Biliary Atresia Imaging

Biliary atresia (BA) is characterized by obliteration or discontinuity of the extrahepatic biliary system, resulting in obstruction of bile flow. It is the most common cause of cholestatic jaundice in the neonatal period, accounting for 25-40% of cases. ^[1]  Although the exact etiology remains unknown, the primary therapy is surgical. ^{[2, 3, 4, 5]}  Approximately 80-90% of currently affected infants are expected to survive to adolescence following Kasai portoenterostomy and/or liver transplantation. ^[6]  If not surgically corrected, secondary biliary cirrhosis invariably results.

There are 3 classifications of BA: the nonsyndromic form, which is the most common (84%); syndromic BA with laterality (eg, situs inversus)  defects (10%); and syndromic BA with at least 1 malformation but without laterality defects (6%). Both syndromic groups have other associated anomalies, predominantly cardiovascular (16%) and gastrointestinal (14%), but the group without laterality defects has more frequent genitourinary anomalies. Patients with BA with laterality defects more commonly have splenic anomalies. ^[1]

Biliary atresia may be classified according to whether the disease can or cannot be corrected. As the image below shows, in the correctable group (10-15% of cases), the proximal common hepatic duct is patent, allowing for primary anastomosis of the extrahepatic bile duct to the bowel.

Preferred examination

Several imaging modalities have been used in the diagnosis of biliary atresia. Although some findings are highly suggestive of the disease, none is pathognomonic, and reliance on a combination of tests is common. Ultrasonography is often the initial investigation in patients with suspected biliary atresia, followed by hepatobiliary scintigraphy (HBS). The triangular cord sign and gallbladder abnormalities are the 2 most accurate and widely accepted ultrasound characteristics currently used for the diagnosis or exclusion of biliary atresia. HBS adds little to the routine evaluation of the cholestatic infant, but it can confirm biliary tract patency, thereby excluding BA. ^{[1, 7, 8]}  Several factors may limit the effectiveness of HBS. For example, severe neonatal hepatitis may result in decreased hepatic radiotracer uptake and therefore decreased excretion into the bowel. Also, because biliary atresia may be an evolving process, excretion of radiotracer into the gastrointestinal tract may be seen in children with biliary atresia in the early stages of the disease. Furthermore, reliability of the test diminishes with serum bilirubin levels greater than 10 mg/dL.

If the diagnosis remains elusive, magnetic resonance cholangiopancreatography (MRCP) may be helpful. MRCP is a well-established noninvasive modality for visualizing the biliary system, including the first-order branches of the intrahepatic bile ducts, extrahepatic bile ducts, and gallbladder. The diagnostic value of 3-dimensional MRCP for BA in a large cohort of cholestatic infants and neonates was evaluated, with a reported specificity of 36% and sensitivity of 99%. ^[9] ​ MRCP findings in infants with biliary atresia include incomplete visualization of the extrahepatic biliary system and periportal high-signal intensity on T2-weighted MRI scans (which may represent cystic dilatation of fetal bile ducts with surrounding fibrosis). ^{[9, 10]}  Complete visualization of the extrahepatic biliary system excludes biliary atresia, whereas nonvisualization of the common or hepatic bile ducts suggests the disease. 

Liver biopsy is often used to confirm the diagnosis of biliary atresia and may be done at the same time as surgical or percutaneous cholangiography. Some case series have documented the feasibility of percutaneous transhepatic cholecysto-cholangiography (PTCC) to exclude BA. In the largest series reported, PTCC was performed in combination with simultaneous liver biopsy. Although this was reported to effectively exclude BA with a lower negative laparotomy rate, there is concern that PTCC may be used unnecessarily in infants in whom a liver biopsy alone would have excluded biliary obstruction. Moreover, the specificity of liver biopsy in diagnosing biliary obstruction in this case series was much lower than frequently reported values. ^[11]

The diagnostic role of endoscopic retrograde cholangiopancreatography (ERCP) remains controversial. ERCP is an invasive technique that requires an experienced endoscopist, specific infant endoscopy equipment not readily available at many centers, and a general anesthetic. In some centers with particular expertise, ERCP is used as a first-line diagnostic tool, ^{[12]   [13]}  ERCP allows direct visualization of the extrahepatic biliary tree with the injection of radiologic contrast agent into the extrahepatic biliary system through the papilla of Vater. This technique can show obstruction in the common bile duct and enables visualization of the extrahepatic biliary system distal to the common hepatic duct and the extrahepatic biliary system with bile lakes at the porta hepatis. ERCP has proved effective, with high positive and negative predictive values for BA (sensitivity 86–100%, specificity 87–94%, positive predictive value 88–96%, negative predictive value 100%). ^[13]

Types of biliary atresia. (A) Operable, or correctable, biliary atresia; a major portion of the extrahepatic bile ducts are patent. (B) The inoperable group does not have the patency shown in A. Reproduced with permission from BC Decker, 2000.

View Media Gallery

Resection of the fibrous bile duct remnant may be done, followed by a Roux-en-Y anastomosis of the bowel to the bed of the porta hepatis, according to the Kasai hepatic portoenterostomy (HPE) procedure. In the uncorrectable group, the extrahepatic bile ducts do not have the same patency as in the correctable group.

