0943 Biliary atresia update

A useful review of biliary atresia covering literature for the period 1948 to 2008 was published in a recent issue of the Lancet. Prevalence estimates for the condition range from 1/5000 in east Asian countries to the more usual figures of 1/15000 – 1/19000 in the USA and Europe. Up to 20% are associated with other congenital abnormalities, the most common being biliary atresia splenic malformation syndrome as reported in ~10% of European and USA series, but associations with trisomies also exist. The latter suggest underlying genetic defects but genes have also been implicated in non-syndromic biliary atresia e.g. polymorphisms might lead to susceptibility to inflammation. In this regard CFC1, ICAM1, macrophage migration inhibitory factor gene, CD14 endotoxin receptor gene and hepcidin antimicrobial peptide gene have been implicated. Knowledge of the role of these genes might provide therapeutic targets to modify progression of the fibrosis that is fundamental to the disorder. In terms of aetiology, whereas viruses such as reovirus, rotavirus and cytomegalovirus have been implicated, the absence of viral particles in the livers of affected infants and the increased rate of viral detection with age suggest that viruses are secondarily involved in the process. Ultimately lymphocyte-mediated biliary inflammation appears to be the mechanism by which bile duct damage takes place, but the trigger for this response remains unknown. There could be upregulation of proinflammatory genes with upregulation of inflammatory cytokines such as IL-2, IL-12, IFN-γ and TNF-α and of cells such as CD3+ and CD8+. An alloimmune graft vs host type response has also been proposed since maternal chimeric CD8+ cells have been identified in biliary atresia liver cells. The disease progresses in 70% of children in whom bile drainage is established by portoenterostomy, with recurrent cholangitis playing a major role in rate of progression. Despite this, >80% of infants in whom bile drainage is established survive for >10 years with their native livers. Hepatic and serum markers of progression include osteopontin, fibroblast growth factor and hepatocyte growth factor, whereas elevated levels of transforming growth factor-β and epidermal growth factor are associated with a good outcome.

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Lancet 2009; 374: 1704-13
J Pediatr Surg 2005; 40: 1852-5
Eur J Pediatr Surg; 18: 224-9