CIRRHOSIS OF T H E LIVER: CLINICAL ASPECTS W I T H PARTICULAR
REFERENCE TO LIVER FUNCTION TESTS*
C. J. WATSONf
I suppose there are few diseases having more of common interest to the clinical
pathologist and internist than cirrhosis of the liver. Having approached this
problem first as pathologist, later as clinician, I feel that my interests are equally
divided between the bedside and laboratory manifestations of the disease, and
it is therefore, a particular pleasure to take part in this symposium.
As you are well aware, the clinical diagnosis of cirrhosis may be quite simple
and obvious, or it may be a difficult and many sided problem. Table I includes
only a partial list of the features which need to be kept in mind, some of which
I should like to discuss in more detail.
Previous jaundice in the above table refers to an attack unrelated to obvious
biliary obstruction, such as gall stone colic with jaundice. Previous hepatitis
is believed to be of considerable importance, while true catarrhal jaundice or
mucous choledochitis probably has no etiologic significance. Unfortunately,
the clinical distinction of these two members of the catarrhal jaundice group is
very difficult, but the weight of evidence indicates that hepatitis is much the
more common of the two. Recent serial liver biopsy studies by Iverson and his
co-workers 1,2 - 3 clearly confirm earlier beliefs of a genetic relationship in some
cases between hepatitis and later cirrhosis. An example of this relationship
will be given subsequently.
Evidence accumulating in the past few years indicates that alcoholism is
important in the etiology of cirrhosis (1) by producing a .fatty liver, which in
itself is more likely to become cirrhotic, and (2) because of associated chronic
dietary deficiency, the relation of which to cirrhosis has already been considered
by Dr. Gyorgy. There is no reason to believe that moderate use of alcohol,
with adequate dietary protein, is productive of cirrhosis. In general it appears
probable that the greater the alcohol consumption the more important are the
two factors just mentioned. A further effect of severe chronic alcoholism is the
production of anorexia which then enhances the protein deficiency factor. Persistent anorexia is a very grave symptom in patients with either alcoholic fatty
liver or cirrhosis, since it is responsible for a vicious cycle which is very difficult
to break.
Unexplained hematemesis is always suggestive of cirrhosis and calls for careful
x-ray studies for esophageal varices, as well as studies of liver function. In regions where schistosomiasis is endemic, hematemesis is frequently observed.
In common with other tropical diseases we will undoubtedly have to give much
more attention to this condition in the future. I think you are well aware that
*Read by request of the Council as part of a symposium at the Twenty-Second Annual
Meeting of the American Society of Clinical Pathologists, Chicago, June 5,1943.
t From the Department of Medicine, University of Minnesota, Minneapolis.
129
130
C. J. WATSON
the latter stage of the disease as caused by S. Mansoni or S. japonicum, is rather
uniformly characterized by cirrhosis of the liver, congestive splenomegaly, and
esophageal varices.4
Jaundice in cirrhosis is of importance only as it focuses attention on the likelihood of liver disease. In approximately one half of the cases jaundice does not
occur. The jaundice may be slight or intense^ and of retention or regurgitation
type. These variations are of little moment in differential diagnosis. The tint
of a marked jaundice has some significance, outspoken biliverdin jaundice speaking much more strongly in favor of neoplastic biliary obstruction, rather than
cirrhosis. Pigmentation of the skin is common in patients with hepatic cirrhosis.
I should like to stress that this pigment is usually melanin, not hemosiderin.
The hepatic facies and habitus are often suggestive but do not deserve special
emphasis. Spider nevi and the "hepatic foetor," however, are relatively important.
Demonstration of a small liver by percussion and x-ray is often very helpful
in leading to a diagnosis of cirrhosis. Mental changes are at times quite sugTABLE I
CERTAIN FEATURES TO BE K E P T IN M I N D IN THE DIAGNOSIS OF HEPATIC CIRRHOSIS
History
Physical
Laboratory
findings
findings
Previous jaundice: alcoholism and dietary deficiency; chemicals; unexplained hematemesis; schistosomiasis;
Jaundice, pigmentation; hepatic facies and habitus; spider
nevi; foetor hepaticus; collateral circulation; ascites and
edema; enlarged or small liver; enlarged spleen; mental
changes or coma.
Jaundice of retention or regurgitation type; urobilinogenuria; variable disturbances in liver function.
gestive, so much so that one might well speak of an "hepatic encephalopathy."
Drowsiness, mild disorientation, at times euphoria, later apathy and coma, may
be mentioned.
