St. Louis, Missouri
(Submitted \lav 14; revision accepted for pub1icatiii October 1, 1963.)
PRESENT ADDRESS: Capt. l)ale E. Bennett, MC., 7272 U.S.A.F. Hospital, Box 4107, A.P.O. 231, New York, New York.
PEDIATRICS, May 1964
735
I
N SPITE OF the abundant literature 011 thesubject, there remain many unresolved
problems regarding the natural history and management of neonatal obstructive jaun-dice. Differentiation between hiliary atresia
and neonatal hepatitis, and criteria for sur-gical intervention are sources of
consider-able controversy. It was felt, therefore, that a clinicopathologic study of a large group of
cases, drawn entirely from surgical mate-rial, might place these controversies in a more meaningful perspective.
MATERIALS AND METHODS
All liver biopsies from St. Louis Cliil-dren’s Hospital on patients less than 3 years
of age were reviewed. Only those cases
showing histologic evidence of bile stasis
were included in the studs’. Neoplasms,
granulomatous diseases , hemolytic disease,
metabolic diseases, and the like were cx-cluded because they were not germane to the problems. This left a total of 57 cases
suitable for the study (Table I).
Pertinent laboratory and clinical data
were abstracted from all patients’ records. The microscopic features of each biopsy
were recorded without knowledge of the
clinical course. Multiple hematoxylin and
eosin stained sections and one Masson
tn-chrome stained section were studied in each case. Other appropriate special stains were
prepared when indicated. Autopsy mate-rial (6 cases) was included only if a previous
surgical specimen was available. In the
event another surgical procedure or autopsy was performed at some other institution, these slides were obtained for review.
The major criteria for regarding a case
as biliary atresia were the operative and
cholangiographic findings. The subsequent clinical course was also taken into
consider-ation. Thus, unless the patient has died, or has evidence of persistent hepatobiliary
disease, or had a corrective surgical proce-dure, the diagnosis of hiliary atresia was regarded as untenable, in spite of the din-ical impression at the time of surgical
cx-ploration.
With the exception of one case of chole-dochal cyst and one of intrahepatic atresia,
the remaining cases are grouped under the heading of “neonatal hepatitis syndrome.” Most of the cases in this group have the
characteristics of giant-cell hepatitis. In
order to qualify as giant-cell hepatitis, the following criteria had to he fulfilled: (1)
presence of giant-cell transformation of
parenchyrnal cells; (2) disorganization of
hepatic architecture; (3) absence of atresia
at laparotomy, or clinical recovery
follow-ing biopsy only; and (4) absence of
dem-onstrable blood incompatibility or other disorder capable of producing neonatal
icterus.
In addition to the 16 cases of giant-cell hepatitis, there are 7 cases that do not fiil-fill all the foregoing criteria. Furthermore, their clinical course has proven them not to
be examples of atresia. These are tabulated
as “obstructive jaundice, etiology unknown.”
For purposes of discussion, these cases are grouped with those of giant-cell hepatitis under the heading of the “neonatal
hepa-titis syndrome.”
Follow-up information is complete in all
the 32 cases of extrahepatic atresia and in
NEONATAL JAUNDICE
TABLE I
CAUSES OF NEONATAL OBSTRUCTIVE JAUNDICE AT
ST. Louis CI1IiDREN’s HOSPITAL
Cause .vu
mber of Cases
Exploration and biopsy
Extrahepatic atresia
Intrahepatic atresia Choledochal cyst
Giant cell hepatitis
Obstructive jaundice, et iology unknown
1
1
1 5
Needle biopsy only
Giant cell hepatitis
Obstructive jaundice, etiology unknown
Total 57
PATHOLOGY
Extrahepatic Atresia
The gross patterns of atresia in this series (Table II) were very similar to those
de-scribed in the tu in which com-plete atresia of the bile ducts is stated to be the most common malformation. Four cases (12%) were restricted to all or part of
the common bile duct and were, therefore,
theoretically correctable lesions. This is by far the most frequent type of correctable
anomaly.3
TABLE II
TYPES OF EXTRAIIEPATIC ATRESIA
.
