Cytomegalovirus-associated biliary atresia: An aetiological and prognostic subgroup

J Pediatr Surg. 2015 Oct;50(10):1739-45. doi: 10.1016/j.jpedsurg.2015.03.001. Epub 2015 Mar 7.

Abstract

Background and aims: Perinatal cytomegalovirus (CMV) infection is a possible cause or trigger of biliary atresia though clinical evidence is scant. We hypothesised that CMV IgM+ve biliary atresia is a separate clinical entity compared to CMV IgM-ve biliary atresia.

Methods: Prospective single-centre study. 210 infants with histologically confirmed biliary atresia were treated in our institution (Jan. 2004 to Dec. 2011); of these 20 (9.5%) were CMV IgM+ve at presentation. We compared these with 111 infants who were CMV IgM-ve (controls) for clinical features, biochemistry at presentation and outcome following Kasai portoenterostomy (KPE). A blinded comparison of age-matched liver histology was also performed. Data are quoted as median (interquartile range). A P value ≤ 0.05 was regarded as significant.

Results: Infants with CMV IgM+ve biliary atresia were older at Kasai portoenterostomy (or laparotomy) [70 (60-80) days vs. 56 (44-75)days; P = 0.003] and were more jaundiced [175 (147-224) vs. 140 (121-181) μmol/L; P = 0.002+ with higher AST*287 (157-403) vs. 180 (133-254) IU/L; P = 0.005] and aspartate aminotransferase-to-platelet ratio index [1.1 (0.79-3.0) vs. 0.63 (0.43-0.95)] levels. Liver histology: CMV IgM+ve biliary atresia was characterised by a greater degree of inflammation (P < 0.0001) and fibrosis (P = 0.02), whereas CMV IgM-ve isolated biliary atresia had a higher degree of lobular cholestasis (P = 0.001). This effect was independent of the effects of age at KPE.

Outcome: CMV IgM+ve biliary atresia had a poorer outcome with a reduced clearance of jaundice (15% vs. 52.2%; P = 0.002), native liver survival (P < 0.0001) and increased mortality (P = 0.002).

Conclusions: CMV IgM+ve biliary atresia is a distinct clinical and pathological entity with a diminished response to Kasai portoenterostomy.

Keywords: Biliary atresia; Cytomegalovirus (CMV); Kasai portoenterostomy; Neonatal cholestatic jaundice.

MeSH terms

  • Age Factors
  • Aspartate Aminotransferases / blood
  • Biliary Atresia / pathology
  • Biliary Atresia / surgery
  • Biliary Atresia / virology*
  • Cholestasis / etiology
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / complications*
  • Female
  • Humans
  • Immunoglobulin M / analysis
  • Infant
  • Liver / enzymology
  • Liver / pathology
  • Liver / surgery
  • Male
  • Platelet Count
  • Portoenterostomy, Hepatic
  • Prognosis
  • Prospective Studies

Substances

  • Immunoglobulin M
  • Aspartate Aminotransferases