2. Properties of HBV
A member of the hepadnavirus group
They are Circular partially double-stranded DNA viruses
Its Replication involves reverse transcriptase.
Hyper endemic in many parts of the world.
A number of mutant variants
It has not yet been possible to propagate the virus in cell culture
2
4. HBV : Structure
Virion also referred to as Dane particle (ds-tranded DNA)
42nm enveloped virus
Core antigens located in the center (nucleocapsid)
* Core antigen (HBcAg)
* e antigen (HBeAg)- an indicator of transmissibility (minor component of
the core- antigenically distinct from HBcAg)
Other forms:
22nm spheres and filaments other forms- no DNA in these forms so they are
not infectious (composed of surface antigen)- these forms outnumber the actual
Virion
4
8. 8
4 Overlapping – Open Reading Frames which encode structural and non structural
viral proteins.
• S gene encodes 3 Surface Proteins
[ Small(S),Middle(M),Large(L) ]
• C gene encodes Core Proteins Hepatitis B core Antigen( HBcAg)
& Hepatitis B e (Hbe) Protein (Non structural protein)
• P gene encodes HBV Polymerase (has 2 motifs- Reverse transcriptase motif
RNAse H Motif)
[ Code for 2 enzymes involved in HBV replication ]
• X gene encodes X Protein (Transcriptor involved in HBV replication)
HBV Genome
10. 8 Genotypes ( A to H ) are identified which are associated with different
clinical outcomes
Predominant in Common in
Genotype A Northern& Western Europe Homosexuals
Genotype D Mediterranean sea & Eastern Europe Intravenous
drug abusers
Genotype B & C In Asia & Asian immigrants
Genotype C Higher incidence of Severe liver disease &
Hepatocellular Carcinoma
10
11. •Incubation period = 30-150 days
•Jaundice in 1/3rd of Adult Patients with Acute hepatitis B
•most cases are unrecognised
11
13. Diagnosis
4 Markers should be sought for Diagnosis
•HBsAg
•Total Anti HBc Antibodies
•Anti HBc IgM Antibodies
•Anti HBs Antibodies
13
14. 14
Acute Hepatitis B characterised - HBsAg & Anti HBc IgM antibody
Anti HBs Antibodies are not seen
In Convalescence Phase Patient lose HBsAg, before appearance of Anti HBs Antibody
Recovery is characterised by appearance of Anti HBs antibodies & Total Anti HBc Antibodies
Anti HBc IgM levels remains at high levels for Patients life time
Anti HBs Antibody titres Flucuate and become undectable after several years
15. Quantitative HBsAg Assessment during the course of Acute hepatitis B
may be useful, if the levels doesn’t decrease rapidly the patient is at risk
for chronic evolution.
Patients who remain HBV-DNA & HBeAg positive for 6 weeks after
the onset of symptoms likely to develop chronic infections
15
17. 17
Interferon Alfa:
- Effective in patients with - low viral load
Serum Transaminases twice the upper limit of normal
- Acts by Augmenting native immune response
- Response is lower in HBeAg –ve patients
- Contraindicated in Cirrhosis ( as it increases Serum transaminase levels which may
precipitate liver failure)
Adverse effects:
Fatigue, Depression, irritability, Bone marrow depression, and thyroid disease
Treatment
18. 18
Lamivudine:
- It is a nucleoside analogue
- It inhibits DNS polymerase thus supresses HBV DNA levels
- Effective in improving liver function in Decompensated cirrhosis and prevents need
for transplantation
- Long term therapy (after 9 months) may lead to HBV DNA polymerase mutants
- These viral mutants are less hepatotoxic than the native virus
- Tendency to relapse on cessation of treatment
19. 19
Adefovir:
- It is also a nucleoside analogue
- It inhibits DNA polymerase
- It may be used to treat Lamivudine resistance
- Reduces HBV DNA by 3-4 logs
- Enhances HBeAg seroconvesion and leads to histological improvement
CONTRAINDIACTED IN RENAL FAILURE
Entecavir:
- It is more effective than Adefovir and Lamivudine in reducing the viral load in
HBeAg – positive and negative chronic Heaptitis
- Antiviral resistance mutations occur in 1% after 3 years of Drug exposure
20. Prevention
Vaccination
- highly effective recombinant vaccines
Hepatitis B Immunoglobulin (HBIG)
- exposed within 48 hours of the incident/ neonates whose
mothers are HBsAg and HBeAg positive
Other measures
- screening of blood donors, blood and body fluid precautions.
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21. 21
Vaccination:
• Highly effective recombinant vaccines are now available.
• Vaccine can be given to those who are at increased risk of HBV
infection such as health care workers, Dialysis patients,
Homosexuals, Pregnant women, sexual partners of HBV carriers.
• Recombinant HBsAg in 3 injections (0,1 and 6 months)
• Lower dose at same time points (0,1 and 6 months)
for – New Borns, Children & adolescents
• Infants
-mother HBsAg Positive: vaccine and Hepatitis B immunoglobulin
within 12 hours of birth and at 1st and 6th months
• Adults on Dialysis
- 4 injections at 0,1,2 and 6 months
22. 22
• Hepatitis B Immunoglobulin - HBIG may be used to protect
persons who are exposed to hepatitis B. It is particular efficacious
within 48 hours of the incident. It may also be given to neonates
who are at increased risk of contracting hepatitis B i.e. whose
mothers are HBsAg and HBeAg positive.
• Other measures - screening of blood donors, blood and body fluid
precautions.