Biliary atresia

Abstract

Biliary atresia is a rare disease of infancy, which has changed within 30 years from being fatal to being a disorder for which effective palliative surgery or curative liver transplantation, or both, are available. Good outcomes for infants depend on early referral and timely Kasai portoenterostomy, and thus a high index of suspicion is needed for investigation of infants with persistent jaundice. In centres with much experience of treating this disorder, up to 60% of children will achieve biliary drainage after Kasai portoenterostomy and will have serum bilirubin within the normal range within 6 months. 80% of children who attain satisfactory biliary drainage will reach adolescence with a good quality of life without undergoing liver transplantation. Although much is known about management of biliary atresia, many aspects are poorly understood, including its pathogenesis. Several hypotheses exist, implicating genetic predisposition and dysregulation of immunity, but the cause is probably multifactorial, with obliterative extrahepatic cholangiopathy as the common endpoint. Researchers are focused on identification of relevant genetic and immune factors and understanding serum and hepatic factors that drive liver fibrosis after Kasai portoenterostomy. These factors might become therapeutic targets to halt the inevitable development of cirrhosis and need for liver transplantation.

Genetic Contributors and Modifiers of Biliary Atresia

“…Among those with restored biliary drainage, as evidenced by a total serum bilirubin 3 months after Kasai HPE <2 mg/dl (or <34 micromolar), the majority of patients are able to postpone or avoid liver transplantation, while children whose jaundice does not resolve typically develop stigmata of cirrhosis and require evaluation for liver transplantation in the first year of life [6,11,19,24,25,26,27]. Unfortunately, there is no medical therapy that has been shown to alter the outcome of the Kasai HPE, including a recent double-blind study evaluating a potential role for corticosteroids [28].…”

Maximizing Kasai portoenterostomy in the treatment of biliary atresia: Medical and surgical options

“…This aetiological heterogeneity is complex and our broad classification which seeks to categorise syndromic BA and cystic BA as examples of developmental BA and cytomegalovirus (CMV)-IgM-positive BA as a clinically defined virus-associated BA, still leaves many cases of isolated BA with no obvious definable aetiology. 18 However, compared with isolated BA, infants with syndromic BA splenic malformation (BASM) respond less well to KPE and have a poorer overall outcome with a higher risk of death. 5,19 By contrast, higher proportions of infants with cystic BA (usually type 1 and 2) clear their jaundice after KPE and have a better long-term outcome (Fig.…”

A New Clarification Method to Visualize Biliary Degeneration During Liver Metamorphosis in Sea Lamprey (<i>Petromyzon marinus</i>)

“…Infant biliary atresia is a rare pediatric liver disease with severe medical complications 4,5,6,7,8,9,10 , however the pathogenesis and etiology of biliary atresia are largely unknown 4 . Patients with biliary atresia die within two years after birth unless surgical intervention (Kasai procedure) is performed 5 .…”

“…Many theories of biliary atresia etiopathogenesis have been proposed, such as viral infection, congenital malformation, autoimmune disease, and toxic insult. However, the contribution of each to the development of biliary atresia remains inconclusive 7,8,9,10 . Unlike infants that suffer pathological biliary atresia, sea lamprey undergo developmentally programmed biliary atresia without extensive necroinflammation, fibrosis or cirrhosis 10 .…”