The hepadnaviridae viruses.
The hepatitis B viruses are small
and enveloped with a circular,
partially double-stranded DNA genome,
and importantly, they encode their
own reverse transcriptase.
The viruses themselves are
resistant to low pH,
which is important as they're aspirated and
enter the circulation via the stomach.
They also are resistant to moderate heating,
as well as detergents in terms of
cleaning in the hospital or
And typically, as we'll see,
the hepatitis B virus can
cause both an acute
and/or a chronic infection. It's quite
versatile in its cause of disease.
Transmission, as you are probably aware,
is anything and everything, especially
exposure to blood and body fluids.
So a parenteral exposure, sexual exposure,
babies born to mothers actively infected
or even chronically infected,
of course, are at risk.
The incubation, then, of hepatitis B virus
is months and sometimes
even longer than that.
So, let's walk our way through the
replication of hepatitis B virus.
Again, it's a little bit different because
it carries its own reverse transcriptase.
We'll start with the complete virus as it
attaches to and embeds itself
to its target hepatocyte.
It then sheds its external envelope,
injecting the capsid into the cytoplasm,
and ultimately injects the core,
the DNA material,
into the nucleus of the hepatocyte.
There, the viral genome is first
transcribed into long,
double-stranded RNA, and then
back transcribed to DNA circles,
which again, remember are not
These then exit the nucleus
and are packaged into new capsid material,
which then gains further envelope
material on its way out,
and eventually lyses and extrudes
itself from the hepatocyte.
So it's, again, as we're seeing is
a recurring theme in viruses,
when the fully formed virus leaves the cell,
in this case, the hepatocyte,
is when lysis occurs and the affected
cell creates an inflammatory reaction.
Let's then look,
serologically, at the course of infection
because there are multiple different ways,
different antigens expressed by hepatitis B
that can help us understand at what
stage in that life cycle we just saw,
we're at in terms of infection.
If we're able to detect
the presence of the surface antigen,
and the E antigen represented
by hepatitis B,
that means the virus is present.
Doesn't mean necessarily
that it's doing anything, but it's simply that
it's present and starting to expose
itself to the hepatocyte.
When we start to see in the blood stream
antigen to the E antigen, the serum HBeAg,
and actual viral DNA being released,
that means there's active
processing going on
and the virus is very transmissible.
Once we then start to see immunoglobulin M
like in a humoral or an antibody response
to the core antigen for hepatitis B,
that means that infection has occurred,
but it's been quite recent that we haven't
yet had time to create an
immunoglobulin G response.
Therefore, when we see IgG antibody
to hepatitis core antigen,
that means that previous infection
and this takes typically about
6 months to convert
from an immunoglobulin M
to an immunoglobulin G response.
The hepatitis B surface
antigen antibody or some people abbreviate
this to be HBsAg antibody.
This means that either the infection
has occurred and it has resolved
and that patient is lucky. They
have lifelong immunity.
Or that we have vaccinated the patient
with hepatitis B surface antigen,
the typical vaccine strategy,
and they have made an appropriate
and protective response.
However, if there is persistent
hepatitis B surface antigen
in the setting of a known infection,
this means that there's chronic infection.
The body's immune system has been
unable to convert to lifelong protective
response with immunoglobulin G antibody.
If we further look at presence or
absence of antibody
to the E antigen, as well as presence
or absence of DNA
from the virus that suggest either in
the setting of chronic infection,
that the patient is a healthy
carrier if they're negative
for both E antigen and DNA,
or they are actively infectious
as a carrier.
And in this case, they have both
E antigen and DNA to hepatitis B
present in the bloodstream.
To, again, refresh our memory of where these
different components are that we test for,
we'll look first at the core antigen.
It's a major core antigen.
And as you can see, it lies underneath
the envelope shown in purple on this image,
and instead, is the red ring-like
structure that that represents
a surrounding group of core antigen
to protect the internal capsid.
And this contains both genome
and core enzymes.
The surface antigen -- as the name
would suggest, it's not too hard --
lives on the surface, and that would be
present in that purple surrounding
envelope material which you
see present on the image.
