Semin Liver Dis 1998;18(3):281-93

Biliary atresia: pathogenesis and treatment

Bates MD, Bucuvalas JC, Alonso MH, Ryckman FC
Division of Pediatric Gastroenterology and Nutrition, Childrens Hospital Medical
Center, Cincinnati, Ohio 45229, USA.

Abstract
Biliary atresia is a disorder of infants in which there is obliteration or
discontinuity of the extrahepatic biliary system, resulting in obstruction of
bile flow. Untreated, the resulting cholestasis leads to progressive conjugated
hyperbilirubinemia, cirrhosis, and hepatic failure. Biliary atresia has an
incidence of approximately one in 10,000 live births worldwide. Evidence to date
supports a number of pathogenic mechanisms for the development of biliary
atresia. An infectious cause, such as by a virus, would seem most pausible in
many cases. The clinical observation that biliary atresia is rarely encountered
in premature infants would support an agent acting late in gestation. However,
no infectious or toxic agent has been conclusively implicated in biliary
atresia. Genetic mechanisms likely play important roles, even regarding
susceptibility to other specific causes, but no gene whose altered function
would result in obstruction or atresia of the biliary tree has been identified.
The variety of clinical presentations support the notion that the proposed
mechanisms are not mutually exclusive but may play roles individually or in
combination in certain patients. Biliary atresia, when untreated, is fatal
within 2 years, with a median survival of 8 months. The natural history of
biliary atresia has been favorably altered by the Kasai portoenterostomy.
Approximately 25 to 35% of patients who undergo a Kasai portoenterostomy will
survive more than 10 years without liver transplantation. One third of the
patients drain bile but develop complications of cirrhosis and require liver
transplantation before age 10. For the remaining one third of patients, bile
flow is inadequate following portoenterostomy and the children develop
progressive fibrosis and cirrhosis. The portoenterostomy should be done before
there is irreversible sclerosis of the intrahepatic bile ducts. Consequently, a
prompt evaluation is indicated for any infant older than 14 days with jaundice
to determine if conjugated hyperbilirubinemia is present. If infectious,
metabolic, endocrine disorders are unlikely and if the child has findings
consistent with biliary atresia, then exploratory laparotomy and intraoperative
cholangiogram should be done expeditiously by a surgeon who has experience doing
the Kasai portoenteostomy. Biliary atresia represents the most common indication
for pediatric liver transplantation, representing more than 50% of cases in most
series. Transplantation is indicated when symptoms of end stage liver disease
occur, including recurrent cholangitis, progressive jaundice, portal
hypertension complications, ascites, decreased synthetic function, and
growth/nutritional failure