Medical Science Publication No. 4, Volume II
VIRAL HEPATITIS: INFORMATION OBTAINED DURINGTHE KOREAN WAR*
CAPTAIN THOMAS C.CHALMERS, MC
During the recent Korean conflict infectious hepatitis was a prominentand serious cause of medical disability. In the absence of a specific chemotherapeuticagent the treatment of the disease has continued to be symptomatic, anda conservative approach, relying primarily on prolonged bed rest in thehospital, had been adopted by the Army Medical Corps during the periodfollowing World War II.
SOURCE: Reprinted with permission "Health of theArmy," January, February, and March 1953.
This resulted in a prolongation of the total period of disability fromaround 50 days in World War II to around 80 days during the recent hepatitisepidemic among troops fighting in Korea. As a result of controlled studiesconducted at the Army Hepatitis Center in Kyoto, Japan, summarized below,it has become apparent that the "routine" treatment has beentoo conservative, and that from 2 to 3 weeks can, with safety, be eliminatedfrom the average duration of disability.
*Presented 27 April 1954, to the Course on Recent Advances in Medicine and Surgery, Army Medical Servive Graduate School, Walter Reed Army Medical Center, Washington,
D. C.
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The incidence of acute infectious hepatitis among American troops inKorea (1) is shown in figure 1. It is of interest that there wasa 3-month lag period between the first peak in incidence and the time atwhich sanitation was at its worst and the dysentery rate highest, duringthe defense of the Pusan perimeter in August 1950. The first peak of 31per thousand was reached in November 1950, while the United Nations troopswere advancing to the Yalu River. During the next 3 months the rate felloff in spite of the retreat southward, and then rose to its highest levels,33 to 35 per thousand, during February, March and April of 1951. Therewas again a sharp fall, and for the last year of the war the rate was nohigher than it had been during the peacetime occupation.
These rates are partially explained by the epidemiological observationson hepatitis made during World War II. The incidence is highest duringthe spring and fall and at times when, owing to rigorous fighting conditions,the ordinary principles of sanitation are difficult to follow. It seemsprobable that the rather steady rates during the occupation and after themajor campaigns of the war had ended are more associated, as in post-warGermany, with contact with the native population, while the peaks in incidencewere principally due to breakdown in sanitation contingent on the fightingand unstable front line.
It is assumed that most of the patients discussed above had infectious,or epidemic, rather than homologous serum hepatitis. Those whose illnessfollowed plasma or blood transfusions have been tabulated separately andaveraged 0.2 per thousand. This figure, however, is undoubtedly low. Eighty-eightpercent of the patients diagnosed as having infectious hepatitis had hadsome kind of parenteral injections in the 6 months before onset, and thereforemay have had "needle" hepatitis. Only in the last half of thewar was the multiple-dose syringe technic, known to transmit the hepatitisvirus, abandoned completely.
A surprisingly high incidence of homologous serum hepatitis among woundedmen was revealed in a survey conducted by Sborov, et al. (2) inthree Army hospitals during 1950 and 1951. Patients on surgical and orthopedicwards who had received plasma and blood transfusions at the time of woundingwere followed closely at weekly intervals and liver function tests wereperformed when clinically indicated. The results are summarized in table1. This rate was higher than any previously reported following plasma orwhole blood transfusions. The most important contribution of the study,however, lies in its comparison of the rates before and after the introductionof ultraviolet
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Table 1. The Incidence of Hepatitis Among PatientsTransfused with Plasma and Blood (From Sborov, et al. (2))
Plasma and blood | Blood alone | |
Total number of patients | 255 | 322 |
Average units per patient | 1.4 (plasma) | 5.6 |
Number with hepatitis | 56 | 12 |
Percent of patients | 22 | 4 |
irradiated plasma. There was no difference. Thus it was clearly demonstratedduring the Korean War that irradiation of plasma as practiced commerciallywas ineffective.
When it became apparent that the incidence of infectious hepatitis hadreached epidemic proportions among the troops in Korea, it was decidedto assign the patients to one hospital where the treatment could be standardizedand the disease studied. The 35th Station Hospital in Kyoto, Japan, laterthe U. S. Army Hospital, 8164th Army Unit, was therefore designated asa hepatitis center. Patients were transferred there by air from the varioushospitals in Korea as soon as the diagnosis of hepatitis was made. In thefirst 2 years that the Hepatitis Center was in operation over 4,000 patientswere admitted and much useful knowledge of the natural history and treatmentof the disease was acquired.
