Neonatal cholestasis has various causes with different treatment protocols. It is important to differentiate between BA and other causes of infantile cholestasis because BA is treated surgically (with some degree of urgency) while other causes might be managed medically. Initial treatment of BA is the Kasai portoenterostomy, which can re-establish bile flow in up to 80% of cases if performed prior to 60 days of age [1
]. This number decreases to only 20% if the operation is performed after 90 days of life—hence the importance of early diagnosis. A liver transplant is required if the Kasai procedure is unsuccessful. To date, BA remains the leading indication for liver transplantation in children in the United States [14
BA is characterized by the obliteration of all or part of the extrahepatic bile ducts and/or the most central part of the intrahepatic bile ducts. The precise etiology of BA has not been established, although several pathogenetic mechanisms have been proposed including a developmental disruption of the biliary tree occurring antenatally (fetal form in approximately 20% of cases of BA) and an immunological response to a viral pathogen (perinatal form 70–80% of cases) [15
]. Current thinking suggests an association of an autoimmune response to a viral infection such as cytomegalovirus, group C rotavirus or reovirus type 3 [16
]. Others have described the additional possible role of human papilloma virus [21
] and retroviruses [22
] as well as several other risk factors including advanced maternal age, increased parity, small for gestational age, low birth weight and prematurity [18
Sonography is the initial imaging modality of choice when evaluating the neonate with cholestasis and helps to exclude overt anatomical causes of obstruction such as a choledochal cyst. Initial US research in BA focused on the presence or absence of the gallbladder and whether the gallbladder contracted following feeding [23
]. The presence of a normal gallbladder (without other abnormal findings in the biliary tree) is usually thought to essentially exclude the diagnosis of BA. In this study we describe a potential important imaging pitfall of a pseudo gallbladder sign, which if misinterpreted as a normal gallbladder could delay important diagnostic testing and the correct diagnosis.
Since BA can occur at any level of the biliary tree, the presence of a gallbladder, cystic duct and a distal bile duct does not completely exclude a more proximal ductal atresia [9
]. Clinical and histopathological suspicion of BA can be confirmed by an intraoperative cholangiogram [1
], which shows failure of contrast agent reflux into the proximal/intrahepatic ducts.
Attention has also been directed to the identification and dilatation of bile ducts, echotexture of the liver and the TC sign. Choi and co-workers [5
] first described the TC sign in 1996 in BA patients as a tubular or triangular echogenic tissue (fibrous ductal remnant) adjacent to the portal vein and correlated this sonographic finding with a biopsy-proved diagnosis of BA (Fig. ). However, they recommended close follow-up of all patients given the possibility of false-positive and false-negative findings. Lee et al. [7
] found that the TC sign has a 94% PPV and NPV, 98% specificity and 80% sensitivity. Compared to 73% sensitivity and 100% specificity for the TC sign, demonstrated by Humphrey and Stringer [26
], our study shows 60% sensitivity and 95% specificity (Table ). Li et al. [27
] suggest that the TC sign should not be viewed as the only imaging criterion for diagnosing BA. Tan Kendrick et al. [11
] have reported high sensitivity and specificity for the diagnosis of BA using the gallbladder ghost triad.
Fig. 4 The triangular cord sign (TC sign) in a BA patient. a The TC sign (arrowhead) measured 4.8 mm in this case of BA. b The PsGB sign in this case (arrow) is seen as a fluid-filled structure demonstrating an irregular contour but without a normal (more ...)
Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for various imaging criteria
In our study, the reviewers were not blinded to the diagnosis at the time of the review and although there is an inherent bias in this method, the case and control groups were so clearly segregated based on the findings that we do not believe this would be significant to the general results. Of the 15 infants with pathologically proven BA, we found that no gallbladder was seen in 27% of our BA cases (n
4), but that 73% (n
11) of our BA patients had a gallbladder-like structure—the pseudo gallbladder sign. This structure was ≤15 mm in length in the majority (9/11) of cases and is indicated by the presence of a small ovoid to tubular fluid-filled structure in the expected region of the gallbladder (Fig. ). It is smaller than a normal gallbladder and can have irregular margins but without
a well-defined or normal-appearing wall. The term “pseudo gallbladder” emphasizes the potential to misconstrue this finding as a normal gallbladder, which can distract from the diagnosis of biliary atresia.
The presence or absence of a gallbladder wall helps distinguish a normal gallbladder from a PsGB[11
]. A normal wall is measurable with a central echogenic mucosal interface and a thinner peripheral fibromuscular layer (Fig. ), whereas the PsGB does not display a normal wall but rather has only a thin nonmeasurable echogenic rim around the fluid collection (Fig. ). A normal gallbladder wall was absent in 82% of our BA cases with PsGB but was clearly identified in 95% of the non-BA control group. Absence of the gallbladder wall had an 87% sensitivity and 95% specificity with a 93% PPV for BA (Table ).
Among the 11/15 BA cases demonstrating the PsGB sign, surgical pathology showed no gallbladder in five cases and a hypoplastic gallbladder in three, and the remaining three were labeled as “not a true gallbladder, atretic gallbladder, and no epithelium seen,” respectively. Thus, there was no single pathological correlate to the PsGB in our study. Histologically, hyaline cartilage at the portal plate [28
], in the bile ducts [30
] and in an atretic gallbladder [31
], and squamous epithelium within biliary ductules [29
] has been reported. However, the wide spectrum of previously described histopathological findings in BA is mostly without sonographic correlation. The complete absence of smooth muscle bundles in the wall of an atretic gallbladder, noted by Altamirano [31
], might correspond to our observation of the absence of a sonographically normal gallbladder wall in most of our PsGB cases. The varied surgical pathology of the PsGB in our study and in other reported BA cases suggests the need for a larger clinical-radiological-pathological study in the future to provide a more definitive pathological correlate to the PsGB.
A common misconception is that the identification of what appears to be a gallbladder more or less dismisses the possibility of BA. We contend that awareness should be raised that a gallbladder-like structure can be present in association with BA and that its presence should not dissuade one from a diagnosis of BA.