Extent of Atrena Nsslnbfr
ofCases
Noncorrectable
Complete atresia 13
Complete atresia, except gall bladder
present 6
Absent right and left and common
lie-patic ducts 7
Absent right and left hepatic ducts 1 Absent gall bladder, cystic duct, and
both hepatic ducts 1
Total 28 (88%)
Correctable
Isolated atresia of all or part of
cotit-mon bile duct 4
Total 4 (12%)
The microscopic features have been de-scribed in detail by several authors.36 There
is, however, considerable disagreement
upon important points, such as the presence
or absence of giant-cell transformation, S
and the architectural pattern of the liver
early in the disease.’
The most striking feature in our cases was prominent bile stasis. In every
in-stance there was moderate to marked par-enchymal bile and numerous bile thrombi
in canaliculi. These changes were extensive
both periportally and centrally. Prolifera-tion of small bile ducts was another
char-acteristic. In only 4 cases was this change not demonstrable. In addition, there was
usually a dilatation of intrahepatic bile
ducts with inspissation. The one change
pathognomonic of extrahepatic obstruction was the presence of bile infarcts or lakes.
These are peniportal foci of degenerating or necrotic liver cells which are intensely bile
stained and may have a center of
precipi-tated bile pigment (Fig. 1). Four biopsies
(
12) contained one or more bile lakes orinfarcts. Hepatic fibrosis was present in all
but two of these livers. The fibrosis was portal and peniportal, as is seen with cx-trahepatic obstruction from any cause. The degree of fibrosis bore little relation to the age of the patient. Syncytial multinucleated giant cells were seen in 41% of the cases. The giant cells did not differ morphologi-cally from those of giant-cell hepatitis (Fig.
2). Extramedullary hematopoiesis, paren-chymal iron, portal inflammation, and ne-crosis were inconstant features, and when present, were usually of only slight degree.
Giant-Cell Hepatitis
Giant-cell hepatitis was first described by
Craig and Landing in 1952.10 There have
been many discussions of the microscopic
picture since that time,8’ #{176} but little can
be added to the original description.
In our cases, microscopically, the most striking features were disorganization of
Fic. 1. This is a periportal bile lake from a case of extrahepatic atresia. This change is pathognomonic of extrahepatic obstruction (x 280).
many were replaced by syncytial giant cells, each surrounded by a net of reticu-lum. These giant cells contained from 2 to over 30 uniform nuclei. The arrangement
of the nuclei was either haphazard or on-ented around the periphery or a central clear area. The bile pigment was clumped or scattered diffusely through the cyto-plasm. Giant-cell transformation was most often only partial, and in almost one-third
of the cases only scattered small foci were present. Another frequent finding in
giant-cell hepatitis was so-called tubular or acinar
transformation of the parenchyma. This is an alteration in which the liver cords form a multicellular tubular structure with a central bile-filled lumen. The cells forming the tubule are obviously of parenchymal rather than ductular origin. Bile stasis was
a prominent feature in all cases, but bile duct dilatation and inspissation were much less prominent than in extrahepatic ob-struction. Bile infarcts or lakes were never seen. In contrast to the cases with atresia,
where small bile duct proliferation was a
characteristic feature, over half of these livers showed a decrease in number of bile ducts in the portal tracts. Not only were
ducts decreased, but they also were hypo-plastic with collapsed lumens lined by
flat-tened epithelium (Fig. 3). Extramedullary
hematopoiesis was usually present and often
prominent. There was a good correlation
between degree of hemosiderin deposition and hematopoiesis and the age of the pa-tient, both in giant-cell hepatitis and in
atresia. Patients over 4 months of age rarely demonstrated more than a minimal degree of either abnormality. In 10 of the 16 cases
(
62%) there was no fibrosis, and only onepatient had cirrhosis at the time of
opera-tion. The fibrosis that occurred was
pre-dominantly intralobular, and portal tracts showed little or no widening. Regeneration
was usually minimal, even in cases of long
duration.
