00:01
Welcome!
In this talk, we're
going to be discussing
a variation on hepatitis
inflammation of the liver.
00:07
In this case, due to
the immune system,
turning against it or
autoimmune hepatitis.
00:14
So simply it's an autoimmune
liver inflammation.
00:17
The epidemiology
of this suggests
that it's not a
public health menace,
maybe one person per
100,000 people each year.
00:25
It is for reasons that
are not entirely clear,
more commonly seen
in women than in men.
00:30
And that's pretty true of
most autoimmune diseases.
00:34
There is a bimodal distribution,
so late teens,
and then in the
older years 45 to 70.
00:42
Frequently there is
concurrent immune disorders
or in family members,
autoimmune diseases
can be quite prevalent.
00:52
So either up 40% of cases,
there will be something
else suggested
or suggesting a lack
of immune regulation.
01:01
And so Hashimoto thyroiditis,
Graves disease,
rheumatoid arthritis
may all be present.
01:07
The pathophysiology is
reasonably straightforward,
except we don't
really understand
why we lose tolerance
for self antigens.
01:14
But once we lose tolerance
for self antigens,
we generate, one,
cytotoxic T-lymphocytes,
but also antibodies that can bind
to the surface of various antigens
on the hepatocytes.
01:26
Those then will recruit
FC receptor bearing cells
that can kill the hepatocyte
through the activity
of antibody dependent
cell mediated cytotoxicity.
01:37
To hear more about ADCC,
you can go back to the immunology
talk in basic pathology.
01:44
Once we have that activity going
on, the antibodies binding,
we will release
porphyrins and granzymes
and we will cause the apoptotic
cell death of the hepatocyte.
01:54
I will also say
that in some cases,
it's not antibody driven.
01:57
It's cytotoxic
T-lymphocyte driven.
02:00
The same idea is obtaining.
02:03
How does your patient with
autoimmune hepatitis present.
02:08
It's going to look
like hepatitis,
and we're going to have to rule
out a variety of other things
before we can make a
diagnosis of autoimmune.
02:15
So it's like any other
inflammation of the liver,
there will be generalized
malaise, fever, lethargy, nausea,
right upper quadrant pain
as we have inflammation
and expansion of the liver
and the stretching
of glistens capsule,
there may be weight
loss due to anorexia,
there maybe an erythematous rash
is part of the secondary
autoimmune phenomena.
02:36
Patients may present
with jaundice,
because they are not able to
excrete bilirubin appropriately.
02:42
The diagnosis is
made on exclusion
of other causes of hepatitis.
02:48
So infections and drugs,
metabolic disease such as non
alcoholic fatty liver disease,
or other genetic causes.
02:55
We will see elevated
trans emanations
and that's to be expected
anytime you injure a hepatocyte,
so that's definitely
not specific.
03:03
There may be elevated
gamma globulins,
so hypergammaglobulinemia.
03:08
But that again is
not entirely specific
and could be also present
with unrelated infections
or other disorders.
03:17
Somewhat specific,
our auto antibodies directed
against smooth muscle antigens,
or anti nuclear antigens,
or liver and kidney
microsomal antibodies,
so sub cellular organelles,
and we can specifically look for
the presence of these antibodies.
03:34
And if positive,
that really puts us down into the
range of autoimmune hepatitis.
03:41
And then of course, we
would want to do a biopsy
to make sure there's
not some other cause
for the inflammation
within the liver.
03:47
How are we going to
manage our patients?
Well, it's what we
would do pretty much
for any autoimmune disease.
03:52
Once we have identified
that as a cause,
we can give immunosuppression,
so we can do corticosteroids,
and fortunately, in the vast
majority of patients about 80%,
they will get a good
therapeutic response
and we're good to go.
04:06
You may also use other agents
that don't require steroids
for someone who may not
be a good candidate,
someone who has
osteoporosis for example.
04:13
So use an Azathioprine.
04:16
In extremis, when you
have severe disease
that has destroyed the liver
and you have no other option,
you can offer the possibility
of liver transplantation.
04:25
The problem is whatever
autoimmune auto antibodies
and or cytotoxic T-lymphocytes
that have been
elicited previously,
they're still there.
04:34
So liver transplant,
even in the setting
of immunosuppression
for the liver transplant
may still have the disease
recurring that autoimmune hepatitis.
04:44
Overall, because of the really
good response to corticosteroids,
the 10 year survival is
excellent, about 90%.
04:50
If there is no
treatment, however,
this is a rapidly fatal disease
with 40% mortality
within six months.
04:58
With that,
you know everything that I know
about autoimmune hepatitis.