Identifying the etiological profile of children presented with hepatomegaly admitted to a tertiary care hospital
Hue Central Hospital
Original Research
IDENTIFYING THE ETIOLOGICAL PROFILE
OF CHILDREN PRESENTED WITH HEPATOMEGALY ADMITTED
TO A TERTIARY CARE HOSPITAL
Nguyen Khoi Quan1, Nguyen Huu Chau Duc2,3*
DOI: 10.38103/jcmhch.2020.64.15
ABSTRACT
Objectives: To identify the pattern and etiology of diseases in children presented hepatomegaly at
Pediatrics Department in Hue Central Hospital, Vietnam.
Material and Methods: The Present study was conducted to evaluate the possible etiology and clinical
features of children presented with hepatomegaly. A total of 107 children, from one month to fifteen years
of age with hepatomegaly admitted in the Pediatric Department of Hue Central Hospital, Vietnam from May
2018 to April 2019 were included in this study.
Results:Themostcommoncausesofhepatomegalywereinflammation/infectionoftheliver(miscellaneous
cause included), hematological diseases and congestion heart failure with the percentage of 50.5%; 27,1%
and 12,1%; respectively. Among the hepatitis group, viral agents account for nearly 50.0%, of which the
most common one was Cytomegalovirus accounting for nearly 30.0%. Distribution of causes by age group
revealed most cases in 1 year-old or younger children was caused by inflammation (53.8%), and in the older
than 1 year-old children were hematological disorders (47.3%) which has statistical significance (P<0.05).
Conclusions: Our research observed that the most common causes of the group of ≤ 1 year old were
hepatitis, followed by cardiovascular disease and biliary obstruction due to congenital biliary atresia, and in
the older than 1 year group, hematological disorders was the most common.
Keywords: hepatomegaly, etiology, hepatitis
the other hand, the size of the liver in children also
varies depending on the age and the development of
the body, so it is difficult to determine the abnormal
liver enlargement in clinical practice.
I. INTRODUCTION
Hepatomegaly is an enlargement of the liver.
Abnormal liver enlargement is a manifestation
of many different causes: liver disease such as
hepatitis, biliary obstruction, or it is a sign of
systemic causes such as sepsis, blood disease, and
heart disease. There are many causes that can be
cured, but others can also lead to death, or certain
complications if the treatment is not appropriate. On
Treatment of hepatomegaly strongly depends on
the pathological mechanisms behind, so accurate
diagnosis is crucial. Identification of the mechanism
behind an enlarged liver is a challenge, because the
patients rarely present with a single symptom, but
1 Faculty of Medicine, Hue University of Medicine and Pharmacy, - Received: 2/6/2020; Revised: 13/8/2020;
Hue University
- Accepted: 4/9/2020
- Corresponding author: Nguyen Huu Chau Duc
2 Pediatrics Department, Hue University of Medicine and
Pharmacy, Hue University
3 Pediatrics Center, Hue Central Hospital
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often contemporary associated many symptoms. The were analyzed from patient case record form (1)
differences in many causes and their serious effects demographic characteristics including age and
onchildrenalsorequireearlydetectionandprognosis gender, (2) final diagnosis of the patient. Data
of the serious risk factors, in order to have an early were collected from register book of the patient
and appropriate treatment to prevent complications by using data entry preform, which was prepared
and death. Currently, thanks to modern testing by the researchers themselves. After collection
techniques, most causes of hepatomegaly have been of relevant information the data were checked,
discovered, and the disease has been prevented verified, edited manually for consistency, accuracy
and treated with efficiency. Unfortunately, some and to reduce error. Statistical analysis was done
laboratory tests are not available in many healthcare by statistical software SPSS for windows version
facilities. A simple algorithm using a few common 20. P values were calculated using Pearson chi-
parameters with easy-approach is needed in the square test. P < 0.05 was considered as significant
facilities and also for primary medical care.
All over the world as well as in Vietnam, studies
about the etiology of hepatomegaly is limited [1].
Most studies focus on one specific cause, separately
on each different study subject [2] [3]. In order to
contribute to the subject and improve the capacity
of diagnosis, we conducted the research with three
objectives: to reveal the etiology of hepatomegaly
in children; to describe the clinical and laboratory
characteristics of hepatomegaly children, and we
also present a clinical-approach algorithm to apply
into practice.
and P < 0.01 as highly significant.
