The Modern Treatment of Cirrhosis of the Liver

THE MEDICAL CLINICS of

NORTH AMERICA NATIONWIDE NUMBER

SYMPOSIUM ON NEW DEVELOPMENTS IN MEDICINE THE MODERN TREATMENT OF CIRRHOSIS OF THE LIVER

W.

HALSEY BARKER,

M.D.*

PRIOR to the last decade the treatment of cirrhosis of the liver was largely symptomatic. A high carbohydrate diet was sometimes utilized on the grounds that carbohydrates exerted a sparing action upon the liver. Since alcohol was thought to be an important etiologic factor, the victim of cirrhosis was urged to become a total abstainer. Diuretics and paracentesis were employed as indicated for relief of ascites, and at times the surgeon was called upon to perform an omentopexy. However, none of these measures was of more than temporary value, and the prognosis in cirrhosis, once ascites had developed, continued to be practically hopeless. Indeed, it was in the rarest of cases that ascites ever cleared up. Ratnoff and Patek 1 present an excellent discussion of the natural history of Laennec's cirrhosis of the liver in their analysis of 386 cases. ETlOLOGY OF CIRRHOSIS

The etiology of cirrhosis of the liver remains far from settled. In searching for factors that predispose to cirrhosis and thus may bear upon its etiology, Patek 2 found one glaringly prominent fact, namely, that alcoholism is the most common antecedent factor in this disease in the Western Hemisphere. Yet in about 30 per cent of cases seen at autopsy, there had been no story of alcoholism. Furthermore, when he examined the data on chronic alcoholism, he found that only a small proportion of the victims, variously estimated at from 1 to 25 e

From the Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. "Associate in Medicine, Johns Hopkins University School of Medicine, and Physician-in-charge, Clinic for Gastro-Enterology and Nutritional Diseases, Johns Hopkins Hospital. 273

274

w.

HALSEY BARKER

per cent, develop Laennec's cirrhosis. It seemed probable that the association was intimate but not direct; that alcoholism per se did not cause cirrhosis of the liver. The fact that the disease occurs commonly in India, Java and Ceylon, where alcoholism is rare, would support this interpretation. Moreover, there would seem to be incontrovertible evidence that cirrhosis may follow severe toxic hepatitis (e.g., from carbon tetrachloride or arsenical drugs) and so-called infective or epidemic hepatitis in nonalcoholic individuals. Since alcoholic beriberi and pellagra had been shown to be similar to the endemic forms of these diseases, it seemed plausible to Patek that the correlation between alcoholism and cirrhosis of the liver might also be due to a coexisting nutritional deficiency. This hypothesis appeared particularly attractive in view of the high incidence of vitamin B-complex deficiency noted in patients with cirrhosis, as, for example, Wayburn and Guerard's3 report of multiple peripheral neuropathy in 17 per cent of a large series of cirrhotic patients. The trouble with the severe alcoholic is that he forgets to eat; thus it seems fair to assume that many of the various morbid states to which an alcoholic is subject are primarily manifestations of vitamin deficiency. Although alcohol conceivably may exert toxic effects in the face of a poor diet, it must play a minor role at best, since all of the deficiency syndromes may develop in total abstainers on deficient diets. An abundance of experimental evidence has accumulated attesting to the etiologic role of nutritional deficiency in the production of liver disease. In 1924, Allan and his associates 1 reported that depancreatized dogs receiving adequate amounts of insulin and a diet of lean meat, sucrose and bone ash did not survive for longer than a few months. They also observed that failure of liver function due to fat infiltration of the liver found in such animals could be prevented by adding raw pancreas to the diet. These observations provided the necessary stimulus for a tremendous amount of research on lipotropic substances,5 or substances preventing fat deposition in the liver, among them lecithin, "lipocaic," choline and inositol. Mac Lean and Best6 in 1934 reported that fat was deposited in the liver of rats kept on a high-fat intake and this fatty deposition could be prevented by giving sufficient choline (now generally regarded as a member of the vitamin B complex). Subsequently, Gyorgy and Goldblatt 7 produced fatty livers with necrosis in rats maintained on a diet deficient in the vitamin B complex even though supplemented with thiamine, riboflavin and pyridoxine. The addition to the diet of yeast, a yeast extract, or 2 mg. of choline a day usually prevented the changes in the liver. Rich and Hamilton8 succeeded in reproducing true cirrhosis of the liver in rabbits fed a deficient diet. The development of this experimental cirrhosis was not prevented by the addition of thiamine, riboflavin, pyridoxine, nicotinic acid or vitamins A, D and E to the basal diet,

MODERN TREATMENT OF CIRRHOSIS OF LIVER

275

whereas a daily supplement of 5 gm. of dry brewer's yeast gave full protection. Rhoads and Miller 9 observed that the ability of the liver to excrete intravenously injected bilirubin was reduced in dogs when the animals were fed a diet lacking in the vitamin B~ complex and that this function could be restored by the feeding of a normal diet or by the administration of crude liver extract. Many other studies indicate a protective action against hepatotoxins by the feeding of yeast, choline, methionine or high protein diets. Interpretation of disease in man in the light of experimental work in animals must be made with the utmost caution. However, certain clinical observations already mentioned suggest that vitamin deficiency may be an all-important etiologic factor in fatty liver and cirrhosis of the liver in human beings. Undoubtedly, clinical and experimental observations were of equal importance in giving impetus to the development of the modern treatment of cirrhosis by a nutritious diet high· in calories, protein and vitamins. Before taking up the details of this dietary treatment of cirrhosis, it might be well to review briefly the symptomatology of the disease and the factors affecting the prognosis SYMPTOMATOLOGY AND PHYSICAL SIGNS

The most important symptoms of cirrhosis in Patek's large series were, in order of frequency, as follows: abdominal swelling, peripheral edema, weight loss, nausea and vomiting, abdominal pain, and hematemesis. The most common initial symptoms and signs occurred in the following order: swollen abdomen, abdominal pain, hematemesis, edema of legs, jaundice, nausea and vomiting, and weakness. Physical signs in the series of 386 patients were listed thus: ascites 78 per cent, palpable liver 75 per cent, jaundice 65 per cent, edema 61 per cent, palpable spleen 44 per cent, hemorrhoids 27 per cent, fever 24 per cent, collateral venous circulation 23 per cent, vascular spiders 15 per cent, and a number of other less specific manifestations, among them hemorrhagic phenomena. CLINICAL COURSE AND PROGNOSIS

Ratnoff and Patek succeeded in following 245 of their series of 386 patients until their death; more than 60 per cent of these deaths occurred within one year of the first symptoms of the disease. An additional 117 patients were lost to follow-up, leaving only twentyfqur patients known to be alive at the time the records were reviewed. Spontaneous loss of ascites occurred in only about 7 per cent of the cases. After the onset of ascites 47 per cent of the patients survived six months, 32 per cent one year, and but 17 per cent survived two years. Following the onset of jaundice (superimposed upon preexisting cirrhosis) the survivorship curve was very similar to that following the onset of ascites. Of the 106 patients in the series who

