Key points

Introduction

Congenital biliary tract diseases are rare in children compared to adults. Presenting signs and symptoms in toddlers and older children are often nonspecific, and diagnostic findings may be incidental. Congenital biliary tract diseases typically manifest themselves with cholestasis in the neonatal period, and prompt diagnosis and management are essential in ensuring optimal outcomes. Given the rarity of these disorders and the subtle nuances differentiating them, infants with cholestatic liver disease benefit from evaluation at a multispecialty pediatric center.

The differential diagnosis for neonatal cholestasis is broad and includes congenital anatomic abnormalities, infection, endocrine disorders, neonatal hepatitis, and metabolic and genetic diseases ( Box 1 ). Despite a usually extensive evaluation for neonatal cholestasis, the cause may remain unclear. Because of the importance of a prompt and accurate diagnosis, endoscopy can aid in the diagnosis of congenital biliary tract diseases, and at times, definitively treat the anomaly. As in adults, the endoscopic approach to children with congenital biliary tract diseases may involve ERCP. When performed by an experienced endoscopist, pediatric ERCP is technically successful, safe, and therapeutically effective for a broad range of pancreaticobiliary diseases. ERCP with a therapeutic duodenal scope is usually feasible in children weighing more than 10 kg. With the availability of smaller pediatric duodenoscopes ranging from 7.5 to 8 mm in diameter, infant ERCP has also been shown to be technically feasible and safe, with a success rate ranging from 87% to 93%. But with a 2-mm working channel, therapeutic accessories for the pediatric duodenoscopes are limited. More recently, EUS with fine-needle aspiration has also been shown to be technically feasible and safe while providing diagnostic information in children with pancreaticobiliary diseases. Unfortunately, because of the small size of infants and the relatively large size of the current EUS echoendoscopes (insertion tube diameters ranging from 11.8 to 12.8 mm), EUS has limited diagnostic value in infants with congenital biliary tract diseases. This article discusses the role of endoscopy in the diagnosis and management of various congenital biliary tract anomalies.

Introduction

Congenital biliary tract diseases are rare in children compared to adults. Presenting signs and symptoms in toddlers and older children are often nonspecific, and diagnostic findings may be incidental. Congenital biliary tract diseases typically manifest themselves with cholestasis in the neonatal period, and prompt diagnosis and management are essential in ensuring optimal outcomes. Given the rarity of these disorders and the subtle nuances differentiating them, infants with cholestatic liver disease benefit from evaluation at a multispecialty pediatric center.

The differential diagnosis for neonatal cholestasis is broad and includes congenital anatomic abnormalities, infection, endocrine disorders, neonatal hepatitis, and metabolic and genetic diseases ( Box 1 ). Despite a usually extensive evaluation for neonatal cholestasis, the cause may remain unclear. Because of the importance of a prompt and accurate diagnosis, endoscopy can aid in the diagnosis of congenital biliary tract diseases, and at times, definitively treat the anomaly. As in adults, the endoscopic approach to children with congenital biliary tract diseases may involve ERCP. When performed by an experienced endoscopist, pediatric ERCP is technically successful, safe, and therapeutically effective for a broad range of pancreaticobiliary diseases. ERCP with a therapeutic duodenal scope is usually feasible in children weighing more than 10 kg. With the availability of smaller pediatric duodenoscopes ranging from 7.5 to 8 mm in diameter, infant ERCP has also been shown to be technically feasible and safe, with a success rate ranging from 87% to 93%. But with a 2-mm working channel, therapeutic accessories for the pediatric duodenoscopes are limited. More recently, EUS with fine-needle aspiration has also been shown to be technically feasible and safe while providing diagnostic information in children with pancreaticobiliary diseases. Unfortunately, because of the small size of infants and the relatively large size of the current EUS echoendoscopes (insertion tube diameters ranging from 11.8 to 12.8 mm), EUS has limited diagnostic value in infants with congenital biliary tract diseases. This article discusses the role of endoscopy in the diagnosis and management of various congenital biliary tract anomalies.

Biliary atresia

Biliary atresia is a neonatal cholestatic disease in which a fibroinflammatory process leads to complete obliteration of all or part of the extrahepatic biliary system. Incidence is higher in Asians and ranges from 1 in 5000 to 1 in 18,000. Presentation occurs within the first 2 to 3 weeks of life with prolonged neonatal jaundice, conjugated hyperbilirubinemia, acholic stools, and hepatomegaly. Affected infants are usually otherwise well for the first few months of life. Biliary atresia can also present in a syndromic form with splenic malformation, intestinal malrotation, preduodenal portal vein, and congenital cardiac defects. Untreated biliary atresia leads to liver failure and progressive biliary cirrhosis with a 100% mortality rate. Surgical treatment with a portoenterostomy biliary diversion, first described by Kasai and Suzuki in 1950, reestablishes bile flow by resecting the fibrosed bile duct and anastomosing a Roux limb to patent intrahepatic bile ducts within the porta hepatis. Although the procedure has since been refined, diagnosis remains time sensitive because delayed surgical treatment is associated with poor outcome. Despite timely surgical intervention, the chronic inflammatory process continues to progress and biliary atresia remains the leading cause for pediatric liver transplantation.

