2. Key Features of Hepatitis B Virus
Relevance
• 250 million people infected worldwide.
• In areas of Africa and East Asia, 50% of the population may
be seropositive, 5-15% may be chronically infected
(carriers).
• Carriers are 200x more likely than non-carriers to develop
primary hepatocellular carcinoma.
• 300,000 cases per year in the US; 4,000 fatalities.
70-90% of maternal-neonatal infections result in chronic
infection.
3. Key Features of Hepatitis B Virus
• Enveloped virion containing partial double-stranded
circular DNA genome
• Replication occurs through an RNA intermediate
• Virus encodes and carries a reverse transcriptase
• Virus encoded several antigenically and clinically
predictive important proteins
5. Key Features of Hepatitis B Virus
• Virus has a strict tissue tropism to the liver
• Virus infected cells produce and release large amounts
of HBsAg particles lacking DNA
• Viral DNA can integrate into the host chromosome
6. Hepatitis B Virion, Dane particle and HBsAG
From Murray et. al., Medical Microbiology 5th
edition, 2005, Chapter 66, published by
Mosby Philadelphia,,
7. The growth cycle of
Hepatitis B virus
From Murray et. al., Medical Microbiology 5th edition, 2005,
Chapter 66, published by Mosby Philadelphia,,
8. Incubation period: Average 60-90 days
Range 45-180 days
Clinical illness (jaundice): <5 yrs, <10%
5 yrs, 30%-50%
Acute case-fatality rate: 0.5%-1%
Chronic infection: <5 yrs, 30%-90%
5 yrs, 2%-10%
Premature mortality from
chronic liver disease: 15%-25%
Hepatitis B - Clinical Features
9. Prevalence of Hepatitis B carriers
Figure 66-9. Worldwide prevalence of hepatitis B carriers and primary hepatocellular
carcinoma. (Courtesy Centers for Disease Control and Prevention, Atlanta.)
From Murray et. al., Medical Microbiology 5th edition, 2005,
Chapter 66, published by Mosby Philadelphia,,
10. Figure 66-11. Clinical outcomes of acute hepatitis B infection. (Redrawn from White DO, Fenner
F: Medical virology, ed 3, New York, 1986, Academic Press
Clinical outcomes of Hepatitis B infections
From Murray et. al., Medical Microbiology 5th edition, 2005, Chapter 62, published by Mosby Philadelphia,,
11. Clinical interpretation of the Hepatitis B antigen
panel
CDC WEB site: http://www.cdc.gov/ncidod/diseases/hepatitis/b/Bserology.htm
12. Determinants or acute and chronic HBV infection
From Murray et. al., Medical
Microbiology 5th edition, 2005,
Chapter 66, published by Mosby
Philadelphia,,
14. Notes:
HDV infection can be acquired either as a co-infection with HBV or as a superinfection of persons with chronic HBV
infection. Persons with HBV-HDV co-infection may have more severe acute disease and a higher risk of fulminant
hepatitis (2%-20%) compared with those infected with HBV alone; however, chronic HBV infection appears to occur
less frequently in persons with HBV-HDV co-infection. Chronic HBV carriers who acquire HDV superinfection usually
develop chronic HDV infection. In long-term studies of chronic HBV carriers with HDV superinfection, 70%-80%
have developed evidence of chronic liver diseases with cirrhosis compared with 15%-30% of patients with chronic
HBV infection alone.
CDC website: http://www.cdc.gov/ncidod/diseases/hepatitis/slideset/hep_d/slide_1.htm
15. Key features of Hepatitis Delta Virus
•Single stranded, self complementary RNA,
encapsidated in HbsAg
•Small, amorphous particle
•RNA encodes one protein: delta antigen
•Replicates via RNA directed RNA synthesis,
catalyzed by host RNA polymerase II
16. Key features of Hepatitis Delta Virus
•Delta antigen required for replication, role unknown
•Dependent on HBV as a “helper”
•HBV provides HbsAg
•May be acquired as co-infection with HBV, or
superinfection of HBV infection
•Exacerbates HBV induced disease
17. Hepatitis Delta Virion
From Murray et. al., Medical
Microbiology 5th edition, 2005,
Chapter 66, published by Mosby
Philadelphia,,
Figure 66-14
18. Consequences of hepatitis B and delta virus infection
Figure 66-15. Consequences of deltavirus infection. Deltavirus (d) requires the presence of
hepatitis B virus (HBV) infection. Superinfection of a person already infected with HBV
(carrier) causes more rapid, severe progression than co-infection (shorter arrow).
From Murray et. al., Medical Microbiology 5th edition, 2005, Chapter 66, published by Mosby Philadelphia.
20. Diagnosis
• A battery of serological tests are used for the diagnosis of
acute and chronic hepatitis B infection.
• HBsAg - used as a general marker of infection.
• HBsAb - used to document recovery and/or immunity to HBV
infection.
• anti-HBc IgM - marker of acute infection.
• anti-HBc IgG - past or chronic infection.
• HBeAg - indicates active replication of virus and therefore
infectiveness.
• Anti-Hbe - virus no longer replicating. However, the patient
can still be positive for HBsAg which is made by integrated
HBV.
• HBV-DNA - indicates active replication of virus, more
accurate than HBeAg especially in cases of escape mutants.
Used mainly for monitoring response to therapy.
Wong’s virology WEB site: http://virology-
online.com/presentations/hepatitis.htm
21. Summary :Hepatitis B Virus
• Structure
– Small (3.2 kb) circular partially dsDNA genome, envel.
capsid
• Pathogenesis
– Sexual, parenteral, and perinatal transmission
– Replication via an RNA intermediate (reverse transcriptase)
– Tropism for liver
– Acute vs. chronic infections occur: highly age dependent
– Chronic infections are a major cause of PHC (primary
hepatocellular carcinoma)
• Diagnosis
– Multiple serological components (viral proteins and anti-
bodies)
• Treatment/prevention
– Subunit vaccine (based on HBsAg)
