Hepatitis Viruses

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Hepatitis Viruses

• HAV, HBV
• NonA-NonB HCV, HDV, HEV

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HAV

• Disease
• Hepatitis A
• Important properties
• Typical enterovirus (enterovirus72) classified in
  Picornavirus
• Single-stranded RNA genome
• Non- enveloped icosahedral nucleocapsid
• Replicates in the cytoplasm of the cell.
• One serotype.
• Humans and chimpanzees are the only natural hosts.

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Replicative cycle

• A positive strand RNA
• Genome replication occurs by synthesis of a
  complementary negative strand which then serves
  as the template for the positive strands which
  are needed both for replication and protein
  synthesis.

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Transmission Epidemiology

• Transmitted by fecal-oral rote.
• Virus in feces 2 weeks before the symptoms. So
  quarantine of patients is ineffective.
• Children the most frequently infected group.
  Outbreaks arise from fecally contaminated water
  or food.
• The level of viremia is low and chronic infection
  does not occur.

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Pathogenesis

• HAV replicates in gasterointestinal tract
  epithelial cells and spreads to the liver via the
  blood.
• Very low level of viremia
• Hepatocytes are infected. HAV infection of
  cultured cells produces no cytopathic effect.
• Immune attack on the hepatocytes plays no role in
  pathogenesis (against HBV).
• No chronic infection.
• The infection cannot be distinguished
  pathologically from other hepatitis infections.

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Clinical findings (HAV)

• Clinical manifestations of hepatitis are
  virtually the same
• Fever
• Anorexia
• Nausea
• Vomiting
• Jaundice
• fatigue

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Clinical findings (HAV)

• Usually resolve spontaneously in 2-4 weeks.
• Incubation period average 1 month

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Immunity

• Immune response is initially IgM antibody
  detectable at the time jaundice appears.
• The appearance of IgM is followed 1-3 weeks later
  by the production of IgG antibody which provides
  lifelong protection.

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Jaundice
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Laboratory diagnosis

• Detection IgM (the most important test).
• 4-fold rise in IgG titer.
• Treatment Prevention
• No antiviral therapy.
• vaccine is available.
• Immune prophylaxy is available
• Resolves itselfe spontaneously.

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HBV
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HBV

• A member of hepadenavirus.
• 42-nm enveloped virion with an icosahedral
  nucleocapsid.
• Partially double-strand circular DNA genome.

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Antigenes and fragments

• HBsAg (important both in diagnosis and
  immunization).
• DNA-dependent DNA polymerase
• 3 different types of particles 42-nm virions,
  22-nm spheres, long filaments 22 nm wide.
• HBcAg (Core antigen )
• HBe Ag (an indicator of transmissibility)

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Serotypes based on HBsAg

• HBsAg
• A group-specific antigen, a and 2 sets of
  exclusive epitopes, d or y and w or r leading to
  4 serotypes adw, adr, ayw, ayr which are useful
  in epidemiologic studies.

Humans are the only natural host of HBV.
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Replicative cycle

• DNA polymerase synthesize the missing portion of
  DNA ---? Fully double-strand circular DNA in
  nucleus ---? Some DNA copies integrates into
  hepatocyte DNA /// Some DNA copies serves as a
  template for mRNA synthesis ---? mRNA functions
  both in protein synthesis and template for the
  DNA minus strand (by RNA-dependent DNA
  polymerase) ---? DNA minus strand serves as
  template for plus strand.

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Transmission Epidemiology

• Blood is Most important way of transmission.
• In addicts using intravenous drugs.
• Sexual transmission.
• Mother to child during birth or breast feeding.
• Immunization reduces the incidence.

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Clinical finding

• Incubation period 2-3 months
• The acute disease is similar to that of HAV.
• Symptoms in HBV tend to be more severe than HAV.
• Most chronic carriers are asymptomatic.

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Pathogenesis

• Entering HBV the blood ---? infecting hepatocytes
  ---?necrosis and inflammation (Immune attack
  against viral antigens on infected hepatocytes).
• 10 of patients become chronic carriers of HBV
  (probably due a persistent infection of
  hepatocytes mediated DNA integrated into cell
  DNA) Chronic persistent hepatitis
• Some chronic carriers have chronic active
  hepatitis may leading to cirrhosis,
  hepatocellular carcinoma and death.

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Laboratory diagnosis

• Immunoassay for HBs Ag
• HBsAg during the incubation period and mostly
  during the prodome and acute disease.
• Prolonged presence of HBsAg indicates carrier
  state and the risk of chronic hepatitis.
• Windows phase no HBsAg and HBsAb but HBcAb
• HbeAg During incubation period and is present
  during prodrome and early acute disease (an
  indicator of transmissibility).
• HBeAb indicates low transmissibility.
• DNA polymerase during incubation and early in the
  disease but assay not available in clinical lab.

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Treatment Prevention

• Alpha interferon
• Lamivudine (inhibits hepatitis B viral DNA
  synthesis)
• Baraclude (inhibiting hepatitis B viral DNA
  synthesis)
• Rest, combined with a high protein/high
  carbohydrate diet to repair damaged liver cells.
• Prevention by using vaccine and hyperimmune
  globulin (HBIG)
• No one with a history of hepatitis (of any type)
  should donate blood.

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NON-A, NON-B hepatitis viruses

• HCV
• Distributed worldwide
• The most major agent of Non-A, Non-B
• An enveloped single-strand RNA virus (a
  flavivirus).
• Incubation period an average of 2 months
• No immunity

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HCV
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HCV

• 80 of cases go to chronic forms tend to cause
  cirrhosis (20-50) or hepatocellular carcinoma
  (5-25).
• Mild infection and only 25 show jaundice. Most
  cases are asymptomatic
• There are at least 6 genotypes of HCV
• Diagnosis is based on serologic methods (ELISA)

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HEV

• An enterically transmited virus
• Nonenveloped, single-stranded RNA virus (from
  calcivirus).
• Diagnosis is serologic (ELISA) based on IgM and
  IgG
• No antiviral agent for treatment

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HVD (Delta agent)

• Single-stranded circle RNA
• RNA genome surrounded by an envelope composed of
  HBsAg.
• A defective virus as its genome does not code for
  its own envelope protein.
• HDV can only replicate in HBV-infected cells.
• Delta antigen is a distinctive determinant
  present in this virus but not in HBV.

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HDV

• HDV HBV infection tends to be a fulminant
  hepatitis.
• Transmission the same as HBV
• A chronic carrier state can occur.
• Infection can be detected by the appearance of
  IgM to delta antigen.
• No treatment
• No vaccine