Congenital cholestatic syndromes: what happens when children grow up?

Abstract

Although advances in the management of children with congenital cholestasis have enabled many to survive into adulthood with their native livers, even the most common of these conditions remains rare in adult hepatology practice. Among four congenital cholestatic syndromes (biliary atresia, Alagille syndrome, Caroli disease and congenital hepatic fibrosis, and progressive familial intrahepatic cholestasis), the published data on outcomes of the syndromes into adulthood suggest that a spectrum of severity of liver disease can be expected, from cirrhosis (almost universal in adults with biliary atresia who have not required liver transplantation) to mild and subclinical (eg, in the previously undiagnosed affected parent of an infant with Alagille syndrome). Complications associated with portal hypertension and nutritional deficiencies are common, and other associated features of the cholestatic syndrome may require appropriate attention, such as congenital heart disease in Alagille syndrome. Indications for liver transplantation include synthetic failure, progressive encephalopathy, intractable pruritus, recurrent biliary sepsis and recurrent complications of portal hypertension. Improved understanding of biliary physiology will hopefully translate into improved therapy for children and adults with cholestasis.

Figure 1)

Classification of biliary atresia according to the extent of involvement of the biliary tree. A Normal. B Type 1; atresia of the common bile duct. C Type 2; atresia of the common hepatic duct. D Type 3, atresia of the entire extrahepatic biliary tree

Figure 2)

A 16-year-old girl with Alagille syndrome (reproduced with the patient’s permission)

Figure 3)

Embryological development of bile ducts from the ductal plate

Figure 4)

Ductal plate malformation, showing abnormally formed bile ducts (B) around a portal vein radical (V) in a portal triad expanded by fibrosis. The trichrome stain was supplied by Dr I Wanless, Department of Pathology, Dalhousie University (Halifax, Nova Scotia)

Figure 5)

Canalicular transport molecules involved in the three types of persistent familial intrahepatic cholestasis (PFIC). BSEP Bile salt export pump (now called ABCB11); FIC1 Familial intrahepatic cholestasis 1 (now called ATP8B1); MDR3 Multi-drug resistance protein type 3 (now called ABCB4)