Large, multiple spider nevi, especially those occurring over the shoulders,
arms and chest, or the back of the neck, are highly suggestive of cirrhosis. Single
nevi on the nose or cheeks are much less significant, although the reason for this
is not clear. Appearance of nevi on the chest or upper extremities, while the
patient is being observed, is especially significant. They occur but very rarely,
except in the area drained by the superior vena cava, although it is doubtful
that this is anything more than coincidental, since the nevi are arterial in character, consisting of a central aneurysmal dilatation with many small radiating
branches. Pulsation may be noted in the larger lesions. The reason for their
occurrence is unknown. Bean 5 has recently reported experiments which indicate
a relationship with the sex hormones, at the same time advancing the view that
the cirrhotic liver does not remove these substances in the normal manner.
The significance of the "foetor hepaticus," or "amine odor" has not been
adequately appreciated. When identified beyond doubt, this odor accurately
indicates a diffuse liver disease. I t is most marked in cases of atrophy of the
liver or hepatic coma due to cirrhosis.
CIRRHOSIS OF THE LIVER
131
The qualitative urobilinogen test, especially if used serially and if strongly
positive, may be quite sufficient, in company with the history and physical findings, to permit the diagnosis of cirrhosis. In my opinion, the Ehrlich reagent, as
described in most text books, is too concentrated. A long experience with the
following formula has shown it to be most satisfactory: Pure p-dimethylamino-'
benzaldehyde 0.7 gm.; Concentrated (37-38 percent) HC1, 150 c c ; Distilled
water, 100 cc.
The use of sodium acetate is very helpful in bringing out the maximum color
and in reducing that due to indol or skatol. The test is carried out by adding
5 cc. of the Ehrlich's reagent to 5 cc. of urine, followed by 10 cc. of a saturated
aqueous sodium acetate solution. If the urine is quite dilute, significant increases of urobilinogen may be missed with the qualitative test. For this, and
other reasons, the quantitative procedure is advantageous. The amount in the
normal urine probably does not exceed 3.0 mg. in 24 hours. In severe liver
damage the amount in the urine may exceed that in the feces.6 If there is a
high grade suppression of biliary outflow, evaluation of the urine-stool ratio is
helpful.
Under several conditions there may be relatively little urobilinogen returning
to the liver in the portal circulation: (1) complete or high grade interference to the
outflow of bile; (2) diminished formaticm of bilirubin because of a reduced rate
of blood destruction, or "throttling," as in certain anemias; (3) diarrhea or other
cause of malabsorption from the colon; (4) renal insufficiency. When such
factors, with exception of the last named, are present, one may use the stercobilin
tolerance test, in which a fixed load is given to the liver in a short time. Crystalline stercobilin is readily isolated from human feces, that of hemolytic jaundice
patients constituting a particularly rich source. 50 mg. of the crystals are
dissolved, with the aid of stirring, in 20 cc. of hot M/20 Na 2 C0 3 solution, exactly
as in the preparation of the bilirubin solution for the bilirubin tolerance test of
v. Bergman-Eilbott. After cooling to room temperature, the water-clear solution
is injected slowly intravenously. All of the urine is collected for the subsequent
24 hour period, and the total urobilinogen* is determined. Under normal circumstances little or none of the injected stercobilin appears in the urine, while
it is evident from repeated observations that considerable amounts quickly
appear in the bile. In patients with liver damage large fractions or even the
entire 50 mg. may be excreted in the urine. The test is not employed in cases
where the native uribilinogen has already been found to be greater than 5 mg. in
24 hours.
