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Mhm.
Well
a United States Army Medical Department continuing
education program,
liver dysfunction,
post transplantation
with William A.
Briggs,
Lieutenant Colonel,
US Army Medical Corps Chief nephrology
service walter reed Army Medical center Washington,
D.
C.
Now the insidious but
progressive or abrupt and
striking elevations of serum liver
enzymes.
With or without hyperbole room anemia
or with or without clinical symptoms
occur with annoying frequency
In this particular population of patients
and in the walter reed experience
slightly more than a half of patients
have demonstrated elevations of serum serum
trans am in its and lactic di hydrogen is
enzyme levels at some time in their course,
which were not readily attributed to extra hepatic
disease.
This problem is particularly troublesome
because in addition to the need to sort out the
differential diagnosis,
a number of other considerations arise.
For example,
is the patient infectious
and is the handling of the patient's blood
hazardous to the staff and other
laboratory personnel of the hospital?
Will alterations in drug therapy
be necessary?
And what effects will this development or its
management have on the overall course of
the patient?
Well,
like any problem in clinical medicine,
we have to face problem of
liver dysfunction with the differential
diagnosis.
I could have the first lot.
First of all,
it's necessary to consider
and exclude or rule in
potential sources of confusion
relevant to the interpretation of
abnormal elevations and S.
G.
O.
T.
Or even S.
GPT.
Or the LDH is so enzymes,
muscle necrosis from recent surgery
from intra muscular injections,
our potential source of confusion
resolving large hematomas as red cells
break down release can release
striking amounts of
enzymes,
pulmonary disease.
Either pneumonia or infarction
can cause elevations in enzymes,
which might be interpreted as coming from
liver renal infarction
related to severe
rejection or cortical necrosis
may cause elevations in serum enzyme.
And then interestingly enough,
there are a number of drugs which have been reported
to interfere with the cholera
metric essay for Trans AM
in Aces.
And looking over the list drugs which
have been reported to do this and which might
be given to transplant
recipients include
Aretha mason,
hydra,
lysine ison,
is it alpha methyl dopa?
So for fires all and tom you know,
mine.
So the implication is to not only in terms of
considering hepatitis cellular
disease or hypersensitivity liver
disease,
one should look at the drugs of the patients on
and then find out from the clinical pathologist running the
laboratory where the particular essay or
the techniques for the essay would allow
a possible interference with S.
A.
Congestive heart failure,
obviously with right sided failure,
and the paddock congestion can
result in striking liver function
abnormalities.
In addition,
any patient who has recently sustained shock
syndrome for many cause may
have had a period of inadequate hepatic profusion
in the schema,
ca paddock necrosis.
Now more commonly is the
problem of infection
Again,
patients with factory MIA,
predominantly gram negative bacteria,
MIA,
but also indo toxemia.
In some cases with gram positive,
back to re miA,
one can get Apache non specific
hepatitis cellular necrosis or
infiltration with abnormal liver function.
Test
much more commonly considered is that
infection related to
viral hepatitis and its
differential diagnosis.
Now,
first of all,
a lot of attention has been given to the
high incidence of cytomegalovirus
infection and immuno suppressed patients.
In general,
patients with cancers and renal
transplant patients
in the walter reed experience
ed Morrison of the infectious disease Service
has determined that almost 1/2
of the patients Show a
four fold or greater rise in
complement fixing
anti cmv.
E antibody tighter following
transplantation.
This including rises in
antibody tigers,
on the basis of both primary
responses and secondary responses.
A fair proportion of patients come to
transplantation already with greater
than 1-4 antibiotics.
Fighters against c.
m.
v.
And I mentioned earlier that slightly more than
half of the patients at some point in time
also have abnormalities and liver
enzymes.
However,
in only approximately half of those
patients manifesting liver
function abnormalities has there
been a temporal relationship between
the liver dysfunction,
often with clinical symptoms
and C.
M.
V.
C.
Zero conversion to reasonably
implicate that virus in the
pathogenesis of the hepatitis.
