Symposium on Gastrointestinal and Liver Disease

Hepatomegaly
An Approach to Differential Diagnosis

W. Allan Walker, M.D.,*

and Richard K. Mathis, MD.t

The finding of liver enlargement in infancy and childhood is not an

uncommon occurrence and is a situation which may require extensive
evaluation in order to distinguish benign, self-limited disease processes
from serious, life-threatening conditions involving the liver. Hepato-
megaly is a physical finding which may suggest either intrinsic liver
'disease or may represent the presenting component of a more general-
ized disorder. Unfortunately very little comprehensive information
exists in the pediatric literature which may be helpful in dealing with
this important clinical problem. Accordingly, the purpose of this paper is
to provide pediatricians with a working approach to the evaluation of pa-
tients presenting with an enlarged liver. The scope is not meant to be
comprehensive but representative of conditions that should be considered
in clinic settings involving hepatomegaly. Mechanisms of hepatic en-
largement will be reviewed as a background for a reasonable approach
to further clinical and laboratory evaluations needed to establish a diag-
nosis.

MECHANISMS ACCOUNTING FOR HEPATOMEGALY

The pathophysiologic mechanisms involved in the sudden or grad-

ual onset of liver enlargement are varied and complex, and include con-
gestion, Kupffer cell hyperplasia, cellular infiltrates, storage, inflamma-
tion, fatty infiltration, and intrinsic tumors. Several of these
mechanisms discussed separately below may in concert account for the
':'Associate Professor of Pediatrics, Harvard Medical School, and Chief, Pediatric Gastroin-
testinal V nit, Massachusetts General Hospital, Boston, Massachusetts
tInstructor in Pediatrics, Harvard Medical School, and Assistant in Pediatrics, Massachu-
setts General Hospital, Boston, Massachusetts

Supported in part from NIH Grants (AM-16269 and GM-21700) and a V.S. Army Research
and Development Contract (DADA-17-70-C-0113). Dr. Walker is a recipient of an Aca-
demic Career Development Award (K04-AM00021), from the NIAMDD. Dr. Mathis is a
recipient of a Clinical Investigator Award (K08-AM000136) from the NIAMDD.

Pediatric Clinics of North America- Vol. 22, No.4, November 1975 929
930 W. ALLAN WALKER AND RICHARD K. MATHIS

hepatomegaly associated with a variety of diseases. However, for pur-

poses of clarity this section deals with these mechanisms separately. A
more comprehensive list of clinical diseases based on mechanisms of
hepatomegaly is presented in Table 1.
CONGESTION. About 15 per cent of the liver is normally accounted
for by sinusoidal and vascular spaces which are capable of rapid and
massive expansion associated with increased venous pressur&2 (right
heart failure, atrial tachycardia, constrictive pericarditis) or post sinusoi-
dal block (Budd Chiari syndrome).3o One should consider congestion as
the mechanism for hepatomegaly in any patient with known cardio-
vascular disease.
KUPFFER CELL HYPERPLASIA. The liver is the largest reticuloen-
dothelial organ of the body and Kupffer cells comprise about 10 per cent
of the total cells of the liver.31 These metabolically active phagocytes
commonly line hepatic sinusoids. They actively phagocytose bacterial
endotoxin, antigen-antibody complexes, defective red blood cells, etc.,
and act as a general filter, particularly for potentially toxic substances
absorbed from the intestinal lumen. A proliferative, hyperplastic re-
sponse is seen in septicemias, hepatitis, and a variety of other condi-
tions.
CELLULAR INFILTRATES. Normal erythropoietic tissue may be
found within the hepatic sinusoids of term infants as a remnant of the
liver's role as a major fetal hematopoietic organ. In erythroblastosis
fetalis large clumps of blood forming elements distend sinusoidal
spaces. Leukemic, lymphomatous, and lymphohistiocytic infiltrates may
be prominent in portal and periportal areas. Uniform enlargement of the
liver is usually seen unless intrinsic or occasionally metastatic tumors
or cysts are present.
STORAGE. As a result of derangement of hepatocytic function due
to an inborn error in metabolism51 or an acquired block,17 storage of sub-
stances (glycogen22 and lipids42 ) within hepatic parenchymal cells and/or
Kupffer cells produces diffuse distortion of hepatic architecture. In such
instances abnormalities progress from the periportal area centrally,
except in glycogen storage diseases which have most marked centro-
lobular storage. Hepatocellular storage may persist or in some instances
may progress to cirrhosis. 22
INFLAMMATION. An inflammatory response to hepatocellular de-
struction, Kupffer cell lysis and/or hyperfunction is common to a variety
of intrinsic liver diseases (hepatitis8 and drug toxicity4). Hepatic ab-
scesses manifest acute inflammatory infiltrates of predominantly poly-
morphonuclear leukocytes, whereas chronic active hepatitis manifests
largely mononuclear cell infiltrates including distinct plasma cells.
Transplacental and interpartum infections often produce inflammatory
changes in the liver of the newborn infants.
FAT ACCUMULATION. Several conditions can result in an increased
accumulation of fat within the hepatocyte. In the pediatric age group, a
common cause is protein malnutrition45 which produces progressive
periportal fatty metamorphosis of hepatocytes, presumably because of
defective synthesis of lipoproteins and consequent decrease in the
HEPATOMEGALY
931