In the past many have thought that the presence or absence of urobilinogenuria
was a sufficient index of liver function. Others have advocated one or another
liver function test as sufficient unto itself. The more one sees of the clinical
study of liver function, the more convinced one becomes that a single test is likely
to be quite insufficient. In many cases, at least, it is essential to gain a composite view of liver function, a profile, or general index, or, if you will, an hepatogram. One might say that it was necessary to take a vote of the various func* The term urobilinogen includes the chromogens mesobilirubinogen and stercobilinogen.7
132
C. J. WATSON
tions of the liver in order to determine its ability to work as a unit. With my
associates, Doctors F. W. Hoffbauer and G. T. Evans, a means has been devised
of recording such a composite, as shown in fig. 1. The line in boldface type
indicates a relatively arbitrary normal value for the various procedures indicated
a t the bottom. In general a departure above this line is indicative of diminishing
liver function, although in the case of the serum bilirubin and the feces urobilinogen, interpretation depends upon knowing whether the jaundice is due to
extrahepatic biliary obstruction or not. It may be noted that a somewhat
different study is needed for the jaundiced, as compared with the non-jaundiced
patient. Thus, in the latter, the feces urobilinogen, serum phosphatase, total
cholesterol and prothrombin need not be done routinely, while in the jaundiced
patient the bromsulphalein test is omitted. If the standard procedures are indecisive, supplementary and more sensitive tests may be employed, as noted
in fig. 1. One of the purposes of employing some such plan as shown in fig. 1
and in presenting it in a preliminary way at this time is to stimulate further
composite studies of liver function and to seek a more uniform method of recording. We regard the plan shown as entirely subject to revision pending further
experience with it. I t would require too much time to discuss the relative merits
of the various procedures shown in fig. 1, but it may be said that those tentatively
slated for omission in the next revision, at least insofar as value to clinical diagnosis is concerned, are: (1) the serum phosphatase, (2) the intravenous galactose
test, (3) the bilirubin tolerance test. Our information, as yet, is much too scanty
as regards urinary porphyrin excretion, but the method is believed to have
considerable promise, especially if a simple procedure can be developed for
quantitative estimation of the coproporphyrin isomers. Encouraging results
in this direction have been obtained and will be reported separately.
Obviously, it is quite impracticable to employ the liver function study, as
shown in fig. 1, for purposes of "mass screening", as for example in chemical
industries or in the armed forces. I believe that there are four procedures which
should be employed for this purpose: (1) Icterus index (fasting); (2) Urine
urobilinogen (serial qualitative test); (3) Cephalin-cholesterol flocculation test
of Hangar; (4) Bromsulfalein, 2 mg./kilo, 20'. Of these, it is probable that the
second and third will yield the most information as to incipient liver damage.
Before going on to discuss clinical examples, let me say something of a general
nature about dietary management. Many clinicians have undoubtedly been
living in a sense of false security in the belief that carbohydrate was of chief
importance and that the daily administration of glucose intravenously would
accomplish everything that could be accomplished. The fallacy and danger of
this belief have been emphasized particularly well by Ravdin and his associates.8
I t will be sufficient to recall that the administration of three liters of five per cent
glucose solution will supply but 600 calories, an amount far below the basal requirement, especially as the latter is likely to be increased because of the patient's
disease. If the amount of glucose be increased, it is necessary to bear in mind
the limiting factor of rate of utilization which, under most circumstances, at
least, is 0.8 gram per kilo per hour. This will usually permit a safe administra-
CIRRHOSIS OF THE LIVER
133
LIVER FUNCTION STUDY
Hospital No..
Name
Working diagnosis.,
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
4+
3+
2+
1+
40
35
30
25
20
15
10
5
0
0
•
H
SA
SG C C B ( 2 )
20'
100.0
90.0
SO.O
70.0
65.0
60.0
55.0
50.0
45.0
40.0
35.0
30.0
25.0
20.0
15.0
10.0
9.0
8.0
7.0
6.0
5.0
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
UU
Stan dard , noc -jaun diced
H
SA
SG
CC
B(2)
B(5)
SB
UU
FU
TC
PT
BT
ST
G
PR
SP
UCP
USR
2.5
2.0
1.5
1.0
0.5
0.0
SB
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
H
SA
SG C C T C
4+
3+
2+
1+
0
100
125
150
175
200
250
300
350
400
500
600
700
0
10
20
30
40
50
60
0 70
5 80
10 100
15
20
25
30
40
50
SP
s bandard,
1.0
.9
.8
.7
.6
.5
.4
.3
.2
.1
.05
.01
.005
.001
PT USR
j aunc iced
100.0
90.0
80.0
70.0
65.0
60.0
55.0
50.0
45.0
40.0
35.0
30.0
25.0
20.0
15.0
10.0
9.0
8.0
7.0
6.0
5.0
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
UU
Dates, ind..
Final diagnosis
30.0
25.0
20.0
18.0
16.0
14.0
12.0
10.0
9.0
8.0
7.0
6.0
0
1
2
3
0
50
4
40 40 100 10 1000
5 5.0
750
35 30 90 20
10 4.0
500
30 25 80 30
20 3.5 30
400
25 20 70 40
25
30 3.0 25
300
20 15 60 50
20
20
200
40 2.5
15
15 10 50 60
50 2.0 15
150
8 40 70
10
10
1.5 10
75
100
6 30 SO
5
5
5
100 1.0
50
4 20 100
0
0
150 0.5
40
2 10
200 0.0
30
0
0
20
300
10
400
0
500
600
700
800
1000
F U S B B ( 5 ) B ( 5 ) B T S T G P R UCP
30'
45'
i3upp ieme n t a r Y
Hippuric acid in gm., one-hour urine specimen (1.77 gm. Na benzoate i.-v.)
