Journal Reading

Prevalence and Outcome of

Hepatobiliary
Dysfunction in Neonatal
Septicaemia
Sumaira Khalil, Dheeraj Shah, M.M.A. Faridi, Ashwani
Kumar, and Kiran Mishra
(JPGN 2012;54: 218222)

Oleh:
Fajar Ahmad Prasetya
FK UNSRI
2011

Background
Neonatal

sepsis contributes 25% to neonatal

mortality in developing countries. Gramnegative organisms are mainly responsible for
sepsis in developing countries and are
commonly associated with multiorgan
dysfunction, resulting in high mortality and
poor outcome

Hepatobiliary

dysfunction in the form of

cholestatic jaundice and elevated liver
enzymes has been reported in more than
two-thirds of preterm neonates
experiencing Gram-negative septicaemia

cont
Cholestatic

jaundice in a neonate may also signify

mechanical obstruction of the biliary tract because
of biliary atresia or a metabolic disorder.

To

plan further investigations towards a primary

liver disease and appropriate management,
including referral to specialised centres, it is
important to distinguish the newborns having
cholestatic jaundice because of septicaemia
from those having obstructive, hereditary, or
metabolic disorders.

The

exact course, pattern of abnormalities, and

outcome of sepsis associated hepatobiliary
Problem
dysfunction in neonates have not been
described.

Objective
The

present study was conducted

to determine the prevalence,
pattern, and course of
hepatobiliary dysfunction in
neonatal sepsis, and to evaluate
its effect on the survival and
growth.

Patients and Methods

Patients
One

hundred fifty-three neonates with blood

culturepositive sepsis. The data was taken
from March 2006 to November 2006 in the
University College of Medical Sciences and
Guru Tegh Bahadur Hospital, Delhi, India.
Neonates with major congenital malformation
were excluded.
Ultrasonography of the abdomen was done in
all of the babies to evaluate for any
choledochal cyst or extrahepatic biliary atresia

cont
Methodes
Those

patients were recruited from the

neonatal intensive care unit of an urban
hospital. Liver function tests were done on
day 3 and day 10 in all of the cases.
In babies with abnormal results (direct
bilirubin >20% of total with a minimum level
of 2 mg/dL or alanine aminotransferase [ALT]
>50 U/L), tests were repeated weekly for 1
month and then fortnightly for 3 months, or
until normalization of values.
Anthropometry was recorded at all of these
visits.

Results
Prevalence

of Hepatobiliary Abnormalities

Any

hepatobiliary dysfunction (direct bilirubin

>20% of total with a minimum level of 2
mg/dL or ALT>50 U/L) was found in 83
(54.2%) subjects.

Cholestatic

jaundice was seen in 65 (42.5%)

subjects, whereas deranged ALT was seen in
57 (37.3%) cases.

One-fourth

(25.4%) of septicaemic babies had

cholestatic jaundice as well as derangement
of ALT (Table 1).
Outcome

Outcome

cont
Onset,

Pattern, and Course

The onset of cholestasis (n 65) was seen at day 3 of
onset of sepsis in 80% (52 of 65) babies. It was
present by day 10 in another 15%. Only <5% of babies
developed cholestasis after day 10
The maximum value of direct bilirubin was achieved
by day 10 of onset of sepsis in 68% (44 of 65) babies,
whereas in 22% the maximum value was achieved as
early as day 3 of sepsis. In the remaining 10% cases,
maximum value of direct bilirubin was seen at or after
day 17 of sepsis.
The direct bilirubin level normalised by day 10 of
sepsis in 15% of babies, and in 48% it normalised by
day 17. In 85% of babies having cholestatic jaundice,
the levels normalised by 1 month. Cholestatic jaundice
resolved in all survivors by the age of 2 months.

