Vaccination against Hepatitis B Dose 0,1, 6 and
0,1, 2.Presentation. Heberbiovac HB 0.5 ml for 0 to 19 years and
Heberbiovac HB 1 ml for 20 years and above

2.1 How is Hepatitis B Transmitted
Hepatitis B (HB) is transmitted by the exchange of body fluids e.g.
Blood, Semen, Breast Milk and in some circumstances saliva. People
most at risk include: Anybody who has unprotected sexual intercourse;
IV drug users who share needles and syringes; Health care workers in
contact with potentially contaminated blood or body fluids; Babies
born to mothers with the virus; Anyone in intimate contact with the
infected person. Many cases of acute hepatitis B occur sporadically
with no known source and studies have shown that prior unrecognised
infection is common.

2.2 What happens when infected with Hepatitis B
It is possible to be infected with the hepatitis B virus (HBV) and
experience no illness or symptoms whatsoever. Commonest is an acute attack
of hepatitis during which you may feel unwell, tired and lose your
appetite. Sometimes there is the characteristic yellowish colour of
jaundice (Fig 1.) best seen in the whites of the eyes. This can last from a
few days to a few months. Itching skin and pale stools may also occur. 90%
of people infected with hepatitis B recover completely and become immune to
the virus. Blood tests will show antibodies to hepatitis B indicating you
have had hepatitis B but are now immune and cannot get hepatitis B again.
However 10% of people infected with hepatitis B develop chronic infection,
may have ongoing symptoms and they continue to be infectious for a variable
length of time. Chronic infection is defined as having hepatitis B present
for 6 months or more.

People with a chronic hepatitis infection are at risk of liver damage
20-30% of those will progress to cirrhosis.
.3 How Can I prevent infection

i) Vaccination
A safe and effective genetically engineered vaccine for
hepatitis B is available. It is given in 3 subcutaneous
injections (just under the skin) generally over a period of 6
months and conveys immunity in 90 to 95% of people treated. At
the end of the course of injections a blood test is taken to
see if you have developed the required antibodies. For the 5 -
10% of people who do not respond some new research has shown
that a repeat course of injections given intramuscularly can
create an immune response in between 62-98% (depending on
several factors) of those who did not respond or whose response
did not last when given subcutaneously.
Once vaccinated present it is important to be periodically
tested to ensure that the body has sufficient levels of
antibodies to prevent infection and a single booster dose may
be required every 5 to 10 years to ensure immunity from
infection.
At present vaccines are ineffective for those already infected
with the hepatitis B virus.
New vaccines are being developed and some of these promise
increased response rates, only require a single injection and
some may be effective for people with chronic hepatitis B.
However these are still in the research stage and not generally
available.

ii) After exposure to the virus
If an unvaccinated individual is exposed to the virus
accidentally, hepatitis B Immune globulin can be given. Ideally
within 24 hours of exposure and no later than 7 days after
exposure, a repeat dose is necessary 28 - 30 days later.
Hepatitis B Immune globulin is generally given where there is a
known risk of infection, e.g. via needle stick injury or to
new-born infants born to HBsAg positive mothers. In many cases
hepatitis B Immune globulin can prevent initial infection with
hepatitis B but there are also a significant number of cases
where it has not prevented infection after exposure.

3. The hepatitis B virology and immunology
In order to understand what happens when a person is infected with
hepatitis B it is helpful to know more about the virus. This section
attempts to convey information about the hepatitis B virus, how it
reproduces and the human bodies response to the virus. This one chapter
could fill a text book, or more, and so the information is simplified.

3.1 What is the Hepatitis B Virus.
Hepatitis B is a DNA Virus of the hepadnaviridae family of viruses.
It replicates within infected liver cells (hepatocytes ). The
infectious ("Dane") particle consists of an inner core plus an outer
surface coat.
In real life (Fig 3.) the virus is a spherical particle with a
diameter of 42nm (1nm = 0.000000001 metres) and is composed as
follows. There is an outer shell (or envelope) composed of several
proteins known collectively as HBs or surface proteins (indicated by
's' in Fig 2.). This outer shell is frequently referred to as the
surface coat. The outer surface coat surrounds an inner protein
shell, composed of HBc protein (shown as 'c' in Fig 2). This inner
shell is referred to as the core particle or capsid. Finally the core
particle surrounds the viral DNA ('D') and an enzyme DNA Polymerase
('p').
3.2 How does the virus replicate.
When the virus enters the body of a new host it's initial response,
if it's gets past the immune system, is to infect a liver cell. To do
this the virus attaches to a liver cells membrane and the core
particle enters the liver cell. The core particle then releases it's
contents of DNA and DNA polymerase into the liver cell nucleus.