Serum albumin in gm. per cent
Serum globulin in gm. per cent
Cephalin cholesterol, 0 to 4 +
Bromsulphthalein, 2 mg. per kilo, in per cent retained
Bromsulphthalein, 5 mg. per kilo, in per cent retained
Total serum bilirubin in mg. per cent
Urine urobilinogen in mg. per 24 hours
Feces urobilinogen in mg. per 24 hours
Total serum cholesterol in mg. per cent
Prothrombin in per cent of normal
Bilirubin tolerance, per cent retained 4 hours after 1 mg. per kilo, i.-v.
Stercobilin tolerance, mg. (as urobilinogen) appearing in 24-hour urine after 50 mg., i.-v.
Mg. galactose in blood 75' after 0.5 gm. per kilo, i.-v.
Per cent response of prothrombin toward normal after 1 mg. 2 methyl, 1,4 naphthoquinone, i.-v.
Serum phosphatase in units
Urine coproporphyrin in y per 24 hours
Urine-stool urobilinogen ratio
FIG.
1
134
C. J. WATSON
tion of 3000 cc. of 10 per cent glucose in six hours. Larger amounts of intravenous fluid over longer periods, especially if given day after day, are generally
inadvisable; the amount of fluid that may be given parenterally with safety
must, of course, be determined for any given case, depending upon age, cardiovascular efficiency, and other factors. If 3000 cc. of 10 per cent glucose are given,
the 1200 calories provided will still not approximate the number of calories
required to spare body protein. In some clinics it has been customary to employ
even more hypertonic glucose solutions, (e.g., 15 to 20 per cent). These have
the disadvantages of loss of glucose in the urine when the critical rate of utilization is exceeded, and also, of producing thromboses with considerable frequency.
Inadequate provision of glucose at once results in utilization of body protein for
energy, so that it is easy to understand how an individual with liver disease and
profound anorexia or even vomiting, receiving only parenteral glucose, can very
quickly develop a marked protein deficiency. You have just heard from Dr.
Gyorgy as to the essential character of protein, insofar as the protection of the
liver is concerned. Whether all of this protective action is due to the amino
acid methionine, and whether cholin is important only as a methyl donator
for the formation of methionine, remain to be determined. The animal experiments which you have heard described indicate that neither cholin nor cystin
alone are nearly as effective as methionine, while, given together, their cirrhosis
preventing effect is almost as effective. Methionine, of course, is not yet available in sufficient quantity for any satisfactory clinical trial in the treatment of
hepatic cirrhosis or even of more acute liver injuries; nor has the clinical experience with cholin-cystin mixtures as yet been appreciable. Broun 9 and Gordon10
have each noted evident benefit. We have employed cholin-cystin in a capsule
containing 0.5 gram of each, given four times daily, in three cases of cirrhosis.
Two of these were advanced; both had marked ascites, and one a marked jaundice. The latter patient received the mixture for one month, without evident
benefit. Liver (punch) biopsy revealed an extensive cirrhosis. This patient
left the hospital and it was ascertained that she died two months later. The
other patient with ascites received cholin-cystin for but 10 days, during which
period there was no subjective or objective improvement. The third case mentioned is one of latent cirrhosis following epidemic hepatitis. This case is considered to be of unusual interest and significance. The important clinical features are given in the following.
M.M., 9 , 38 housewife.
3-20-42: Onset of jaundice with chills, fever, pruritis, anorexia. Jaundice also present
amongst other members of family and neighbors.
4-1: Jaundice receding. Onset of ascites and edema of legs.
4-24: Mild jaundice, marked ascites and edema. Liver and spleen not felt. Spider
nevi. Admitted to hospital.
Period of 4-29-42 to 5-15-42: "Liver" diet = P 150 (50 per cent meat), C 350, F 50 +
frequent feedings of skim milk-Ca caseinate mixture + Vitamin B complex, capsules two
t.i.d., + Brewer's yeast powder, Grams 16 daily. Serum bilirubin: 2.2 to 1.1 mg. per 100 cc.