276

\\T. HALSEY BARKER

suffered from hematemesis, 40 per cent died within one month of the initial hematemesis, with an additional 30 per cent succumbing by the end of the first year. However, if a patient survived one year following hematemesis, he had a good chance of surviving several years longer. The most common causes of death in cirrhosis, according to these same authors, are liver failure or cholemia, an ill-defined state in which the patient may become stuporous or delirious, finally sinking into coma (jaundice is usually but not invariably present); hematemesis from ruptured esophageal or gastric varices; and secondary infections. The prognosis following omentopexy, should the patient survive the initial postoperative period, was at first considered to be better than without treatment. Recent studies, however~ indicate that although improvement may be noted in individual instances, the average prognosis for patients with cirrhosis is not appreciably changed by operative therapy. There were thirty-four postoperative deaths in Ratnoff and Patek's series, representing an operative mortality of 40 per cent. DIETARY TREATMENT OF CIRRHOSIS

In 1937 PatePO published a preliminary report on the treatment of alcoholic cirrhosis with a nutritious diet together with vitamin supplements. Convinced that the improvement that followed treatment appeared to be outside chance expectations, he was encouraged to extend the program of treatment to embrace a larger series of patients over a longer period of time and he recognized the importance of comparing the course of patients so treated with that of a similar group of hospitalized patients who had not received special dietary therapy. This led to the review of the 386 "untreated" cases by Ratnoff and Patek,l the 1941 report by Patek and PostI l on fifty-four patients with decompensated cirrhosis treated with the new dietary regimen, and the 1943 paper by Patek 2 furnishing a more recent follow-up on the 1941 series. Through a careful analysis of the symptomatology and physical signs in his group of fifty-four "treated" patients and a comparison of the figures thereby obtained with those for the "untreated" group of 386 patients, Patek was able to present convincing evidence that the "treated" group prior to receiving treatment was, if anything, more severely afflicted than the "untreated" group. Eighty-nine per cent of the "treated" patients had ascites when first observed, while 63 per cent had jaundice and 24 per cent gave a history of hematemesis. In other words, it is fair to conclude that the "treated" and control series are entirely comparable as far as severity of the liver condition is concerned. And as a corollary to this conclusion, it would seem justifiable to accept any statistically supported improvement in the average survival period for the treated group as distinctly significant. What then is this Patek dietary regimen? The diet is rich in protein and ample in carbohydrate and fat. Containing approximately 3600

MODERN TREATMENT OF CIRRHOSIS OF LIVER

277

calories, it is distributed in the following proportions: protein 139 gm. (including the protein in the brewer's yeast), fat 175 gm., and carbohydrate 365 gm. The diet* consists largely of meat, milk, eggs, fruit and green vegetables. Meat is served twice daily; milk five times dailythree times with meals and twice with 25 gm. of powdered brewer's yeast. The yeast is fed in graded, increasing doses up to the final amount. Even so, certain patients cannot tolerate brewer's yeast; for these, oral vitamin B complex has been substituted in the form of liquid yeast concentrates. In addition, thiamine hydrochloride (5 mg.) is injected intramuscularly every day, and concentrated liver extract (5 cc.) twice weekly. During the critical period of hepatic decompensation the cirrhotic patient, to whom food is often loathsome, presents a real challenge to nursing and dietetic care. Patek urges that the intake at each meal be charted in order to keep accwmt of the actual consumption. In patients with ascites salt intake is restricted only by the exclusion of a salt shaker from the tray; fluids are allowed up to 2000 cc. daily. Too rigid restriction of salt and water may prove harmful to these patients by precipitating symptoms of hypochloremia and dehydration. It should be pointed out that, with each abdominal tap, considerable salt is removed as well as an appreciable quantity of protein. Nonetheless, it is desirable to tap abdominal fluid before the patient is too distended, for this interferes seriously with the appetite. In an attempt to space out the intervals between paracenteses, mercurial diuretics may be injected once or twice a week following the oral administration of 3 to 4 gm. of ammonium chloride daily for several days. Of Patek's fifty-four patients treated on this regimen, twenty-two showed signs of progressive failure and went on to die, eighteen of them succumbing within the first five months of starting treatment. Twelve of the fifty-four patients were partially improved as shown by the loss of ascites and improvement in liver function tests; five were lost sight of, three remained free of ascites but failed to regain robust health, while four subsequentlv died after being ascites-free for over two years in each instance. The remaining twenty of the fifty-four patients were regarded as showing signs of "clinical recovery," their improvement fulfilling three criteria: (1) gain in weight and strength permitting the patient to resume his previous activity; (2) loss of ascites, edema and jaundice without recurrence; (3) changes in serum proteins, Takata-Ara, and bromsulfalein excretion tests towards norm?1 values. In the latter group, although it seemed highly unlikely that the histologic changes were completely reversed, it was clear that the process had been arrested or partially reversed. Comparing the control and "treated" series, Patek and his associates showed that 60 per cent of the treated patients, in contrast to only about 7 per cent of the control group, experienced the, spontaneous • Complete dietary list may be found in the article by Patek and Post. l l

278

w.

HALSEY BARKER

disappearance of ascites. The period of survival of patients after the onset of ascites showed the following differences: Control At 6 months ............... " ... , ........... 57% At 1 year ................................... 37% At 2 years .................................. 22%

Treated

72%

57% 45%

These figures have been subjected to statistical analysis and their significance has been established beyond the shadow of a doubt. Patek predicts that far superior results might be expected if the dietary treatment could be instituted earlier in the disease before signs of hepatic decompensation had appeared. His interest stimulated by Patek's original report on the dietary treatment of cirr~osis and the volume of suggestive experimental work already mentioned, Snell12 began treating cirrhotic patients with a nutritious diet supplemented with various vitamins. His regimen differed materially from that recommended by Patek. The diet was high in carbohydrate (500 gm.), low in fat (about 60 gm.), and rich in proteins not derived from meat sources (110 gm.), providing roughly 3000 calories per day. The protein component of the diet was derived chiefly from vegetables, milk and egg-white, meat being kept at a minimum. The basis for this change in protein composition was Bollman's report that animals with experimentally produced hepatic injury are made worse by the administration of meat or meat extracts while tolerating protein from other sources without harmful effect. Snell supplemented his diet with various pure vitamins, crude oral liver extract, and yeast or yeast concentrates. In order to facilitate absorption of fat-soluble vitamins, patients were given animal bile salts, 0.3 to 1.0 gm. with each meal. This program gave very encouraging results in a group of fifty decompensated cirrhotic patients so treated. A few remarkable "cures" with disappearance of ascites were encountered, one of the most striking in a man aged 72 who after two years of almost weekly parencentesis remained free of ascites and in good health for one year. The results of treatment were regarded as "excellent" in 44 per cent of the entire group,13 although only 22 per cent were entirely free from ascites at the time of the report. Snell agrees with Patek that an even higher incidence of "cures" is to be expected among patients who present various degrees of fatty metamorphosis, degeneration and necrosis without extensive periportal fibrosis and great restriction of portal blood flow. In a recent report on the diagnosis and clinical course of fatty liver in seventy alcoholic patients, Keefer and Fries 14 stress the therapeutic value of a high-carbohydrate, low-fat diet with a moderate amount of protein, supplemented with vitamin preparations and liver extract. They regard the fatty liver as the precursor of cirrhosis, but point out that ascites, jaundice, and death may occur during the stage when the

