STUDIES OF VARIATIONS OF GLUTAMIC-OXALACETIC TRANSAMINASE IN SERUM IN INFECTIOUS HEPATITIS

(1)

(Accepted May 16, 1959; submitted March 25.)

PRESENT ADDRESS: (A.J.S.) State University of New York Upstate Medical Center, 766 Irving Avenue,

Syracuse 10, New York.

367

PEDIATRICS, September 1959

STUDIES

OF VARIATIONS

OF GLUTAMIC-OXALACETIC

TRANSAMINASE

IN SERUM

IN INFECTIOUS

HEPATITIS

By

A. J.

Schneider, M.D., Ph.D., and James W. Mosley, M.D.

Communicable Disease Center, Public Health Service, U. S. Department of Health,

Education and Welfare, Atlanta, Gerngia

E

PIDEMIOLOCIC investigations of infec-tious hepatitis have been hampered by difficulties and uncertainties in identifying

those persons who have been infected but

who do not become clinically jaundiced. At present the diagnosis of infectious hepatitis in the patient without jaundice rests upon

widely varying combinations of clinical,

epidemiobo gic and laboratory criteria, with

heavy reliance on the last. Until virus

isola-tion and specific immunologic procedures

become available, a single reasonably re-liable and simply obtained laboratory

cri-terion would greatly facilitate further study of the epidemiology of infectious hepatitis.

While changes in activity of glutamic-oxalacetic transaminase in serum (S-GOT) are certainly not specific for viral hepatitis,

nevertheless the very marked elevations

described in jaundiced patients with the

disease’’ suggest that this test might be of

practical value in establishing a diagnosis in the non-icteric or even asymptomatic

case. Wroblewski

et

al. suggested such a possibility, but since their studies did not include control observations it is uncertain

whether the particular criteria used by

these workers do, in fact, reflect the

pres-ence of subclinical infection.

The

present

investigation

was

undertaken

to establish whether, and under what con-ditions, changes in S-GOT might be used to characterize subclinical cases of infectious hepatitis. A concommitant study was made

of

the

effects

of

immune

globulin0

on

S-GOT in household contacts of patients

with

infectious

hepatitis.

In

addition,

ob-Kindly supplied by the American Red Cross.

servations on the patterns of S-GOT

varia-tion in both jaundiced and non-jaundiced

patients with infectious hepatitis were

made.

CLINICAL

MATERIAL

Sixty-six families, comprised of 364 individ-uals, were selected for study during a period of observation of sporadic cases of infectious hepatitis in Atlanta, Georgia, during a focal epidemic of infectious hepatitis in Atlanta, and during a community-wide epidemic of infec-tious hepatitis in Ely, Nevada.

The 66 families were classified, as sum-manized in Table I, into seven groups on the basis of: geographic location; type of illness in

the family; and use of immune globulin among

household members. In groups A, C, E and F,

one or more members of the families had ac-quired infectious hepatitis with jaundice within 6 weeks prior to observation. The members of groups A and C did not, while the members of groups E and F did, receive immune globu-lin for prophvlaxis. The globulin was given in

a dosage of at least 0.01 ml/lb within 3 weeks of onset of symptoms in the index case.

Groups B and G were control groups com-posed of volunteer families which contained one or more children who attended the same school, but not necessarily the same classroom, as children in families of groups A and F, re-spectively. Group D, also a control group, was selected because one or more children in each family had recently been to a local clinic for some illness other than infectious hepatitis dur-ing the period of observation of the families in

group C. These illnesses were generally mild

respiratory or gastrointestinal disorders. The

members of group G received immune globulin

in the same dosage as the hepatitis contacts,

while the remaining control groups did not

(2)

mdi-Group Geographic Location

Illness in Family

Received

Immune

Globulin Families

<‘20 yr

Individuals

‘20 yr+ Total

A Ely, Nevada Hepatitis No 7 27 14 41

B None No 7 18 13 31

E Hepatitis Yes 10 22 20 42

C Atlanta, Ga. Hepatitis No 6 38 12 50

D Non-hepatitis No 16 61 29 90

F Hepatitis Yes 13 42 31 73

G None Yes 7 ‘23 14 37

Totals 66 231 133 364

368

TRANSAMINASE

IN

INFECTIOUS

HEPATITIS

TABLE I

CHARM-FERISTICS OF FAMILY GilouPs SELECTED FOR STUDY

Total Number Studied

vidual had been jaundiced or had any known

exposure to persons with infectious hepatitis or

jaundice within the preceding six months. No

cases of recognized infectious hepatitis de-veloped in any of the control groups during the

ensuing two to three months of observation.