Serum proteins: 5.6 to 6.7 grams per 100 c c . Urine urobilinogen: 12.8 to 1.4 mg. per day
Weight: 68.0 to 58.0 kilos. Marked diuresis.
CIRRHOSIS OF THE LIVER
135
5-15: Liver edge 7 cm. below rib margin. Spleen palpable.
6-1: Ascites and edema have completely disappeared.
2-15-43: Feels well. No jaundice. Liver enlarged and firm. Spleen not palpable.
Serum bilirubin 0.8 mg. Serum proteins 6.4 grams per cent, albumin 3.5 grams %." Total
cholesterol 153 mg. Bromsulfalein (5 mg./kilo) 30 min., 13 per cent. Urine urobilinogen
0.4 mg.
Liver (punch) biopsy: Cirrhosis (seefig.2).
4-20: Cholin-cystin gms. 2 daily for past 2 months. Discontinued because of nausea
which the patient attributed to a reduction in her protein intake due to meat rationing.
She stated that as long as she ate enough meat she was able to tolerate the cholin-cystin
mixture. Serum proteins 6.8 grams %, albumin 4.0%. Total cholesterol 144 mg. Stercobilin tolerance 16.3 mg. Bilirubin tolerance normal (0 = 1.87; 5' = 4.57; 4 hrs. = 1.65).
Intravenous hippuric acid 0.99 mg.
In the above instance the marked improvement on the high protein, high carbohydrate, B complex, yeast diet is noteworthy, although it is, of course, quite
impossible to determine the important factors. No additional improvement
was noted after two months of the cholin-cystin mixture, in addition to the high
protein high carbohydrate diet. I t was hoped to obtain another liver biopsy
at the end of this period, but unfortunately two attempts were unsuccessful.*
The histologic changes noted in fig. 2 leave no doubt that this patient is suffering
from a latent cirrhosis, and while there is a bare possibility that she already had
it before the attack of epidemic hepatitis, it is considered much more likely that
the cirrhosis followed rather than preceded the attack.
Despite the evidence favoring a high protein diet in cases of cirrhosis, it is
clear that in some instances marked improvement occurs more or less spontaneously. This is exemplified by the following case:
M. G., o",58. Chr<jnic alcoholism; moderate obesity.
9-23-41: Admitted in semistuporous state. Disoriented. Mild jaundice. Foetor
hepaticus. Right saphenous thrombophlebitis. Temp. 102.4 F . Blood culture negative.
Markedly enlarged liver and spleen. No ascites. Urine urobilinogen: 9-25, +H—I—h;
9-27, + + + + ; 10-1,82.1 mg.; 10-12, 67.0 mg.; 10-16, + + + ; 10-22,34 mg.; 12-29 + . Serum
bilirubin: 1' = 0.7; 15' = 1.17; T = 1.48 (9-27^1). Serum proteins: T* = 5.8; At = 2.7;
G* = 3.1 (9-27^1).
9-23 to 9-26: Fluids, glucose, fruit juices. No protein or vitamins. Marked improvement;
oriented; appetite returning.
9-26 to 10-25: P 150, C 200, F 30. Yeast, liver extract, vitamins. Discharged feeling
quite well.
11-26-42: Readmitted in good condition. Liver edge down 10 cm. Lower pole of spleen
at level of umbilicus. Serum bilirubin: 1 = 0.29; 15' = 1.04; T = 2.46 mg. Serum cholesterol = 110 mg. per 100 c.c. Galactose clearance = 13 mg. per 100 c.c. Bromsulfalein (5
A25
mg.) = 6 per cent at 30'. Serum proteins: - — - Urine urobilinogen = 13.5 mg./24 hrs.
G 3.5
Stercobilin tolerance = 68 mg./24 hours.
* Dr. F . W. Hoffbauer, using the Vim-Silverman needle, according to the suggestion of
Tripoli and Fader", has found that, while the method is often very helpful, the principal
disadvantage is the failure to obtain a satisfactory core of liver in about 40 per cent of
trials. 2-2-44. A modification in the needle which will be described subsequently, has
largely eliminated this difficulty.
t T = total protein, A = albumin, G = globulin.
136
C. J. WATSON
1-29-43: Has been lax about diet. Eating fats and pastry.
Serum bilirubin 2.05 mg. Urine urobilinogen 85 mg. per day.
Considerable alcohol.
In the above case the initial improvement was so rapid that it is questionable
whether one could ascribe it to anything more than fluids and complete rest.
