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Original Article
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Abstract engue is a mosquito-borne viral disease
Background Clinical and biochemical impacts on liver with the most rapid spread in the world. It
dysfunction, as manifested by an increase in serum transaminase LVDPDMRUFDXVHRIPRUELGLW\DQGPRUWDOLW\
levels, are common in dengue infection. However, an association of in Southeast Asia. Disease severity ranges
elevated serum transaminase and dengue shock syndrome (DSS)
has not been well-established.
from undifferentiated acute febrile illness to dengue
Objective To assess for an association between serum transaminase fever (DF) to dengue hemorrhagic fever (DHF) to
levels and the presence of DSS in children. dengue shock syndrome (DSS), which is associated
Methods A nested, case control study was conducted on children with a degree of plasma leakage. 3 Dengue may
DJHG PRQWK WR \HDUV DGPLWWHG WR 6DQJODK +RVSLWDO ZKR occasionally affect other body systems. The liver is a
were diagnosed with dengue infection. Baseline characteristics
target organ of the Dengue virus.4 Hepatic dysfunction
DQGVHUXPWUDQVDPLQDVHOHYHOVZHUHUHFRUGHG3DWLHQWVZKRZHUH
included in the study were observed for the presence of DSS. is common in dengue infection, and is attributed to
Those who had DSS were selected as cases, and those who did not a direct viral effect on liver cells or as a consequence
develop DSS were selected as controls. Data was analyzed using of dysregulated host immune responses against the
ELYDULDWHDQGPXOWLYDULDWHPHWKRGVZLWKFRQILGHQFHLQWHUYDOV virus.5 Hepatic dysfunction may be reflected by
DQG3YDOXHZDVFRQVLGHUHGDVVWDWLVWLFDOO\VLJQLILFDQW
elevated transaminase levels, which may range from
Results Ninety-four children were involeved, 47 children in the
case group and the other 47 were in the control group. Baseline mild to severe.4
FKDUDFWHULVWLFVRIWKHVXEMHFWVZHUHVLPLODUEHWZHHQWKHFDVHDQG Studies on transaminase levels have been
control groups. Serum aspartate transaminase (AST) level of reported and show varying results. Elevation
8/ DQG DODQLQH WUDQVDPLQDVH $/7 RI 8/ ZHUH of aspartate transaminase (AST) and alanine
DVVRFLDWHGZLWK'6625&,WR3 DQG
25&,WR3 UHVSHFWLYHO\
transaminase (ALT) levels were significantly different
Conclusion Elevated AST and ALT levels were associated in DF, DHF, and DSS patients in some studies,
with an increased risk of DSS in children with dengue infection. while other studies showed no significant difference
[Paediatr Indones. 2014;54:181-5.].
Keywords: dengue shock syndrome, aspartate From the Department of Child Health, Udayana University Medical
transaminase, alanine transaminase School, Sanglah Hospital, Denpasar DQG *DGMDK 0DGD 8QLYHUVLW\
6DUGMLWR+RVSLWDO<RJ\DNDUWD; and the Department of Internal Medicine,
Udayana University Medical School, Sanglah Hospital3
in transaminase levels. Therefore, we evaluated /5 5HVXOWV DUH SUHVHQWHG LQ 25 ZLWK
for a possible association between serum transaminase confidence intervals, and a statistical significance
levels and DSS in children. YDOXHRI3
Methods Results
A nested, case-control study was conducted in 'XULQJWKHVWXG\SHULRGFKLOGUHQZLWKVXVSHFWHG
FKLOGUHQZLWKGHQJXHLQIHFWLRQDJHGPRQWKWR dengue infection were admitted in Sanglah Hospital.
years admitted to the Department of Child Health, 7ZR SDWLHQWV LQ WKLV VWXG\ ZHUH H[FOXGHG EHFDXVH
8GD\DQD8QLYHUVLW\0HGLFDO6FKRRO6DQJODK+RVSLWDO they had history of hepatitis. During observation, 47
'HQSDVDUIURP-XQHWR0DUFK SDWLHQWVZLWK'66ZHUHDVVLJQHGDVFDVHV6L[W\FKLOGUHQ
We included all children with a diagnosis of GLGQRWH[SHULHQFHVKRFNDQGRXWRIWKHVHZHUH
suspected dengue infection according to the WHO consecutively selected as the control based on the
FULWHULD3DWLHQWVGLDJQRVHGZLWKPDOLJQDQFLHV GXUDWLRQRIIHYHUDWWKHWLPHRIDGPLVVLRQ6XEMHFWV
immune disorders, hemato-oncology disorders, or DJHV UDQJHG IURP PRQWKV WR \HDUV %DVHOLQH
KDG D KLVWRU\ RI KHSDWLWLV ZHUH H[FOXGHG :H DOVR FKDUDFWHULVWLFVRIWKHVXEMHFWVDQGYDULDEOHVDVVRFLDWHG
H[FOXGHGSDWLHQWVZKRPZHZHUHXQDEOHWRREVHUYH with DSS in children are shown in Table 1.
