INTRODUCTION & HISTORY
The disease known as hepatitis B is caused by the infectious Hepatitis B virus (HBV). HBV alone is estimated to have infected 400 million people throughout the globe, making HBV one of the most common human pathogens. Hepatocellular carcinomas (HCC), one of the most common cancers afflicting humans, is primarily caused by chronic HBV infection.. In the last few decades, the correlation between HBV and the development of HCC has been well established. However, the mechanism by which HBV transforms hepatocytes remains elusive. Before HBV can transform a cell, the virus must first infect it. However, the mechanism through which HBV enters hepatocytes has not been resolved despite further understanding of the viral proteins involved. Vaccines are available against HBV, but they may not be 100% effective against all variants of HBV. Furthermore, there is no cure for individuals already infected. Much more research is needed before we fully understand and control the spread of this infectious agent.

The following pages attempt to provide accurate and comprehensible information regarding the various aspects of the hepatitis B virus. Granted, some parts of this site require some scientific background to fully comprehend (i.e. the structural and molecular biology pages), but I have also included a question and answer page for those who feel some information needs clarification. May you find the information you are looking for within.

Hepatitis B Virus General Information
Genome: partial dsDNA 
Family: Hepadnaviridae
Related Viruses: Duck Hepatitis B Virus, Ground Squirrel Hepatitis Virus, Snow Goose Hepatitis B Virus, Woodchuck Hepatitis Virus, Wooley Monkey Hepatitis Virus
Satellite Virus: Hepatitis D Virus (Delta Virus)
Incubation Period: 30 - 180 days 
Transmission: Blood and Sexual Contact
Acute Attack: Mild or Severe
Serum Diagnosis: anti-HBc, anti-HBs or HBsAg 
Treatment: Symptomatic
Prevention: Vaccination with recombinant hepatitis B surface antigens, Hepatitis B Immunoglobulin Post-exposure prophylaxis

History of the Hepatitis B Virus
Viral hepatitis is the term reserved for infections of the liver by one or more of the distinct hepatitis viruses. The terms, hepatitis A and hepatitis B, were first introduced by MacCallum in 1947 in order to categorize infectious (epidemic) and serum hepatitis. ⁽¹⁾ These terms were eventually adopted by the World Health Organization Committee on Viral Hepatitis. ⁽²⁾

Before the viruses causing hepatitis were isolated, transmission was differentiated on the basis of epidemiological observations. Type A hepatitis was considered predominantly transmitted via the fecal-oral route while type B hepatitis was believed to be primarily transmitted parenterally.

In 1963, when searching for polymorphic serum proteins, Blumberg discovered a previously unknown protein in the blood of an Australian aborigine. ⁽³⁾ This protein was denoted as the Australia (Au) antigen. It became apparent that this protein was related to type B hepatitis. By 1968, other investigators, notably Prince, Okochi, and Murakami, had established that the Au antigen (now known as the hepatitis B surface antigen) was only found in the serum of type B hepatitis infected patients. ^{(4), (5)}

In 1973, Dane found virus-like particles in the serum of patients suffering from type B hepatitis. ⁽⁶⁾ These particles were designated as the hepatitis B virus (HBV). Non-related hepatitis viruses were discovered later, but the hepatitis B virus retained its name.

Kaplan confirmed the viral nature of these particles by detecting an endogenous DNA-dependent DNA polymerase within its core. ⁽⁷⁾ Discovery of this polymerase allowed Robinson to detect and characterize the HBV genome. ⁽⁸⁾ The HBV genome is unique in the world of viruses due to its compact nature, use of overlapping reading frames, and dependence on a reverse-transcriptional step, though the virion contains primarily DNA. In light of this, the human hepatitis B virus became the archetype of the hepadnavirus family, Hepadnaviridae.

Though the hepatitis B surface antigen (HBsAg) from HBV has been detected in other primates, humans remain its primary reservoir. In the recent past, many related viruses have been found in other species, but each particular virus is species specific. With human HBV as the archetype, the members of the hepadnaviridae family include duck hepatitis B virus (DHBV), ground squirrel hepatitis virus (GSHV), snow goose hepatitis B virus (sgHBV), woodchuck hepatitis virus (WHV), and wooley monkey hepatitis virus. There are likely other viruses that have yet to be isolated which would also be classified as a hepadnaviridae.

HBV has been estimated by the World Health Organization (WHO) to have infected over two billion people worldwide. Approximately 500 million are chronic carriers. Transmission of HBV is primarily through blood and/or sexual contact, though other methods of transmission have been suggested. The large reservoir of infected individuals has sustained a satellite virus known as the hepatitis D virus (HDV). HDV can only replicate in cells already infected with HBV since HDV uses hepatitis B surface proteins to package its own RNA. However, the nature of HDV is quite different from HBV. Therefore, it will only be mentioned briefly in this website.

2. World Health Organization. 1973. Viral Hepatitis Reposty of WHO Scientific Group. WHO Technical Report Series 512. Geneva: WHO.

3. Blumberg, B.S., Gerstley, B.S.J., Hungerford, D.A., London, W.T., and Sutnick, A.J. 1967 A Serum Antigen (Australia Antigen) in Down's Syndrome, Leukemia and Hepatitis. Annals of Internal Medicine; 66: 924-931.

4. Prince, A.M. 1968. An Antigen Detected in the Blood During the Incubation Period of Serum Hepatitis. Proc. Natl Acad Sci USA; 60: 814-821.

5. Okochi K. and Murakami, S. 1968. Observations on Australia Antigen in Japanese. Vox Sang; 15: 374-385.

6. Dane, D.S., Cameron, C.H. and Briggs, M. 1970. Virus-like Particles in Serum of Patients with Australia-Antigen-Associated Hepatitis. Lancet; i: 695-698.

7. Kaplan, P.M., Greenman, R.L., Gerin, J.L., Purcell, R.H. and Robinson,W.S. 1973. DNA Polymerase Associated with Human Hepatitis B Antigen. Journal or Virology; 12: 995-1005.

8. Robinson, W.S. and Greenman, R.L. 1974a. DNA Polymerase in the Core of the Human Hepatitis B Virus Candidate. Journal of Virology; 13: 1231-1236.