Pathogens Database

Hepatitis B Virus

by Addie Nesbitt

Characteristics    

Hepatitis B Virus (HBV) is a double-stranded DNA virus in the Hepadnaviridae family.  The infectious particle is 42nm in diameter, with a genome 3200 nucleotides long.  It has an outer envelope and an icosahedral nucleocapsid, which contains viral DNA polymerase and has a diameter of 27nm. The envelope contains the HBV surface antigen (HBsAg); this is the molecule to which anti-HBV antibodies are directed.  The non-infectious hepatitis B particles are composed of HBsAg only and come in the form of filaments and spheres.  Their only likely purpose is binding up antibodies so the infectious particles can remain free.  In humans HBV infects hepatocytes where it replicates within the nucleus, but can also be found in smooth muscle, bone marrow, kidneys, thyroid glands and other sites.    
 

Infection

HBV is usually transmitted from blood to blood and can be contracted via infected needles (IV drugs and tattoos), sexual contact, cuts, hemodialysis, vertical transmission at birth and blood transfusions.  In developed countries blood is screened for the presence of HBsAg before transfusion.  Unlike other forms of viral hepatitis, HBV cannot be transmitted by contaminated food or water. The CDC states that preventive measures for HBV infection are similar to those for HIV.  Diagnosis of HBV can be made by the presence of HBsAg, which can be found in the serum a few weeks before onset of illness.  The anti-HBsAg antibody is found weeks to months after infection and can last, in some cases giving life-long immunity.

Hepatitis B is found mostly in Africa, Southeast Asia, Indonesia, the Philippines, and parts of the Caribbean.  In those areas all socioeconomic groups are affected with rates above 8%.  Infection rates between 2% and 7% occur in central and southwest Asia Israel, Japan, parts of Europe, the Amazon River basin and Russia.  Most other areas including northern and western Europe, North America, Australia, New Zealand, Mexico and the southern part of South America have low rates of infection (North America and northern Europe (10% in some areas of the Far East.  5,000 people in the US die from HBV each year and there are currently 1 million chronically infected people in the US.  Worldwide 2 billion people have been infected, with 350 million chronically and 1.5 million die each year.
 
Symptoms

Symptoms include loss of appetite (anorexia), fever, nausea with vomiting and jaundice.  In this case, jaundice is caused when extra subunits of hemoglobin called bilirubin build up in the body due to liver damage.  The word hepatitis means inflammation of the liver and with HBV infection the 
liver is often enlarged and tender.  A HBV infection can be acute or chronic. An acute infection can resolve itself spontaneously, with rates as high as 90-95% in adults, but is considered chronic if it lasts more than 6 months.

The rates of a HBV infection becoming chronic is 90% in neonates but drops with age to between 5-10% in adults.  Some are chronically infected carriers. These people have hepatitis in their liver but they are otherwise normal.  

Liver diseases such as cirrhosis and hepatocellular carcinoma are the major symptoms.  Hepatitis B increases a person's chance of developing hepatocellular carcinoma by over 100-fold.  The exact mechanism is unknown but this cancer occurs when HBV's genome becomes integrated into the hepatocytes' DNA.  This type of cancer is usually fatal and only a liver transplant can ensure long-term survival after diagnosis.            

Virulence 

The HBV E ("early") protein appears during acute HBV infection, when viral levels are high.  Also, high serum levels of HBe are found in varaemic carriers and may help to suppress the immune system.  Hepatitis also has an X protein. It is 154 amino acids long, and is thought to be involved in tumor production.  HBx can bind to the p53 tumor-suppressor protein and may have kinase activity.   There are also 3 S antigen types.  The smallest is antigenic while the medium and large ones are believed to be responsible for host cell binding.

       
Vaccine

A vaccine is available that produces immunity to HBV via anti HBsAg antibody production.  It is made by recombinant DNA technology where the HBsAg gene is inserted into yeast.  It is administered intramuscularly into the arm.  This is done over a course of three shots at 0-, 1- and 6-months, with full immunity conferred after the final shot.  Anyone who works in health care or handles blood products is strongly recommended to get vaccinated.  This vaccination is also recommended to anyone who travels to an area where HBV infection rates are high.  Both the CDC and WHO agree that this vaccine is safe for all ages.  It has been found that pregnant and lactating women can be vaccinated with no harm to the baby.  This is due to the fact that the vaccine contains only surface protein, and no virus.  Currently over 4 million adults in the US and the same number of children worldwide have been vaccinated.

It is under consideration to vaccinate all infants in the US to eliminate transmission.  The Global Alliance for Vaccines and Immunization has already begun widespread child vaccination.  However, there is opposition to the vaccine, and people have been shown to develop a severe allergic reaction, 
called anaphylaxis, to the vaccine including autoimmunity.      

Treatments

Persons exposed to hepatitis B who have not been immunized receive injections of immune globulins from human donors who produce anti-HBsAg antibodies.  Antiviral drugs are also administered.  Lamivudine (Epivir) and adefovir are both nucleoside analogues.    Chronic hepatitis B infection can be treated with liver transplant. In the U.S.A., viral hepatitis is the most common cause of transplant.  However, there is frequent viral recurrence in the transplanted liver.  The rate of recurrence can be reduced with immune globulins and antiviral drug combo therapy.  There is now a problem with resistance to the drugs.    

Hepatitis D Virus

HDV is a single-stranded, circular RNA virus. It is 1636 bases long and codes for the delta antigen.  It can only replicate in a cell that is also infected with HBV.  Its protein coat is made of HBsAg.  Hepatitis D is contracted the same way as hepatitis B.  People who contract HBV and HDV at the same time have a co-infection.  Interestingly, most co-infections resolve themselves due to competition between the two viruses.  A person who contracts HDV while infected with HBV is said to have a super-infection.  A HBV infection that suddenly becomes worse is a good indication of HDV super-infection.  The presence of HDV is determined by the presence of anti-HDV antibodies.