MODERN TREATMENT OF CIRRHOSIS OF LIVER

279

liver is filled with fat and before actual fibrosis has developed. In some cases, the process appeared to be reversible. The recognition of this disorder in its early stages and the use of appropriate treatment was followed in many instances by recovery. For the past several years we have been keenly interested in the dietary treatment of cirrhosis at the johns Hopkins Hospital. To date toO few patients have been so treated to justify any final conclusions, but we have seen sufficiently encouraging results to warrant a continuation of the regimen. In general, it has been our policy to adhere fairly closely to the Patek diet with the exception that the fat content of the diet has been considerably reduced for patients with jaundice or diarrhea. Since Snell's reasons for withholding meat are based on purely experimental grounds not necessarily applicable to the human liver and since meat is known to contain protein of "highest biologic value," we have not eliminated meat from our diet, but rather supplied it in liberal portions with complete impunity as far as we could ascertain. We have supplemented the diet with 30 to 50 gm. of brewer's yeast powder a day and polyvitamin capsules in numbers sufficient to supply at least twice the estimated normal adult requirement for the vitamins of proven importance in human nutrition, namely vitamins A, C, D, thiamine, nicotinic acid (or the amide), and riboflavin. Where hemorrhagic phenomena were observed with prolongation of the prothrombin time, vitamin K was administered either parenterally or orally along with bile salts to promote its absorption. Intramuscular injections of crude (rather than concentrated) liver extract have been given in some cases, especially when macrocytic anemia was present. Furthermore, the oral administration of crude liver extract powder has been employed in certain instances. In view of the experimental work on the lipotropic action and protective effects exerted by choline on the liver, it seemed plausible to Wintrobe and the writer to administer this substance to patients with cirrhosis as an additional supplement to the measures already outlined. At least ten patients have now received choline chloride, 1.5 gm. a day, administered in the form of a 10 per cent elixir prepared by the hospital pharmacy, in doses of 5 cc. after each meal. No untoward effects have been noted after the continued administration of choline for weeks or even months. It is as yet too early to speculate upon the possible merits of choline therapy in cirrhosis. ADJUNCTIVE THERAPEUTIC MEASURES

Combating Secondary Vitamin Deficiency.-In addition to the highly suggestive evidence already presented that vitamin deficiency plays an important role in the etiology of liver disease, it has been firmly established that preexisting liver disease predisposes toward the development of numerous and varied manifestations of vitamin deficiency. Liver disease may contribute to the deficiency of the fat-soluble vitamins

280

w.

HALSEY BARKER

A and K in one of three ways: (1) failure of proper absorption in patients with jaundice; (2) failure of storage of the vitamins in the diseased liver; (3) disturuance of intermediary metabolism of the vitamins in the damaged liver. In patients with obstructive jaundice or hepatitis the dearth of bile salts in the intestinal tract results in poor absorption of fats and fat-soluble vitamins. Carotene furnishes the chief source of vitamin A in the average diet, and the normal liver converts carotene to vitamin A through the action of an enzyme, carotenase. Since a severely damaged liver will not effect this conversion, it is not surprising that low blood levels of vitamin A along with clinical manifestations of vitamin A deficiency (e.g., night blindness, keratomalacia, and epithelial metaplasia of various organs) have repeatedly been described in patients with cirrhosis or other forms of liver disease. Therapy or prophylaxis should consist in large doses of vitamin A administered orally with bile salts or large parenteral injections of vitamin A. Little improvement is to be expected from a high carotene intake in patients with severe liver damage. The recognition of the etiologic role of vitamin K deficiency in the hemorrhagic diathesis so common in patients with jaundice or severe liver damage represents one of the most important contributions to medical knowledge within the last decade. This hemorrhagic tendency has been conclusively shown to be due to lowered plasma prothrombin, which in turn results from inadequate absorption of vitamin K, failure of the severely damaged liver to utilize vitamin K in the formation of prothrombin, or a combination of these two conditions. The failure of jaundiced patients to absorb vitamin K may be controlled by the oral administration of the bile salts along with vitamin K preparations or the parenteral administration of a purified vitamin K derivative such as 2-methyl-l, 4-naphthoquinone (1 to 4 mg. a day intramuscularly). If the liver is so severely damaged that it cannot produce prothrombin in spite of an adequate supply of vitamin K, bleeding will not be influenced by either of these methods of administering vitamin K and the prognosis becomes extremely grave. Under such circumstances, transfusions of freshly drawn blood should be given to supply prothrombin directly. The full understanding and proper. application of these principles by surgeons and internists alike will go far toward decreasing risk from hemorrhage in jaundiced patients. In addition to the special function of the liver with reference to vitamin A and K, the liver is known to serve as a storage depot for the majority of vitamins (A, B-complex, C, D, K) and probably provitamins as well. Hence, patients with severe liver disease are bound to have inadequate reserves and are, therefore, more likely to develop outspoken manifestations of vitamin deficiency under the added strain of any severe infection or curtailment of food. This situation affords still a~other reason for our advocating the liberal use of pure vitamins