such as those who died or were referred to another Based on multivariate analysis, variables associ-
KRVSLWDO 3DWLHQWV ZHUH REVHUYHG IRU SUHVXPHG'66 ated with DSS were liver enlargement (hepatomegaly),
during treatment according to standard medical care DEGRPLQDO SDLQ KHPDWRFULW OHYHO $67 OHYHO
IRU GHQJXH LQIHFWLRQ 3DWLHQWV ZKR KDG '66 ZHUH 8/DQG$/7OHYHO8/Table 2).
selected as cases and those who did not develop DSS Based on the multivariate analysis, we deter-
(DF, DHF I, and DHF II) were selected as controls. PLQHGWKHULVNRI'66EDVHGRQ$67OHYHO>25
At the admission, in addition to routine blood &,WR3 @DVVKRZQLQTable
H[DPLQDWLRQVDOOSDWLHQWVEORRGVHUXPZHUHWDNHQ 3 DQG $/7 OHYHO >25 &, WR
coded and stored. Serum transaminase level then 3 @DVVKRZQLQTable 4.
evaluated if patient met the criteria as case or control. Based on Table 3, every patient with dengue
:H REWDLQHG VXEMHFWV KLVWRULHV LQFOXGLQJ GXUDWLRQ infection who were found with abdominal pain,
of fever, presence of abdominal pain, vomiting, and KHSDWRPHJDO\KHPDWRFULWDQG$67
bleeding. 8/KDGDSUREDELOLW\RI'66RIDVKLJKDV
6HUXP WUDQVDPLQDVH OHYHOV ZHUH H[DPLQGHG In patients with abdominal pain, hepatomegaly,
on the first day of admission. Hematocrit, leukocyte KHPDWRFULW DQG $67 8/ WKH
count, hemoglobin, and platelet measurements SUREDELOLW\RI'66ZDVDVKLJKDV3DWLHQWVZLWK
were obtained from blood counts with the highest dengue infection and abdominal pain, hepatomegaly,
hematocrit was taken as a baseline value on the first KHPDWRFULW DQG $67 8/ KDG
day of admission. This study was approved by the D SUREDELOLW\ RI '66 RI ,Q SDWLHQWV ZLWK
Research Ethics Committee of Udayana University DEGRPLQDO SDLQ DQG $67 8/ WKH '66
0HGLFDO6FKRRO6DQJODK+RVSLWDO'HQSDVDU SUREDELOLW\ZDVZKLOHLIDEGRPLQDOSDLQDORQH
A minimum required sample size was calculated ZDVIRXQGWKHSUREDELOLW\IRU'66ZDVRQO\
for an unpaired, case control study, according to Based on Table 4, in patients with dengue
assumed odds ratios (OR) of each variable (AST and infection who were found to have abdominal pain,
ALT). The sample size calculated using the highest KHSDWRPHJDO\ KHPDWRFULW DQG $/7
25RI$67ZLWKDW\SH,HUURURIDQGSRZHURI 8/ WKHLU SUREDELOLW\ RI KDYLQJ '66 ZDV
ZDVVXEMHFWVLQHDFKJURXS'DWDZDVDQDO\]HG In patients with abdominal pain, hepatomegaly,
separately for each factor by bivariate analysis (Chi- KHPDWRFULWDQG$/78/WKHSUREDELOLW\
square test and unpaired T-test). Multivariate analysis RIKDYLQJ'66ZDV)XUWKHUPRUHLISDWLHQWV
was performed using backward logistic regression KDGDEGRPLQDOSDLQKHSDWRPHJDO\KHPDWRFULW
Table 1. Characteristics of study subjects and bivariate analyses of variables associated with dengue shock
syndrome
DSS group Non-DSS group
Characteristics P value OR 95%CI
(n = 47) (n= 47)
Mean age (SD), months 75.5 (36.9) 88 (35.3) 0.79*
Gender, n (%) 1.29
Male 26 (55) 23 (49) 0.536 0.57 to 2.9
Female 21 (45) 24 (51)
Nutritional status, n (%)
Underweight 12 (26) 9 (19) 0.268
Normal weight 24 (51) 32 (68)
Overweight 11 (23) 6 (13)
Mean duration of fever at admission (SD), days 4.3 (0.73) 4.5 (0.8) 0.569*
%NKPKECNPFKPIUP
Petechiae 10 (21) 11 (23)
Epistaxis 6 (13) 4 (9) 0.503 1.57 0.4 to 5.98
Hepatomegaly 35 (75) 14 (30) 0.000 6.8 2.78 to 17
Abdominal pain 37 (79) 12 (26) 0.000 10.8 4.1 to 28
Nausea and vomiting 25 (53) 22 (47) 0.536 1.29 0.57 to 2.9
Leucocytes count, n (%)
z. 12 (26) 23 (49) 0.019 0.36 0.2 to 0.85
>4000/L 35 (75) 24 (51)
Hemoglobin, n (%)
IF. 45 (96) 23 (49) 0.000 23.4 5.1 to 188
<14 g/dL 2 (4) 24 (51)