All of the families were of low or middle

socio-economic status without apparent

differ-ences from group to group. The age distribu-lions within families and the family sizes were

not significantly different among the seven

groups.

PLAN

OF

STUDY

Each family was visited at 1 to 3-week in-tervals for a total period of 1 to 3 months. At

the time of each visit a history was obtained

for each person in the family with respect to

illness and other pertinent information, and an

examination was made specifically for jaundice, abdominal tenderness and hepatic enlargement. A blood sample was also Obtailled by capillary or venous puncture.

All

individuals without hepatitis, but with

conditions known to he characterized by

altera-tions in S-GOT were deleted from the studies.

Children less than 18 months of age were not

included because of uncertainty of the nature

of

normal

variation in

S-GOT

at this age

period. Individuals characterized by less than

tvo technically satisfactory determinations of

S-GOT were excluded from the studies.

Final-ly, some individuals were never seen in spite

of efforts to reach all members of each

house-hold. Of the total of 364 individuals

poten-tially available, 302 (83%) were included in the

final analyses. The remaining 17% were lost for

one of the preceding reasons. Of the

individ-uals included in the study, the average number of clinical laboratory observations per person was 3.3, with a range of 2 to 5.

Members of the families having hepatitis

were classified on clinical grounds into three

categories : hepatitis with jaundice, hepatitis

without jaundice, and hepatitis contacts. The

clinical diagnosis of hepatitis without jaundice was made on an four or more of the following six criteria: a) a definite history of contact with

a jaundiced case of hepatitis within 2 to 8

weeks prior to the observed symptoms; b) an

unequivocal history of yellowish-brown urine;

c) anorexia; ci) nausea; e) upper abdominal pain

and/or aI)dominal tenderness on examination;

and f) an enlarged liver by examination. It is

recognized that these criteria are both arbitrary

and not as rigid as would often be employed.

However, the objective was to study the

inci-dence of abnormality of S-GOT in a group

(3)

dis-ARTICLES 369

ease on clinical grounds. For this purpose, only

those in the third category (the hepatitis

con-tacts) were used in the subsequent comparisons except where specifically indicated.

J

ust as the above definition of hepatitis con-tacts is arbitrary, so, for purposes of compari-son, may the definition of abnormality of S-GOT be arbitrary. Subsequent comparisons

of the incidence of abnormalities of S-GOT

in hepatitis contacts and in control persons will be valid so long as the two criteria for

classifi-cation of individuals are applied

independent-ly. As the definition of abnormality of S-GOT

employed in the present studr is rather

differ-ent from the traditional absolute levels of

S-GOT,

a brief summary of unpublished work’ leading to this definition follows. (See section On Method of Assay of S-GOT for technique and expression of results.)

While healthy persons had sporadic values

for S-GOT in the usual range of 10-50 Karmen

units found in adults, with values in occasional

individuals as high as 100 Karmen units, it

was found that the same individual tended to have values from time to time which varied over a range of 2-22 Karmen units. This varia-tion of S-GOT in a single individual was inde-pendent of his mean S-GOT, and was also

approximately the same whether male or

fe-male, child or adult. In contrast, the mean

S-GOT varied from 43 Karmen units at 2 years

of age to about 25 Karmen units after 20 years.

Use of the traditional absolute values for

S-GOT would thus have required numerous

age-specific critical levels for abnormality in

childhood and two sex-specific criteria in

adult-hood. In addition, because the usual range of

values found for a group of individuals of the

same age and sex is greater than that for a single individual, it seemed likely that any

cri-terion of abnormality based on differences

be-tween individuals would be less sensitive than

one based on individual variation.

The computed standard deviation, from

analysis of variance, for variation of S-GOT in

a health person about his own mean value

was found to be consistently 4.0 Karmen units.

This value, multiplied by a factor of 5.5 (from

(uaiity control tables), defines a range of 22

Karmen units, which is not expected to be exceeded more often than 0.2% or less of the

time. In fact, 14 of 480 presumably healthy

individuals (2.9%) had ranges of values for

S-GOT that did exceed the critical value of 22

Karmen units. Since the discrepancy between

theory and fact was no greater than that found

in comparing individual values with the mean

plus three standard deviations for groups

of the same age and sex, a critical range of

22.0 Karmen units was taken as the criterion of normality. Thus any single individual in the present study, who showed variations in S-GOT

exceeding 22.0 Karmen units in a set of two or

more observations, was classified as abnormal, while those with variations less than or equal to 22.0 Karmen units were classified as normal.