MODERN TREATMENT OF CIRRHOSIS OF LIVER

281

in addition to the high-vitamin diet and crude vitamin sources in the

treatment of cirrhosis. Treatment of the Anemia.-Macrocytic anemia with leukopenia is not an uncommon finding in patients with cirrhosis, even though their gastric juice may contain free hydrochloric acid and Castle's intrinsic factor. It has been postulated that this macrocytic anemia is due either to failure of the diseased liver to store adequate reserves of the antipernicious anemia principle or to improper metabolism of this principle in the diseased liver. This macrocytic anemia will respond to oral or parenteral therapy with liver extract in certain instances, but the response is rarely so dramatic or so complete as in patients with true pernicious anemia, and the macrocytic anemia of certain cirrhotics appears to be unaffected by liver therapy. If there has been repeated blood loss from esophageal varices or constant oozing from hemorrhoids, the anemia in cirrhosis may be hypochromic and microcytic. In such cases iron therapy is indicated and best administered in the form of ferrous sulfate 0.2 to 0.4 gm. after each meal. Transfusions, of course, become necessary in patients suffering large or prolonged hemorrhages from ruptured varices. Diuretics and Paracentesis.-When ascites or edema is present, the daily fluid intake should be limited to 2000 cc. and the salt intake moderately restricted to the extent of permitting no salt on the tray. Furthermore, since tense ascites interferes seriously with appetite, intestinal motility and the absorption of food, it is most important to combat this condition vigorously. It is desirable to postpone paracentesis as long as possible; hence, diuretic measures should first be given a trial. As a rule we give ammonium chloride (in the form of enteric-coated tablets) 3 to 4 gm. a day by mouth for several days, followed by one or more intravenous injections of mercupurin, 1 to 2 cc. at a time for one day to three days in a row. This procedure may be safely repeated at seven to ten day intervals. When diuretic measures fail to accomplish adequate relief from ascites, then paracentesis becomes imperative. The intervals between paracentesis can best be gauged by the weight curve, the condition of the abdomen, and the subjective status of the patient. There is no point in encouraging stoicism on this score. Surgical Treatment of Ascites and Varices.-For many years the Talma operation or omentopexy (an operation designed to bring the omentum out into the abdominal wall in the hope of facilitating the development of collateral venous circulation) was thought to be a valuable measure fo~ the relief of ascites. However, the operative mortality was high, since cirrhotics tolerate anesthesia and surgical procedures poorly, and the end results in those who survived were rarely good enough to arouse enthusiasm for this form of therapy. In recent years omentopexy has been largely discarded as a relatively useless therapeutic measure. More recently injection of a sclerosing agent into esophageal varices

282

w.

HALSEY BARKER

through an esophagoscope has been tried in an attempt to thrombose these veins and thereby prevent future hemorrhages. This procedure is a relatively new one and must await the test of time in a larger series of cases before its true value can be assessed. Ligation of the coronary vein of the stomach has been carried out in the hope of taking part of the load off of the esophageal varices. Operative anastomosis of the splenic vein to the renal vein has also been suggested as a means of shunting a considerable volume of blood away from the portal system; this is, of course, a modified Eck fistula. The most radical surgical procedure designed to relieve ascites and to decrease the strain upon esophageal varices is splenectomy. From the hypothetical standpoint it would be desirable to remove the spleen in all cirrhotic patients with ascites or varices in order to reduce by no inconsiderable quantity the amount of blood entering the portal system. 'Unfortunately, the majority of patients with cirrhosis tolerate poorly prolonged anesthesia and the shock of such a major operative procedure. However, in selected cases splenectomy may be followed by striking improvement as illustrated in one of the cases to be reported briefly. CASE REPORTS

In order to illustrate some of the therapeutic principles that have been described, we should like to present brief abstracts of four case records of patients treated by the writer within the last three years. CASE 1.- J. H., a white liquor salesman, aged 34, was first seen in February 1942 complaining of jaundice and abdominal swelling. His father, a heavy drinker, had died of cirrhosis of the liver in his 40's. Although always a nervous, highstrung person, the patient had enjoyed excellent health up until the winter of 1939 when he suffered a severe nervous shock as the aftermath of seeing his son struck by a truck. He lost his appetite, ate little, and slept poorly for the next eighteen months. During this period he took fruit juices, fruit, milk, bread and butter, but no vegetables, meat or eggs. He drank from 4 ounces to a pint of whiskey a day. He lost 30 pounds in weight and became so weak he was obliged to go to bed whence he was admitted to a hospital delirious with generalized edema and albuminuria. He was eventually discharged with a diagnosis of liver and kidney trouble. He returned to work very weak, but was eating better, including meat in his diet twice a week and three polyvitarnin tablets daily. He claimed he took no more alcohol except two to five bottles of beer a day. In August 1941 he began to feel sluggish, lost his appetite, ate poorly once more, chiefly liquids, and again lost weight. In December, jaundice set in and progressively deepened with frequent light pasty stools and dark urine. There had been fluctuating swelling of the abdomen and legs during the six months prior to admission. There was no gross hemorrhage from the gastrointestinal tract, but some blood-streaking on the stools from straining. The principal physical findings were deep jaundice, edema of the legs, numerous "spider" angiomas over the neck and shoulders; dental caries; lungs clear; heart pushed upwards and outwards, sounds clear except for systolic murmur at the apex, pulse regular, blood pressure 145/85; well marked ascites with evidence of collateral venous circulation over both flanks; liver tremendous with upper border of dullness at right fifth rib and lower edge felt 2 cm. below level of umbilicus on the right. The edge extended across the epigastrium just above

~

TABLE 1.-LABORATORY FINDINGS IN CASE 1 ---

Serum Bilirubin (mg. per 100 cc.)

Date

March March March March March April April April April May' May

2. 10. 17. 23. 30. 4. 10 17 ... 24 ... 1.

12.

I . : :1 . .j

. . .. .. . ... ..... .

.........I I

16.5 18.5 19.0 14.0 4.9 3.3 1.6 2.0 1.2 1.6 0.6

Total Serum Protein (gm. per 100 cc.)

Serum Albumin (gm. per 100 cc.)

4.76

2.56

4.65

II !

N.P.N. (mg. per 100 cc.)

40 80 70 60

2.51

:

4.50 5.10

I

5.08 4.75

2.84 2.73

I I

30 30 28 30 32 25

--

I

I I

Serum Chloride (Meq. per L.)

o

-------

CO2 Comb. Power (vols. per 100 cc.)

I

"

t"j

W.B.C.

Hgb. m gm.

Vol. Packed R.B.C.

Prothrombin Time in Seconds

17,200 21,500 28,750

14.5 15.2 14.8

42.2 44.0 42.0

62/20* 18/15

16,500

12.0

36.5

13,000

13.3

38.9

20/16

13,150

13.5

4,800

16.0

48.8

19/19

:;0

Z

>-l

:;0

:: t"j

~

t"j

92.4 90.4 96.6 101.6 105.6 102.6 105.6 103.2 102.8 113.6

53.2 40.9 36.2 33.4 33.4 32.4t 37.2 43.8 51. 3 54.1

* Results of prothrombin time expressed as 62/20 means for patient 62 seconds as compared with normal control 20 seconds.

t At this time the serum sodium was distinctly low, 129.0 rnilliequivalents per liter.

20/14

Z

>-l

o"'l n

~ :;0 :I:

§en o"'l t-<

>-<

< t"j

:;0

N 00 v.J

284

w.

