 60-90 days (range 45-180 days)

  
• HBV signs and symptoms


  • Fatigue
  • Abdominal pain
  • Loss of appetite
  • Nausea, vomiting
  • Joint pain
• Signs and symptoms are less common in children than adults, and chronic infection is more common when infected at a younger age
• Long-term effects of HBV without vaccination


  • 90% of infants infected at birth develop chronic infection
  • 30% of children infected at age 1-5 years develop chronic infection
  • 6% of persons infected after age 5 years develop chronic infection
  • Death from chronic liver disease occurs in 15-25% of chronically infected persons

  
• HBV risk groups


  • Persons with multiple sex partners or diagnosis of a sexually transmitted disease
  • Men who have sex with men
  • Sex contacts of infected persons
  • Injection drug users
  • Household contacts of chronically infected persons
• Interpretation of the Hepatitis B Panel


  • Susceptible
  • Immune due to natural infection
  • Immune due to hepatitis B vaccination
  • Acutely infected
  • Chronically infected
  • Window phase

  
• HBeAg arises during incubation period, antibody against eAg indicates low transmission
• Viral DNA detection in serum indicates acute infection

  
• HBV vaccine recommendations


  • Routine vaccination of 0-18 year olds
  • Vaccination of risk groups of all ages (Engerix-B, Recombivax HB)

  
• Hepatitis B immune globulin (high titer of HBsAb) should be given for passive immunization

  
• ng IP , Ab against eAg


  Low transmission
• Viral DNA detection in serum

  Acute infection

  
• Hepatitis B vaccine available since 1982

  
• Initial HBV vaccine


  Purifying HBsAg associated with the 22-nm particles from healthy HBsAg-positive carriers and treating the particles with virus-inactivating agents

  
• Recombinant DNA-derived HBV vaccines


  HBsAg produced by a recombinant DNA in yeast cells or in continuous mammalian cell lines

  
• HBV vaccine recommendations


  • Routine vaccination of 0-18 year olds
  • Vaccination of risk groups of all ages

  
• Hep B immune globulin


  High titer of HBsAb, given in addition to vaccine in exposures to known HepB infected patients/sources and newborns whose mother is HBsAg+ve

  
• Drugs licensed for treatment of chronic active hepatitis B


  • Adefovir dipivoxil
  • Alpha interferon
  • Lamivudine

  
• WHO recommends the use of oral treatments (tenofovir or entecavir) as the most potent drugs to suppress hepatitis B virus
• Delta agent


  Causes hepatitis D, cannot infect without HepB