In

babies with deranged ALT, in almost twothirds (68.4%), the onset was seen by day 3
of sepsis, and in another 26.3% babies by day
10 of sepsis.
The maximum value was achieved by almost
one-third (31.5%) of babies at day 10 of
sepsis and in another one-third (31.5%), it
was achieved at day 17 of sepsis.
The ALT normalised by 1 month (day 31) in
about half (49.2%) of the babies, whereas in
the remaining half (50.8%) the raised levels
persisted for variable periods up to 3 months

cont
Of

the 83 babies who had hepatobiliary

dysfunction, 35 (42.1%) babies had direct bilirubin
in the range of 2 to 5 mg/dL (Table 2), 25 (30.1%)
babies had direct bilirubin in the range of 5 to 10
mg/dL, and 10 (12%) had levels between 10 and
15 mg/dL. Only 1 baby had direct bilirubin beyond
15 mg/dL.

The

levels of ALT ranged between 51 and 150 IU/dL

in 34 (41%) babies and 23 (28%) had ALT levels
>150 IU/dL. Total protein <4 mg/dL was seen in 50
(60.2%) babies, whereas serum albumin <2.5
mg/dL was found in 66 (79.5%) babies.

cont
Of

the 153 babies with sepsis, 49.7% babies died during the course of
the stay with mean (SD) age of death being 6.1 +- 4.7 days.

The

prevalence of hepatobiliary dysfunction was higher in

survivors as compared with deaths (56.7% vs 43.4%; P<0.01).

On

comparing the biochemical parameters between the deaths and

survivors, it was found that mean direct bilirubin levels in survivors
were higher at day 3 and day 10 of onset of sepsis; however, this was
not statistically significant.

The

maximum value of direct bilirubin reached was significantly

higher (P<0.01) in survivors as compared with deaths (Table 4).

Similarly,

the levels of ALT were higher at all time periods (days 3

and 10) in survivors as compared with the deaths. This was again
not significant, except the maximum ALT, which was significantly
higher in survivors (P<0.01) (Table 4).

Discussion
This

study documented that hepatobiliary dysfunction is

extremely commonly seen early in the course of neonatal
septicaemia.
The study showed that hepatobiliary dysfunction was
signifficantly more common in those babies who survived.
It suggest that acute cholestasis associated with sepsis
has an early onset and is transient.
It may be reasonable to monitor infants with documented
septicaemia carefully for a period of 1 to 2 months before
referring for invasive and expensive towards specialled
centers.
The presence of conjugated hyperbilirubinemia in neonatal
sepsis may carry a better prognosis in terms of survival
and has no effect on growth during early infancy.

Weakness of the Study

The

findings from the study can only be generalised to

the neonates having Gram-negative sepsis, especially
caused by Klebsiella, in developing countries with a high
low birth weight rate.

The

findings may not be extrapolated to low-grade sepsis

with negative blood cultures.

It

has the limitation that the detailed investigations for

other causes of neonatal cholestasis were not performed
in all of the infants.

And

the contribution of other metabolic and genetic

causes could not be conclusively ruled out;

Validity
This

study is valid, because time,

subject and place were clearly stated.
Were the samples taken properly?
Yes they were, because the authors used
clear inclusion and exclusion criterias.
Does

the author use the right method?

Yes, the authors used right inclusion (blood

culture) and exclusion (USG) criterias, and
they did LFT and anthropometry to
determine the plevalence and outcome of
hepatobilliary dysfunction.

Is

the focus of this study in

accordance with the objective?
yes it is, because the authors get the
information needed to determine the
prevalence, pattern, and course of
hepatobiliary dysfunction in neonatal
sepsis.

Importance
This

journal is important because

it helps us to understand the
course and characteristics of liver
dysfunction in neonatal sepsis.
It also helps us to understand the
role of bilirubin, as somehow,
works as proctective agent
aggainst the sepsis occuring in
neonates.
Menegakkan diagnosis sepsis

Applicability
Is

this journal applicable?

Not much. We need to do another

research in indonesia because
bacterial pattern might be diffrent.

This

journal is valid, important,

and not much applicable.