Hepatitis B:The Complexities

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Original Paper

The Hepatitis Knowledge Newsletter is edited by F.H. Anderson, MD.,

FRCP(C), Natalie Rock, BSN, RN, Susan Campbell, RN. Room B-206, Dept. of Medicine, Van. Gen. Hosp. 855 W 12th. Vancouver V5Z 1M9. Phone: (604)209-9976 Fax: (604)875-4429.



      The Newsletter is supported by an educational grant from Schering

Canada Inc. and GlaxoWellcome Canada.





Hepatitis B:The Complexities



Hepatitis B: A Brief History:



In 1965, Dr. Blumberg who was studying haemophilia, found an antibody in two patients which reacted against an antigen from an Australian Aborigine. Later the antigen was found in patients with serum type hepatitis and was initially designated "Australian Antigen". Subsequent study has shown the Australia Antigen to be the hepatitis B surface antigen. Dr. Blumberg was subsequently awarded the Nobel Prize for his discovery. Initially there appeared to be three particles associated with hepatitis B infection: a large "complete" particle called the "Dane particle", a small circular 20nm particle and an oblong 40nm particle. Further research identified the Dane particle as the hepatitis B viron and the other two particles as excess surface protein. This former terminology is no longer used and the virus is referred to according to its structure.



Hepatitis B Virus: A Complex Structure



The hepatitis B viron consists of a surface and a core. The core contains a DNA polymerase and the e antigen. The DNA structure is double stranded and circular. There are four major polypeptide reading frames (genes): the S (surface), the C (core), the P (polymerase) and the X (transcriptional transactivating). The S gene consists of three regions, the pre-S1, pre-S2 and encodes the surface proteins (HBsAg). Very rarely a mutation may occur in the S gene and may abort the HBsAg with the result that a person may be HBsAg negative but still have virus present as determined by HBV DNA. The C

gene is divided into two regions, the pre-core and the core, and codes for two different proteins, the Core antigen (HBcAg) and the e antigen (HBeAg). A not uncommon mutant is the pre-core mutant, which may stop production of HBeAg, and these persons will be HBsAg positive, HBV DNA positive, but HBeAg negative. A third mutant which appears to have a mutant in the core has been described and is referred to as HBV2. These patients are HBsAg positive, but lack HBeAg and HBV DNA, thus also anti-HBc. Another mutant, the YMDD mutant, will be described at a later date.



To make it even more complex, the HBsAg particles are antigenically complex and these antigenic determinants have been identified. There is a single common determinant designated a, and four major subdeterminants designated d,y,w and r. Thus, the four major determinants are: adw, adr, ayw and ayr.



Multiple Tests are Available



Because of the complexity and the antigenic differences of the virus, there are a number of tests available for hepatitis B:



Antigens

HBsAg = presence of the virus

HBcAg = not detected in blood

HBeAg = correlates with the viral replication and infectivity



Antibodies

anti-HBs = antibodies to the surface

anti-HBc = antibodies to the core can be either IgM (acute) or IgG (chronic)

anti-HBe = antibodies to e and indicates low infectivity and probable

recovery



Other Markers

HBV DNA = indicates virus presence and activity

DNA polymerase = determines the presence of HBV DNA

HBsAg in liver cells (Orcein stain = Shakata cells) = HBsAg inside

hepatocytes



Hep B:The Complexities



Carrier Rates Vary Greatly



Carrier rates for hepatitis B vary enormously:



Country and Carrier rate%:

Scandinavia 0.1

USA/Canada 0.1

Spain 2.0

Southern Italy 3.0

Greece 5.0

Hong Kong 15.0

Taiwan 15.0

Alaskan Eskimos 45.0





High Infectivity



Hepatitis B DNA is found in many body fluids including saliva, urine, semen

and menstrual blood. It has also been shown that the virus can be

transmitted by ingesting contaminated blood. Hence, hepatitis B may be transmitted by:



» mother to infant at the time of birth

» sexually

» horizontally through shared utensils such as razors, toothbrushes, etc.

» through unsterile instruments such as tattoo needles, dental equipment,

etc.

» parenteral drug use through shared needles, syringes, etc.

» hospital staff through needle prick

» blood sucking arthropods (usually in the tropics)



Extra-Hepatic Associations



Although uncommon, a number of conditions associated with hepatitis B

antigen/antibody complexes have been recognized. These include:



Polyarteritis - usually involves medium and small arteries, appears early

Glomerulonephritis - largely in children, liver disease is usually mild

Polymyalgia rheumatica - usually in older persons

Essential mixed cryoglobulinemia - sometimes only a test tube finding

Guillain-Barre syndrome

Myocarditis



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Hugs,

Sheree