III. RESULTS
Based on the data collected from 107 subjects,
the children were divided into two age groups: 1
month to ≤1 year old (called ≤1 year) and > 1 to 15
years old (called >1 year) (Table 2). The proportion
of male and female between the two age groups was
not statistically significant.
3.1. The etiologies of hepatomegaly in children
The causes of hepatomegaly were described
in Table 3. Three most common causes of
hepatomegaly was inflammation/infection of
the liver (miscellaneous causes were included),
hematological diseases and congestion heart failure
with the percentage of 50.5%; 27,1% and 12,1%;
respectively. The miscellaneous cases included
were four cases of CMV hepatitis combined with
congenital biliary atresia.
II. MATERIALAND METHODS
A total 107 children from 1 moth to 15 years of
age admitted with hepatomegaly into the Pediatric
Department of Hue Central Hospital, Vietnam from
May 2018 to April 2019 included in the study.
Children with incomplete data were excluded from
this study. Those children presented with pushed
down liver due to various causes are excluded
by measuring liver span for that particular age.
Hepatomegaly was defined as when the liver edge
was palpated below the right costal margin at the
mid clavicular line for infants and older children
and the liver span should be more than the expected
for the corresponding age. Infants 5-6.5 cms; 1-5yrs
6-7cms; 5-10yrs 7-9cms; 10-15yrs 8-10cms. [1].
The following clinical and laboratory in formation
Table 2: Distribution of disease by age
group and sex
Male
Female
Total
n
%
n
%
n
%
≤1 year 28 26.2 24 22.4 52 48.6
>1 year 27 25.2 28 26.2 55 51.4 P>0.05
Total 55 51.4 52 48.6 107 100
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Hue Central Hospital
Table 3: Etiology of hepatomegaly
1 year old, the most common cause of hepatitis was
viral 8/23 cases, of which HAV was presented in 6/8
case. The difference in the proportion distribution
was statistically significant (P=0.001).
Table 4: Distribution of hepatitis causes
by age group
Number of cases
(and percentage)
Etiology
Inflammation and infection
Bile obstruction
50 (46.8)
5 (4.7)
Heart failure
13 (12.1)
4 (3.7)
Number of cases
Hepatitis cause
Liver cancer
≤1 year old >1 year old
Hematological disease
Other rarely causes
29 (27.1)
2 (1.9)
CMV
15
1
1
6
Miscellaneous causes (CMV
infection combined with
congenital biliary atresia)
HAV
4 (3.7)
HBV
0
2
Total
107 (100)
Sepsis
7
4
With the group of 1 moth to ≤ 1 year old,
the three most common cause groups were
hepatitis, followed by cardiovascular disease
and biliary obstruction due to congenital biliary
atresia accounting for 53.8%, 21.2% and 15.4%,
respectively. For the group > 1 to year, the most
common was the hematological cause, accounting
for 47.3%, followed by inflammation and infection
40.0%, the remaining causes include liver cancer,
rare biliary atrophy. The difference in the proportion
distribution was statistically significant between
two age groups (P<0.05) but not significant between
two genders.
Drug
1
1
Autoimmune hepatitis
Hemorrhagic fever
Malaria
0
3
0
1
0
1
Unidentified causes
Total
7
4
31
23
3.2. Clinical manifestations of the children
with hepatomegaly
In table 5, the distribution of liver size by causes
was also remarkable. The mean sub-hepatic edge
compared to the right costal margin was 3.3 ± 1.4
cm. Mean value in the liver cancer group was the
largest (5.3 ± 2.6 cm) and the difference between
causes was statistically significant (P<0.05). Most
causes were presented with a smooth liver surface
(94.4%), except for the group of liver cancer with all
four cases having a rough surface. Most causes had
a solid liver density (86.0%). Liver tenderness was
mainly seen in the group of hepatitis, while 36/107
(more than 30%) cases cannot be evaluated and
the differences in tenderness were not statistically
significant.
The results in table 4 were shown that among
the causes of hepatitis, the viral agent accounts for
nearly half of cases, of which the most common was
CMV, followed by sepsis and neonatal infection.
Some other rare causes such as drugs, autoimmune
and other. However, there still 20.4% of cases were
unknown etiology.
In 54 cases of hepatitis, with the group of ≤1
year old (31 cases), the most common cause of
hepatitis was CMV, accounting for 15/31 (48.4%).