Morphologic findings are presented in
Extrahepatic Atresia Giant-Cell hepatitis
0 Slight Mod. Marked Total 0 Slight Mod. Marked Total
Giant cells
Bile thrombi
Parenchynial bile stasis
Bile-duct proliferation Bile-duct dilatation Bile-duct inspissation Fibrosis Extramedullary hemato-poiesis Iron Necrosis 59 0 0 16 34 34 9 66 55 87 25 12 6 19 9 9 9 9 6 9 41 28 28 31 31 31 16 14 6 6 48 50 51 16 28 53 9 23 0 41 100 10() 84 66 66 91 34 45 13 0 0 0 75 88 81 62 25 38 (i’i 31 31 12 6 0 6 6 25 8 19 25 31 ‘31 6 6 6 6 25 15 19 44 38 56 12 6 6 25 38 0 100 100 100 25 H 19 38 75 62 38 TABLE III
PATHOLOGIC DATA IN PERCENTAGE
COMMENT
There are certain morphologic features that will permit distinction between extra-hepatic atresia and giant-cell hepatitis in well over 90% of the cases. We agree with
Silverberg et al.13 that there are rare cases
which will defy exact interpretation.
Giant-cell transformation is in no way
specific for neonatal hepatitis. While sev-eral recent studies deny the presence of giant cells in biliary atresia,7’ most writers have described giant-cell transformation in
Fic. 3. Marked giant-cell transformation of parenchymal cells and prominent hematopoiesis are present in this biopsy from a case of giant-cell hepatitis (x 340).
Ill) to two-thirds of cases.92 These cells
occur also in congenital syplnlis,14
erythro-blastosis fetalis,T and cytomegalic inclusion
disease.13 An instance of giant cell change
in what may have been herpes simplex
hepatitis is also recorded.14 %Vhile
multi-nucleated giant cells have been seen in adult disease, including viral hepatitis1 and
para-aminosalicylic acid (PAS)
hypersensi-tivity,17 these cells only rarely
morphologi-cally resemble those seen in the neonatal
period. Only two of our cases of atresia
manifested marked giant-cell change.
How-ever, nearly one-half had a few foci of
transformation. The preseiice of almost complete giant-cell change is very strong evidence of hepatitis, but Silverberg et al.
and Stowens describe complete transfor-mation in proven cases of atresia. We have seen one similar case in consultation. The
appearance of the ducts in the portal tracts
is an extremely valuable aid in differential
diagnoses. Virtually every case of
extra-hepatic atresia has some degree of ductal
proliferation and most have ductal
dilata-tion and inspissation. When these are
marked they constitute strong evidence for
atresia. The fact that significant
prolifera-tion can be seen as early as 3-4 weeks of
age enhances its diagnostic value.19 In
giant-cell hepatitis, on the other hand,
prolifera-tion of bile ducts is present in only
one-fourth of cases, and then is of minimal
degree unless complicated by severe portal
fibrosis. More characteristically the bile
ducts are hypoplastic and collapsed. In
our opinion this is one of the most useful points in differentiating giant-cell hepatitis
from extrahepatic atresia.
Bile lakes or infarcts are diagnostic of
extrahepatic obstruction. Unfortunately,
this pathognomonic feature is found in only 12% of the cases.
TABLE IV
CLINICAL DATA
NEONATAL JAUNDICE
giant-cell hepatitis is usually intralobular.
In biliary atresia major architectural
altera-lions of the liver cords appear relatively
late in the disease, at the time fibrosis
be-comes prominent and regenerative nodules appear. In giant-cell hepatitis, however, trabecular disorganization bears little rela-tion to age, and except for cases progress-ing to cirrhosis, the maximal distortion oc-curs early in life. As a matter of fact, Sme-tana and Johnson claim that all giant-cell transformation occurs in utero, and others have described marked giant-cell change in
infants dying at less than 3 days of 221
Therefore, a relatively normal architectural
pattern in infants less than 2 months of age favors a diagnosis of atnesia over giant-cell hepatitis.