The usefulness of needle biopsy of the liver in the management of patientspresenting problems in diagnosis or disposition was established (3).For the first time it was noted that significant amounts of fat could appearin the livers of patients convalescent from acute infectious hepatitis.
Several studies on the efficacy of vitamin B12 early in thecourse of the disease were conducted at the Hepatitis Center by Campbelland Pruitt (4). One hundred patients given 30 micrograms daily ofvitamin B12 for the first 5 hospital days were compared withtwo comparable control groups selected from the records according to theirmaximum serum bilirubin levels. One control group received a high-calorie,high-protein diet plus vitamins and brewer's yeast; the other receivedthe diet alone. The data revealed that anorexia and hepatomegaly disappearedmore rapidly and the total duration of illness was less in the vitaminB12 treated group. No statistical analyses were applied to theresults. A subsequent liver biopsy study revealed no morphological differencesbetween the patients treated with vitamin B12 and the controls.
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During 1951 and 1952 the effects of diet, strict bed rest and exerciseearly in convalescence were investigated at the Hepatitis Center by a groupfrom Harvard Medical School working under the sponsorship of the Commissionon Liver Disease of the Armed Forces Epidemiological Board, in collaborationwith the Army Medical Service Graduate School (5). Since distinctchanges in the routine treatment of hepatitis, based on the conclusionsof this study, have been recommended by the Armed Forces EpidemiologicalBoard to The Surgeon General, the study will be reported in some detailhere.
Four hundred and forty-two patients were studied. They had had symptomsfor an average of 10 days and had been hospitalized elsewhere an averageof 3 days before admission to each of the studies. The severity of theirillness was similar to that encountered in previous epidemics among Americanmilitary personnel. Although the overall mortality of the epidemic wasabout 0.2 percent, none of the study patients died. No relapses with jaundicewere encountered. One hundred and eighty-eight of the four hundred andforty-two patients were selected for follow-up examinations from 6 to 18months following their acute illness. Complete information, including liverfunction tests, was obtained on 179.
Criteria for admission to the studies included the presence of definitejaundice, duration of symptoms of less than 21 days, absence of recentplasma or blood transfusions, and absence of significant complicating disease.The treatment assignments were determined at random before the start ofeach study. Since the medical officer determining eligibility for admissiondid not know what treatment the patient would receive, there was no chancefor unconscious bias to enter into the assignment to treatment groups.Numerous statistical checks at the completion of the studies revealed thegroups to be similar in all details except for the treatments under investigation.
In a first study, involving 253 patients, the effects of strict bedrest were compared with ad lib rest and a forced, high-protein diet, supplementedwith choline and vitamins, with the regular hospital diet eaten ad lib.Patients on the two ad lib rest wards were allowed out of bed all theywished, regardless of the degree of their jaundice, but were required torest for 1 hour after each meal and to stay on their hospital wards. Thoseon the strict bed rest wards were required to stay in bed except for onetrip to the latrine daily. Numerous bed checks were made each day to besure that the patients adhered to their assigned treatment regimens. Bythe end of the first week in the hospital more than 50 percent of the adlib rest patients, regardless of the depth of jaundice, were out of bedmore than half of each day, and never more than 10 percent of the patientson the bed rest
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wards were caught out of bed more than once a day throughout their hospitalization.
As shown in figure 2, the ad lib rest groups had slightly shorterdurations of acute illness than the strict bed rest groups. The differencewas of borderline statistical significance and of no clinical significance.Relapses and residual abnormalities on follow-up examination were the samefor each.
The patients on the forced diets, however, had significantly shorterdurations of acute illness than those who ate the regular hospital dietad lib (table 2).
Table 2. Designof the First Study and Results Expressed as Mean Durations of Illness inDays*
*For computational purposes these are geometric meansand each is about 3 days less than the corresponding arithmetic mean. Durationof illness is defined as the time from admission (an average of 10 daysafter the onset of symptoms) to the time when the serum bilirubin dropsbelow 1.5 mg. per 100 ml. and the bromsulphalein retention in 45 minutesbelow 6 percent.
Follow-up abnormalities were the same for each group. The forced-dietpatients were forced to eat a minimum of 3,000 calories and 150 grams ofprotein. They averaged 4,000 calories and 220 grams of protein. The ad-lib-dietpatients averaged 3,500 calories and 120 grams of protein.