Uh huh.
So in addition to cytomegalovirus,
which obviously is a common cause,
one must still consider other viral
agents.
Hepatitis A is unless one
has a family source of
infection or some point source
of infection to determine
incubation time.
We,
at this point in time do not have access to
laboratory assays which will permit
the detection of antigens associated with
uh hepatitis A virus.
But certainly it has to be retained in the differential
diagnosis,
particularly in patients who are at
a negative or a G.
B.
Negative without evidence
of C.
M.
V.
Serial conversion.
Obviously hepatitis B is an
agent which requires serious consideration
in this population of patients
and in the walter reed experience,
there have been six patients showing Ciro
conversion uh or
serum manifestation of
A G.
B.
In the serum,
some sub clinically others with
evidence of hepatitis.
Now the information is incomplete at
this time on determining how many
patients have evidence of
zero conversion for
anti AGB,
evidence for the development of antibody against
ah hepatitis virus
B.
When this information is available,
perhaps a greater proportion of those patients
with hepatitis,
but without C.
M.
V.
Zero conversion will be determined
to have sustained infection with
hepatitis B.
There's another hepatitis viral agent which has
been proposed and that's Hepatitis
C virus.
This was proposed mainly by Prince
who followed patients receiving transfusions
and determine among those patients
with long incubation
hepatitis
that only approximately half of those
patients had evidence
for the development or infection with hepatitis
B virus.
In their examination of that included
follow serial examinations for
energy and be serial
examinations for
anti H.
A.
Antibody.
And in addition in the negative patients also
testing for antibody against
core an urgent of hepatitis
the virus.
The incubation periods from the point
source which was a transfusion
were entirely
equivalent to the incubation period
seen in patients with and
Hepatitis B infection.
And beyond the point considered
reasonable for hepatitis A.
These patients were also examined for evidence of serial
conversion for antibodies against C.
M.
V.
And what the data showed
was that there wasn't any difference in the rate
of conversion.
Again,
C.
M.
V between uh
different groups that is those not developing
hepatitis,
those developing long incubation hepatitis with
evidence for a hepatitis B
infection and then the others
uh KGB negative,
long incubation hepatitis.
So on the basis of that,
his group felt that
this other group of patients could not be explained
on the basis of cytomegalovirus
hepatitis.
That probably is open to argue,
but these are the major viral
agents considered at this point in time.
Hepatitis and renal transplant patients,
R.
C.
M.
V.
Hepatitis B.
And possibly this other very interesting group
who may be infected with hepatitis C.
Not to be overlooked is the possibility that Epstein
Barr virus may be involved in
causing hepatitis in this population of patients.
Few studies where
examination for Ciro conversion
for Epstein barr has been examined,
it's been found.
In addition,
there have been studies demonstrating
zero conversion for Herpes Simplex
virus around the time of
hepatitis.
But the real confusing thing for me is
the overlap and apparent inter
relationships between
simultaneous zero conversion for
hepatitis and it can be
C.
M.
V.
Herpes virus so that it becomes very
difficult to sort out what's the
primary agent causing the hepatitis
versus those which may be turned on simultaneously
in some sort of animistic response
we're related to the same.
We're actually in fact
simultaneously causing infection.
So this is an area of some
confusion and no doubt there will be other
viruses implicated as time goes
on.
Coxsackie viruses et cetera,
which may be involved
in causing the liver
dysfunction commonly seen in these patients,
which cannot be specifically
diagnosed and attributed to
recognized agents.
Uh,
at this point in time for
completeness sake,
fungal and parasitic involvement of the liver should
not be overlooked,
especially in high risk
patients or in the appropriate clinical setting.
Now,
the other major differential
consideration probably besides viral
infection,
is drug toxicity,
either geppetto cellular or cola stat.
And we must,
I've selected out of
long lists of potential
drugs capable of causing a
paddock dysfunction,
those which may be a
utilised in or
by transplant patients.
Ethanol needs no further comment.