Our studies do not support Stowens’ con-tention3 that the walls of hepatic arteries are thicker in biliary atresia than in other neonatal liver diseases.
We have mentioned that many of the changes described are not uniformly dis-tributed throughout the liver. Figures 4
and 5, which are areas from the same
bi-opsy, illustrate how this lack of uniformity
might lead to misinterpretation. Needle bi-opsies are especially likely to produce
sam-pling errors.
Interpretation of frozen sections on liver biopsies can at times be extremely difficult,
even with perfect sections obtained on a cryostat. It is relatively easy to mistake ductal hypoplasia for the rare case of true intrahepatic atresia, and for this reason frozen section is unreliable in assessing the
status of the intrahepatic ducts. The early case of atresia, or the case of giant-cell hepatitis with only focal disruption of the architectural pattern can also prove
diffi-cult. The cholangiographic findings should determine the surgeon’s course, and when such a study can be performed, frozen sec-Lion is of little value. However, when a cholangiogram cannot be performed, due to the absence of a gall bladder or a readily
injectable duct, the interpretation of the
hepatic frozen section should dictate whether to risk a prolonged and meticulous
dissection of the porta hepatis to search
for a ductal structure. The danger of mis-taking the collapsed extrahepatic ducts of neonatal hepatitis for completely atretic
ones is very real, and dissection can
read-ily damage these delicate ducts.
CLINICAL DATA
The time of onset of icterus in extra-hepatic atresia and giant cell hepatitis was tabulated (Table IV) and the distribution in both groups was almost identical.
Jaun-diee at birth was not unusual in either group. At the other extreme the onset of jaundice was after one month of age in 9
cases of atresia. Poor parental observation was almost certainly the major factor lead-ing to the apparent late onset of jaundice,
but two patients were seen in Well-Baby Clinic at age 3 weeks and were not noted to be icteric. It has been well demonstrated
by Davidson et al.22 that the threshold for clinically evident jaundice varies tremen-dously from patient to patient. Two of the patients with giant-cell hepatitis had the
onset of apparent jaundice at age 3 months and 6 months. Assuming the history is
Extrahepatic biliary Neonatal hepatitis Atresia (S cases) Syndrome (3 cases)
Onset of jaundice (%) (%)
birth 19 19
1-7 days 31 51
8-14 days 9 0
15-8 days 1 58
over 8 days 28 1
Clinical fluctuation of jaundice 31 51
LABORATORY DATA (%)
Ceph. Floe. abnormal 58 45
Alk. Phos. elevated 100 75
SGOT elevated 86 (7 cases) 100 (6 cases)
Urine urobil. positive 0 4
Stool urobil. positive 30 59
Stool bile
strong positive 0 Q4
trace positive 10 15
Bilirubin (value before operation)
lessthan5mgm. % 0 0
5-lomgm.% 41 45
10-is mgm.% 50 59
over 15 mgm.% 9 16
Number with serial bilirubins 11 cases 14 cases
Rising S 0
Steady or fluctuating 5 5
Fig. 4 & 5. (Top,
x
135) This is almost complete giant-cell transformation, as well as marked hypoplasia of bile ducts. (Bottom, X 135) In this area there is bile-duct proliferation, portal fibrosis, and only rare giant cells. These photographs are from different areas of the same biopsy in a case of biliary atresia,reasonably well documented, onset of
jaundice after 6 weeks of age would rule out extrahepatic atresia, and the diagnosis would be highly unlikely with an onset after one month of age.
Clinical impressions of waxing and wan-ing of icterus were of equal frequency in both atresia and giant-cell hepatitis. From
this data it is evident that clinical
informa-lion was of little value in differentiating
between these two conditions.