A second study was designed to determine whether the dietary effectwas related to the calorie, protein or supplement content of the forceddiet. The results are presented in table 3. The only significant differencewas a small one in favor of the high-protein diets. However, the patientson the 4,000-calorie, 190-gram protein diet had significantly more residualabnormalities on follow-up examination.
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Table 3.* Designof the Second Study and Results Expressed as Mean Durations of Illnessin Days
*See footnote to table 2.
The conclusions from these studies regarding the dietary treatment ofinfectious hepatitis may be summarized as follows: Patients should be urgedto eat a diet containing approximately 3,000 calories and 150 grams eachof protein and fat. Intakes above this level should be ad lib. Althoughforced feeding may shorten the average duration of hospitalization by about20 percent, the recommendation that all patients should beforced to a minimum level should be tempered by three items of interest:(1) The potential saving in time, although highly significant statistically,is small from the standpoint of the individual patient; (2) in a recentstudy by Leone, et al. (6) patients with homologous serum jaundiceforced to eat a diet high in protein and low in fat did not do as wellas those fed an ad lib diet; (3) recent studies in patients with severecirrhosis have indicated that a high-protein diet may precipitate the syndromeof impending hepatic coma (7).
A third study was designed to determine whether the 2-week period usuallynecessary for patients to recuperate from the deleterious effects of prolongedrest in bed could with safety be eliminated from the hospitalization timeof patients allowed ad lib rest throughout. All patients in the secondstudy of 189 were allowed ad lib rest in the hospital and half were startedon active physical reconditioning as soon as their total serum bilirubinswere below 1.5 mg. per 100 ml. and
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their bromsulphalein retention in 45 minutes below 6 percent; the otherhalf were kept in the hospital an extra 8 days as controls. There wereno relapses precipitated by the early or late exercise. In some patientsin the early exercise group the serum bilirubin rose above normal but itpromptly dropped again while exercise was continued. In others there wasa transient liver enlargement or return of minor symptoms, all of whichdisappeared while the patient continued to exercise. The two groups weresimilar at the time of their return to duty and on follow-up examinationapproximately one year later. Thus it was demonstrated that by eliminatingstrict bed rest and starting reconditioning earlier the average durationof hospitalization could with safety be decreased from 60 to around 40days.
Summary
The incidence of infectious hepatitis reached epidemic proportions earlyin the Korean conflict.
Homologous serum jaundice occurred in 4 percent of wounded soldierswho received blood transfusions and in 22 percent of those who receivedblood and plasma.
Injections of vitamin B12 were thought to be effective instimulating the appetite and shortening the acute illness.
The forcing of a high-protein diet significantly shortened the durationof jaundice but it is possible that the forcing of large amounts of dietaryprotein may be harmful to the most severely ill patients.
Finally, it was demonstrated in a carefully controlled study that enforcedbed rest has no advantage over ad lib rest in the treatment of the acutedisease. Early return to full activity of patients treated with ad librest was accompanied by no significant increase in residual abnormalities.
References
1. Korea. A Summary of Medical Experience, July 1950,to December 1952: Reprinted from Health of the Army, January, February,and March 1953, Office of The Surgeon General.
2. Sborov, V. M., Giges, B., and Mann, J. D.: Incidenceof Hepatitis Following Use of Pooled Plasma. A Follow-up Study in 587 KoreanCasualties. A. M. A. Arch. Int. Med. 92 : 678-683, 1953.
3. Deschamps, S. H., and Steer, Arthur.: Experience withNeedle Liver Biopsies at the Hepatitis Center for Japan and Korea, 1950-1951.Am. J. Med. 13 : 674-687, 1952.
4. Campbell, R. E. and Pruitt, F. W.: Vitamin B12in the Treatment of Viral Hepatitis. Am. J. Med. Sci. 224 : 252-262,1952.
5. Chalmers, T. C., et al.: The Treatment of AcuteInfectious Hepatitis. Controlled Studies of the Effects of Diet, Rest,and Physical Reconditioning on the Acute Course of the Disease and on theIncidence of Relapse and
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Residual Abnormalities. Report prepared for The SurgeonGeneral, November 1953.
6. Leone, N. C., et al.: Clinical Evaluation ofa High Protein, High Carbohydrate, Restricted Fat Diet in the Treatmentof Viral Hepatitis. Annals of the N. Y. Acad. of Science. In press.
7. Phillips, G. B., et al.: The Syndrome of ImpendingHepatic Coma in Patients with Cirrhosis of the Liver Given Certain NitrogenousSubstances. New England J. Med. 247 : 239, 1952.
