Biliary Atresia Revisited

Abstract

Extrahepatic biliary atresia (EHBA) is an inflammatory fibrosing process affecting the extrahepatic and intrahepatic biliary tree resulting in fibrous obliteration of the extrahepatic biliary tract, ductopenia of intrahepatic bile ducts, and biliary cirrhosis. EHBA is divided into a correctable and a noncorrectable type with focal patency of the otherwise atretic biliary tree in the former and no patency of the biliary tree in the noncorrectable type. EHBA is divided in a fetal, prenatal or embryonic, and a more common, perinatal, acquired form. The symptoms of the former start shortly after birth and there is frequently an association with a variety of congenital anomalies. Children with the perinatal form become jaundiced several weeks after birth; no associated congenital anomalies are present. Morphologically, an inflammatory and fibrosing process of the extrahepatic biliary tree leads to complete lumenal obliteration. The liver is characterized by a nonspecific giant cell transformation, and portal expansion by fibrous connective tissue with marked ductular proliferation. With time, ductopenia and biliary cirrhosis develop. The diffential diagnosis with other conditions with similar microscopic patterns such as as alpha-1 antitrypsin deficiency, total parental nutrition, obstruction by a choledochal cyst, arteriohepatic dysplasia, familial progressive intrahepatic cholestasis, and alteration of the bile acid metabolism is discussed. In the fetal group, abnormalities in different genes seem to play a role; ductal plate malformation is another possibility. Different etiologies have been postulated in the perinatal form of EHBA: genetic susceptibility, vascular factors, toxins, and infections mainly by rotavirus and reovirus. The pathogenesis is complex. EHBA is a heterogenous disease, resulting from a combination of genetic factors, insults, and activation of different genetic and immunologic pathways. The treatment of EHBA is surgical, with anastomosis between the biliary tree and the intestine in the correctable type and a hepatic portoenterostomy (HPE) for the noncorrectable group. HPE is a temporizing treatment allowing the infant to develop and grow, followed in the majority of the patients by liver transplantation.

Analysis of Liver Repair Mechanisms in Alagille Syndrome and Biliary Atresia Reveals a Role for Notch Signaling

“…All diagnoses were based on clinical and laboratory data and on histopathological examination of histological samples. 4,6,16 The demographic, clinical, and biochemical characteristics of patients from the three disease groups are reported in Table 1. Liver tissue was snap-frozen in liquid nitrogen-cooled isopentane and stored at Ϫ80°C.…”

Screening and outcomes in biliary atresia

“…The infiltration of CD4ϩ and CD8ϩ T lymphocytes and macrophages has been consistently observed in the periductal space or along the duct epithelium in conjunction with increased expression of cytokines and receptors commonly seen when these cells are activated. 2 More recently, 2 studies carried out comprehensive molecular and cellular surveys of liver biopsies and found a proinflammatory gene expression signature, with increased activation of interferon-␥, osteopontin, tumor necrosis factor-␣, and other inflammatory mediators. 73,74 In studies using the rotavirus-induced newborn mouse model of biliary injury, interferon-␥ was shown to regulate the tropism of lymphocytes to the duct epithelium and luminal obstruction.…”

“…It occurs in 1 in 5000 to 1 in 18,000 live births and is characterized by persistent jaundice and progressive cholestasis developing within weeks of birth, which are caused by a progressive fibro-obliterative obstruction of extrahepatic and intrahepatic bile ducts. [1][2][3][4] The disease is difficult to identify during the perinatal period. Early diagnosis is important, however, because hepatoportoenterostomy (HPE; the Kasai procedure), if performed in the first 2-3 months of life, can restore bile flow and help prevent worsening of the liver disease.…”

Revival of Landing's Concept of Infantile Obstructive Cholangiopathy – A Plea to Hand Over the 2 Week Old Jaundiced Full Term Neonate to the Surgeon!

“…With advance in age, the chances of finding a patent bile duct at the portahepatis decrease. It can be called correctible (5%) forms depending on the presence and incorrectible with the absence of the patency of the hepatic ducts (95%), available for the bilioenteric drainage procedure 66 . Prognosis has also been corelated with the size of the bile ducts found at the porta hepatis.…”