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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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