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Indian Pediatr 2011;48: 644-646 |
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Evolving Biliary Atresia with Cytomegalovirus |
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Sweta Mohanty, Ira Shah and Sushmita Bhatnagar
From the Pediatric Hepatobiliary Clinic, BJ Wadia
Hospital for Children, Mumbai, India.
Correspondence to: Dr Ira Shah, 1/B Saguna, 271/B
St. Francis Road, Vile Parle (W),
Mumbai 400056. India.
Email;
[email protected]
Received: December 7, 2009;
Initial review: January 5, 2010;
Accepted: May 14, 2010.
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Multiple studies have been conducted to demonstrate the role of viruses
in causing biliary atresia. Although cytomegalovirus (CMV) is
known to cause intrahepatic bile duct destruction, its role in biliary
atresia is not proven. We report two cases of CMV infection, initially
presenting with intrahepatic cholestasis, who subsequently developed
biliary atresia.
Key words: Biliary atresia, CMV, Liver biopsy
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E
xtrahepatic
biliary atresia (EHBA) occurs in 1 in 10,000 live births, more
commonly in Asians. 65-90% of EHBA cases are post-natal, and in
these, a role for infectious agents in causing bile duct
obliteration is suggested [1]. Although cytomegalovirus (CMV) is
known to cause intrahepatic bile duct destruction and paucity, its
role as a cause of EHBA has been a topic of much debate.
Over a period of 2 years, 32 EHBA cases were seen
at our Pediatric Hepatobiliary Clinic. Out of the 13 who were tested
for associated CMV infection, 11 tested positive for CMV either by
positive CMV IgM or CMV PCR (Polymerase Chain Reaction) [2]. We
present two cases of cholestatic jaundice, tested positive for CMV
and had rising titres of CMV IgG on follow-up. Although the biliary
tree was found to be patent at presentation, both children
subsequently developed biliary atresia.
Case Report
Case 1: A 5 months old infant, exclusively
breastfed, immunized and well-developed for age, presented with
jaundice since birth with high coloured urine without clay colored
stools. On examination she had jaundice with hepatosplenomegaly,
ascites, umbilical hernia and corneal xerosis. Other examination and
investigations are depicted in Table I. Liver biopsy
could not be done due to uncorrectable coagulopathy and ascites.
Since HIDA (Hepatobiliary Iminodiacetic acid) scan showed excretion
of dye in the intestines, biliary atresia seemed unlikely. Due to a
positive CMV IgM serology and decompensated liver disease, the child
was treated with oral ganciclovir for 6 weeks along with antibiotics
but liver functions remained deranged. Subsequently, stools became
clay colored and an intraoperative cholangiogram showed no passage
of dye in the intestines. A portojejunostomy was done but the child
died postoperatively.
TABLE I
Patient Characteristics
| History |
Patient 1 |
Patient 2 |
| Examination findings |
Jaundice, ascitis, hepatosplenomegaly, |
Jaundice, |
| |
umbilical hernia, corneal xerosis |
hepatosplenomegaly |
| Investigations |
| Bilirubin (mg/dL) |
13.6 |
6.5 |
| Direct bilirubin (mg/dL) |
5.8 |
3.7 |
| SGOT (IU/L) |
350 |
390 |
| SGPT (IU/L) |
175 |
341 |
| Total proteins (g/dL) |
6 |
6.5 |
| Albumin (gm/dL) |
2.5 |
3.7 |
| Prothrombin time (sec) |
21.7 |
17 |
| Partial thromboplastin time (sec) |
39 |
40 |
| Alkaline phosphatase (IU/L) |
2467 |
1312 |
| GGTP (IU/L) |
10 |
629 |
| Ultrasound abdomen |
Hepatosplenomegaly + portal hypertension |
Gall bladder seen |
| CMV IgM (IU/ml) |
1.7 |
0.96 |
| CMV IgG |
247.6 (AU/ml) |
6.58 IU/ml |
| CMV Viral load (copies/ml) |
– |
Undetectable |
| Alpha 1 Antitrypsin levels |
Normal |
Normal |
| MR cholangiogram |
– |
Normal |
Case 2: A 3 months old child presented to a
peripheral hospital with jaundice since day 15 of life and high
coloured urine. She did not have clay coloured stools initially (Table
I). Her TORCH titres (IgM and IgG for Toxoplasma, Rubella,
CMV and Herpes) demonstrated equivocal CMV IgM (0.96 IU/mL) and
positive CMV IgG (6.58 IU/L). Other viral titres were negative.
