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22/09/2015 19:37

Introduction:
Autoimmune
hepatitis
(AIH),
is
a
disease
state
in
which
the
bodies
immune
cells
attack
the
cells

of
the
liver
...

The
immune

system
causes
hepatitis
that
can
be
acute
or
chronic
...

The

aeitiology
of
the
condition
is
not
known
and
is
proposed
that
a
genetically
pre‐disposed

individual,
and
exposed
to
the
correct
environmental
agent(s)
causes
a
sequence
of
T‐cell

mediated
attacks
against
the
liver
antigens
that
produces
a
necro‐inflammatory
response
that

ultimately
results
in
fibrosis
and
cirrhosis
...

The

mononuclear
infiltrate
will
generally
invade
the
limiting
plate
of
the
periportal
tract,
with

demarcated
hepatocyte
boundaries
surrounding
the
liver
parenchyma
...

In
AIH,
the
billiary
tree
is
spared

usually
unless
in
an
overlap
syndrome
with
Primary
Biliary
Cirrhosis
(PBC)
or
Primary

Sclerosing
Cholangitis
(PSC)
...

(3)



The
diagnosis
of
AIH
is
made
in
the
presence
of
a
compatible
histological
picture,
as
well
as
the

characteristic
serological
and
biochemical
findings
that
would
be
typically
expected
with
a
case

of
AIH;
aminotransferase
elevations
are
a
key
feature
as
opposed
to
bilirubin
and
alkaline

phospahtase
abnormalities,
a
generalized
elevation
of
serum
globulins
in
particular
γ‐globulins

and
IgG
which
are
generally
1
...
0
times
greater
than
the
normal
reference
range
...

Antimitochondrial
autoantibodies
are

sometimes
found
in
circulation
in
cases
of
AIH
but
it
is
important
to
note
that
the
presence
of

these
autoantibodies
are
present
in
other
liver
diseases
and
so
their
presence
is
not
definitive
of

AIH
and
only
in
context
of
these
other
abnormal
biochemical,
histological
and
the
clinical

presentation
can
a
diagnosis
of
AIH
be
made
...

(3)






The
case:



From
the
pathologist
report
multiple
core
liver
biopsies
of
an
eight
year
old
female
patient
was

delivered
to
the
histology
lab
in
order
to
gain
a
diagnosis
by
gross
and
microscopic
examination

of
the
section
...

The

pathologist
began
the
investigation
and
it
was
noted
that
the
samples
received
were
of
excellent

quality
...
(2)
...


Interface
hepatitis
was
also
noted
along

with
piecemeal
necrosis
and
rosette
formation
...

There
was
no
evidence
of
steatosis
in
the

hepatocytes
according
to
the
pathologists
report,
nor
was
there
evidence
of
choleostasis
...

The

routine
liver
specials
panel
was
utilized,
consisting
of:
Masson‐trichrome
stain,
Millers
Elastic

stain,
Periodic‐acid
Schiff,
Diastase‐Periodic
acid
Schiff,
Gordon
and
Sweets
silver
stain
for

reticulin,
Rhodanine
for
copper
and
Perl’s
Prussian
Blue
for
Iron
...

Masson
trichrome,
Millers
elastic
and
Gordon
and
Sweets
stains
were

particularly
useful
in
demonstrating
the
changes
in
the
hepatic
architecture,
highlighting
areas

of
hepatocyte
drop‐out
and
condensation
of
connective
tissue
due
to
repair
processes
and
from

cellular
loss
...

Perls
Prussian
blue
did
not

demonstrate
any
stainable
iron
in
hepatocytes
and
the
rhodanine
stain
demonstrated
minimal

amounts
of
copper
associated
protein
in
rare
cells
ruling
out
Haemachromatosis
and
Wilson’s

disease
or
PBC
or
PSC
respectively
...




Discussion:

The
histology
laboratory
in
conjunction
with
other
laboratories
such
as
biochemistry
and

immunology
will
often
make
the
diagnosis
of
autoimmune
hepatitis
...

Pathological
examination
will
reveal
the
‘traditional’

hallmarks
of
autoimmune
hepatitis
on
examination
however,
inasmuch
as
it
is
possible
to
stage

and
grade
the
degree
of
liver
cirrhosis
caused
by
the
disease,
it
is
not
possible
to
make
a

succinct
diagnosis
of
the
disease
without
the
additional
tests
that
are
preformed
by
serological

examination
and
chemical
examinations
...


