[Music]
welcome 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 ageneral e approach
a patient who has n normal liver lab
tests first
you should always identify the pattern
of injury and then look for the
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 G DT 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 the clinic
his past medical history is notable for
IV drug use eight years ago he has no
family history of hepatitis he feels
well and takes no medications he asked
to be screened for hepatitis B so his
lab studies result as follows 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 looked 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 the hepatitis B
serologies let's take a step back and
talk about the various types of
hepatitis this slide will summarize the
routes of transmission the
characteristics of each type of
hepatitis and their potential for
causing chronic disease so I'm not going
to 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 but blood or body fluids
hepatitis C can be transmitted by
exposure to blood from an infected
person hepatitis D only occurs as a
co-infection 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 present
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 first
begin with acute infection 90% of adults
will develop a cure and 10-4
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 ninety percent of
them will actually develop chronic
hepatitis B if we 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 tests and how to interpret
it 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 cute infection so when it's present it
indicates a recent infection less than
six months ago the last thing you may
see is a Hep B e antigen this simply
indicates that there is 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
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 two
weeks four through 24 which is when you
have the initial infection as you can
see the hepatitis B surface antigen or
HBS AG becomes positive with acute
infection over time then you develop an
IgM antek or antibody which then
disappears over time and then you also
develop this green curve which is the
total antibody 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 antibodies presence indicates
that they have been built up 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 up immunity to the infection
in this case because the Quran Abadi 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 tests 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 different
things 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 these 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've
taken to 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 immunosuppressed or planning to
become immunosuppressed on various
medications or do they have a
co-infection with habit I
see 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 analogues like
tenofovir here or on TECA beer 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
it 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
[Music]
you