After that, it was due to urgent infection accounting
for 7/31 (22.6%). There still a large proportion of
unknown causes was 7/31 (22.6%). For the group >
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Table 5: The mean sub-hepatic edge compared to
the right costal margin
Hematological disease
Other causes
3,5 ± 1,9
3,0 ± 1,4
3,3 ± 1,4
Etiology
Mean size of the liver
Inflammation and
infection
All causes
3,0 ± 1,1
The clinical manifestations distributed by
causes were shown in Table 6. Manifestation of
splenomegaly, changesinthenumberorcomposition
of leukocytes were both not statistically significant
when distributed by group of causes.
Bile obstruction
Heart failure
3,6 ± 0,5
2,9 ± 0,7
5,3 ± 2,6
Hepatoblastoma
Table 6: The clinical manifestations distributed by causes
Total
(n=107)
Inflammation
and Infection obstruction failure
Bile
Heart
Hematological Other
Hepatoblastoma
(n=4)
disease
(n=29)
causes
(n=2)
(n=50)
(n=9)
(n=13)
n
%
Fever
20
30
3
8
0
16
2
1
49 45.8
81 75.7
Fatigue
5
13
4
28
Poor
appetite
33
6
13
4
28
2
86 80.4
Jaundice
34
7
9
8
9
1
0
0
0
4
0
0
1
0
0
0
1
4
0
0
0
0
43 40.2
15 14.0
45 42.1
25 23.4
White stool
Dark urine
Vomiting
34
16
Abdominal
pain
19
5
2
1
0
2
1
3
0
1
9
1
3
0
0
1
35 32.7
Diarrhea
8
0.1
Shortness
of breath
9
13
27 25.2
3.3. Laboratory tests differences according to the causes
In the children whose hepatomegaly were hematological disorders, 83.9% had an anemia condition
attached. Assessing the severity, most causes had a mild to moderate hepatomegaly condition, while in the
hematology group, the rate of severe anemia was 38.7%. The difference in the above rates was statistically
significant (P<0.05). The study revealed markedly differences in laboratory test results which were shown
in Table 7, 8, 9 and 10.
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Hue Central Hospital
Table 7: Different values of the blood count indexes between causes
Inflammation
and Infection obstruction
Bile
Heart
failure
(n=13)
Hematological Other
Hepatoblastoma
(n=4)
disease
(n=29)
causes
(n=2)
(n=50)
(n=9)
RBC
(M/µL)
3.6 ±
0.7
3.8 ± 0.9
3.6 ± 0.7
4.3 ± 0.9
3.3 ± 0.8
9.4 ± 1.8
3.1 ± 0.9
8.4 ± 2.7
P>0.05
P>0.05
P<0.05
P<0.05
P<0.05
HGB
(g/dL)
7.4 ±
3.3
10.0 ± 2.4
10.0 ± 1.8 12.9 ± 2.3
MCV
(fL)
66.8 ±
4.2
79.0 ± 16.2 87.2 ± 6.3 89.2 ± 6.9
86.9 ± 13.8
26.6 ± 5.1
86.5 ± 11.1
28.5 ± 4.3
MCH
(g/dL)
20.1 ±
4.9
28.0 ± 4.7
29.9 ± 2.9 25.0 ± 2.8
376.2
±
373.2
Platelets
(K/µL)
338.4
± 150.1
312.0
± 147.2
371
± 147.3
271.4
± 130.2
189.6
± 155.3
Table 8: Compared values of the liver enzyme between hepatitis versus congenital biliary atresia cause
Inflammationand Infection
Congenital biliary atresia
(n=9)
(n=50)
AST (UI/L)
ALT (UI/L)
ALP (UI/L)
GGT (UI/L)
407.6 ± 546.2
295.4 ± 469.9
301.4 ± 227.6
79.8 ± 66.7
253.0 ± 135.4
110.4 ± 41.5
463.2 ± 152.3
487.6 ± 487.5
P>0.05
P=0.001
P>0.05
P<0.05
Table 9: The De Ritis ratio (AST/ALT) in the hepatitis group
Hemorrhagic
Autoimmune
disease
Unidentified
CMV HAV HBV Sepsis Drug
(n=16) (n=7) (n=2) (n=11) (n=2)
fever
and Malaria
(n=2)
Total
(n=54)
cause
(n=2)
(n=3)
<1
1-2
>2
3
7
6
6
0
1
2
0
0
4
6
1
1
1
0
0
1
2
1
0
0
4
5
2
22
20
12
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Bệnh viện Trung ương Huế
Identifyingthe etiological profile of children ...