METHOD

OF ASSAY

OF S-GOT

All S-GOT

assays

were made according to the procedure of Schneider and Willis.

The

activities are reported in terms of Karmen

units as defined by these authors, i.e., that

amount of transaminase in 1 ml of serum which will cause a decrease in optical density at 340 m of 0.001 per minute at a reaction

temperature of 32#{176}C,an effective light path of

1 cm, and a volume of test solution of 3 ml.

The

error of a determination was consistently within 3% as judged by quality control meth-ods. Each serum sample was assayed once. The assay was made either on freshly prepared serum or on serum which had been promptly

separated and frozen within 6 hours after

col-lection. Such sera were stored at -20#{176}C.

General

RESULTS

Among

the

seven

groups

of

families,

a

total

of 249 individuals

without

clinical

evi-dence

of hepatitis

(as already

defined)

were

available for study. Of these,

145 were

chil-dren

(defined

as persons

less

than

20 years

of

age),

and

104

were adults (persons 20 years of age or older). The overall incidence

of abnormality

in S-GOT

was

22/145

(15.2%)

in children

compared

to 4/104

(3.8%) in the adults. As these rates are significantly dif-ferent

(p

<0.01), comparisons between

family

groups

were

made

separately

for

children and adults. The rates for adults only were so low that meaningful

compari-sons between family groups could not be made, though it may be noted that all four abnormal adults were hepatitis contacts.

(4)

Type Contact Family Group Normal SGOT* (No.) Abnormal SGOT* (No.)

_(%)

Comparison _x2 Probability

Hepatitis A 7 6 46

No illness B 16 1 6 A vs B

-4

0.015

Hepatitis C Ii 7 39

Non-hepatitis I) 37 3 8 C vs D 6.53 <0.025

AvsC 0.14 >0.50

TABLE II

S-GOT VARIATIONS IN HOUSEHOLD CONTACTS; AGES 1.5-19 NEARS

* Normal: Range of S-GOT values for Rh individual ‘2’2.0 Karmen Units.

Abnormal: Range >2.0 Units.

t Fisher’s exact test used rather than x2.

stricted

to

data

from

persons

less

than

20

years of age in the seven groups of families.

Comparisons

Tiu

SENSITIVITY AND SPEcIFIcrry OF

S-GOT VARIATIONS IN DETECTING

SUB-CLINICAL CASES OF INFECTIOUS HEPATITIS:

Table II summarizes the results in children

when no immune globulin was received by

any of the household members. A strikingly

high

incidence

of about

40% abnormal

in-dividuals was found among hepatitis

con-tacts both in Ely, Nevada, and in Atlanta,

Georgia.

From

this

significant

finding

it is inferred that the present use of a range

limit

of

22 Karmen units clearly

distin-guishes household contacts of infectious

hepatitis as a group from other types of

households, whether or not other illnesses

are occurring, provided persons with

condi-tions known to cause abnormalities in

5-GOT

are

excluded.

There

was

no

demon-strable difference in incidence of abnormals

among hepatitis contacts, whether hepatitis occurred in epidemic form (group A) or in

sporadic form (group C).

The reproducibility of results from two

different epidemiologic and geographic

situations makes plausible the assumption

that the abnormal individuals among the hepatitis contacts were, in fact, subclinical

cases of infectious hepatitis. With

exten-sion of this assumption to the adult

popula-tion as well, the pattern of hepatitis

infec-tion by age in the families of groups A and

C combined is summarized in Table III.

TABLE JR

DISTRIBUTION OF IIKI’ATITIS CASES BY AGE AND BY METhoD OF DIAGNOSIS IN ThIRTEEN FAMILIES;

FAMILY GROUPS A AND C COMBINED

Age Group (yr) Total Number Persons Studied

Number with Infectious hepatitis

Persons without Hepatitis Jauiced Clinically Non-jaundiced Abnormal S-GOT Only Total

(No.)

(%)

(No.)

