Hepatitis b infection (hbv)

1. Hepatitis B Infection (HBV)

2. Hepatitis B Infection
Hepatitis B is a potentially life-threatening liver
infection caused by the hepatitis B virus, which
infects the liver of hominoidea, including humans. It
can cause chronic infection and puts people at high
risk of death from cirrhosis and liver cancer.

3. Epidemiology
• >200 million carriers worldwide
• 1 million people die each year from hepatitis B
and its complications
• Established cause of chronic hepatitis and
cirrhosis
• Human carcinogen - cause of up to 80% of
hepatocellular carcinomas

4. Prevalence of Chronic HBV Infection, Worldwide,
2006
HBsAg Prevalence
>8% = High
2-7% = Intermediate
< 2% = Low

5. Global HBV: Major Genotypes
A,B,C,D,G
F
A,D,E
B,CD
G
A,B,C,D
D
A

6. Hepatitis B Virus
• Hepatitis B virus is an hepadnavirus
• Has a circular genome composed of partially
double-stranded DNA
• The viruses replicate through an RNA
intermediate form by reverse transcription
• Replication takes place in the liver
• Retains infectivity for at least 1 month at
room temperature

7. Structure

8. Characteristics
• Lipid envelope
• Icosahedral nucleocapsid
• Core composed of proteins
• Nucleocapsid enclosed viral
DNA
• DNA polymerase
• Outer envelope containing
embedded proteins
• Enveloped 42 nm virus

9. Morphology
Hepatitis B may exist in 3 different forms:
• Spherical 22nm
• Tubular 22 nm varying length
• Double walled spherical 42 nm (Dane
particle)
no DNA in these forms
so they are not
infectious

10. Dane Particle
HBV virion is also referred to as Dane particle.
Core antigens are located in its center:
• HBsAg = surface (coat) protein ( 4 phenotypes :
adw, adr, ayw and ayr)
• HBcAg = inner core protein (a single serotype)
• HBeAg = secreted protein; function unknown
• HBxAg
8 genotypes (A-H) according to overall
nucleotide sequence variation of the genome

11. Dane Particle

12. Replication
 Reverse transcription: one
of the mRNAs is replicated
with a reverse transcriptase
making the DNA that will
eventually be the core of
the progeny virion
 RNA intermediate: HBV
replicates through an RNA
intermediate and produces
and release antigenic decoy
particles.
 Integration: Some DNA
integrates into host genome
causing carrier state

13. Resistance
• HBV is a relatively heat stable virus (viable
room temperature for long periods)
• 60° C for 10 hours (reduce infectivity 100-
1000 times)
• Susceptible to chemical agents(hypochlorine,
gluteraldehyde)

14. Modes of Transmission
• Parenteral: IV drug abusers, health workers
are at increased risk
• Sexual: sex workers and homosexuals are at
particular risk
• Perinatal (vertical): from mother (HBeAg+) to
infant
Though not transmissible by holding hands,
sharing eating utensils or drinking glasses,
kissing, hugging, coughing, sneezing, or
breastfeeding

15. Concentration of HBV in Various Body Fluids
High Moderate Low
Blood Semen Urines
Serum Vaginal fluid Feces
Wound exudates Saliva Tears
Breast milk

16. Pathogenesis
• The incubation period is from 6 weeks to 6 months after
artificial inoculation of infected blood and blood products
• HBV interferes with the functions of the liver by replicating in
hepatocytes
• HBV virions bind to the host cell via the preS domain of the
viral surface antigen and are subsequently internalized by
endocytosis
• PreS and IgA receptors interact with each other
• HBV-preS specific receptors are primarily expressed on
hepatocyte
• During HBV infection, the host immune response causes both
hepatocellular damage and viral clearance
• Adaptive immune response, particularly virus-specific CTLs,
contributes to most of the liver injury associated with HBV
infection

17. Symptoms
o Loss of appetite, nausea, vomiting, headache,
myalgia, body aches, mild fever, dark urine, and then
progresses to development of jaundice
o Itchy skin is a possible indication of all HV types
o At least 50% of infections are asymptomatic
o Tends to cause a more severe disease than Hepatitis
A
o Extrahepatic manifestations of hepatitis B are
present in 1–10% of HBV-infected patients and
include serum-sickness–like syndrome, acute
necrotizing vasculitis (polyarteritis
nodosa), membranous glomerulonephritis,
and papular acrodermatitis of childhood (Gianotti-
Crosti syndrome)

18. Possible Outcomes

20. Laboratory Diagnosis
• Serum or blood tests (detect either viral antigens or antibodies)
• Hepatitis B surface antigen (HBsAg) is most frequently detected
• Hepatitis B core antigen (HBcAg)
• IgM antibodies to the hepatitis B core antigen anti-HBc IgM
• HBeAg in a host's serum means higher rates of viral replication and
enhanced infectivity
• A person negative for HBsAg but positive for anti-HBs has either
cleared an infection or has been vaccinated previously
• Individuals who remain HBsAg positive for at least six months are
considered to be hepatitis B carriers
• Carriers of the virus may have chronic hepatitis B, which would be
reflected by elevated serum alanine aminotransferase (ALT)
• PCR tests have been developed to detect and measure the amount
of HBV DNA

21. Serologic Markers for Phases of Acute and
Chronic HBV Infection
HBsAg HBeAg IgM
anti-
HBc
IgG
anti-
HBc
Anti-
HBs
Anti-
HBe
HBV
DNA
Interpretation
Acute HBV Infection
+ + + + Early phase
+ ± Window phase
+ + + - Recovery phase
Chronic HBV Infection
+ + + + Replicative phase
+ + + - Low, nonreplicative
phase
+ ± + + Flare-up
+ + + Precore/core
promoter mutants

22. Treatment
• Acute hepatitis B infection does not usually require treatment
because most adults clear the infection spontaneously
• Treatment of chronic infection may be necessary to reduce the risk
of cirrhosis and liver cancer
• Although none of the available drugs can clear the infection, they
can stop the virus from replicating, thus minimizing liver damage
• Antiviral drugs:
• lamivudine (Epivir)
• adefovir (Hepsera)
• tenofovir (Viread)
• telbivudine (Tyzeka)
• entecavir (Baraclude)
• Immune system modulators: interferon alpha-2a and PEGylated
interferon alpha-2a (Pegasys)

23. Prevention
• Vaccination - highly effective recombinant
vaccines
• Hepatitis B Immunoglobulin (HBIg) - WHO
recommends joint immunoprophylaxis for the
newborn, multiple injections of small doses
of hepatitis B immune globulin (HBIg, 200–400 IU
per month) and oral lamivudine (100 mg per day)
for HBV carrier mothers with a high degree of
infectiousness in late pregnancy
• Other measures - screening of blood donors,
blood and body fluid precautions

24. Hepatitis B Vaccine
• Composition Recombinant HBsAg
• Efficacy 95% (Range, 80%-100%)
• Duration of
Immunity >15 years
• Schedule 3 Doses
• Booster doses not routinely recommended

25. Hepatitis B Vaccine Routine Infant
Schedule
Dose Usual Age Minimum Interval
Primary 1 0-2 months ------
Primary 2 1-4 months 1 month
Primary 3 6-18 months 2 months