Another method of classification, the Kasai classification system, is widely used and divides cases of biliary atresia according to their location and degree of pathology. As shown in the image below, 3 main types of biliary atresia are defined.

Classification of biliary atresia according to the location of involvement (gray areas). Type I is obliteration of the common bile duct, while the proximal bile ducts are patent. Type IIa is atresia of the hepatic duct, with cystic bile ducts found at the porta hepatis. Type IIb is atresia of the cystic duct, common bile duct, and hepatic ducts. Type III is involvement of the extrahepatic biliary tree and intrahepatic ducts of the porta hepatis.

View Media Gallery

In type I, the common bile duct is obliterated while the proximal bile ducts are patent.

In type II, atresia of the hepatic duct is seen, with cystic bile ducts found at the porta hepatis. In type IIa, the cystic and common bile ducts are patent, whereas in type IIb, the cystic common bile duct and the hepatic ducts are obliterated.

Type III atresia refers to discontinuity of the right and the left hepatic ducts to the level of the porta hepatis. This form of biliary atresia is common, accounting for more than 90% of cases.

Children with biliary atresia are treated with HPE, liver transplantation without prior HPE, or liver transplantation after HPE. Although infants with biliary atresia can survive more than 20 years after HPE, most develop progressive complications in the liver. ^[14] Overall, survival has greatly improved in the era of liver transplantation. ^{[15, 16]}

Timely diagnosis is important to optimize the response to a Kasai HPE aimed at reestablishing bile flow. If the HPE is performed within the first 60 days of life, 70% of patients will establish bile flow; after 90 days of life, less than 25% of patients will have bile flow. Late diagnosis of BA is a worldwide problem, and the optimal management of infants with delayed diagnosis remains controversial. ^[17]

Guidelines

In 2017, the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), along with the European Society for  Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHN), issued joint guidelines for the evaluation of cholestatic jaundice in infants. The guidelines find evaluation by intraoperative cholangiogram and histological examination of the duct remnant to be the gold standard to diagnose biliary atresia. Key imaging recommendation include ^[1] :

• Abdominal ultrasound is useful in excluding choledochal cyst or gallstone disease causing extrahepatic bile duct obstruction. It may demonstrate an absent or abnormal gallbladder or other features suggestive, but not diagnostic, of BA.
• Limited specificity precludes the use of the hepatobiliary scintigraphy (HBS) for making a definitive diagnosis of BA. However, definitively demonstrated bile flow by selective use of HBS may be of value in excluding BA. 
• Magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), and percutaneous transhepatic cholecysto-cholangiography (PTCC) have a limited role in the diagnosis of BA due to poor specificity.
• Histopathologic findings of bile duct proliferation, bile plugs, and fibrosis in an appropriately timed liver biopsy is the most supportive test in the evaluation of the infant with protracted conjugated hyperbilirubinemia.
• Diseases other than BA that cause cholestasis can be determined via histologic examination of the liver.

Ultrasonography is generally the initial investigation in patients with suspected biliary atresia. It can be used to assess the neonatal hepatobiliary system and may exclude other anatomic anomalies. High-frequency ultrasound has been shown to provide improved sensitivity, specificity, and accuracy for the diagnosis of biliary atresia. ^[18]

Various sonographic features have been reported as being useful for the diagnosis of biliary atresia, including the triangular cord sign, defined as echogenic, thick soft tissue at the anterior wall of the right portal vein. ^[19]  The hepatic parenchyma is often inhomogeneous, with a marked increase in periportal echoes due to fibrosis. Sonograms in infants with biliary atresia often show a circumscribed, focal, triangular or tubular echogenic density more than 3 mm thick located cranial to the portal vein bifurcation (see the images below). 

Triangular cord. Transverse (a) and longitudinal (b) scans of the triangular cord in a baby with biliary atresia, which appears as a focal echogenic triangular or ovoid density just cranial to the bifurcation of the portal vein. Reproduced with permission from Tan Kendrick AP et al, 2003.

View Media Gallery

Findings in infants with biliary atresia typically include an atretic gallbladder and a thin, indistinct gallbladder wall with an irregular or lobulated contour. Although a normal (1.5 cm) or long (>4 cm) gallbladder may be seen in up to 10% of patients with biliary atresia, a length of less than 1.9 cm is most common. The constellation of findings constituting the gallbladder ghost triad, seen in babies with biliary atresia, are a gallbladder length less than 1.9 cm, a thin or indistinct gallbladder wall, and an irregular and lobular contour. (The image below shows the gallbladder ghost triad.)

Gallbladder ghost triad in babies with biliary atresia. Longitudinal scans of the gallbladder in (A) a 3-week-old girl and (B) a 5-week-old boy demonstrate a short gallbladder, an irregular or lobulated contour, and a relatively indistinct lining and wall. Reproduced with permission from Tan Kendrick et al, 2003.

