Biliary atresia is defined as a complete or partial obstruction of the extrahepatic biliary tree that occurs within the first 3 months of life. It underlies approximately one-third of cases of neonatal cholestasis and is the single most frequent cause of death from liver disease in early childhood. Approximately 50% to 60% of children referred for liver transplantation have biliary atresia.
Two major forms of biliary atresia are recognized; these are based on the presumed timing of luminal obliteration.
The fetal form accounts for as many as 20% of cases and is commonly associated with other developmental anomalies involving the thoracic and abdominal organs, including malrotation of abdominal viscera, interrupted inferior vena cava, polysplenia, and congenital heart disease.
Much more common is the perinatal form of biliary atresia, in which an apparently normally developed biliary tree is injured and obstructed following birth. The etiology of perinatal biliary atresia is unknown; viral infection and toxic exposures are considered prime suspects.
fibrosing stricture of the hepatic or common bile ducts; insomeindividuals,periductularinflammationalsoextendsinto theintrahepaticbileducts,leadingtoprogressivedestructionoftheintrahepaticbiliarytreeaswell.Whenbiliaryatresiaisunrecognizedoruncorrected,cirrhosisdevelopswithin3to6monthsofbirth.
Thereisconsiderablevariabilityinthepatternofbiliaryatresia.Whenthediseaseislimitedtothecommonductorrightand/orlefthepaticbileductswithpatentintrahepaticbranches,thediseaseissurgicallycorrectable(Kasai procedure).Unfortunately,in90%ofpatientstheobstructionalsoinvolvesbileductsatorabovetheportahepatis.Thesecasesarenotcorrectable,sincetherearenopatentbileductsamenabletosurgicalanastomosis.
Infants with biliary atresia present with neonatal cholestasis, but exhibit normal birth weight and postnatal weight gain. There is a slight female predominance. Initially stools are normal, but they become acholic as the disease progresses. Ascending cholangitis and/or intrahepatic progression of the disease may impede attempts at surgical resection of the obstruction and bypass of the biliary tree. Transplantation of a donor liver and its accompanying bile ducts is the primary hope for saving these young patients. Without surgical intervention, death usually occurs within 2 years of birth.
Autoimmune cholangiopathies comprise two distinct immunologically-mediated disorders that involve intra-hepatic bile ducts: primary biliary cholangitis and primary sclerosing cholangitis. The salient features of these are listed in
Table 16.5
Primary biliary cholangitis (PBC) is an autoimmune disease whose primary feature is nonsuppurative, inflammatory destruction of smalland medium-sized intrahepatic bile ducts. Large intrahepatic ducts and the extrahepatic biliary tree are not involved. Previously, this disease was known as primary biliary cirrhosis, but most patients do not progress to this stage, and the name primary biliary cholangitis is now preferred.
PBC is primarily a disease of middle-age women, with a female-to-male ratio of 6:1. Its peak incidence is between 40 and 50 years of age. The disease is most prevalent in Northern European countries (England and Scotland) and the Northern United States (Minnesota), where the prevalence is as high as 400 per 1 million cases. Recent increases in incidence and prevalence along with geographic clustering suggest that both environmental and genetic factors are important in its pathogenesis. Family members of PBC patients have an increased risk for developing the disease.