Table 1. Mechanisms of Hepatomegaly and Clinical Disease States

MECHANISM(S) CONDITION

Inflammation Infection (intrauterine and intrapartum)

Viral hepatitis
Hepatitis with generalized viral infection
(CID, mononucleosis, Coxsackie A, B)
Neonatal hepatitis
Hepatic abscess (pyogenic, parasitic)
Parasitic infection (visceral larva migrans, schistosomiasis,
flukes)
Toxin and drug reactions (hepatitis, cholestasis)
Biliary tract obstruction

Kupffer Cell Hyperplasia Septicemia and infection (extrinsic or intrinsic to liver)

Malignant disease (extrinsic or intrinsic to liver)
Granulomatous hepatitis (sarcoidosis, tuberculosis, etc.)
Phagocyte stimulation (hypervitaminosis A, Thorotrast)

Congestion Congestive heart failure, pericardial tamponade

Budd-Chiari syndrome
Jamaican vomiting disease

Infiltration Erythroblastosis fetalis

Metastatic tumors (neuroblastoma, Wilm's tumor, etc.)
Histiocytosis syndromes
Leukemias
Lymphomas

Storage Glycogen storage diseases

Mucopolysaccharidoses
Gaucher's disease
Niemann-Pick disease
Gangliosidosis M,
Alpha-I-antitrypsin deficiency
Amyloidosis
Hepatic porphyrias

Fat accumulation Malnutrition (Kwashiorkor)

Hyperalimentation
Cystic fibrosis
Diabetes mellitus
Galactosemia
Wolman's disease
Reye's syndrome
Tetracycline toxicity

Tumor, intrinsic Congenital hepatic fibrosis-polycystic liver disease

Hereditary hemorrhagic telangiectasia
Hepatoblastoma
Hepatoma
932 W. ALLAN WALKER AND RICHARD K. MATHIS

secretion of triglycerides. In addition to fatty infiltration, specific disease

states (Reye's syndrome) ,38 hydrocarbon ingestion,47 and hepatotoxic
medications (corticosteroids, tetracycline)1s.17 may result in steatosis (or
abnormal concentrations of fat) and associated cell damage. The mecha-
nism of lipid accumulation is not completely understood but may result
from organelle damage leading to a defect in secretion of fat.
INTRINSIC LIVER TUMORS. Although exceedingly rare, intrinsic be-
nign and malignant liver tumors may cause liver enlargement.9 • 11 Ab-
normal development of epithelial, mesenchymal, or endothelial ele-
ments separately or in a mixed form may assume benign or malignant
characteristics. Focal and asymmetrical liver enlargement is often en-
countered. Traumatic events may also produce local enlargement of a
liver lobe with massive extravasation of blood and must be considered
as part of the differential diagnosis of asymmetrical enlargement of the
liver.