(%)

1.5-4 5-9 10-14 15-19 20+ 10 17 20 7 22 1 3 13 1 3 1 2 2 0 1 1 8 ‘2 2 3 3 13 17 3 7 30 76 85 43 32 7 4 3 4 15 70 24 15 57 68

(5)

TABLE IV

S-GOT VARIATIONS IN hEPATITIS HOUSEhOLD CONTACTS; AGES 1.5-19 YEARS WITh AND

WITHOUT ADMINISTRATION OF IMMUNE GLOBULIN

Treatment Family Group Normal S-GOT (No.) Abnormal S-GOT (No.) None (;lobulihl None Globuliii

Globulin (no illness)

(%)

Comparison A E C F G x2 7 8 11 24 20 Probability 6 4 0 46 33 39 4 0 ARTICLES 371

Lack of complete specificity of the test

is indicated by the finding of four

ab-normals in the control groups. Since the

choice of 22 Karmen units as an upper

limit of normal variability is arbitrary, the

test can be made more sensitive and less

specific by lowering the range limit, or less

sensitive and more specific by raising the range limit. It should be noted, however,

that a range limit corresponding to 22

Kar-men units in sensitivity and specificity is

ap-plicable only when the laboratory error is

3% or less. The appropriate limit will be

larger with larger laboratory error.

Tiw EFFECTS OF IMMUNE GLOBULIN ON

S-GOT VARIATIONS IN HEPATITIS CONTACTS:

The

results

of the

immune

globulin

studies

are summarized in Table IV. Hepatitis

con-tacts receiving immune globulin in Ely,

Nevada (group E) showed essentially the

same high incidence of abnormality in 5-GOT as those who did not receive globulin

(groups A and C). In striking contrast,

hepatitis contacts receiving globulin in

At-lanta, Georgia (group F) showed essentially

the same low incidence of abnormality as the control groups (B, D, and G), whether

the

latter

received

globulin

or not.

Apparently under some conditions

im-mune globulin prevents the abnormality of

S-GOT expected in hepatitis contacts, while

under other circumstances it does not.

Retrospective examination of the records

suggested that the globulin may have been given too late in the course of the presumed

infections to exert its effects. Further stud-ies will

be required

to test

this

hypothesis.

AvsE 0.06 >0.75

CvsF 6.04 >0.025

THE PATTERN OF S-GOT VARIATIONS IN

CLINICALLY JAUNDICED CASES OF INFECTIOUS

HEPATITIS

: As a part

of the

general

study,

a total of 181 S-GOT measurements from

48 jaundiced patients were made at

vary-ing time intervals with respect to the onset

of symptoms. In four instances one or more

measurements were obtained prior to the

onset of symptoms. Table V summarizes

the pertinent findings.

It is apparent that diagnostic variations

in S-GOT are more apt to be found the

sooner after onset of symptoms the

meas-urements are begun. Six of 14 cases,

ap-proximately

40%,

still showed sufficient

ab-normality to permit diagnosis by the

pres-ent criterion when the first S-GOT

measure-ment was made 1 to 2 months after onset of

symptoms. In confirmation of this point,

there were 33 cases from whom more than

one measurement was made after 30 days.

In 12 of these cases the critical range of

22 Karmen

units

was

exceeded,

yielding

a

diagnostic rate of

36%.

This

persistence

of abnormality

in S-GOT

is even more apparent from Figure 1, which shows the individual time courses for the

12 individuals with abnormal variations in

S-GOT 30 days or more after onset of

symp-toms. Only 4 of these 12 cases showed a

progressive

decline

in

S-GOT

with

time,

while the

other

8 exhibited

elevated

levels

and marked fluctuations in S-GOT long

after the onset of symptoms. In none of

these cases were the alterations in S-GOT

paralleled by clinical relapse or persistent

(6)

TABLE V

RELATIONShIP BETWEEN TIME OF CoLLEcTIoN OF SERUM AND S-GOT ACTIVITIES IN

JAUNDICED CASES OF INFECTIOUS hEPATITIS

.4bnormal S-GOT Ranges

Number of Cases Variation of S-GOT Ranges

No. %

117-833

.588; ,020

5.3-1,849 4.4-692

3.0-92.0 3.6-75.0

41.5 6.1; 1.4

406

4

6

8

0

4 1

(1

I

100 100

75

53

49 40

It is important to distinguish between the Time of First

Serum (oliection*

(days)

<0 4

1-7 ‘2

8-14 8

15-21 15

22-28 5

29-35 10

36-42 1

53,55 2

63 1

Time is dated from onset of symptoms.

Figure 2 illustrates the time course of

S-GOT in the four individuals from whom

observations were obtained prior to onset of symptoms. Diagnostic changes in S-GOT first occurred 5 days prior to onset of

symp-toms in two cases, and 5 and 6 days after

onset in two cases, although different

re-sults might vell have been obtained if sam-ples had been taken at more frequent in-tervals.

