The hepadnaviridae viruses.
The hepatitis B viruses are small
and enveloped with a circular,
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 healthcare setting.
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.
as you are probably aware,
is anything and everything, especially
exposure to blood and body fluids.
So a parenteral exposure,
babies born to mothers
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.
When we see the anti-HBcAg
IgG together with anti-HBs
an antibody to the
HBV surface antigen,
we know we're dealing with someone
who has previously been infected.
If we see anti-HBs alone
without an antibody to HBc,
then the immunity is likely
secondary to vaccination.
And both of these cases the patient
will typically have lifelong immunity.
Now if we see persistence
of the HBs surface antigen,
HBV DNA with or
without HBe antigen,
or we see HBs antigens persisting
for more than 6 months,
we know we're dealing
with a chronic infection.
It is possible for these patients
to have anti-HBs antibodies,
but if you still have
persistent HBs antigen,
it means they're not effectively
neutralizing the virus.
These images are schematic
representations of serological responses
during an acute and
chronic HBV infection
in relation to the serum
The left panel shows
an acute infection.
It is characterized initially
by the presence of HBe antigen,
HBs antigen and HBV DNA beginning
in the preclinical phase.
IgM anti-HBc appears early
in the clinical phase.
This is an important
point as the combination
of this antibody and HBs antigen
make the clinical diagnosis
of an acute infection.
Recovery is accompanied by
normalization of the serum ALT levels,
disappearance of HBV DNA,
the seroconversion of
HBe antigen to anti-HBe
subsequently HBs antigen
to HBs seroconversion
and to switch from
IgM to IgG anti-HBc.
Thus, a previous HBV infection is
characterized by anti-HBs and IgG anti-HBc.
The right panel shows that a
chronic infection is characterized
by persistence of HBs antigen,
HBV DNA and HBe antigen
for a variable period
Anti-HBs is not usually seen but
an approximately 20% of patients,
a non-neutralizing form of
anti-HBs can be detected.
Persistence of the HBs antigen for more
than 6 months after an acute infection
is considered indicative
of a chronic infection.
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.
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
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
we can have a very strong,
cell-mediated immune response
from the human's immune system.
And if there is a
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 complete resolution
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 initial response,
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,
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 hypersensitivity reaction,
which can cause or contribute
to that active hepatitis.
in the setting of chronic infection,
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, fulminant hepatitis,
get it over with and get
a seroprotective response,
than to be cursed with
a mild initial reaction,
mild or no hepatitis,
but then a chronic infection.
Vaccinations also exist
and vaccinations include
a non-functioning hepatitis
B surface antigen subunit.
This vaccine is administered
to all newborns,
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 treatment of chronic HBV infections
depends on several factors including:
ALT levels, which are an indirect
measure of liver inflammation,
the presence of cirrhosis,
the patient's immunological
response to the infection,
and for example,
their HBeAg levels,
the HBV viral load and genotype,
as well as the patient demographics
including things such as age over 40,
a family history of cirrhosis
or hepatocellular carcinoma.
The goals of therapy are
to suppress HBV DNA levels,
and to lose HBsAg positivity.
For patients without cirrhosis,
who are treatment naive and not pregnant,
the first line therapy
is pegylated interferon
such as tenofovir and entecavir.
The efficacy of this
treatment is not perfect,
with only 5% losing
their HBsAg positivity
and 40% who are HBeAg+
(seroconverting to anti-HBeAg)
but only after 5
years of treatment.
Typically, lifelong reverse
transcriptase inhibitors are recommended,
but the interferon side effects limit
its use to only a 48-week course.
For patients with cirrhosis,
we also treat with reverse
though all of these patients will
require a lifelong treatment.
You must also screen for
hepatocellular carcinoma every 6 months
as chronic HBV is a leading cause of
hepatocellular carcinoma in the world.
Patients are typically monitored
with biomarkers of disease activity,
such as HBV DNA, ALT levels,
HBeAg, anti-HBeAg and HBsAg levels.
Creatinine and phosphate supplementation
can help patients with RTI side effects.
Additionally, all patients with
chronic HBV should avoid alcohol,
get the hepatitis A vaccination
and reduce transmission to
others through practices
including safe sex,
encouraging partner HBV vaccination,
not sharing their
toothbrushes or razors
and not donating blood
products, organs or sperm.
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
transfusion, parenteral, etc.
It's a complicated virus,
but it's quite instructive
how a viral growth pattern can
inform its testing strategy.