Ultrasound showed presence of gall bladder. HIDA scan showed
decreased extraction of tracer by liver with non visualization of
tracer after 24 hours. She was subsequently referred to us at 5
months. On presentation, her weight was 5 kg, length was 58 cm. She
had jaundice and hepatosplenomegaly. Other systems were normal. A
Magnetic Resonance (MR) cholangiogram showed patent biliary tract.
Her hearing and ophthalmological evaluations were normal. Urine
organic acids and reducing substances were negative. Blood CMV viral
load was undetectable, but rising CMV IgG was seen. Her bilirubin
had decreased to 4.2 mg/dL (direct = 3.06 mg/dL). She was started on
valganciclovir (250mg/mm 2/day
in 2 divided doses). However, after 15 days, she started passing
persistent clay coloured stools. Liver biopsy showed features
suggestive of biliary atresia without inclusion bodies. She
underwent a Kasai portoenterostomy at 6 months. She continues to
have jaundice post-operatively.
Discussion
Landing suggested that neonatal hepatitis and
EHBA represent two ends of a spectrum of a single disease process.
Viruses have been proposed as a likely cause, CMV, reovirus and
rotavirus among the probable agents [3]. The rarity of EHBA in
neonates, the presence of inflammatory changes in the biliary tree
soon after birth, and their persistence following portoenterostomy
argue in favour of an infectious agent [4,5].
CMV infection has been found in a large number of
EHBA cases. However, normal infants are also commonly infected with
CMV, without developing overt disease. In a Canadian study of 12
children with biliary atresia, bile duct biopsy did not show CMV
inclusions or DNA(4). On the
other hand, a study from Sweden showed CMV DNA to be present in
livers from 9 of 18 patients with EHBA [5]. In a study by Tarr,
et al, CMV infection was documented in 5 of 21 i.e. 24% of
patients with EHBA [7]. The study concluded that the establishment
of CMV infection in infants with cholestasis should not deter the
search for EHBA [7].
In both our cases, the presentation was classical
of EHBA; full-term infants with jaundice and dark urine, with
otherwise normal growth, who develop acholic stools over the first
few weeks of life. Case 1 initially showed evidence of intrahepatic
cholestasis without biliary atresia on HIDA scan, but subsequently
developed EHBA, as evidenced by change in stool form and the
intraoperative cholangiogram. Case 2, with evidence of recent CMV
infection, showed patent biliary tracts on MR cholangiogram, but
subsequently developed acholic stools and liver biopsy evidence of
EHBA. In a similar case of CMV infection in a 2 month old, confirmed
by PCR analysis of blood and urine, HIDA scan showed biliary atresia,
and though urine samples turned negative with ganciclovir treatment,
progressive damage of the liver continued with subsequent
development of portal hypertension and hepatic coma [8].
In a Norwegian study on 10 patients of EHBA, 4
tested positive for CMV and 5 for EBV infection [6]. While 3 of
these had positive CMV PCR on liver biopsy, serum or urine, only one
had CMV IgM positive, thus indicating that newer PCR techniques can
pick up viral disease which may otherwise be missed by serology [5].
Another interesting example is of two non-identical twins with CMV
infection in utero, one of whom developed neonatal hepatitis while
the other developed EHBA after birth [9].
In summary, infants with EHBA should be tested
for viral antibodies, like CMV. The association of CMV infection
with EHBA is too often seen to rule out its role as an etiological
agent; and cases of CMV hepatitis must be monitored for subsequent
development of biliary atresia.
Contributors: IS and SB were
involved in management of the patients. IS drafted and
critically appraised the case report. She will act as
guarantor. SM reviewed the literature and wrote the manuscript.
Funding: None.
Competing Interests: None stated.
References
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