LABORATORY DATA
The laboratory data are presented in Table IV. Laboratory tests have been re-garded by many as of little value in differ-ential diagnosis of obstructive neonatal
913 23, 24 The most extreme
expres-sion of this view is that of Silverberg et
who place no reliance on these tests. In support of this view, in our series the
cephalin flocculation, prothrombin time, al-kaline phosphatase, serum bilirubin, serum transaminases, and total serum proteins with A/G ratio showed similar alterations in both atresia and neonatal hepatitis. We
cannot evaluate the radioactive rose bengal test or the serum leucine aminopeptidase, as neither test has been employed at St.
Louis Children’s Hospital in these cases. However, Silverberg et al.13 maintain that the rose bengal test lacks diagnostic spe-cificity, and a recent report by Miller and Weintrub25 indicates that the leucine
amino-peptidase probably is of little value in
dis-tinguishing between biliary obstruction and
hepatic parenchymal disease.
We agree with Norris and Hays,2c Krovetz,28 and Hsia and Gellis2#{176}that serial serum bilirubin levels are of definite value. To obtain worthwhile data, determinations should be made over at least a 4-week pe-nod. Values obtained in the first two weeks of life should not be used since physiologic
jaundice may be misleading. In this series, 11 cases of atresia and 14 of neonatal hepa-titis had serial bilirubin determinations over at least a 2-week period (Table IV). While fluctuating levels were not uncommon in either atresia or neonatal hepatitis, a
con-sistently downward trend in total bilirubin
is distinctly uncommon in biliary atresia,
except as a terminal phenomenon, and is strong evidence for neonatal hepatitis.
A positive test for urobilinogen in the
urine or a strongly positive test for bile in
the stool or duodenal drainage is extremely rare in atresia. Contamination of the stool
by bile-rich urine accounts for the occa-sional strongly positive test for stool bile.
COMMENT ON THERAPEUTIC ASPECTS
The major reason for distinguishing be-tween atresia and the neonatal hepatitis syndrome is the selection of patients for exploratory laparotomy. The majority of
writers favor early operation, by 4-8 weeks
of age.1132’#{176}4 However, Kiesewetter
et a!. favor waiting until at least 2 months
of age,2 Krovetz until 3 months,3 and
Han-ris et (ii. until 4 months of age.
The number of cases of extrahepatic bili-any atresia that are theoretically correctable
is low, and the number living and vell
fol-lowing definitive surgery is much smaller
(Table V). The proponents of early
opera-tion (4-8 weeks) claim that this low cure rate is due to cirrhosis and irreversible liver damage developing before operation is
performed.13 30. :n They stress that operation
should be carried out as soon as possible after the age of 1 month.
In this series there was little correlation
between age of the patient and amount of
fibrosis in the liver (Fig. 6). Although there
was a trend toward increasing fibrosis with
age, fibrosis was seldom a prominent
fea-tune in patients under 6 months of age.
This is in agreement with the observations
of Christy and Boley,3#{176} Craig et a!., and
Cameron and Hou.’9
True cirrhosis, implying the presence of regenerative nodules in addition to fibrosis,
was present in only one of 14 livers
hiop-sied prior to 3 months of age. \Vhile a rare
case of cirrhosis has occurred prior to that
age4’#{176}’3’ this data supports the contentions
of Craig et al. and Stowens’ that cirrhosis
develops late in biliary atresia. As a matter of fact, iii extrahepatic obstruction due to
any cause, cirrhosis, portal hypertension,
-1uthor lear. of.
Publication
‘‘u mber of ( ases
,
( orrectabie
. .
Lunng and H ell*
Gerrish36 Gross’ Moore3#{176} Koop’7 Redo’8f Myers4 (‘lat,vortliyhl Norris26 Selniug3’ Silverberg#{176} Krovetz28 Bennett 1951 1953 1953 1954 1954 I956 1956 1957 1958 196(1 1960 1963 25 146 31 39 25 4(1 16 54 10 I20 28 32 1(4%) 28 (18%) 8 (26%) 4(10%) 8 (32%) 9 (22%) 2(12%) 11(20%) 5 (50%) 12(10%) 2(7%) 4(12%) 12(8%) 1(3%) 2(5%) 1(4%) 4(10%) I (6%) 2(4%) I (10%) 0 (0%) 1 (3%)
* These are niaxiniutu figures. Since the j)(ri(l of follow-up is short in IiiiIiy series, the actual “cures are
proti-ably less tlnin those listed.
t (ases 6 III1(l 7 have l)een omitted OS tiot representing extrahepatic atresia.