He's a thigh.
A prim to me is a very interesting
consideration.
There's always been talk about
primary is a thigpen HEPA no
toxicity.
However,
in the vast majority
of reported cases or cases talked
about it was very difficult for
me to be sure
that in fact,
as a fire brown was the culprit,
since they're often multi factorial
considerations in the patient who develops
hepatic dysfunction.
However,
there's no question in my mind that
is a thigh a prin maybe
synergistically HEPA toxic
or help a toxic superimposed on
previously injured liver.
However,
there have been cases reported and other
people have seen cases
where it has felt certain today is a fire
pit has in fact been the
primary HEPA toxic agent.
Al appear in all is an agent which may be
prescribed to patients with hyper
euros anemia and in addition to the
danger associated with its use in
a patient on a South I appear in this drug also
not infrequently causes liver
dysfunction.
Virtually all the anti tuberculosis drugs have been
associated with
liver enzyme elevations if not
hepatic dysfunction.
Almost all the anabolic steroids,
which are not used very commonly but
may be utilized been associated
with liver dysfunction
as have contraceptive medication
and then young women who
ah In whom birth control is
exercised.
This is one modality which may be
associated with liver disease
and a convulsant drugs.
Matthias scenes alpha method opa
are commonly recognized agents
patient undergoes another surgical procedure.
One must always look at the record to see if there's any
possible association with halothane
anesthesia.
And then just about all these phantom I'd
derivatives,
antibiotics,
oral hypoglycemic agents,
diuretics,
et cetera,
et cetera,
et cetera have been reported to cause
hepatic injury or hispanic dysfunction.
So obviously it's very important to go back and
critically scrutinize the patient's drug
list to see if there's any possible agent which can be
removed and reverse the the
paddock disorder.
And again,
for completeness sake,
it's very important not to forget.
Many of the patients who come to transplantation
May at one point in time developed
separate biliary tract disease
and require either medical or surgical treatment for that.
And of course the other common association
with liver function abnormalities with or without
hyper billy,
Rubin,
EMEA,
etcetera.
Is that not uncommonly seen in association
with pancreatitis,
which also is a problem which
comes up with some frequency and post
transplant patients.
The other thing,
assuming that one does not
identify some
extra hepatic disease or is unable
to identify a
drug which can be
discontinued with resolution of the problem.
The other consideration is what to do,
first of all,
is the liver biopsy in the kids.
Now,
unfortunately,
I think in most people's experience liver
biopsy all too frequently
is not diagnostic and
not terribly helpful in the absence of
specific hissed a pathologic findings
for certain problems.
So in individual cases,
liver biopsy uh
is not necessarily indicated.
I think probably an important role for liver
biopsy with being a
protocol type prospective evaluation
of the paddock dysfunction in these patients.
Where at the end of collecting a large amount of
data,
one could hope to come up with some uh
correlation between history,
pathologic abnormalities and certain
ideology.
The other consideration is whether there should be any
modification in drug therapy,
particularly in patients with clinical hepatitis
can a disease liver metabolizes
Ethiopian appropriately so that the drug
is still immuno suppressive.
Is there any reason to believe that
discontinuing as Cynthia Perrin will speed up the
recovery rate of the
hepatitis.
And in those patients with let's say
uh H.
A.
Positive hepatitis will altering
immuno suppressive therapy improve the patient's ability
to clear the energy.
Well I used to have some thoughts about all that,
all of which has been annihilated by
various peoples different experience
such that many patients with
clinical hepatitis of whatever variety with
no alteration in their drug therapy,
the problem resolves.
And in fact I just heard this
meeting that
Wilford Hall group has had patients who have
developed a G.
B.
Hepatitis with serial conversion
positive and then back to negative again with no
modification of the recent thigpen therapy.
She's very,
very interesting,
liver dysfunction,
post transplantation
with William A.
Briggs,
Lieutenant Colonel,
US Army Medical Corps Chief nephrology
service,
walter reed Army Medical Center Washington D.
C.
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