L5 Virology Hepatitis B Virus

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L5 VirologyHepatitis B Virus

• Dr Mike Kotiw

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HBVLecture aims

• To understand the structure of HBV
• To understand the pathogenesis of HBV
• To understand how HBV is diagnosed with
  particular emphasis on HBV serology

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Hepatitis

• Hepatitis defined as inflammation of the liver
• Not a single disease
• Central role of the liver in metabolism
  predisposes the organ to many different viruses
• At least six viruses specifically infect and
  damage hepatocytes.
• None belong to the same family!

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Hepatatis

• The most common viral causes of Hepatitis are
• HBV
• HCV
• HAV
• There are others eg HGV, CMV, EBV

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HBVIncidence

• In the past high incidence in users of blood
  products
• Markedly reduced with compulsory testing of all
  blood donors
• Endemic in many countries especially Asia
• These countries have high rates of chronic
  infection

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HBVIncidence

• In some areas of Africa and Asia transmission
  often occurs during infancy and early childhood.
• In developed nations infection is most common in
  young adults

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HBV High risk groups

• Drug abusers
• Babies of positive mothers
• Familial contacts of HBsAg positive patient
• Prisoners
• Institutionalised people
• Healthcare workers
• Emergency service workers
• Patients of Asian descent

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HBVReservoir

• Man prime host
• Chimpanzees are susceptible but not recognised as
  an important source of infection.

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HBV structure

• HBV is a Hepadnovirus
• Particle
• Icosohedral form 42nm in diameter
• 27nm nucleocapsid core surrounded by an outer
  lipoprotein coat
• Genome
• Predominantly ds DNA partially ssDNA

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The Hepadnoviridae

• Hepadnaviruses have the among the smallest
  genomes of all known viruses
• consist of two uneven strands of DNA
• (-)sense strand, 3.0 - 3.3kb
• ()sense strand, 1.7 - 2.8kb

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HBV Replication

• There are 4 main genes in HBV
• C - the core protein
• P - the polymerase
• S - the 3 polypeptides of the surface antigens
• X - activator of viral transcription
• HBsAg consists of 3 polypeptides responsible for
  receptor binding to hepatocytes?

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HBV replication

• Closed circular DNA is found soon after infection
  in the nucleus of hepatocytes
• DNA is produced by repair of the gapped virion
  DNA by following process
• Completion of the ()sense strand
• Removal of a protein primer from the (-)sense
  strand and oligoribonucleotide primer from the
  ()sense strand
• Removal of terminal redundancy at the ends of the
  (-)sense strand
• Ligation of the ends of the two strands

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HBV replication

• A 3.5kb RNA transcript, core antigen and
  polymerase form core particles in the cytoplasm
• A polymerase converts the RNA to DNA inside
  these particles

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HBV mode of transmission

• Has been found in virtually all body secretions.
• Including saliva, semen and vaginal fluids.
• Needle stick
• Toothbrushes and razors
• IV drug abuse
• Sexual
• Perinatal by exposure to parental blood and
  secretions (and transplacental--low)
• Faecal /oral has not been demonstrated.

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HBV infections

• Incubation average 60-90 days
• Infectivity
• If HsAg positive always infectious
• Highly infectious if concurrently HBeAg positive
• Susceptibility Universal

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HBVProphylaxis and treatment

• Prevention
• HBVSag, recombinant vaccine
• HBV immune globulin
• Chronic infection
• HBsag pos gt6months ---gtinterferon

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HBV Pathogenesis

• HBV infection has 3 possible outcomes
• Acute course with complete recovery and immunity
  from reinfection (gt90).
• Fulminant hepatitis with liver failure and
  mortality (1 )
• Chronic infection - carrier state with virus
  persistence (10 cases).
• Estimated t here are gt200m HBV carriers worldwide

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HBV pathogenesis

• Primary Hepatocellular Carcinoma
• (forms lt2 fatal cancers in western societies)
• S.E. Asia and China it is the most common fatal
  cancer
• Relationship between HBV infection and PHC is not
  clear
• Cirrhosis appears to be a prerequisite chronic
  liver damage.
• Co-factors may be involved (alcohol?)

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HBV chronicity

• Factors involved
• Age
• Risk decrease with increasing age
• Gender
• Chronic Infection marginally greater in males
• Cirrhosis Greater in males at 3 1
• Hepatocarcinoma Greater in males a t6 1
• Route of infection less risk with routes other
  than blood infection

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HBV Diagnosis

• Predominantly serological and LFTs
• Elimination of differential diagnosis
• HBA, HCV, CMV, EBV, other

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HBVSerology

• Variety of markers are tested for by Elisa
• Marker Interpretation
• HBV sAg infectious?
• HBV eAg infectious
• HBV eAg gt6m -gt high risk chronicity
• HBV sAb immune
• HBVcAb exposure to infectious agent
  has occurred

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HBV Serology
HBVsAg
HBVSab
HBVcAb
Titre
Time
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HBVNotes on interpreting serology

• Vaccinated people have HBV sAb only
• Naturally infected and recovered have HBV cAb
  and HBV sAb
• Carriers have HBVSag and usually HBV cAb
• Carriers are monitored by LFTs

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HBVprocedure in event of exposure

• If you have a needle stick accident with a person
  who is HBV positive
• Find out status of patient especially HBVeAg
• Get HBVIG within 72 hours
• Start vaccine program about 7 days later