Hepatitis VirusesHAV, HBV

NonA-NonB: HCV, HDV, HEV

HAV• DiseaseHepatitis A

• Important propertiesTypical enterovirus (enterovirus72) classified in

PicornavirusSingle-stranded RNA genomeNon- enveloped icosahedral nucleocapsidReplicates 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 & PreventionNo antiviral therapy.vaccine is available.Immune prophylaxy is availableResolves 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

• 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 AgHBsAg 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

• 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