HALSEY BARKER

the umbilicus to disappear beneath the left costal margin. The liver felt hard 'but smooth except for a notch between the lobes in the epigastrium. The spleen was not felt. There were no external hemorrhoids. Neurologic examination was normal. The admission diagnosis wa& cirrhosis of the liver with a superimposed episode of acute hepatitis or hepatic necrosis. Neoplasm of the liver was considered possible but unlikely. Laboratory Findings: The blood count on admission showed no anemia but a marked polymorphonuclear leukocytosis: red blood cells 4,870,000, hemoglobiI1 14.5 gm. or 100 per cent, volume packed red blood cells 42.2, giving normal indices; leukocytes 17,200 with juveniles 11 per cent, segmented neutrophils 81 1942 MARCH

Fig. 45 (Case I, J. H.).-Chart shows weight curve, fluctuating ascites, disappearance of jaundice, and various therapeutic measures employed over the 11week period of hospitalization. "P" equals paracentesis; the volume of ascitic fluid in cubic centimeters removed is designated for eacll paracentesis. per cent, lymphpcytes 5 per cent, mOllocytes 3 per cent; sedimentation rate (Wintrobe method) markedly accelerated, 44 mm. corrected to 36 mm. Urine was slightly cloudy, dark brown, specific gravity 1.010, acid, albumin 2 plus, bile 4 plus, urobilinogen negative'; microscopic examination showed bile-stained hyaline and granular casts, but no erythrocytes, leukocytes or amino acid crystals. Serologic test for syphilis was negative. Stool was pasty gray, negative for occult blood and bile pigment. The remainder of the laboratory findings during the patient's stay in the hospital are summarized in Table 1. Clinical Course: Certain of, the more important clinical features and therapeutic measures employed are depicted graphically in Figure 45. This patient was desperately ill on admission and seemed to grow worse during the first two

MODERN TREATMENT OF CIRRHOSIS OF LIVER

285

weeks with increasing jaundice, ascites which recurred rapidly after each paracentesis and failed to respond to diuretic measures, and an intractable fatty diarrhea which persisted for seven weeks, unaffected by orally administered bile salts or pancreatic enzymes. A diet high in protein, carbohydrate and vitamins but low in fat was prescribed, supplemented with brewer's yeast power 30 gm. a day, polyvitamin capsules" (two a day), choline chloride 1.5 gm. a day, and intramuscular injections of 6 cc. crude liver extract every third day. Since the patient was too ill to consume his full diet, additional carbohydrate was supplied in the form of 10 per cent glucose intravenously almost every day for the first four weeks. He ran an irregular fever as high as 102° F. at times. As a result of toO rigid salt restriction and loss of sodium chloride at paracentesis, he became dehydrated with hypochloremia, prerenal azotemia and moderate acidosis. When the salt intake was increased, the nonprotein nitrogen fell to normal as the blood chloride rose to a normal level. However, at this stage the acidosis was still pronounced as shown by the persistent reduction in the carbon dioxide combining power. Dr. George Thorn interpreted this acidosis as resulting from bicarbonate loss in which the prerenal azotemia and the strongly acid ash (high protein) diet were the chief contributory factors. The low serum sodium at a time when the serum chloride had returned to normal fits in with Dr. Thorn's interpretation. The patient became delirious and was extremely difficult to manage during the azotemic acidotic phase of his illness. The marked leukocytosis was thought to be due to extensive hepatic necrosis. In view of the much prolonged prothrombin time on admission, the patient was given synthetic vitamin K 2 mg. intramuscularly daily for the first three weeks, 1 mg. every second day thereafter. The fact that the prothrombin time improved under vitamin K therapy was one of the few encouraging signs during the early weeks of treatment. Througliout the first three weeks little hope was held out for the patient's recovery. Then he rather suddenly began to improve as shown by incre¥e in appetite, cessation of loss of flesh weight, return of mental faculties, diminution in size of the liver, decrease in jaundice with eventual return of serum bilirubin , to normal, and gradual decline of white blood cells to normal. He was discharged from the hospital on May 12, ten weeks after admission on the full dietary regimen, and required no further paracentesis although it was necessary to administer intravenous mercupurin on May 22 and June 1 'to combat recurrent ascites. He experienced an excellent diuresis on each occasion, and thereafter the ascites slowly subsided spontaneously. When the patient was last seen on June 18 there was practically no ascites, the liver was ouly 3 cm. below the right costal margin, and the tip of the spleen was felt for the first time. He was feeling fine and had regained flesh. Shortly thereafter he returned to work. Repeated efforts to persuade the patient to report at regular intervals were unsuccessful. It was learned from his wife that after remaining abstemious and following his therapeutic regimen for several months, during which period he seemed perfectly well, he began drinking once more, stopped eating and eventually died in August 1943 with jaundice and ascites.

Comment.-A 34 year old alcoholic liquor salesman was admitted to the hospital desperately ill with what was regarded as acute hepatic neorosis, presum'ably superimposed on underlying cirrhosis. His illness was characterized by fever, leukocytosis, deep jaundice, ascites .. The polyvitamin capsule used in treatment of this patient and the other three patients was Dayamin (Abbott). Each capsule contained: vitamin A. 10,000 V.S.P. units; vitamin D, 1000 V.S.P. uruts; thiamine hydrochloride, 3 mg.; riboflavin, 2 mg.; ascorbic acid, 50 mg.; nicotinamide, 20 mg.; pyridoxine hydrochloride, 1 mg.; pantothenic acid, 1 mg.

286

W. HALSEY BARKER

and fatty diarrhea. On a modified Patek regimen, including the oral administration of choline chloride and intramuscular crude liver extract, he made a remarkable recovery with complete clearing of jaundice and ascites, only to succumb fifteen months later after returning to his alcoholic ways and abandoning his therapeutic regimen. This type of patient should have excellent prospects of a permanent "cure" provided he could be maintained indefinitely on a nonalcoholic regimen with a nutritious diet. CASE n.-p. B., a white retired businessman and farmer, aged 66 years, was admitted to the hospital on March 10, 1944 complaining of jaundice, abdominal swelling and loss of appetite. His father had died of cancer of the throat. The patient had enjoyed excellent general health throughout his life up to the onset of the present illness. For ten years he had noted a postnasal drip and nasal obstruction, attributed to sinusitis. He had also suffered from arthritis of his shoulders and back for at least ten years. For many years he had been a heavy drinker with the exception of one period of seven to eight years when he stopped drinking entirely. Throughout the ten years prior to the onset of the present illness he had consumed at least 1 quart of distilled spirits a week. He claimed to have eaten fairly well over this period. During the summer of 1943 the patient began to suffer from postprandial epigastric pain; he lost his appetite and was afraid . to eat, although he remained partial to small servings of rare red meat. His total daily food intake was very poor and he lost a great deal of weight. Six weeks before admission he developed jaundice with generalized pruritus. This was followed by marked swelling of the abdomen and legs. There had been. no hemorrhagic phenomena. . On physical examination the patient was an unusually tall, large framed man who seemed somewhat confused mentally. He showed evidence of weight loss over the upper half of the body, with pronounced soft pitting edema over the legs, abdomen and lower back. The complexion was bronzed with slight icterus; no vascular "spiders" were seen. The tongue was normal; lungs were clear with definite emphysema; the heart was not enlarged, sounds distant with a soft systolic blow all over; pulse regular, moderate arteriosclerosis, blood pressure 155/80. The abdomen was hugely distended with bulging in the epigastrium and both flanks, marked shifting dullness and suggestive fluid wave. The liver and spleen were not felt; there were no hemorrhoids. The neurologic examination was negative except for absent ankle jerks and questionably diminished vibratory sense in the legs. The admission diagnosis was cirrhosis of the liver with ascites and mild jaundice, probably on a dietary deficiency basis in a man with a background of overindulgence in alcohol. Carcinoma of the tail of the pancreas was considered possible but less likely. Laboratory Findings: Blood count: red blood cells 4,320,000, hemoglobin 13.8 gm. or 95 per cent, volume packed red blood cells 39.6 giving normal indices (the blood remained normocytic and normochromic throughout); leukocytes 8300 with polymorphonuclear neutrophils 81 per cent, polymorphonuclear eosinophils 1 per cent, lymphocytes 8 per cent, and monocytes 10 per cent; sedimentation rate 50 mm. corrected to 36 mm. in one hour (Wintrobe method). Urine was orange, clear, acid; specific gravity 1.016; no sugar or albumin; faintly positive for bile; strongly positive for urobilinogen up to 1:320 dilution; occasional leukocytes, hyaline and granular casts. Serologic test for syphilis was negative. The prothrombin time was 17 seconds as compared with normal control of 16 seconds. The remainder of the more important laboratory results throughout the period of observation are summarized in Table 2.