From within the cell nucleus the hepatitis B DNA causes the liver
cell to produce, via messenger RNA; surface (HBs) proteins, the core
(HBc) protein, DNA polymerase, the HBe protein, HBx protein and
possibly other as yet undetected proteins and enzymes.

DNA polymerase causes the liver cell to make copies of hepatitis B
DNA. I.e. it is believed that the replication of HBV DNA it does not
go via RNA(?). Via the above process, versions of the hepatitis B
virus are constructed by the liver cell . These copies of the virus
and are released from the liver cell membrane into the blood stream
and from there can infect other liver cells and thus replicate
effectively. However when reproducing, mistakes may be made in
copying viral DNA and this results in different strains and mutant
strains of hepatitis B occurring.

The incubation of the Hepatitis B Virus (hepatitis B) is about 6 to
25 weeks (i.e. before physical and generally detectable histological
or physical symptoms occur) however there are several biochemical and
histological changes that occur in stages after infection with the
hepatitis B virus.
3.3 Hepatitis B Antigens and Markers.
The various components produced by hepatitis B, while reproducing,
are detailed below. Some of these components enter the blood stream
and cause detectable changes, some may only be determined via liver
biopsy and others require sophisticated, experimental or unreliable
tests.

i) Hepatitis B DNA (HBV DNA)
This is one of the first things that can be detected in the
bloodstream after initial infection. It can be detected as soon
as 1 week after infection using sensitive tests. It is believed
that the level of HBV DNA may indicate how fast the virus is
replicating(?). The test for HBV DNA is however expensive and
difficult to perform, it is therefore not frequently used.
Tests for HBV DNA are not performed as a standard test and
generally only used as indicators of disease progression,
suitability for therapy and research purposes.

ii) Hepatitis B DNA polymerase. (HBV DNA Polymerase, DNAp)
This enzyme can be detected in the bloodstream soon after
initial infection by hepatitis B at about the same time as HBV
DNA. I.e. generally within a 1 week or so after infection.
Tests for HBV DNA polymerase are not performed as a standard
test and generally only used as indicators of disease
progression, suitability for therapy and research purposes.

iii) Hepatitis B Core protein. (HBcAg)
The core protein (HBc) is not detectable in the bloodstream,
however it can be detected in the sample of liver cells taken
after a liver biopsy. Generally the HBc proteins link together
to form the hepatitis B core that encapsulate HBV DNA and DNA
Polymerase.

iv) Hepatitis B Surface protein(s). (HBsAg)
The outer surface coat composed of hepatitis B surface proteins
is produced in larger quantities than required for the virus to
reproduce. The excess surface proteins clump together into
spherical particles of between 17-25nm in diameter but also
form rods of variable length. In some cases these particles
encapsulate a core particle and produce a complete, and
infectious, virus particle that enters the blood stream and can
infect other liver cells. The excess spheres, rods and also
complete viral particles enter the blood stream in large
numbers and are easily detectable. It does however take a while
for these proteins to appear.
The incubation of the Hepatitis B Virus (hepatitis B) is
between 6 to 25 weeks. After infection and 1 to 6 weeks before
symptoms occur HBsAg appears. A positive test for the presence
of hepatitis B surface protein (HBsAg), is the standard
currently taken to indicate current infection with hepatitis B.
If HBsAg is present for more than 6 months this is generally
taken to indicate chronic infection.
It is thought that excess HBs proteins produced may allow
infectious viral particles to escape the immune system by
mopping up any low levels of surface antibodies that may be
produced by the immune system(?).

