Home            Past Issues            About IP            About IAP           Author Information            Subscription            Advertisement              Search  

Case Report

Indian Pediatr 2011;48: 644-646

Evolving Biliary Atresia with Cytomegalovirus

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; irashah@pediatriconcall.com 

Received: December 7, 2009;
Initial review: January 5, 2010;
Accepted: May 14, 2010.


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

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.


Patient Characteristics
History Patient 1 Patient 2
Examination findings Jaundice, ascitis, hepatosplenomegaly, Jaundice,
  umbilical hernia, corneal xerosis hepatosplenomegaly
  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/mm2/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.


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.


1. Schwarz SM. Biliary Atresia. Available at URL: http://www.emedicine.medscape.com/article/927-29-overview. Accessed on 1st August, 2009.

2. Sanghai SR, Shah I, Bhatnagar S, Murthy A. Incidence and prognostic factors associated with biliary atresia in western India. Ann Hepatol. 2009;8:120-2.

3. Etiopathogenesis of biliary atresia: Viruses and Biliary atresia. Available at URL: http://www.medscape.com/viewarticle/418332_3. Accessed on 1st August, 2009.

4. Jevon GP, Dimmick JE. Biliary atresia and cytomegalovirus infection: A DNA study. Pediatr Dev Pathol. 1999;2:1-14.

5. Fischler B, Ehrnst A, Forsgren M, Orvell C, Nemeth A. The viral association of neonatal cholestasis in Sweden: a possible link between cytomegalovirus infection and extrahepatic biliary atresia. J Pediatr Gastroenterol Nutr. 1998;27:57-64.

6. Fjaer RB, Bruu A-L, Nordbo SA. Extrahepatic bile duct atresia and viral involvement. Pediatr Transplantation. 2005;9:68-73.

7. Tarr PI, Haas JE, Christie DL. Biliary atresia, cytomegalovirus, and age at referral. Pediatrics. 1996;97:828-31.

8. Mandraveli-Hatzikosta K, Pape-Chrisafi M, Fotoulaki M, Papadopoulou D, Alexiou-Daniel S. Cytomegalovirus infection and biliary atresia in a newborn infant. (Abstract) 15th European Congress of Clinical Microbiology and Infectious Diseases; Copenhagen / Denmark, 2005. Available from www.blackwellpublishing.com/ @ccmid15/ abstract. asp?id=38036. Accessed on 1 August, 2009.

9. Hart MH, Kaufman SS, Vanderhoof JA, Erdman S, Linder J, Markin RS, et al. Neonatal hepatitis and extrahepatic biliary atresia associated with cytomegalovirus in twins. Am J Dis Child. 1991:145:302-5.


Copyright© 1999 by the Indian Pediatrics (Disclaimer)