THE PATTERN OF S-GOT VARIATION IN

HEPATITIS CONTACTS DIAGNOSED AS

SUB-CLINICAL INFECTIONS SOLELY ON THE BASIS

OF ABNORMALITIES IN S-GOT: Figure 3

il-lustrates the time course in S-GOT in hepa-titis contacts

with

abnormal variability in S-GOT. It is worth emphasizing that, in spite of living in the same households with one or more jaundiced patients and in spite of the very liberal criteria for diagnosis of hepatitis without jaundice, none of these individuals could be considered hepatitis cases clinically. The striking elevations of S-GOT seen in 9 of these 13 cases are in

every way comparable with those observed

in hepatitis with jaundice. In one case

ab-normality of S-GOT was still evident 103 days after onset of symptoms in the index case and 75 days after the initial value of

111 Karmen units.

DISCUSSION

observation that persons with variations in

S-GOT in excess of 22 Karmen units occur

much more frequently among hepatitis

con-tacts than among otherwise comparable

in-dividuals, and the assumption that such

ab-normal hepatitis contacts have infectious hepatitis themselves. In spite of the plausi-bility of this assumption, it cannot be cor-rectly argued that all the abnormal

hepa-titis contacts did have subclinical hepatitis or that all the normal hepatitis contacts did not have hepatitis. Similarly it is impossible

to argue that the abnormal controls did or did not have hepatitis. Such problems can-not be resolved without specific virologic or

immunologic methods.

In spite of these difficulties, a substantial

number of persons in households in which

infectious hepatitis occurred have been

identified as presumably subclinical cases

by means of this single laboratory criterion. It is felt that the chances of being wrong in this identification are not so great as to invalidate the use of the test in

epidemio-logic studies for case-finding purposes.

However, it would be quite inappropriate to use the test as a screening procedure in the general population for the detection of subclinical cases of infectious hepatitis.

The low incidence of abnormality in

S-GOT among adults made it impossible

to test the range of S-GOT variation as a

(7)

ARTICLES

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600

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w

155

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bc 0

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30 ‘2 24 36 48 60 72

TIME

IN DAYS AFTER

ONSET

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TIME

COURSE

OF

S-GOT

ACTIVITIES

IN

12 CLINICALLY

JAUNDICED

CASES

OF

INFECTIOUS

HEPATITIS

WHO

SHOWED

PERSISTANT

ABNORMALITIES

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SHADED

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BETWEEN

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REPRESENTS

T.I1ETRA.SITION

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S-GOT

ACTIVITI

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of age or over. It is presumed that this low jaundiced adult as were seen in the jaun-incidence was a consequence of the low diced child, it is suggested that the test is

attack rates of clinical hepatitis among probably just as valid for the adult as for

the adults in the groups studied. Since the the child in the non-jaundiced case,

(8)

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4 CLINICALLY

JAUNDICED

CASES

OF

INFECTIOUS.

HEPATITIS

STUDIED

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THE SHADED

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BETWEEN

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CONTACTS

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INDEX

CASE

ARTICLES 375

(10)

The present studies suggest, but do not

clearly establish, that immune globulin

given soon enough and in sufficient dosage will prevent not only clinical disease but

also the abnormalities in S-GOT associated

with infectious hepatitis. Such a conclusion

is consistent with the assumption that the

cause for the abnormality of S-GOT in

asymptomatic hepatitis contacts is indeed

infection with IH virus.

The question of whether infection with

IH

virus can occur without provoking a

significant alteration in S-GOT in the host

is of some interest. Ward ci

demon-strated excretion of virus in stools 2 to 3

weeks after inoculation of virus and a

simi-lar period prior to onset of symptoms;

S-GOT

at this time was normal. The

pres-ent work confirms previous 78 that

the elevation of S-GOT usually occurs with-in 1 week prior to the onset of symptoms, or thereafter. Thus during most of the usual incubation period, normal S-GOT is not

equivalent to absence of infection, and the

ultimate development of abnormality in

S-GOT is related in time to the appearance

of alterations in other parameters of hepatic dysfunction. There is no evidence at pres-ent that infection occurs without alteration of S-GOT after the usual incubation period, but such a possibility exists.

This sequence of events suggests that

ab-normal S-GOT may be a consequence of

virus invasion of the liver itself. Prevention

of abnormality in S-GOT by immune

globulin under as yet undefined conditions

is compatible with the following three al-ternative hypotheses:

1. Neither infection nor invasion of liver is prevented by globulin, but the

interac-tion between virus and liver is modified.