Hematocrit, n (%)
34 (72) 3 (6) 0.000 38.4 10 to 145.4
<46 % 13 (28) 44 (94)
Platelets count, n (%)
z. 30 (64) 34 (72) 0.376 0.68 0.3 to 1.6
>50,000/L 17 (36) 13 (28)
Serology, n (%)
IgG and IgM positive 37 (79) 34 (72) 0.472 1.4 0.5 to 42.8
IgG or IgM positive 10 (21) 13 (28)
Transaminase levels (IU/L)
AST, n (%)
+7. 37 (79) 9 (19) 0.000 15.6 5.7 to 42.8
<128.5 IU/L 10 (21) 38 (81)
ALT, n (%)
+7. 20 (43) 2 (4) 0.000 8.46 3 to 23.7
<40 IU/L 27 (58) 45 (96)
Mean length of hospital stay (SD), days 4.7 (1) 3.15 (1)
*Unpaired T-test
Table 4 consisted of abdominal pain, hepatomegaly, ,.$ ,,, ,'$, 0D\ <RJD\NDUWD %XNX 1DVNDK
KHPDWRFULWDQG$/78/ /HQJNDSFS
7KHGHJUHHRIKHSDWLFLQMXU\LQFUHDVHGWUDQVD GH6RX]D/-1RJXHLUD506RDUHV/&5LEDV%)$OYHV)3
minase levels) has been strongly associated with the Vieira FR, et al. The impact of dengue on liver function
presence of severe complications of dengue infection. as evaluated by aminotransferase level. Braz J Infect Dis.
7KHUHIRUHDWDPLQLPXPWUDQVDPLQDVHH[DPLQDWLRQV
should be performed regularly during follow-up of 0RKDQ%3DWZDUL$.$QDQG9.+HSDWLFG\VIXQWLRQLQ
dengue patients.Understanding of variables related FKLOGKRRGGHQJXHLQIHFWLRQ-7URS3HGLDWU
to DSS should make physicians more alert to early &KKLQD56*R\DO2&KKLQD.'*R\DO3.XPDU53XUL6
signs of DSS. Although plasma leakage and bleeding Liver function test in patients with dengue viral infection.
cannot be prevented, deterioration into DSS may 'HQJXH%XOO
be prevented with close monitoring for early signs of 'DUDMDW$6HNDUZDQD16HWLDEXGL'+XEXQJDQNDGDUDV-
shock and adequate fluid therapy. partat aminotransferase (AST) dan alanin aminotransferase
/LPLWDWLRQVWRRXUVWXG\LQFOXGHGWKHH[FOXVLRQ (ALT) serum dengan spektrum klinis infeksi virus dengue
of patients with a history of hepatitis only by history- pada anak. 6DUL3HGLDWUL
WDNLQJDQGWUDQVDPLQDVHH[DPLQDWLRQVSHUIRUPHGRQO\ *XSWD 9 <DGDY 73 3DQGH\ 50 6LQJK $ *XSWD 0
once at the time of admission. Future studies should .DQDXML\D3et al. Risk factors of dengue shock syndrome in
be conducted using the cohort method with serial FKLOGUHQ-7URS3HGLDWU
WUDQVDPLQDVH H[DPLQDWLRQV WR GHWHUPLQH D FDXVDO 7DQWUDFKHHZDWKRUQ 7 7DQWUDFKHHZDWKRUQ 6 . Risk factor
relationship between serum transaminase levels and of dengue shock syndrome in children. J Med Assoc Thai.
severity of dengue infection.
In conclusion, elevated serum transaminase is ,WKD6.DVK\DS5.ULVKQDQL16DUDVZDW9$&KRXGKXUL
associated with increased risk of DSS in children G, Aggarwal R. 3URILOHRIOLYHULQYROYHPHQWLQGHQJXHYLUXV
with dengue infection. In addition, abdominal pain, LQIHFWLRQ1DWO0HG-,QGLD
KHSDWRPHJDO\DQGKHPDWRFULWOHYHORIPD\ 6HQHYLUDWQH6/0DODYLJH*1GH6LOYD+-3DWKRJHQHVLVRI
also be associated with increased risk for DSS. liver involvement during dengue viral infection. Trans R Soc
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References the pattern of liver involvment in dengue hemorrhagic fever
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DQGFRQWUROS .XR&+7DL',&KDQJ&KLHQ&6/DQ&.&KLRX66/LDZ
&KDFNR % 6XEUDPDQLDP * &OLQLFDO ODERUDWRU\ DQG YF. Liver biochemical test and dengue fever. Am J Trop Med
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3. WHO. Dengue haemorrhagic fever: diagnosis, tretament, 7.
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ween serum transaminase and plasma protein levels and MA. The impact of dengue on liver function as evaluated
shock in dengue demorragic fever.3URFHHGLQJVRIWKH 3,7 E\DPLQRWUDQVIHUDVHOHYHO-0HG