Table 10: Bilirubin level varies by causes
Inflammation
and Infection obstruction failure
Bile
Heart Hepatoblas- Hematological Other
Total
(n=107)
toma
(n=4)
disease
(n=29)
causes
(n=2)
(n=50)
13
(n=9)
(n=13)
0
12
4
29
2
61
Normal
27.1%
19
0
92.3%
100.0%
96.8%
100.0% 57.0%
Predominant
conjugated hyper-
bilirubinemia
8
0
0
0
0
0
0
0
0
0
0
0
0
0
0
27
25.2%
10
39.6%
9
88.9%
0
1
0
0
Predominant
unconjugated
hyperbilirubinemia
0
16.7%
9
0
1
7.7%
0
3.2%
0
9.3%
9
Mixed
16.7%
11.1%
0
0
8.4%
IV. CONCLUSIONS
In our study, the most common cause of atrophy were under 1 year old. In the group of
hepatomegaly in children was inflammation and children older than 1 year old, the hematological
infection. This result was similar to the study of group took the lead, with inflammation and infection
Ajay Kumar et al. [4]. The second leading cause was group took the second. This could be explained due
hematological diseases including acute leukemia, to the age of detection of these diseases, especially
lymphoma, bone marrow dysplasia, hematopoietic the lymphoma and leukemia are rarely found
syndrome, thalassemia, and several other causes, before 1 year of age in East Asia [5] [6]. Other
followed by heart failure in third place. Meanwhile, mechanism cause hepatomegaly in this group may
according to the study of Kumar, the second be due to infiltration, so it takes time to cause liver
leading cause was congestive heart failure and enlargement.
the hematological group is accounting for a small
The results show that up to 50.5% of large liver
percentage (6%). The difference may be due to the cases due to inflammation and infection. Among
small sample size of Kumar’s study and different hepatitis causes, viral agents were the most common
study region, while the group of hematological (especially CMV). Infants may acquire CMV
pathology was often hospitalized in central hospital. infection from their mothers through intrauterine
The results of the distribution of causes by age infection(congenitalinfection),throughcontactwith
group were also remarkable. The difference between infected genital secretions during passage through
the age groups may be due to the inadequate the birth canal (perinatal infection), or postpartum
development of the liver in children under 1 through breastfeeding (postnatal infection) [7].
year old, easily reacting to infections and toxins.
The most common clinical symptoms were
Moreover, this was an age group of incomplete nonspecific such as fatigue and poor appetite.
immune systems, and inadequate immunization. However, signs of jaundice and discolored stools
Congenital abnormalities in metabolism as well could help navigate the cause due to inflammatory
as structure will often manifest mainly during this infections or bile congestion. Other studies
period. As in our study, 8 of all 9 cases of congenital conducted in Vietnam share the similar model
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Hue Central Hospital
[8] [9]. Dyspnea were also valuable to suggest cytoplasm (20%) therefore increasing AST suggests
deep and progressive damage. Beside, ALP was
synthesized by hepatocytes and bile duct epithelial
cells and GGT was found with high concentrations
in the cylindrical epithelial cells of the bile duct,
it reveals that ALP and GGT were very sensitive
tests to detect biliary obstruction. Bilirubin level
was normal in most causes. Bilirubin increase was
seen in all cases with biliary obstruction and also
in a large number of hepatitis. The obstructive
group had direct bilirubin dominance, while in the
hepatitis group the difference between the causes
was not really clear.
heart failure as an underlying condition. We had
also evaluated accompanying splenomegaly, but
differences were not significant.
Changes in complete blood count were most
common in the hematological group, characterized
by a decrease in both erythrocytes and thrombocytes,
with an inconsistent sign of leukopenia. The MCV
alterations between the groups were remarkable.
These signs were consistent with pathogenesis of
liver malfunction. Due to the heterogeneousness
of tests, this study focused on differences between
the inflammation, infection and biliary obstruction
group. In the hepatitis group, increasing AST and
ALT were dominant than ALP and GGT; while
in the bile obstructive condition, in contrast,
ALP and GGT were markedly increased. This
difference was explained based on the origin of
these enzymes. AST, ALT in hepatitis children
reflects the destruction of hepatocytes. ALT mainly
originated from cytoplasm while AST was highly
localized in the mitochondria (80%) and a little in
Our research strengthens the current
understanding of the etiology, clinical and
laboratory manifestations of hepatomegaly. Based
on these insights, we also propose two schemes for
approaching the diagnosis of hepatomegaly by two
age groups below (algorithm 1, 2).
Conflict of interests
All the authors have no conflict of interests to
declare.
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