Today we'll talk about disorders of the liver,
specifically hepatitis and acute liver failure.
So, before we begin, let's talk about
how to interpret abnormal liver tests.
So, how do you generally approach a
patient who has abnormal liver lab tests?
First, you should always identify the pattern
of injury and then look for underlying cause.
So what do we mean by the pattern of injury?
There are two types of liver injury.
The first type is hepatocellular injury pattern
where you have a predominant elevation
in the aspartate transferase or the alanine
transferase, or we read it as AST and ALT.
The second type of pattern
is a cholestatic injury pattern
where there is a predominant elevation in
the alkaline phosphatase or ALP or GGT.
So if you remember these two key patterns in liver
injury, you'll be able to interpret most liver tests.
So now let's go to a case.
A 48-year-old man is seen in clinic.
His past medical history is
notable for IV drug use 8 years ago.
He has no family history of hepatitis.
He feels well and takes no medications.
He asks to be screened for hepatitis
B, so his lab studies results as follows:
So ALT is normal, hepatitis B surface antigen is
negative, hepatitis B surface antibody is positive,
his hepatitis B core antibody is positive and when
tested for viral DNA, he has less than 20 copies.
So, how do we interpret his serologies?
This is a difficult question
so we'll break it down.
First, he has a history
of intravenous drug use
which places him at elevated
risk of having a hepatitis B infection.
We first look at his ALT.
Because it's normal, this suggests to us
that there is no active hepatitis currently.
He has both, however, a positive surface
antibody and a positive core antibody.
So we'll talk about
what that means next.
So, the big question is:
Does he have an active infection or did
he have a prior infection that was cleared?
So, before we go into hepatitis B
serologies, let's take a step back
and talk about the
various types of hepatitis.
This slide will summarize the relative transmission,
the characteristics of each type of hepatitis
and their potential for
causing chronic disease.
So, I'm not gonna go into them in
that much detail but you should know
that hepatitis A is fecal-oral transmission, and
does not have the ability to cause chronic disease.
Hepatitis B is transmitted by
exposure to blood or body fluids.
Hepatitis C can be transmitted by
exposure to blood from an infected person.
Hepatitis D only occurs as a coinfection with hepatitis B
since it depends on hepatitis B to replicate.
And lastly, hepatitis E like A,
is a fecal-oral transmission.
The important distinguishment
here to point out is that
both hepatitis A and E do not have the
potential to cause chronic disease.
So, all types of viral
hepatitis presents similarly.
Patients may come in with fatigue,
a general lack of appetite,
they may develop jaundice,
bleeding or bruising,
nausea or vomiting and
they may have dark urine.
If we talk specifically about
hepatitis B, as a quick review,
it is transmitted from exposure to blood
or body fluids from an infected person.
It can also be transmitted vertically from
mother to child when acquired at birth,
this is most likely to
cause chronic infection.
In most cases, about 90% of those who
acquire an acute infection will resolve
and only 10% will then go on to
develop chronic hepatitis B.
So, to summarize its natural progression of
disease, you'd first begin with acute infection.
90% of adults will develop a cure, and 10% of them
will then go on to develop chronic inflammation.
Note here that in children, to acquire hepatitis B from
vertical transmission, their disease is very different
and over 90% of them will actually
develop chronic hepatitis B.
To go back to adults, however, chronic
inflammation then leads to fibrosis
which can then lead to the end
stage of cirrhosis of the liver.
and that may lead in turn to cancer
or hepatocellular carcinoma.
Hepatitis B, however, is unique
and that you do not need to develop
fibrosis or cirrhosis to develop cancer.
So you can go straight from chronic infection
or chronic inflammation to cancer.
So now, let's get to the
hepatitis B serologies.
We'll go through first each serology test
and how to interpret it and then we'll go
and then we'll go through some
common scenarios you may encounter
since this is quite a challenging topic.
So the first test is the
hep B surface antigen.
Its presence indicates that the
person is infected in general.
The second test is a surface antibody.
When this is present, it indicates that
the person has developed immunity.
Either they have been vaccinated
or they had a prior infection.
The next test is a core antibody.