2. Infection is not prevented by globulin, but virus invasion of liver is prevented.

3. Both infection and invasion of liver by

virus are prevented. These possibilities

clearly require further investigation.

Reports of cases in which the S-GOT first

became elevated a month or more prior to onset of symptoms4’#{176} imply either an ab-normally long incubation period or a

nor-mal incubation period with initial

subclini-cal infection followed later by exacerbation

or relapse to the clinically recognizable

dis-ease state. The latter interpretation seems

more reasonable and provides a partial

ex-planation for cases with unusually long

ap-parent incubation periods. Capps

et

al.bo

advanced a similar interpretation to account

for the observation of other abnormal liver

function tests 7 to 8 weeks prior to onset of

jaundice in one of their patients.

Madsen et al. observed a positive

correla-tion between the height of elevation of

5-GOT

and the severity of illness in infectious

hepatitis. They also found that the trend

of the level of S-GOT paralleled the clini-cal course. Limited observations in about

60%

of the jaundiced patients in the present

study are consistent with these findings.

However, in the remaining jaundiced

pa-tients and in all the subclinical cases, it was not possible to predict the clinical state of the patient or the duration of illness (if any)

from either the level or the direction of the

changes observed in S-GOT. By chance, the

highest S-GOT value (3,150 Karmen units)

was observed in a completely asymptomatic

hepatitis contact in whose family there

were three jaundiced cases of hepatitis at

the same time. Whether the failure of other

workers to note such discrepancies between

clinical and laboratory manifestations of

in-fection is the result of hospital sampling,

too short a period of follow-up, or other

and unknown causes cannot be determined.

A knowledge of the relative frequency

with which non-icteric cases occur is

es-sential for estimating the prevalence of

in-fectious hepatitis. That this frequency is

not uniform at all ages is indicated by the

finding that in the 5 to 9-year age group

there were 3 cases with jaundice and 10

without, while in the 10 to 14-year group

there were 13 with jaundice and 4 without.

This difference is statistically significant

(p < 0.02). Data for other age groups are

too fragmentary to be meaningful, but it

seems clear that one should not apply a

uni-form factor to epidemiologic data based

(11)

jaun-ARTICLES 377

diced patients, to estimate the total

prey-alence of infectious hepatitis.

SUMMARY AND CONCLUSIONS

Comparison of the incidence of abnormal

variability in activity of glutamic-oxalacetic

transaminase in the serum (S-GOT) in two

groups of children who were household

contacts of infectious hepatitis with the

in-cidence in suitable control groups, demon-strated differences with a high degree of statistical significance.

This difference was interpreted as evi-dence that a person with: a) a range of variation in S-GOT in excess of 22 Karmen units, b) exposure to a clinically recognized

case of infectious hepatitis, and c) no other

condition known to cause abnormality of

S-GOT,

may be considered to have in-fectious hepatitis himself, whether

sympto-matic or not.

Immune globulin apparently prevented

the abnormality in S-GOT expected in

hepatitis contacts in one epidemic, but did

not do so in another.

Both in the presence and in the absence

of jaundice, a significant percentage of

pa-tients with infectious hepatitis are

charac-terized by persistent or recurring

abnor-malities in S-GOT for periods of at least

several months. No correlation between

magnitude and duration of abnormality in

S-GOT and degree of clinical illness was

observed.

The ratio of icteric to non-icteric cases of

infectious hepatitis was found to be a

func-tion of the age of the patient. The ratio was greater than one in the 10 to 14-year

age group and less than one at other ages.

Addendum

Since preparation of this report, the authors

have been informed by Dr. Saul Krugman that

viremia has been experimentally demonstrated in a volunteer infected with known icterogenic

material, in whom the infection was clinically

inapparent and all tests of hepatic dysfunction

were within normal limits except the S-GOT.

Blood taken at the height of the S-GOT

eleva-. tion produced icteric infectious hepatitis in 3

of 8 subjects. (Krugman, S., Ward, H., Giles,

J. P.,

Bodanskv, 0., and Jacobs, A.M. :

Infec-tirnis hepatitis: detection of virus during

l)ation I)eriocl and in clillically inapparent

in-fection. New England

J.

N’Ied. , to be

pub-lislied.)

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1959;24;367

Pediatrics

A. J. Schneider and James W. Mosley

SERUM IN INFECTIOUS HEPATITIS

STUDIES OF VARIATIONS OF GLUTAMIC-OXALACETIC TRANSAMINASE IN

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