I t appeared probable that the thrombophlebitis and associated fever were precipitating factors insofar as a temporary hepatic decompensation was concerned.
With rest and replenishment of fluid balance improvement was surprisingly
prompt. The possible role of the glucose was doubtful. This simply reveals
again how difficult it is to interpret clinical therapeutic studies in which a scientific control is out of the question. Certainly if the above case had been treated
from the outset by means of intravenous methionine, or a high protein or amino
acid intake, one might readily have made an incorrect interpretation.
The liver function studies in the above instance are of considerable interest.
First it may be noted that the serum bilirubin was remarkably constant and that
it was, in fact, less during the period of impending hepatic coma, than later when
the patient had considerably improved. In other words, the serum bilirubin in
this case failed to indicate the marked hepatic dysfunction which was, however,
quite well shown by the patient's behavior, the marked foetor hepaticus, and the
very large amounts of urobilinogen in the urine. The qualitative Ehrlich test
alone, as indicated by the 4 plus reactions on 9-25 and 9-27 was quite sufficient
to point strongly toward severe liver functional impairment. Later the urobilinogenuria diminished somewhat but the more sensitive stercobilin tolerance
test was strongly positive.* At the same time the galactose and bromsulfalein
tests were almost normal. It is exactly this type of apparent discrepancy that
it is hoped the liver function index or profile (fig. 1) will throw more light upon,
particularly as concerns prognosis and the effect of treatment.
As already noted, the problem of supplying adequate protein to the patient
with cirrhosis and associated anorexia is often a most difficult one. In many
instances nothing more than liquids can be tolerated. Diarrhea occurs in a
small proportion of the cases receiving this treatment. For some time now we
have used frequent feedings of skim milk enriched with a commercial milk
powder containing a liberal supply of vitamins.f In a number of instances this
mixture has been administered by constant drip through a nasal tube during a
part of each 24 hours, usually from 10 p.m., to 8 a.m. Diarrhea occurs in a
small proportion of the cases receiving this treatment. More recently we have
been impressed with the possibilities of pasteurized beef serum, mixed with
tomato juice. This is a very palatable beverage and one whose general utility
ought to be thoroughly explored since beef serum at the present time is being
sold at ridiculously low prices as "tankage" for hogs. The beef serum albumen
is undoubtedly an excellent protein both from the standpoint of nutrition generally, and insofar as provision of methionine and protection of the liver is con* Actually, this need not have been carried out in this instance, since the native urobilinogen was well over 5 mg. per day.
t Dietene, supplied through the courtesy of the Dietene Corporation, Minneapolis.
1:6 or 1:8 mixture with skim milk.
ERRATUM
FIG.
2
The above figure was omitted from the Paper "Cirrhosis of the Liver:
Clinical Aspects with Particular Reference to Liver Function Tests" by C. J.
Watson. March issue, Vol. 14, No. 3.
137
CIRRHOSIS OF THE LIVER
cerned. In this day of increasing protein deficiency, it would seem highly desirable to consider storage of large amounts of dried beef serum against a time of
severe need. To date we have not given this material in sufficiently large quantities, nor over a long enough period of time to determine whether it could be
used to good advantage as the chief source of protein in patients with liver
disease, and to what extent it might have therapeutic usefulness from the standpoint of protection of the liver parenchyma. A study intended to answer these
questions is in progress at the present time.
REFERENCES
(1) IVEHSON, P . , AND RoHOLM, K . : On
and pathological hemoglobin m e a s p i r a t i o n b i o p s y of t h e liver w i t h
tabolism. I n Downey's Handbook
r e m a r k s on i t s d i a g n o s t i c signifiof H e m a t o l o g y , P a u l H o e b e r a n d
cance. Acta Med. Scandinav.,
C o . , N e w Y o r k , 1938, v o l . 4 , p .
2500.
102:1,1939.
(2) K B A R U P , N . B . , A N D R O H O L M , K . :
(7) W A T S O N , C . J . : T h e bile p i g m e n t s .
T h e d e v e l o p m e n t of c i r r h o s i s of
N e w E n g l a n d J . M e d . , 227: 665,
t h e liver after a c u t e h e p a t i t i s , e l u 1942.
cidated by aspiration biopsy. Ac(8) R A V D I N ,
I.
S.,
THOKOGOOD,
E.,
t a M e d . S c a n d i n a v . , 108: 306, 1941.
RIEGEL,
C,
P E T E R S , R.,
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