Transcript Hepatitis Viruses

Hepatitis Viruses
HAV, HBV
NonA-NonB: HCV, HDV, HEV
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.
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.
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.
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.
Clinical findings (HAV)
Clinical manifestations of hepatitis are virtually
the same
• Fever
• Anorexia
• Nausea
• Vomiting
• Jaundice
• fatigue
Clinical findings (HAV)
• Usually resolve spontaneously in 2-4 weeks.
• Incubation period: average 1 month
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.
Jaundice
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.
HBV
HBV
• A member of hepadenavirus.
• 42-nm enveloped virion with an icosahedral
nucleocapsid.
• Partially double-strand circular DNA genome.
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)
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.
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.
Transmission & Epidemiology
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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.
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.
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.
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.
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.
NON-A, NON-B hepatitis viruses
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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
HCV
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)
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
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.
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