The diagnosis of biliary atresia is considered when evaluating infants with cholestasis, and several studies are typically carried out, including laboratory tests, abdominal ultrasonography, hepatobiliary iminodiacetic acid (HIDA) scan, and percutaneous liver biopsy. Despite this extensive evaluation, the diagnosis of biliary atresia occurs before cholangiography in approximately 86% of cases. Definitive diagnosis requires an intraoperative cholangiogram to distinguish this obliterative cholangiopathy from other neonatal cholestatic diseases. Because the gold standard for diagnosis involves surgery, studies have assessed the role of ERCP as a minimally invasive means of evaluating cholestatic infants suspected to have biliary atresia.

There are 3 main variants of biliary atresia: type 1, atresia of the common bile duct; type 2, atresia of the common hepatic duct; and type 3, atresia of the hepatic ducts within the porta hepatitis. Guelrud and colleagues reported 3 ERCP findings suggesting the different variants of biliary atresia ( Fig. 1 ): type 1, opacification of the pancreatic duct only with no visualization of the bile duct; type 2, opacification of the common bile duct and gallbladder with no visualization of the common hepatic and intrahepatic ducts; and type 3, opacification of the common bile duct, gallbladder, and hepatic duct with bile lakes at the porta hepatitis ( Fig. 2 ). In this prospective study, the investigators were able to demonstrate a normal biliary tract in 10 patients who had findings of liver biopsy suggesting extrahepatic biliary atresia, therefore avoiding surgery for those patients.

Anatomic variants of biliary atresia seen with ERCP. Black area represents the atretic biliary segment not visualized on cholangiogram by ERCP.

Cholangiogram of infants with biliary atresia. ( A ) Type 2 ERCP finding with the gallbladder and common bile duct opacified ( curved arrow ). ( B ) Type 3 ERCP finding with gallbladder, common bile duct ( straight arrow ), common hepatic duct ( curved arrow ), and bile lakes ( double arrows ).

( From Guelrud M, Jaen D, Mendoza S, et al. ERCP in the diagnosis of extrahepatic biliary atresia. Gastrointest Endosc 1991;37(5):525; from Elsevier with permission.)

Further studies have shown the utility of ERCP for diagnosing and excluding biliary atresia ( Table 1 ). ERCP demonstrating a normal and patent biliary system can exclude biliary atresia and prevent unnecessary surgery in 12% to 43% of infants with an indeterminate precholangiogram evaluation. For diagnosis of biliary atresia, ERCP has been reported to have a sensitivity of 86% to 100%, specificity of 73% to 94%, positive predictive value of 86% to 88%, and negative predictive value of 100%. Although Petersen and colleagues include ERCP in their algorithm for all infants suspected with biliary atresia, its use remains uncommon when evaluating for biliary atresia. Centers that have studied the use of ERCP in biliary atresia recommend its selective use in infants in whom the precholangiogram evaluation is indeterminate and the diagnosis of biliary atresia is not certain. Yet, most pediatric gastroenterologists continue to rely on the clinical presentation, laboratory values, ultrasonography, HIDA scan, and liver biopsy to determine if a cholestatic infant requires a surgical intraoperative cholangiogram.

Alagille syndrome

Paucity of bile ducts can be divided into nonsyndromic and syndromic (Alagille syndrome). Diagnosis of paucity of bile ducts is made on liver biopsy when the bile-duct-to-portal-tract ratio is less than 0.9. There should be at least 6 to 10 microscopic portal tracts present in the core needle biopsy specimen for an accurate analysis. Although nonsyndromic bile duct paucity can be seen in other infectious, metabolic, or inflammatory diseases, Alagille syndrome is an autosomal dominant disorder that also includes congenital cardiac, renal, vertebral, and ocular diseases. Patients may also have characteristic facial features including prominent forehead, deep-set eyes, and pointed chin. Mutations in JAG1 and Notch2 have been shown to cause Alagille syndrome, and detection of the mutations can aid in diagnosis.

The features of Alagille syndrome frequently become apparent in the neonatal period or during early infancy and are nearly indistinguishable from those of biliary atresia. During childhood, jaundice may wax and wane and children may show signs of malnutrition and growth failure. Pruritus is the most unbearable symptom, leading to excoriation of the skin, difficulty with sleep, and poor concentration. Severe pruritus can be treated at experienced pediatric liver centers with an externalized surgical biliary diversion, which is thought to ameliorate the condition by decreasing enterohepatic recirculation of bile salts.

Paucity of bile ducts on liver biopsy, along with the extrahepatic features noted above, can differentiate Alagille syndrome from other neonatal cholestatic diseases. As mentioned, it is not uncommon for the presentation of Alagille syndrome to resemble that of biliary atresia in young infants. Infants with Alagille syndrome may have indeterminate results of liver biopsies and also abnormal HIDA scan results. It is important to make a timely and proper diagnosis to ensure that patients are not incorrectly diagnosed with biliary atresia because the Kasai portoenterostomy is not beneficial for patients with Alagille syndrome and it may actually worsen their outcomes. As with patients with biliary atresia, in patients with an indeterminate diagnosis, ERCP may be helpful in diagnosing Alagille syndrome while at the same time excluding biliary atresia. In patients with Alagille syndrome, ERCP can show a normal or diffuse narrowing of the extrahepatic biliary ducts and narrowing of the intrahepatic ducts with reduced arborization.