.. . C
I... B #{149}$#{149}#{149} #{149} #{149}
4+ (I) C,) 0 U 2 0 1 (2 0 0 earlier.
developments.i Furthermore, it has been
shown that regeneration can replace
con-siderable amounts of fibrous tissue when
the obstruction is relieved.41 42 Krovetz has
presented data indicating the prognosis is
better when corrective surgery is carried
out between 2-4 months of age than when
carried out at an earlier or a later date.
Since there is little evidence that tile
de-gree of fibrosis and hepatic damage prior
to 3 months of age is a major factor in the
low survival rate, what are the reasons for
the disparity between the number of the-oretically correctable lesions and the cure
rate? The major factor is the significant
morbidity and mortality following biliary
tract surgery in infants, irrespective of the
age at operation. A review of the case
his-tories of our five patients with correctable
lesions will illustrate that recurrent
obstruc-tion and ascending infections are serious
complications of biliary surgery in infants
at any age.
CASE REPORTS OF CORRECTABLE EXTRAHEPATIC OBSTRUCTION
Case I: L. H. (50-2286)
This patient was operated on at age 8%
weeks. The distal common duct was atretic
and a choledochoduodenostomy was
per-formed. He did well until 16 months of age when jaundice reappeared. At 19 months he was re-explored and the anastomosis was found to be obliterated and no patent bile ducts could be identified. In spite of
no further therapy he survived until age 10,
but was stated to be “in serious condition.”
A third operation was performed elsewhere
in 1960, but more details are not available.
He is at present living and well at age 12
years.
. .0. . . S
..
.
I 2 3 4 5 6 9 2 24
-AGE IN MONTHS AT BIOPSY
Case 2: D. H. (55-538)
This patient was explored at age 9 months and an injection study showed com-plete atresia of the common duct. A
chole-cystogastrostomy was performed. Liver
bi-opsy was unusual in the complete absence
of fibrosis at age 9 months. He died at age
2 from gastrointestinal hemorrhage
second-ary to liver disease. Autopsy was not per-formed.
Case 3: M. A. (57-8231)
At exploration at age 10 weeks, cholan-giogram showed complete atresia of the
common bile duct, and a cholecystoduoden-ostomy was performed. Five weeks later,
because of icterus and signs of intestinal obstruction, she was re-explored, intestinal adhesions lyzed, and the anastomosis re-vised. She died 20 days later and autopsy
revealed fibrous obliteration of all ducts and a suppurative cholangitis with multiple hepatic abscesses.
Case 4: D. S. (58-6471)
Exploration at age 6% weeks revealed a large choledochal cyst. It was drained
cx-ternally and 2 months later was anasto-mosed to the jejunum. She did well until age 2 years when obstruction reoccurred. Re-exploration at age 25 months revealed a
stricture at the anastomotic site and liver biopsy showed severe biliary cirrhosis. The anastomosis was revised. At age 4 years she was admitted to another hospital for massive gastrointestinal bleeding, presum-ably secondary to varices.
Case 5: W. T. (59-9352)
Exploration was performed at age 10% weeks and cholangiogram revealed an
atresia of the distal common duct. A chole-dochoduodenostomy was performed. The patient is living and without jaundice 39 months postoperatively, but the liver is firm and 3 cm below the costa! margin. The alkaline phophatase is elevated.
Thus, none of the 5 patients in this series with theoretically correctable biliary atresia
had a successful and uncomplicated course
after surgery.