CLINICAL EVALUATION OF HEPATOMEGALY

When a child with apparent liver enlargement is encountered, the

physician must begin a clinical evaluation which establishes (1)
whether the apparent hepatomegaly is indeed pathologic, (2) whether
the child may safely be observed for any progression in liver abnormali-
ty, or (3) whether preliminary evaluation suggests immediate hospital-
ization and an extensive investigation to determine the actual cause of
liver enlargement. The preliIninary evaluation, oftentimes done in the
pediatrician's office, should include an accurate evaluation of liver size,
consistency, and contour, as well as a good history and general physical
examination. The aspects of the evaluation are discussed below.
Size, Consistency, and Contour of Liver
The presence of a palpable liver to the examining hand does not
always mean hepatomegaly. Therefore, a complex examination of the
liver is necessary before the diagnosis of hepatomegaly is made. Be-
tween birth and adulthood the liver normally increases in mass by at
least 10-fold.34 On physical examination the apparent size of the liver
depends largely on its relationship to adjacent structures. The patient
with pneumothorax, retroperitoneal mass, perihepatic abscess, or chole-
dochal cyst will present frequently with apparent hepatomegaly.33 Palpa-
tion of the lower anterior margin in the Inidclavicular line (normally the
right lobe) is usually the initial maneuver, but, alone, is a highly unrelia-
ble method for the evaluation of liver size. Laterally to the axillary line,
the remainder of the right lobe, and medially (mid-line) the left lobe, are
available for examination. The upper border is percussible anteriorly, la-
terally, and posteriorly. Percussion of the lower margin is valuable la-
terally in the axillary line, but anteriorly, gas in the hepatic flexure of
the colon may obscure liver dullness. Liver span (height in the right
midclavicular line) measured superiorly by percussion and inferiorly by
palpation may be a reliable measure of liver size. Figure 1, taken from a
HEPATOMEGALY 933
14 y~0.025 X+ 7.128 y~ 0.022 X+ 6.481
r~ O. 503 p< 0.01 r~0.453 p<O.OI

• •• i-"
• +
.... ~+
"._1..,. +. ++++t t

+
:.
+. e. + .,
+.
: +~ +
\ ••
••+ +
~
+ ~+:.
+
,
+
6 +

20 30 40 50 60 5 7 9 11 13
BODY WEIGHT (Kg.) AGE (yr5)
Figure 1. Liver span (estimates of height in the right midclavicular line) in normal male
and female children was obtained by palpating the lower border and percussing the upper
border. The closed circles (e) represent values for females and crosses (+) values for males.
Each mark is a mean of the measurements obtained by two investigators. Liver span is
plotted against body weight (left) and against age (right). The middle lines are the regression
lines, and the outer lines represent the 95 per cent confidence limits. The slopes of the lines
were significantly different from zero (p<O.Ol). (From Younoszai, M. K. and Mueller, S.:
Clinical assessment of liver size in normal children. Clin. Pediat., 14:378-380, 1975, repro-
duced with permission.)

study by Younoszai et al.,50 compares liver span in normal male and

female children with age and body weight and may act as a guide in es-
tablishing liver size. Unfortunately, no similar information exists for the
normal size of the infant liver.
Palpation should be gentle enough to feel downward movement of 1
to 3 cm during inspiration, and extremes of percussion pressure should
be avoided. If the upper border is at or near the 5th intercostal space in
the midclavicular line, then the palpable margin becomes a better
clinical index of liver size. 48 One centimeter distance between costal
margin and liver margin is acceptable as normal throughout childhood
and 2 cm are considered normal in infancy.
Several pitfalls in evaluation of liver size should be noted: narrow
costal angle, flared costal margins, pectus excavatum, ptosis (floating
liver), accessory lobes, Reidel's lobe. In older children and adolescents,
for example, body habitus must be considered in evaluating liver size.
The liver may normally not be palpable in a child with a wide costal
angle but may be normally felt more than 2 cm below the costal margin
when the costal angle is narrow. Epigastric palpation revealing a liver
edge below the xyphoid is frequently neglected but may be an excellent
indication of generalized hepatomegaly in childhood.
In addition to definition of the size and shape of the liver, the consis-
tency (soft, firm, rock-hard) and character of the surface (smooth, irreg-
ular, nodular) and palpable edge (sharp, rounded) should be noted. Ac-
centuation of normal liver tenderness should be assessed and
auscultation for bruits performed. Frequent reevaluation of the liver by
the same observer applying similar techniques of percussion and palpa-
tion will give the most reliable and clinically revealing information with
respect to liver size and pattern of change.
934 W. ALLAN WALKER AND RICHARD K. MATHIS