And then the E antigen. Now this is
closely approximated in the space
around the core antigen. And so,
when one sees expression of the E antigen,
that means that initial uncloaking
or removal of the envelope has occurred,
and this typically is detected
in the bloodstream.
So, pathogenesis. Hepatitis B virus enters.
It's typically either injected through
parenteral or through some other
exposure to blood and body contents.
It survives any acid challenge,
and it creates a viremia. Travels through
the bloodstream to the liver.
If the patient has been previously
Hepatitis B surface antigen,
then no further action can occur.
There's no ability
for the virus to attach,
and in fact, the immune system can
detect this new virus and get rid of it.
However, assuming the patient is unimmunized,
then we have attachment of the hepatitis
B virus as we talked about before,
to the hepatocyte, and it replicates
causing low-level inflammation,
but no liver damage.
During this incubation period, however,
we can have a very strong,
cell-mediated immune response from
the human's immune system.
And if there is a strong response,
meaning it's attacking those
inflamed or lytic hepatocytes,
that acute disease, acute
hepatitis will develop,
occurring in about a quarter of patients
who are infected with hepatitis B.
And this is highly likely to cause
and development of a strong and
protective immune response.
The patient will survive that quite well.
If, as is more common,
the patient has a mild immune
this is unfortunate because it means
that they are highly likely to have
a chronic infection.
And if so, that means that they can develop
further disease, further cirrhotic
disease going on.
Looking even more specifically at what
happens with the infected hepatocytes,
the hepatitis B surface antigen
is a very active or very highly able
antigen to trigger an immune response.
And it frequently creates a type III
which can cause or contribute to
that active hepatitis.
If, however, in the setting of
there is a reactivation
and/or there is a co-infection with
hepatitis D or delta,
then the patient is at high risk to
develop permanent liver damage
accompanying with cirrhosis,
which occurs in 10%.
The patients, then, who have over
30 years of that chronic,
low-level infection, the ones who had
a mild immunologic response
to the initial acute infection
are at high risk to develop, ultimately,
a hepatocellular carcinoma.
So, in this case, although it
may be unpleasant,
it's far better to have the acute,
get it over with and get a
than to be cursed with a
mild initial reaction,
mild or no hepatitis, but then
a chronic infection.
So, how do we prevent the disease and
then how do we eventually test for it?
Well, prevention starts with looking at
the most common source; a transplant
or a blood transfusion-related --
a transfusion --
excuse me, transmission of the virus.
And this is countered by doing ELISA,
enzyme-linked immuno assay
of blood from donors
to screen out those who are
hepatitis B positive.
Vaccinations also exist
and vaccinations include a non-functioning
hepatitis B surface antigen subunit.
This vaccine is administered
to all newborns,
typically, in the first 2 weeks of life,
and again at 2 other points
in a primary care series,
depending on what country one lives in.
Health care workers, if not previously
vaccinated as newborns themselves,
also deserve immunization.
And then of course, those patients who
are at risk. So, transplant coming up,
patients require multiple transfusions.
The diagnosis we've talked about
for the different antigens that
we've talked about,
and looking at an IgM and/or
an IgG response.
Those patients then determine to have
active infection at risk for progression,
deserve treatment, and that's typically shown
when they have evidence of
a doubling in the liver enzymes, AST and ALT,
some degree of jaundice,
some degree of liver dysfunction,
like being coagulopathic, etc.
If we then decide to treat,
currently, the primary treatment includes
reverse transcriptase inhibitors
uch as we use in treating human
immunodeficiency, HIV, virus.
And these include these viruses --
our anti-viral agents here:
lamivudine, entecavir, emtricitabine,
The dipivoxil and famciclovir are
which also has some putative
or proposed activity
in the setting of hepatitis B treatment.
But discovery continues, as we speak,
to see about how effective
they actually are.
So, hepatitis B virus is
absolutely something which
occupies the attention
of those of us in hospital-acquired
infection prevention careers,
but also, for those who work
with high risk patients
who are at risk for acquiring
the virus through
sexual practices, transfusion, parenteral, etc.
It's a complicated virus, but it's quite
instructive in understanding
how a viral growth pattern can
inform its testing strategy.