Aetiopathogenesis
of
AIH

1:
Environmental
agents:

It
has
been
postulated
that
the
pathogenesis
of
AIH
has
an
environmental
component
of
the

aeitiology
that
leads
to
a
cascade
of
T‐cell
mediated
events
directed
against
liver
antigens
in
a

host
that
is
genetically
predisposed
to
the
disease
that
leads
to
auto‐aggressiveness,
necro‐
inflammation
and
fibrotic
processes
in
the
liver
...

This
adds
credence
to
the
hypothesis

of
the
disease
being
a
virally
triggered
disease
(3)
...

According
to
“The
New
England
Journal
of
Medicine”,
the

measles
virus,
Epstein
Barr
virus,
Cytomegalovirus
and
the
hepatitis
viruses
are
believed
to
be

triggers
...

Focus
on
the
abberations
has
provided

some
suggestive
evidence
that
particular
traits
that
have
been
inherited
will
lead
an
individual

to
have
a
higher
propensity
to
develop
AIH
...

A
paper
published
by
the
journal
of

Autoimmunity
describes
several
“complex
trait
inheritance
patterns”
that
are
believed
to
be

linked
to
the
development
of
AIH
...

Whereas
studies
on
populations
in
Japan,
Argentina
and

Mexico
have
found
that
susceptibility
is
linked
to
DRB1*405
and
DRB1*404
alleles
encoding
an


arginine
instead
of
a
lysine
at
position
71
but
still
sharing
the
same
hexameric
motif
with

DRB1*401
and
DRB1*301
...

(4)

...

Transition
of
an
adenine
to
guanine
in

exon
1
at
position
49
confers
susceptibility
to
an
number
of
autoimmune
diseases
including

AIH
...

(4)

3:
Immunopathogenesis

The
mechanisms
that
lead
to
the
breakdown
of
self‐tolerance
in
AIH
have
not
been
fully

elucidated,
though
there
is
evidence
to
suggest
that
there
is
a
defect
in
the
homeostatic

processes
normally
keeping
the
response
to
self‐antigens
under
control
is
involved
...


In
AIH,
T‐regs

(T
regulatory
cells)
are
defective

in
number
with
the
defect
being
most
marked
at
the
presentation
of
disease
than
during
drug‐
induced
remission
when
there
is
partial
restoration
of
T‐regs
...

Recent
experimental
data
that
a
decrease
in
the
number
of
T‐regs
is
possibly
due
to
decrease


production
of
scrufin,
a
protein
product
of
the
FOXP3
gene
(which
is
a
member
of
the
forkhead

protein
family
of
transcription
factors),
the
observations
of
the
study’s
data
suggests
that
the

decrease
in
production
of
scrufin
may
be
a
factor
that
leads
to
immune
dysregulation
and
poor

proliferation
of
T‐regs
thus
leading
to
the
development
or
at
least
conditions
that
would

promote
the
development
of
AIH
...

These

substances
induce
hepatocellular
injury
that
mimics
the
findings
in
AIH
on
histological

examination
...

To
date
the
correlation

remains
unclear
but
particular
drugs
such
as
methyl‐dopa,
diclofenac,
interferon
and

minocycline
have
all
been
found
to
cause
hepatocellular
injury,
with
subsequent
development
of

AIH
in
some
patients
...

(3)




5:
Molecular
mimicry

Another
mechanism
that
has
been
suggested
in
the
development
of
AIH
has
been
molecular

mimicry,
whereby
the
immune
response
to
the
external
pathogens
has
been
redirected
to
self‐
antigens
that
share
a
structurally
similar
component
to
self‐antigens
...

In
chronic
HCV

infection,
up
to
10%
of
patients
demonstrate
LKM‐1
autoantibodies
...

(4)

LKM‐1
antibodies
recognize
the
linear
epitopes
within
CYPD26
,
a
member
of
the
cytochrome

P450
family
of
liver
proteins

and
is
the
main
target
AIH
type
2
...

Interestingly,
CYP2D6
is
believed

to
share
homologous
regions
with
not
only
HCV
but
also
regions
within
CMV
and
HSV
...
(3,4)









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