Biliary Atresia as a Disease Starting In Utero: Implications for Treatment, Diagnosis, and Pathogenesis

Abstract

Biliary atresia (BA) is the most common reason for pediatric liver transplant. BA's varied presentation, natural history, and treatment with the Kasai portoenterostomy have been well described; however, when BA starts relative to birth has not been clearly defined. In this review, we discuss laboratory, imaging, and clinical data which suggest that most if not all forms of BA may start before birth. This early onset has implications in terms of delivering treatments earlier and identifying possible factors underlying BA's etiology.

Figure 1

Earlier KPs correlate with higher transplant-free survival. Age cut-offs among studies varied, but all showed better outcomes when the KP was performed earlier. Studies included were those with ≥100 total participants and ≥10 participants with KP ≤30 days. Percentages based on data from Karrer FM et al. (1990) Journal of Pediatric Surgery 25:1076-80, Schreiber RA et al. (2007) Journal of Pediatrics 151:659-65, Serinet M-O et al. (2009) Pediatrics 123:1280-86, and Shneider BL et al. (2006) Journal of Pediatrics 148:467-74.

Figure 2

Approach to diagnose BA. PCPs use clinical signs and/or screening to identify and refer infants. Specialists then perform a series of tests to exclude BA, grouped as commonly ordered tests (a normal result does not necessarily exclude BA), exclusionary tests (a normal result excludes BA), and tests for other diseases. If BA cannot be excluded, invasive gold-standard testing is performed. *tests which detect biliary abnormalities, which can help in early diagnoses; ^†screening performed by parents as well; ^‡ tests which detect liver injury; ^§must be performed expeditiously.

Figure 3

Etiological Considerations for BA. By the second trimester, BA has already started as evidenced by gall bladder abnormalities and low amniotic fluid GGT levels. A BA pathogenic factor affects one but not both fetuses in twin pregnancies (affected fetus with atretic GB and low GGT in amniotic fluid). Proposed pathogenic factors include genetic changes, infection, immune dysregulation, and/or toxins.