In general, when we refer to the total core
antibody, we're referring to the IgG antibody.
This appears initially
during the first infection
and then its presence later on
indicates a prior or ongoing infection.
The next test is the core IgM antibody.
So this appears during a acute
infection, so when it's present,
it indicates a recent infection
less than 6 months ago.
The last thing you may see
is a hep B e-antigen.
This simply indicates that there's
active viral replication going on.
So now that we've covered that long
list of different types of serologies,
let's go through some common scenarios that you
might encounter on a test or in a patient.
Before we do that, let's talk a bit about
what these antibodies and antigens look like
over the course of the disease.
So here, you can see a graphical depiction of the various
antigens and antibodies that are present during disease.
I'll first point to weeks 4 to 24, which
is when you have the initial infection.
As you can see, the hepatitis B surface antigen or
HBsAg becomes positive with acute infection overtime
then you develop an IgM anti core
antibody which then disappears overtime
and then you'll also develop this green
curve which is the total core antibody.
This is the IgG that
develops after infection
and remains positive for the
rest of that person's lifetime.
Over time after the acute initial infection, the core
IgM antibody and the surface antigen will resolve.
Then, after a period of time, at
about weeks 32 after exposure,
the person will then
develop a surface antibody.
The surface antibody's presence indicates that they
have then built an immunity to the prior infection.
Note that there is a small period
in time between weeks 24 and 32
where you may have an IgM
core antibody that stays positive.
That's the pink line here.
So, that's a particular type of clinical picture that
can be very confusing and we'll talk about that soon.
So now let's get to our various scenarios.
The first scenario you may
encounter is a positive surface antigen
with a positive core antibody
- that's an IgM antibody.
This indicates that you
have an acute infection
because the only way to have a positive surface
antigen is to be exposed to the virus.
On the other hand, if you have a positive surface
antigen with a positive IgG core antibody,
this means that you have now progressed
to the chronic state of infection.
Our next scenario is a negative surface antigen with a
positive surface antibody and a positive core antibody.
So, for this one, you should remember
that a surface antibody only appears
when the person has built an
immunity to the infection.
In this case, because the
core antibody is also positive,
you know this person has
been infected at some point
and they now have a resolved infection
because they've built up immunity.
Our next scenario is one you may
commonly encounter in real life.
So you may have a negative surface antigen, a positive
surface antibody and a negative core antibody.
This means that the person has been
vaccinated or immunized against hepatitis B.
This is the only way in which you
have a positive surface antibody
and that is the only thing that is positive.
Our next scenario is where you have
negative test all across the board.
This indicates that this person
has never been exposed to the virus
and they've never been vaccinated, as you can tell
from the surface antibody also being negative.
So this person is what we call
susceptible to developing infection.
Lastly, we mentioned that window period where
you may have an isolated core antibody.
This can be many
It can either be that window period between acute
and chronic infection that we discussed earlier.
It can mean that the
person has recovered.
It can be a latent or dormant phase of the
virus or it could be a false positive.
So since there are very many scenarios that could
appear with this particular test scenario,
you will often not be tested on this
because it's so difficult to interpret.
So, who to treat with hepatitis B
is a very complicated decision
but we take into account
several different factors
including pregnancy, whether
they've developed cirrhosis,
do they have an elevated ALT, a high level
of DNA replication, acute liver failure,
are they immunosupressed or planning to become
immunosuppressed on various medications,
or do they have a coinfection
with hepatitis C.
Also, you should remember that
hepatitis B is entirely preventable.
So anyone who is at risk of the disease or who asks
about a vaccination should be offered the vaccine.
Treatment options include nucleoside analogs like
tenofovir or entecavir or pegylated interferon.
So now, we can return to our case.
Our 48-year-old man with a history of IV drug
use which puts him at risk for hepatitis B.
He has a normal ALT which suggests
no active hepatitis currently.
His surface antibody and core antibody
are positive which we now know
indicates that he has had prior infection
and has now developed immunity.
So, how do we interpret this?
He most likely has a prior
infection, has developed immunity
and he should be reassured and
counseled to avoid future exposure.