As part of the complete initial evaluation of patients with suspected

hepatomegaly, the physician should further examine the abdominal cav-
ity for unusual masses or organomegaly. One should note particularly
whether the spleen is enlarged, tender, or in any way abnormal. The im-
portance of this physical finding will be discussed below.
Additional methods used to establish liver size may be helpful in
confirming the initial physical evaluation.36 These include isotopic scan-
ning which may give important adjunctive information about liver size
in addition to its primary purpose of demonstrating local abnormalities
within the liver substance. A less invasive technique is the use of ul-
trasound scanning. These methods do not substitute for the initial phys-
ical examination.
History and Physical Examination
The evaluation of hepatomegaly is simplified by complete historical
inquiry and physical examination. Silverman et aUl have catalogued
most symptoms and physical signs of differential value in liver diseases
responsible for hepatomegaly. A representative listing of symptoms and
signs is recorded in Table 2. For example, the age at which hepatic
enlargement becomes apparent may provide an important clue as to
etiology. Hepatomegaly is most common in early infancy and specific
conditions should be considered as part of the differential diagnosis.
A listing of disease states according to age of presentation is provided in
Table 3.
There are several additional areas requiring specific attention: (1)
Nutritional history. Assessing the type and amount of protein ingested
or in the hospitalized patient, the composition of hyperalimentation
preparation is critical to the evaluation of suspected steatosis. Such fac-
tors as short periods of starvation10 or excessive vitamin A supple men-
tation37 may result in liver enlargement. (2) Hepatotoxins. Medications
commonly prescribed in the pediatric age group, such as phenobarbital,
diphenylhydantoin, sulfonamides, acetaminophen, tetracycline, cortico-
steroids, and androgens, may cause hepatomegaly due to fatty infiltration
or peliosis hepatitis,23 and some have been implicated in cases of hepa-
toma. 25 (3) Geographic factors. Patterns of liver disease producing hepa-
tomegaly by infection differ widely the world over.14 A history of geo-
graphic exposure allows the clinician to consider and rule out possible
infestations with schistosomiasis, amebiasis, and nematodes or deter-
mine infections such as leptospirosis and malaria as etiologies of liver
enlargement.

Jaundice Associated with Hepatomegaly

Predominant elevation of conjugated (direct-reacting) bilirubin is
seen associated with many cases of hepatomegaly and is of particular
importance as part of the evaluation. Therefore, this physical finding
will be considered separately. In early infancy, infections acquired
transplacentally or perinatally usually show this association as do less
commonly encountered metabolic, biliary tract, and hepatotoxic dis-
eases. Sass-Kortsak has reviewed the importance of careful diagnosis
HEPATOMEGALY 935

Table 2. Helpful Physical Findings in Differential Diagnosis

of Hepatomegaly

SIGN CONDITION

Skin
Carotenemia Hypervitaminosis A
Erythema nodosum Hepatitis with inflammatory bowel disease or
tuberculosis
Telangiectasia Hereditary hemorrhagic telangiectasia
Hemangiomas Multinodular hemangiomatosis of liver
Scratch marks Biliary obstruction
Eczematoid rash Histiocytosis

Head
Microcephaly Congenital rubella, toxoplasmosis, or cytomegalovirus
infection
Hydrocephalus Congenital syphilis
Craniotabes Hypervitaminosis A

Eyes
. Telangiectasia Hereditary hemorrhagic telangiectasia
Iritis Hepatitis with inflammatory bowel disease
Kayser-Fleisher rings Wilson's disease
Cataracts Wilson's disease
Galactosemia
Papilledema Hypervitaminosis A

Mouth
Gingival inflammation Malnutrition
Wilson's disease
Glossitis Hepatitis with regional enteritis
Cirrhosis of any cause

Chest
Abnormal breath sounds Cystic fibrosis
Tuberculosis

Abdomen
Enlarged cystic kidneys Congenital hepatic fibrosis-polycystic kidney disease

Genitalia
Testicular abnormalities Cystic fibrosis
Histiocytosis

Joints
Arthritis Hepatitis with inflammatory bowel disease or
juvenile rheumatoid arthritis

Neurologic exam
Tremors, dystonia, dysarthria Wilson's disease, lipid storage diseases
936 W. ALLAN WALKER AND RICHARD K. MATHIS