There are several reasons for the over-all poor prognosis of patients with biliary
atresia. First, the vast majority of the pa-tients will die because their lesions are un-correctable surgically. Secondly, there will be a high incidence of postoperative
mor-bidity and mortality in the small group of patients (12% in our series) who have theo-retically correctable lesions. Finally, biliary atresia is complicated by other congenital
anomalies in 10-25% of the cases, and these are often lethal #{176}
Perhaps the strongest argument against
early operation (4-8 weeks), is that an
in-creasing number of patients with nonsurgi-cal jaundice (neonatal hepatitis) will be subjected to a relatively dangerous and poorly tolerated procedure. There is ample support for this concept in the literature. Gellis et al., for example, reported 16 pa-tients with neonatal hepatitis who were explored. At the time of the report in 1954
7 of these were dead and 3 were living with persistent jaundice and cirrhosis. Thirteen other patients, similar in all respects, were
not explored, and only one of these had
died and one was living with jaundice and cirrhosis at that time.43 Shorter et al.,8
Kiesewetter et al.,23 Clatworthy and Mc-Donald,24 and Norris and Hays26 reported a total of 35 patients with neonatal hepa-titis who were explored. Of these, 17 were known dead and 9 others had severe per-sistent liver disease at the time of reporting.
In the present series more patients with hepatitis died as a result of surgical inter-vention than were cured because of opera-tive correction of an extrahepatic atresia.
Of the 14 patients with neonatal hepatitis syndrome who were explored and on whom follow-up information is available, 7 are
known dead and the remainder are alive without evidence of liver disease from one
to more than 10 years postoperatively. Of the dead, 2 are unequivocal results of op-erative procedures (Cases 1 and 5).
Post-operative fistulae and obstruction in Cases
mor-Case Patient. Surg. (No.)
Age at .
Operatron
Operative . .
Fzndzngs
. .
Diagnosts Age at
Death Cause of Death
1 K.T. 45553 16 wk Normal hiliary
tree
Giant cell hepatitis
17 wk Wound dehiscence and
evis-ceration with death from peritonitis 10 days postop.
2 M.H. 5-4239 4 wk Normal biliary
tree
Giant cell hepatitis
20 mo Hepatic disease and pneu-monia
3 D.B. 53-1308 6 wk Normal bile
ducts, absent gall bladder
Giant cell hepatitis
8 mo Hepatic failure
4 PT. 56-8083 17 wk Normal bile
ducts, absent gall bladder
Giant cell
hepatitis
13 mo Hepatic failure Biliary fistula developed postop.
5 C.L. 57-524 34 yr Normal biliary
tree
Giant cell hepatitis
34 yr Died 24 hours postop. (Au-topsy failed to reveal iiii-mediate cause of death)
6 T.F. 61-7917 16 mo Normal biliary
tree
Giant cell hepatitis
19 mo Pneumonia. At autopsy liver had returned to normal
histology, and liver
func-tion was normal prior to
death.
7 R.L. 57-1832 4 yr Normal biliary
tree
Neonatal hepatitis
syndrome
6 yr Hepatic failure. Developed cholecystoileal fistula and
scarred off ducts. Two later operations required.
bidity contributing to death. Two other
pa-tients (Cases 2 and 3) developed fatal he-patic failure after discharge, but the rela-lion to the operative procedure is not clear (see Table VI).