a:.:

o ~ ;>:l

TABLE 2.-LABORATORY FINDINGS IN CASE II

Z >-l

Date

:NIarch March April April May June Sept.

11 ... 14 .. 5.

25 ........... . 16. 28. 20 ............ .

Serum Bilirubin (mg. per 100 cc.)

Total . Serum Protein (gm. per I 100 cc.) I 11

Serum Albumin (gm. per 100 cc.)

(mg. per 100 cc.)

N.PS.

_

2.7

6.75

2.31

25

0.8 0.9 0.8 0.8 0.9

7.81 6.63 6.13 7.31 6.13

2.19 2.00 2.13 3.00 3.19

25 31 23 29 34

I.

_",

Serum Chloride (Meq. per L.)

104.8 101.0

95.0 107.0

BromHippuric, sulfalein Acid Retention Excretion After in 30 Minutes gm.*

gm.

Vo!. Packed R.B.Co

8300

13.8

39.6

25%

7200 7950

13.7 13.0 12.3 12.6

37.7 36.5 34.0 38.2 34.7

7%

W.B.C.

4150 6300

5000

Hgb . in

11.9

* Normal result is 1 gm. or more excreted within one hour after intravenous injection of 1.77 gm. of sodium benzoate.

7%

0.28

1.15

;>:l

M

~

a:.:

M

Z

>-l

~

~

o

rJ)

..... rJ)

~ t"'

~ N

00

--J

288

W. ltALSEY BARKER

Clinical Course: Important features in the clinical course and therapy or this patient are charted in Figure 46. He was kept upon the full Patek diet from the start. This was supplemented daily with 30 gm. of brewer's yeast powder, three polyvitamin tablets, and later 1.5 gm. of choline chloride. In addition he was given an intramuscular injection of 2 cc. of parentosol-B· daily for the first seven weeks .. Two intramuscular injections of crude liver extract caused so much local discomfort that this form of therapy was abandoned. The chart demonstrates the striking diuresis obtained on each occasion from combined therapy with oral ammonium chloride (enteric-coated tablets) and intravenous mercu-

P:'

B.).-Chart shows progressive loss of weight (due largely Fig. 46 (Case 11, to clearing of ascites and edema), the daily urine output (with striking diuresis on each occasion that oral administration of ammonium chloride was followed by intravenous mercup'u rin), and various therapeutic measures employed over the lO-week period of hospitalization in March, April and May; also status of patient at subsequent periods of observation in June and September. purin, also the increasing tendency to spontaneous diuresis after the patient had been under treatment for several weeks. Since the fluid intake was. kept fairly constant throughout (never over 2000 cc. in one day), the fluctuation in urinary output may be regarded as significant. The loss of 40 pounds in weight shown on the chart may be attributed almost entirely to steady decrease in edema and ascites, as there was little evidence of actual loss of flesh. The ascites had dis"' Parentosol-B (Squibb) is provided in sterile ampules for parenteral use. Each cubic centimeter contaitls thiamine hydrochloride 10 mg., riboflavin 4 mg., and niacinamide 200 mg.

MODERN TREATMENT OF CIRRHOSIS OF LIVER

289

appeared completely after seven weeks, at which- tiine the hard liver was readily palpable 4 cm. below the right costal margin and the tip of the spleen could ~~~

.

After four weeks on the therapeutic regimen the patient began to exhibit evidence of steady improvement as shown by the diminishiilg ascites and edema, the disappearance of the slight icterus with return of the serum bilirubin to normal, and the decrease in bromsulfalein retention. The setum albumin remained low around 2.0 gm. per 100 cc. throughout his hospital stay: This hypalbuminemia was thought to be an important contributory factor in the edema, ascites and the right hydrothorax which developed six weeks after' admission. The only peculiar features of the hydrothorax were: (1) that it appeared at a time when the edema and ascites had almost cleared up and (2) that the chest fluid had an unusually high protein content ~3.88 gm. per 100 cc.) and cell count (7650) for a transudate. An underlying J\plmonary infarct and cardiac failure on an arteriosclerotic basis were considered as possible alternative explanations for the hydrothorax. In view of a potential element of cirdiac failUre, the patient was digitalized without obvious effect on the hydrothorax or the urinary output. The patient was discharged from the hospital on May 17 in excellent condition. He was reexamined in June and September. There was no recurrence of ascites or jaundice on either occasion; moderate edema of the legs had been present ever since he became ambulatory once more. The steady rise in serum albumin to 3.19 gm. per 100 cc;. on September 20 along with the normal' hippuric acid excretion test on the same date furnished convincing objective evidence of improvement in his' liver function. Latest reports from the patient in November 1944, eight months after dietary treatment was inaugurated, attest to his continued good health. He has adhered strictly to the Patek diet with yeast and vitamin supplements, while taking courses of choline intermittently, ever since discharge from the hospital.

Comment.-This 66 year old man with cirrhosis of the liver, quite conceivably on a dietary deficiency basis, made an excellent response to the Patek regimen supplemented with choline chloride. Since there was an excellent response to djuretic measures on three separate occa, sions, paracentesis was at no. time necessary. The patient has remained free of jaundice and ascites for over six months, while a steady rise in serum albumin, decrease in bromsulfalein retention, and increase in hippuric acid excretion (following the injection of sodium benzoate) furnish additional objective evidence of improvement in liver function.