Table 3. Clinical Disease States and Age of Presentation

of Hepatomegaly

Newborn
Intrauterine and intrapartum acquired infection
Erythroblastosis fetalis
Biliary tract obstruction
Neonatal hepatitis
Congestive heart failure
Viral hepatitis
Infection, septicemia

Infant
Cystic fibrosis
Metabolic
glycogen storage
galactosemia
Gaucher's disease
alpha-l antitrypsin
mucopolysaccharidosis
Wolman's disease
Histiocytosis syndromes
Malnutrition
Tumors
intrinsic (hepatoblastoma multinodular hemangioendothelioma)
metastatic (neuroblastoma, Wilm's tumor, gonadal)

Young child
Toxic and drug reaction
Parasitic (visceral larval migrans)
Leukemia

Older Child and Adolescent

Chronic active hepatitis
Liver disease with inflammatory bowel disease with juvenile
rheumatoid arthritis
Drug and alcoholic hepatitis
Lymphoma
Wilson's disease
Hepatic porphyrias
Congenital hepatic fibrosis - polycystic liver disease
Amyloidosis
Alpha-I-antitrypsin deficiency

and management of this group,39 A comprehensive discussion of causes

of hepatomegaly and jaundice is beyond the scope of this review. Young
infants with choledochal cysts may present with apparent hepatomegaly
and the classic associated features of jaundice and abdominal pain may
be absentP Infants with cystic fibrosis may have accentuated neonatal
jaundice and extensive fatty infiltration producing hepatomegaly.28 The
classic lesion of biliary cirrhosis may be present but most often this en-
tity presents later with symptoms due to portal hypertension. Older in-
fants and children commonly have jaundice associated with hepato-
megaly either in the acute stage of inflammatory liver disease or later in
the course of chronic liver disease. Jaundice is a less prominent feature
HEPATOMEGALY 937
of liver disease associated with juvenile rheumatoid arthritis or inflam-
matory bowel disease but is frequently seen associated with toxic drugs
used in the adolescent age group.20

Splenomegaly Associated with Hepatomegaly

Splenomegaly associated with hepatomegaly is encountered fre-
quently in all age groups and has particular value in differential diag-
nosis. Increased portal venous pressure, infiltrations, and reticuloen-
dothelial hyperplasia are the most common mechanisms accounting for
its presence. Two representative groups deserve further comment: mas-
sive splenomegaly, and splenomegaly with polycystic disease-hepatic
fibrosis syndrome.
Massive enlargement of the spleen is usually not seen with portal
hypertension but with infiltrative diseases (stored material or cells) af-
fecting both liver and spleen. Storage diseases such as Gaucher's dis-
ease,2 Neimann-Pick disease,!o the histiocytosis diseases,! and other
malignancies of blood elements produce this striking finding.
Polycystic liver disease and congenital hepatic fibrosis are probably
due to a single defect, at present incompletely understood develop-
mental disorders.44 Both usually manifest some hepatomegaly but have
relatively normal liver function studies except with hypotensive or
a,noxic stresses. Splenomegaly is due to portal hypertension produced by
thick fibrous bands compressing the intrahepatic venous circulation. 46 A
careful physical examination during childhood may identify these pa-
tients prior to their presentation with major upper gastrointestinal hem-
orrhage.
Mass Lesions of the Liver
An isolated mass palpated in an otherwise normal liver or an asym-
metric enlargement of the liver is a particularly ominous finding. This
less commonly encountered problem should be evaluated extensively in
hospital in order to establish a diagnosis as quickly as possible. Primary
and secondary liver tumors are usually encountered in the child less
than 2 years of ageP In the newborn infant, the triad of cardiac failure,
generalized hepatomegaly, and cutaneous hemangioma~ should suggest
the presence of multinodular hemangiomatosis of the liver. A signifi-
cant number of such patients respond to therapeutic efforts, although
histologic tumor maturation does occur in some cases. 24 Newborn infants
may also present with cavernous hemangioma and solitary cysts produc-
ing asymmetric hepatomegaly. Cystic and pedunculated tumors of the
liver are frequently benign. Focal nodular hyperplasia or a benign
tumor, sometimes difficult to diagnose histologically, may produce
asymmetric hepatomegaly, and the liver may have a firm cirrhotic-like
consistency to palpation. A flat plate x-ray view of the abdominal cavity
may reveal calcification of liver-cell carcinomas, mixed tumors, tera-
tomas, adrenal rest tumors, cavernous hemangiomas, and solitary cysts.
Liver cell carcinomas of infants and young children are usually histo-
logically hepatoblastomas with a smaller cell type than adult hepatomas.
These tumors may produce precocious puberty by gonadotropin produc-
938 W. ALLAN WALKER AND RICHARD K. MATHIS