View Media Gallery

Although dilatation of the intrahepatic bile duct occurs infrequently, it suggests biliary atresia when present. ^[19] Central biliary cysts and choledochal cysts may be associated with biliary atresia and are well depicted on sonograms, as demonstrated in the image below.

Biliary atresia and central cyst. (A) Oblique sonogram demonstrates a large cystic structure in the porta hepatis. (B) Intraoperative cholangiogram demonstrates filling of the cyst and mildly dilated intrahepatic ducts but no communication with the duodenum. Reproduced with permission from BC Decker, 2000.

View Media Gallery

A prominent hepatic artery is often seen in children with cirrhotic changes.

The absence of gallbladder contraction is only suggestive of biliary atresia. As many as 20% of children with biliary atresia have normal gallbladder contraction. Furthermore, the absence of gallbladder contraction is seen in children with cholestasis due to other causes.

Congenital anomalies may be present in children with biliary atresia. In particular, situs inversus and polysplenia are among the associated congenital anomalies that may be seen on sonograms.

Degree of confidence 

The triangular cord sign and gallbladder abnormalities are the 2 most accurate and widely accepted ultrasound characteristics currently used for the diagnosis or exclusion of biliary atresia. The combination of the triangular cord sign and gallbladder abnormalities can improve diagnostic sensitivity, and the absence of a gallbladder is as specific as the triangular cord sign in the diagnosis of biliary atresia. Other ultrasound characteristics, including the absence of a common bile duct, enlargement of the hepatic artery, and the appearance of hepatic subcapsular flow, are less valuable findings for diagnosis. ^[20]

A meta-analysis of 23 studies reported that sensitivity and specificity were 0.85 (95% CI, 0.76–0.91) and 0.92 (95% CI, 0.81–0.97), respectively, for gallbladder abnormalities in 19 studies; 0.74 (95% CI, 0.61–0.84) and 0.97 (95% CI, 0.95–0.99), respectively, for the triangular cord sign in 20 studies; and 0.95 (95% CI, 0.70–0.99) and 0.89 (95% CI, 0.79–0.94), respectively, for the combination of the triangular cord sign and gallbladder abnormalities in 5 studies. Subgroup analysis of an absent gallbladder in 10 studies yielded a summary specificity of 0.99 (95% CI, 0.93–1.00). ^[20]

Another meta-analysis, of 17 studies, found that the triangular cord sign had high accuracy for diagnosing biliary atresia, with the meta‐analytic summary sensitivity and specificity being 85% and 97%, respectively. ^[19]

Hepatobiliary scintigraphy (HBS) has been used in the diagnosis of biliary atresia for many years. ^[8]  A technetium-labeled iminodiacetic acid (IDA) analogue is typically used. For example, radiopharmaceuticals used include ^99mTc (technetium-99m) DISIDA (diisopropyl-iminodiacetic acid) and ^99mTc mebrofenin (trimethylbromo-iminodiacetic acid). Infants with biliary atresia usually have normal hepatocyte uptake of the radiotracer if they are younger than 2 months.

Improved sensitivity and specificity have been reported with delayed imaging, and following tracer administration, images are often acquired at 4 to 6 hours and 24 hours. The administration of phenobarbital (5 mg/kg/day in 2 equal doses for 3-5 days before the study) may increase diagnostic accuracy. Hepatobiliary scintigraphy has been found to be up to 100% sensitive, 93% specific, and 94.6% accurate in diagnosing biliary atresia following pretreatment with phenobarbital. ^[7] The addition of single photon emission computed tomography (SPECT) may increase specificity.

If excretion of radiotracer into the bowel is seen, biliary atresia is virtually excluded. If radiotracer excretion is absent after 24 hours (as it is in the image below), biliary atresia is suspected.

Anterior technetium-labeled diisopropyl iminodiacetic acid (IDA) scan in a patient with biliary atresia shows no excretion of the radiopharmaceutical into the bowel at 24 hours.

View Media Gallery

Hepatobiliary scintigraphy may also be useful for the assessment of biliary excretion following surgical correction for biliary atresia.

Degree of confidence

A meta-analysis addressing the utility of HBS with ^99mTc-IDA for differentiating biliary atresia from nonbiliary atresia causes of cholestasis yielded a pooled sensitivity of 98.7% and a specificity of 70.4% of a nondraining HBS. Factors that increased specificity included using radiotracers that have high hepatic extraction; administering hepatic-inducing drugs (eg, phenobarbital); using a calculated dose/kg; and administering a booster dose in cases of nonexcretion of tracer in the bowel. ^[21]

Several factors, however, may limit the effectiveness of HBS. For example, severe neonatal hepatitis may result in decreased hepatic radiotracer uptake and therefore decreased excretion into the bowel. Also, because biliary atresia may be an evolving process, excretion of radiotracer into the gastrointestinal tract may be seen in children with biliary atresia in the early stages of the disease. Furthermore, reliability of the test diminishes with serum bilirubin levels greater than 10 mg/dL.

Patients should not have barium studies done within 48 hours before undergoing HBS. If a barium study has been performed, an abdominal radiograph may be indicated to make sure the bowel is clear of barium, a high-density material that can result in artifacts.