v) HBe Protein. (HBeAg or 'e' antigen)
The Hepatitis 'e' antigen (HBeAg) is a peptide and normally
detectable in the bloodstream when the hepatitis B virus is
actively reproducing, this in turn leads to the person being
much more infectious and at a greater risk of progression to
liver disease. The exact function of this non structural
protein is unknown, however it is thought that HBe may be
influential in suppressing the immune systems response to HBV
infection(?). HBeAg is generally detectable at the same time as
HBsAg and disappears before HBsAg disappears. The presence of
HBeAg in chronic infection is generally taken to indicate that
HBV is actively reproducing and there is a higher probability
of liver damage. In acute infection HBeAg is generally only
transiently present.
However mutant strains of HBV exist that replicate without
producing HBeAg. In many cases infection with these mutant
strains is more aggressive than HBe producing strains(?).

vi) HBx Protein.
The function of this protein is not yet known. Although it can
be detected current tests are unreliable as other proteins
interfere with the results(?).
3.4 How the Human Body Responds to Infection.
This section details how the human body responds to an initial
infection with hepatitis B. In people with immune suppression,
undeveloped immune systems (I.e. infants and children), certain
genetic traits or other as yet unknown factors these may not occur.
Round 90% of infected people will recover from Hepatitis B and around
half of these will have had no symptoms. Recovery means that no HBsAg
is found in the blood and the Hepatitis B Antibody (HBsAb) is
present. HBsAb usually persists for life after recovery.

i) Antibodies to HBc (HBcAb).
The first detectable antibody to appear around 8 weeks after
infection with HBV are antibodies to the HBV core protein.
These antibodies to HBcAg (HBcAb) do not neutralise the virus.
HBcAb's persist in serum after an infection with HBV has been
defeated and testing for this antibody has been used to detect
previous exposure to the live virus.

ii) ALT alanine aminotransferase and AST (aspartate
aminotransferase).
ALT and AST are enzymes produced in liver cells that can be
detected in the blood stream. The normal range for ALT is
between 0-40. When liver cells are damaged these enzymes are
released and elevated levels are detected in serum. The value
of ALT in the blood stream is generally taken to be an
indicator of the damage that hepatitis causing to liver cells.
However damage may be occurring with little or no elevation of
ALT (this is especially true for hepatitis C and people with
end stage liver disease).
ALT and AST and other substances are measured when a liver
function test is taken. However other drugs and especially
alcohol can elevate these readings artificially. It is
therefore important to avoid these things before a liver
function test and/or inform your doctor of any drugs you may be
taking or have taken in weeks previous to the test. You may
find it useful to keep a record of your ALT to track disease
progression and the effects any treatments) you are taking is
having.
After an initial infection and at around the same time as HBcAb
appears in the blood stream the level of ALT starts to rise
sharply. The rise in ALT is due to damage to the liver cells,
one theory is that the damage to liver cells is not caused
directly by the virus, i.e. the virus does not kill liver
cells, but by the human bodies own immune system killing
infected and surrounding cells. In patients with compromised
immune systems and/or with HIV infection there is increased
risk of the infection becoming chronic but damage done by the
chronic infection appears mild in comparison to people not
infected with HIV. In cases of acute infection ALT starts to
drop at around the same time as when the 'e' antigen is no
longer detectable and is down to normal when antibodies to the
surface antigen appear.

iii) Interferon.
When a human cell is exposed to a new virus it usually produces
a group of substances known as interferons. It is believed that
interferons modulate (alter) the immune system, alter cell
membranes to reduce infection of surrounding uninfected cells
and also causes many changes. This naturally produced
interferon assists the body in fighting hepatitis B. However it
was discovered that the interferon response was deficient in
some people and also infants/ children with immature immune
systems. This finding lead to interferon being considered as a
treatment.

iv) Antibodies to HBe protein (HBeAb)
Antibodies to the 'e' antigen (HBeAb) normally appears a few
weeks after HBeAg is no longer detectable. The presence of
HBeAb is generally taken to be a good sign and indicates a
favourable prognosis.

v) Antibodies to HBs protein (HBsAb)
These are generally the last antibodies to appear. HBsAb can
neutralise the hepatitis B virus and there appearance taken as
an indicator that an initial infection has been defeated.
HBsAb can also be induced to appear by vaccination and so
provide protection against hepatitis B. However the immune
response produced by vaccination may not be 100%. Although very
rare, hepatitis B infection has occurred in vaccinated
individuals. It is believed that this may be due to mutant
virus strains that express different surface proteins to those
used in the genetically engineered vaccine(?).