tion3 and some cause extensive skeletal demineralization during rapid

growth. Since Clatworthy14 has reported that nearly 50 per cent of hepa-
toblastomas are resectable, every effort should be made to determine the
extent of the disease early in the clinical course. About a 33 per cent
survival was reported in surgically treated hepatoblastomas. 14 The adult-
type of hepatomas are seen in later childhood or adolescence and are
often associated with pre-existing cirrhosis. These tumors unfortu-
nately have the same poor prognosis attributed to hepatomas in adults.
Secondary liver tumors in the newborn period usually produce firm dif-
fuse hepatomegaly. Wilm's tumor of the kidney, neuroblastoma of adre-
nal origin, and gonadal tumors make up the majority of metastatic
tumor cases. 26

DIAGNOSTIC AIDS

Laboratory Investigations
When a careful clinical evaluation of the patient with hepatomegaly
suggests hospitalization and further investigation, laboratory techniques
can give the physician valuable information about the major mechanisms
responsible for the hepatomegaly and the extent of disease. Again a
comprehensive review of this area is beyond the scope of this article.
However, a suggested approach to laboratory evaluation is provided in
Table 4. Only those special techniques used to evaluate hepatomegaly
will be discussed in detail.
Inflammatory diseases resulting in hepatocyte necrosis produce dra-
matic deviations of serum transaminases (SGOT and SGPT) usually
proportional to the extent of damage. Further necrosis impairs synthesis
of proteins involved in coagulation and may alter the prothrombin time
and reduce ammonia clearance. Hepatomegaly due to other mecha-
nisms such as storage (eg., iron43 and copper9) or congestion may affect
hepatocellular functions. Late stage liver disease may occur with nor-
mal serum enzymes but abnormal serum albumin and clotting studies.
Isotopic Scanning Procedures
The use of radiolabeled substances injected intravenously has
helped considerably in the evaluation of hepatomegaly, particularly in
the diagnosis of space occupying conditions affecting the liver. In gener-
al, two types of scans are used. Kupffer cell distribution and function are
evaluated by the technetium-99m sulfur colloid scan. 19 ,36 Defects in the
uniformity of colloid uptake by reticuloendothelial tissue may expose
extensive parenchymal disease or delineate mass lesions. Relative up-
take of colloid by the liver normally is slightly greater than splenic up-
take, and an altered uptake ratio is an indication of altered reticuloen-
dothelial function. When inflammation, massive necrosis, or Kupffer
cell hyperplasia are considered as part of the differential diagnosis, this
scanning procedure should be used. Alternatively, evaluation of biliary
obstruction and hepatocellular disease encountered in infants and chil-
dren ultimately relies on studies with 131 1 or 1251-labeled rose-bengal
HEPATOMEGALY 939
Table 4. Diagnostic Aids in Hepatomegaly

Laboratory Studies
General: Complete blood count, sedimentation rate, reticulocyte and platelet counts,
protein electrophoresis
Liver function tests: Bilirubin (direct and indirect), SGOT, SGPT, alkaline phosphatase,
BSP excretion, ammonia
Serum proteins: Ceruloplasmin, alpha-antitrypsin
Clotting studies: Prothrombin time, partial thromboplastin time

Scanning Procedures
Technetium-99m sulfur colloid: Kupffer cell function
131 I-rose bengal: Hepatocyte function
Ultrasonic scanning: Mass lesion (cystic vs. solid)

Selective Angiography
Mass lesion (benign vs. malignant)

Liver Biopsy (Percutaneous)

