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Biliary atresia: pathogenesis and treatment
M D Bates1, J C Bucuvalas, M H Alonso
1Division of Pediatric Gastroenterology and Nutrition, Childrens Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Insights
Biliary atresia, a severe infant liver disorder, obstructs bile flow, leading to failure if untreated. Early Kasai portoenterostomy surgery offers improved survival rates, but prompt diagnosis is crucial for infants with jaundice.
Area of Science:
- Pediatric Gastroenterology and Hepatology
- Infant Liver Disease Pathophysiology
- Surgical Interventions for Biliary Atresia
Background:
- Biliary atresia is a critical infant disorder characterized by extrahepatic biliary system obliteration, causing bile flow obstruction.
- Untreated, it leads to cholestasis, conjugated hyperbilirubinemia, cirrhosis, and fatal hepatic failure within two years.
- The incidence is approximately 1 in 10,000 live births globally.
Purpose of the Study:
- To review the pathogenic mechanisms, clinical presentations, and treatment outcomes of biliary atresia.
- To emphasize the critical role of early diagnosis and surgical intervention.
- To highlight the impact of Kasai portoenterostomy on long-term survival and the indications for liver transplantation.
Main Methods:
- Review of existing evidence on biliary atresia pathogenesis, including infectious and genetic factors.
- Analysis of clinical observations regarding disease presentation and progression.
- Evaluation of the efficacy of Kasai portoenterostomy and criteria for liver transplantation.
Main Results:
- While infectious and genetic causes are suspected, no definitive agent or gene has been identified.
- Kasai portoenterostomy improves survival, with 25-35% surviving over 10 years without transplant.
- One-third of patients develop cirrhosis and require transplantation, while another third have inadequate bile drainage post-surgery.
Conclusions:
- Biliary atresia requires prompt evaluation for infants with jaundice beyond 14 days, especially those with conjugated hyperbilirubinemia.
- Early surgical intervention via Kasai portoenterostomy before irreversible intrahepatic bile duct sclerosis is vital.
- Biliary atresia is the leading indication for pediatric liver transplantation, necessary for end-stage liver disease symptoms.
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.