It is agreed that much of the morbidity and mortality following surgery in cases of neonatal hepatitis has been due to the
pro-longed and extensive dissections carried out. Initial operative cholangiography and liver biopsy, as advocated by Swenson and Fisher,44 should decrease these hazards. This technique has been utilized in only 4
patients at St. Louis Children’s Hospital, and the small number of cases and the brief follow-ups prevent a meaningful
com-parison of morbidity and mortality with our earlier patients who had extensive and lengthy dissections. In these few patients
at our institution who had only cholangiog-raphy and liver biopsy, anesthesia time
ranged from 2) to 2% hours. Gellis et al.3
stress the dangers of prolonged anesthesia in these patients. The trauma of anesthesia and a 2-hour operation might severely affect the already damaged liver, with
ne-croses of liver cells leading to hepatic fail-nrc or postnecrotic cirrhosis. Until more definitive data are available, there should
be reservations about the innocuous nature of the limited exploration as advocated by Swenson and Fisher.44
The exact incidence of neonatal hepatitis is unknown and is difficult if not impossible
to determine. However, it is almost cer-tainly higher than the incidence,
NEONATAL JAUNDICE
autopsy cases 013, 22. 24 Krovetz
be-lieves neonatal hepatitis to be more
fre-quent than biliary atresia.25 My review of all charts at St. Louis Children’s Hospital of patients with obstructive jaundice at age 1 month revealed an approximately equal
incidence of extrahepatic atresia and of “neonatal hepatitis syndrome.” Evidence
of clearing of jaundice or of bile in stools spared many of the latter group from opera-tion. It is the opinion of the author that
early operation will be accompanied by an increase in the percentage incidence of neo-natal hepatitis among patients with neo-natal obstructive jaundice coming to
sur-gery, while judicious delay will permit
many cases of neonatal hepatitis to be
diag-nosed clinically from falling levels of serum bilirubin.
The percentage of surgically correctable
lesions among patients with neonatal ob-structive jaundice is very low. Since there is evidence to suggest that utilization of only surgical material tends to
underesti-mate the incidence of neonatal hepatitis,35
it is probable that the 9% figure (5/57 cases) derived from our surgical material is too high. Swenson and Fisher have found only 2-3% correctable lesions among their
patients.
Most of this very small group with theo-retically correctable lesions will die
irre-spective of age at operation. On the basis of review of the cases at St. Louis
Chil-dren’s Hospital and study of the series of
other investigators, it is the opinion of the author that a conservative policy is mdi-cated to minimize the number of patients with neonatal hepatitis subjected to explo-ration. There is evidence that a delay until three months of age will permit many cases of hepatitis to be diagnosed. Such a delay will have little if any adverse affect on the rare correctable atresia.
SUMMARY
All cases of neonatal obstructive jaundice at St. Louis Children’s Hospital were re-viewed. The total of 57 included 32 cases
of extrahepatic biliary atresia and 16
bi-opsy-proven cases of giant-cell hepatitis. As
a result, the author has reached the follow-ing conclusions:
Giant-cell hepatitis can be distinguished from extrahepatic atresia in almost all cases
by study of a liver biopsy. The important morphologic criteria include the presence in atresia of bile duct proliferation and of intraductal bile stasis, and the absence of significant hepatic architectural
disor--- ganization early in the course of the
dis-ease. Clinical data and most laboratory tests
are of little use in distinguishing between
atresia and neonatal hepatitis. Serial
hili-rubin determinations are useful, as falling levels over a period of weeks is strong cvi-dence for hepatitis. At laparotorny cholan-giography is the most valuable diagnostic tool, with frozen section of value when
radiographic studies cannot be made.
Biliary atresia carries an extremely poor
prognosis, for few patients have a
cor-rectable lesion (12% in this series).
Further-more, the mortality and morbidity of biliary tract surgery in infants is high, irrespective of the age of the patient at operation. This poor prognosis is not due to delay in opera-tion, since cirrhosis and hepatic insuffici-ency develop relatively late in hiliarv
atresia. Delay of operation until age three
months vill adversely affect only a very
rare patient with atresia.
Neonatal hepatitis is a frequent cause of
neonatal obstructive jaundice. Exploratory laparotomy in these patients has a high
morbidity and mortality, especially when a prolonged ductal dissection is performed.
Early operation (4-8 weeks) will result in
more cases of hepatitis being subjected to a hazardous procedure. There is evidence to indicate that if operation is delayed until
3 months of age, many of these patients
will show evidence of resolution of their
disease, especially a serial fall in bilirubin, and need not be explored.
It is the final conclusion of the author that the management of obstructive jaun-dice in this age group should be
conserva-tive, and that operation should not be
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Acknowledgment
I wish to express my appreciation to Dr. Lauren
V. Ackerman, Washington University School of Medicine, St. Louis, for his encouragement and
advice,and to Dr. John Porterfield, University of
Missouri School of Medicine for his invaluable