Generalized hepatomegaly, metastatic tumor

Special Procedures
Bile salt distribution in serum and urine
Cholangiography (percutaneous): Okuda needle
131I-rose bengal in stool collection
Sweat test
Hepatitis B antigen and antibody
Upper gastrointestinal barium x-rays

dye. 13 . 4o Rose-bengal dye is preferentially taken up into hepatocytes and

excreted into the biliary collecting system. Any defect in hepatocyte
function or bile flow may be reflected in an abnormal liver scan and/or a
decrease in excretion of radioactivity into the gastrointestinal tract. This
procedure is particularly helpful in the differential diagnosis of space
occupying lesions of the liver and in obstructive liver disease during in-
fancy. In the latter condition, the excretion of 131I-rose-bengal into the
intestine may help to distinguish between complete obstruction asso-
ciated with extrahepatic biliary atresia from the cholestatic syndromes
of neonatal hepatitis. 13 . 40
Ultrasonic scanning35 promises to be a useful diagnostic technique
and is particularly helpful in distinguishing between cysts and solid
mass lesions of the liver. As more experience is gained from this nonin-
vasive technique, further use of this technique in storage disease states
and other metabolic processes should prove helpful. However, for small
intrinsic mass lesions, as well as traumatic lesions of the liver, hepatic
angiography (which has a resolving capacity of 1 cm diameter) still
remains the procedure of choice.5
Needle Biopsy
When the etiology of hepatomegaly is obscure the question of the
advisability of needle biopsy frequently arises. Under appropriate condi-
940 W. ALLAN WALKER AND RICHARD K. MATHIS

tions, the closed liver biopsy in the pediatric age group, employing the
Menghini or Klatskin needle and the procedure of the Hong and Schu-
bert,t6 is generally recognized as a safe diagnostic procedure. 49 It is the
least invasive method for obtaining a tissue diagnosis in patients with
hepatomegaly; yet its use should be considered carefully in each indi-
vidual.
Comprehensive analysis of the biopsy specimen may include en-
zyme or heavy metal assay, isolation of an infectious agent, special
fluorescent or histochemical procedures, and/or fine structure analysis
of organelle pathology with electron microscopy. Although the closed
biopsy is most valuable in generalized hepatomegaly, the procedure
should also be considered in selected patients with asymmetrically
enlarged livers. However, the biopsy should be done only after a special
procedure such as a scan or angiography has helped to localize the
lesion. Under no circumstances should a closed biopsy be done when a
hemangiomatous or septic lesion is suspected. Furthermore, to mini-
mize complications, the closed biopsy should only be done after coagula-
tion studies are available or after any coagulation defect has been cor-
rected. In situations in which surgery is probable or a closed biopsy may
be too dangerous (hemangiomatosis), an open biopsy may be more ap-
propriate. This decision is based on an individual evaluation of each case.
Additional Diagnostic Tests
In addition to those special diagnostic procedures discussed above,
many new laboratory18 and x-ray studies 7• 27 have been described that may
be of particular importance in establishing the diagnosis of specific types
of hepatomegaly. Many of these procedures are included in Table 4. Okuda
and coworkers27 have introduced a special needle that may be used for
transhepatic cholangiography using a nonsurgical percutaneous method.
This technique may be very important in the diagnosis of hepatic dis-
orders in critically ill infants and in patients with suspected obstructive
jaundice.

"BENIGN" HEPATOMEGALY

Hepatomegaly in the infant and young child may quite frequently

be associated with mild self-limited illnesses, often viral infections with
some gastrointestinal involvement. Reticuloendothelial tissue in the
liver responds dramatically to septicemias of even limited duration.
Increased numbers of Kupffer's cells and minimal nonspecific portal in-
flammatory infiltrates are present. Fatty infiltration during periods of
decreased protein intake may produce a transient increase in liver size.
In general, the healthy infant or child with minimal abnormality in liver
function tests and without jaundice or splenomegaly requires only ob-
servation. The decision to observe may be very difficult but in general,
good clinical judgment proves reliable and many expensive and painful
procedures may be prevented.
HEPATOMEGALY 941
SUMMARY AND CONCLUSIONS

Hepatomegaly is not an uncommon occurrence in infancy and

childhood. When the pediatrician encounters a patient with an enlarged
liver, he must carefully evaluate that patient in order to determine the
necessary approach to establishing a diagnosis. Specific emphasis must
be made as to those conditions which necessitate hospital admission and
complete evaluation and those self-limited conditions which may re-
solve with time.

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Pediatric Gastrointestinal Unit

Massachusetts General Hospital
Boston, Massachusetts 02114