.~

CASE IlL-E. H., a white male J:estaurant owner and bartender, aged 56 years, was admitted to the hoSpital on March 3, 1943 complaining of abdominal swelling of three months' duration. Family history was noncontributory. Past history revealed nothing of unusual interest except for the fact that the patient had been a heavy drinker of both beer and distilled spirits for many years. For six months prior to admission· he had been eating very poorly; as he put it, he was "too busy to eat." He would ·eat chiefly potatoes and butter, rarely meat, fruit or vegetables. During the six months he lost 30 pounds in weight. In December 1942, there was insidious onset of painless abdominal swelling which gradually increased. He had not noticed jaundice;and had never suffered a gastrointestinal hemorrhage. There had been some swelling of the legs for several months. The principal findings on physical examination were as follows: evidence of marked weight loss with striae on arms; slight icterus; soft pitting edema over legs and lower back with stasis eczema on lower legs; red papular eruption over

290

W. HALSEY BARKER

face and numerous vascular "spiders" over neck, arms and upper trunk; beefy red smooth geographical tongue; chest emphysematous, lungs clear; heart normal in size with regular rhythm and blood pressure 140170; abdomen hugely distended with ascites; collateral venous circulation over abdominal wall. No organs or masses were felt prior to tapping the abdomen. Following paracentesis the abdomen was soft; the hard, somewhat irregular liver edge was felt just below the right costal margin and extending across epigastrium 5 cm. below xiphoid. Spleen was not felt. Neurologic examination was entirely normal. The admission diagnosis was cirrhosis of the liver with jaundice and ascites, probably on a dietary deficiency basis in a heavy alcoholic. Important Laboratory Findings: Blood count: red blood cells 4,280,000, hemoglobin 13.8 gm. or 95 per cent, volume packed red blood cells 39.9 giving mean corpuscular volume of 93 cu. microns (a figure slightly on the macrocytic side); leukocytes 7850 with normal differential count; sedimentation rate markedly elevated to 51 mm. (corrected to 37 mm.) in one hour; icterus index 18. Urine showed 1 to 2 plus albumin, urobilin but no bilirubin. Serologic test for syphilis was negative. The blood nonprotein nitrogen was 30 mg. per 100 cc., fasting sugar 85 mg. per 100 cc., chloride 102.6 milliequivalents per liter, total serum protein 7.50 gm. per 100 cc. with albumin 3.06 gm. and globulin 4.44 gm. per 100 cc., van den Bergh test gave a delayed biphasic re~ction with serum bilirubin 1.8 mg. per 100 cc. Liver function tests: Bromsulfalein test showed 30 per cent retention after thirty minutes; hippuric acid test revealed only 0.11 gm. excreted at the end of one hour. Prothrombin time 24 seconds compared with normal control of 13* seconds. Stool showed bile and gave a faintly positive test for occult blood. Course: The patient was placed on the Patek diet (except that fat content was reduced), supplemented with brewer's yeast 45 gm., 10 per cent elixir choline 15 cc., one polyvitamin capsule, and 3 mg. of vitamin K daily by mouth. Paracentesis was performed the day after admission, yielding 10,500 cc. of strawcolored fluid with specific gravity 1.016, protein 10 gm. per liter, 300 cells (chiefly lymphocytes). The patient remained in the hospital for eight weeks during which time he lost ground steadily, his weight falling from 175 to 137 pounds. He experienced great difficulty in taking his full diet although he made a sincere effort. Paracentesis was performed six times in all, yielding 8000 to 13,000 cc. of fluid at each tap. Ascites reaccumulated rapidly after each tap in spite of restricted intake of fluid and salt. Attempts to relieve the ascites with ammonium chloride and mercupurin met with only slight success, insufficient to forestall the necessity for repeated paracenteses. The prothrombin time failed to improve materially following the administration of vitamin K either orally or intramuscularly (this observation is of ominous import as regards the severity of the liver damage). The bromsulfalein retention was 25 per cent at the end of the hospital stay, a value almost identical with the original figure. After discharge from the hospital the patient attempted to follow the entire regimen at home, but continued to lose weight. He required taps at weekly intervals, eventually became wildly delirious and died on July 14 following a massive hematemesis.

Comment.-This case represents an instance of cirrhosis so advanced that the pathologic changes must have been completely irreversible. In spite of the dietary regimen instituted, the course was progressively downhill to death. One point of special interest was the failure of the prothrombin time to return to normal after adequate parenteral therapy with vitamin K, an indication of the severity of the parenchymal liver damage.

MODERN TREATMENT OF CIRRHOSIS OF LIVER

291

CASE IV.-E. K., a white male electrician, aged 39 years, was admitted to the hospital March 26, 1943 complaining of abdominal swelling for nearly two years. The family history was noncontributory. In the past history it was of interest that up to 1936 he had worked in a rubber heel business where he was exposed to fumes of sulfur and various solvents. There was no exposure to chemicals thereafter. Early in 1940 he suffered a severe electric shock which knocked him unconscious and caused serious burns. He spent six weeks in a hospital at the time. Appetite had been excellent with well balanced diet, and alcohol had been taken sparingly at best, not over four glasses of beer a month. In August 1941 he noticed increasing weakness, malaise and fatigue. One month later he suffered massive hematemeses two days apart, requiring admission to a hospital for transfusion. His abdomen then began to swell and exploratory laparotomy was performed with the possibility of perforated ulcer evidently in mind. A large volume of ascitic fluid was removed at operation and an omentopexy was performed. During the next four months he required paracentesis every eight to ten days, until January 1942 when a spontaneous remission in the ascites occurred and he was able to return to work. In December of that year he suddenly experienced another massive hemorrhage into the gastrointestinal tract with both hematernesis and tarry stools. Shortly thereafter abdominal swelling recurred. After several transfusions he was strong enough to go to a hospital in Philadelphia where his esophageal varices were injected in an attempt to thrombose them. Two days later he again bled profusely and there was one more hematemesis in January 1943. The patient had been treated for several months outside the hospital on the Patek regimen. In spite of this and the surgical procedures, he required four paracenteses between January and March 1943 when he was admitted to the hospital. The last paracentesis was performed ten days before, yet he was already uncomfortable from abdominal distention at the time of admission. He had lost 20 pounds during the previous six months. There had been no jaundice at any time. On physical examination the important findings were as follows: moderate pallor without icterus, evidence of weight loss, soft edema about ankles, several vascular "spiders," "liver palms," tongue a beefy red but no papillary atrophy present; lungs clear, bases high; heart pushed upward, split first sound with soft systolic blow at apex, pulse regular, blood pressure 105/55; abdomen hugely distended with shifting dullness and striking fluid wave; pronounced collateral venous circulation over abdomen and lower chest; moderate-sized hemorrhoids. No organs or masses could be felt in the tensely distended abdomen before paracentesis. After tapping, the abdomen was soft and relaxed; there was an upper midline scar with a large ventral hernia through which the markedly enlarged spleen protruded like an Aleutian isle rising out of the sea. The spleen was very hard, the edge fairly sharp with a distinct notch in the median border; no bruit or friction rub heard over the spleen. A hard nodular liver edge could be felt 4 cm. below the xiphoid in the epigastrium but could not be traced below the right costal margin. Neurologic examination was entirely normal. Admission impression was Banti's syndrome (due to splenic vein thrombosis) with marked splenomegaly and secondary cirrhosis of the liver, although the possibility of primary cirrhosis following exposure to toxic substances years before was considered . . Laboratory Findings.: Blood count: red blood cells 3,780,000, hemoglobin 9.3 gm. or 64 per cent, volume packed red blood cells 30.3; leukocytes 3850 with normal differential formula, sedimentation rate 33.0 mm. corrected to 9.0 mm. in one hour. Urine was normal. Serologic test for syphilis was negative. Blood chemistry: nonprotein nitrogen 40 mg. per 100 cc., sugar 112 mg. per 100 cc., serum chloride 110.4 milliequivalents per liter, total serum protein 5.75 gm. with albumin 2.81 gm. and globulin 2.94 gm. per 100 cc. Prothrombin time was 20 seconds compared with control of 15 seconds. Bromsulfalein liver function test

292

W. HALSEY BARKER

showed 28 per cent retention after thirty minutes. The phenolsulfonphthalein kidney function test showed 95 per cent excretion in two hours, an abnormally high value as is frequently seen in liver disease. Clinical Course: The patient was placed under the Patek diet supplemented with yeast, choline and polyvitamin capsules as in the previous cases. The day after admission he vomited bloody fluid. At paracentesis 10 liters of straw-colored fluid was removed with specific gravity 1.014 and practically no cells. Six days later, 7500 cc. of fluid were removed. The patient was given a transfusion and on April 6 -splenectomy was performed by Dr. W. M. Firor under sodium pentothal, nitrous oxide and local anesthesia. The liver was found to be small, hard and nodular, and about one-half normal size. The operator noted several branches of the splenic vein fully 1 cm. in diameter. The left coronary vein was ligated with the splenic pedicle. The spleen weighed 840 gm. Microscopic report by Dr. S. S. Blackman and Dr. R. C. Clay: 'The splenic tissue reveals changes which are· characteristic of elevated venous tension in the splenic system. These are characterized by dilated venules and splenic sinuses which are now emptied of their blood. There is some fibrosis surrounding these sinuses and the tissues of the pulp seem quite empty. The malpighian bodies are somewhat atrophic." Final pathologic diagnosis was changes in the spleen indicating an increased venous pressure. The postoperative course was essentially uneventful. Ascitic fluid drained from the abdominal wound for two weeks before the wound closed. The patient was discharged on the seventeenth postoperative day with only a small amount of ascites present. Two weeks later he was readmitted to the Urologic Service with acute postcatheterization cystitis due to staphylococcus. This cleared up rapidly with one week of sulfathiazole therapy. On May 10, 7500 cc. of fluid was removed at paracentesis. Since then the patient has been seen in June, August and November 1943; also in March and November 1944. He experienced no further recurrence of ascites, hematemesis or melena. He gained strength and weight and has been able to hold a forty-eight-hour week defense job without difficulty, returning from work in the evenings so full of energy that he frequently takes his wife out to the movies or to dance! By August 1943 his blood count had returned to a perfectly normal level and it has remained normal ever since. The patient has continued to follow the Patek diet supplemented with yeast, choline and vitamin capsules ever since splenectomy. Although his liver remains palpably hard and nodular in the .epigastI:ium,he is to all intents and purposes suhjectively "cured" at the time of the present writing, nineteen months after splenectomy.

C01nment.-This 39 year old nonalcoholic man with severe cirrhosis of the liver either primary or secondary to Banti's splenic anemia, who had suffered from repeated hematemesis and recurrent ascites over a twenty-month period in spite of omentopexy, injection of esophageaJ varices, and a lengthy trial of the Patek regimen, made a dramatic recovery following splenectomy and has remained clinically well with 110 further ascites, hematemesis or anemia over a nineteen-month period since the removal of his spleen. It would appear that splenectomy was a life-saving measure in this particular instance. Since the liver was found to be about one-half normal in size at operation, the patient was impressed with the importance of continuing on the Patek diet supplemented with yeast and choline. He has followed this regimen religiously and is enjoying excellent health while holding down a full-time defense job at the present writing.

MODERN TREATMENT OF CIRRHOSIS OF LIVER

293

SUMMARY AND CONCLUSIONS

1. An abundance of experimental and clinical evidence points to dietary deficiency as a most important factor in the etiology of f:itty liver and cirrhosis of the liver. 2. Treatment of fatty liver and cirrhosis by a nutritious diet high in calories, protein and vitamins, especially the vitamin B-complex, appears to be the most promising form of therapy for this disease, even after signs of hepatic decompensation such as jaundice, ascites and hem at emesis have developed. 3. This dietary treatment of cirrhosis has been discussed in some detail along with adjunctive therapeutic measures including various surgical procedures designed to relieve ascites and to prevent hematemesis. 4. Four cases are presented to illustrate the various aspects of dietary therapy. In one of these cases splenectomy was followed by dramatic relief from both ascites and hematemesis.

2.

3. 4. 5. 6. 7. 8. 9. 10.

11. 12.

13.

14.

o.

BIBLIOGRAPHY

D. and Patek, A. J.: Medicine, 21:207, 1942. Patek, A. J.: Bull. N. Y. Acad. Med., 19:498, 1943. Wayburn, E. and Guerard, C. R.: Arch. Int. Med., 66:161, 1940. Allan, F. N., Bowie, D. J., MacLeod, J. J. R. and Robinson, W. L.: Brit. J. Exper. Path., 5:75, 1924. Frame, E. G.: Yale J. BioI. & Med., 14:229, 1941-42. MacLean, D. L. and Best, C. H.: Brit. J. Exper. Path., 15:193, 1934. Gyorgy, P. and Goldblatt, H.: J. Exper. Med., 70:185, 1939, and 72:1, 1940. Rich, A. R. and Hamilton, J. D.: Bull. Johns Hopkins Hosp., 66:185, 1940. Rhoads, C. P. and Miller, D. K.: J. Exper. Med., 67:463, 1938. Patek, A. J.: Proc. Soc. Exper. BioI. & Med., 37:329, 1937. Patek, A. J. and Post, J.: J. Clin. Investigation, 20:481, 1941. Snell, A. M.: Minnesota Med., 23:551, 1940. Fleming, R. G. and Snell, A. M.: Am. J. Digest. Dis., 9:115, 1942. Keefer, C. S. and Fries, E. D.: Tr. A. Am. Physicians, 57:283,1942.

1. Ratnoff,