Biliary Atresia: Clinical Phenotypes and Aetiological Heterogeneity

Abstract

Biliary atresia (BA) is an obliterative condition of the biliary tract that presents with persistent jaundice and pale stools typically in the first few weeks of life. While this phenotypic signature may be broadly similar by the time of presentation, it is likely that this is only the final common pathway with a number of possible preceding causative factors and disparate pathogenic mechanisms-i.e., aetiological heterogeneity. Certainly, there are distinguishable variants which suggest a higher degree of aetiological homogeneity such as the syndromic variants of biliary atresia splenic malformation or cat-eye syndrome, which implicate an early developmental mechanism. In others, the presence of synchronous viral infection also make this plausible as an aetiological agent though it is likely that disease onset is from the perinatal period. In the majority of cases, currently termed isolated BA, there are still too few clues as to aetiology or indeed pathogenesis.

Keywords: Kasai operation; adjuvant therapy; biliary atresia; etiology; liver transplant.

Figure 1

(A) Biliary atresia: Liver is mobilized and exteriorized to expose the porta hepatis. (B): Dissection of the Porta Hepatis. The bile duct remnant has been transected and is lying on segment 4 of the retracted liver. The white dotted area outlines the extent of the porta hepatis which will then be anastomosed to the Roux jejunal loop.

Figure 2

Variation in prevalence of Biliary Atresia in England and Wales (n = 713, 1999–2015).

Figure 3

Suggested immunopathogenesis of Biliary Atresia. (A) Transient virus infection of cholangiocytes results in upregulation of Toll-Like Receptors (TLR) and a broad-based activation of the innate immune system involving macrophages, dendritic cells and NK cells. (B) Adaptive T cell proliferation (Th2 and Th17 predominant), supported by B cells and activated macro-phages cause cholangiocyte damage, possibly unrestrained by the absence of Tregs. Dissection of the Porta Hepatis. The bile duct remnant has been transected and is lying on segment 4 of the retracted liver. The white dotted area outlines the extent of the porta hepatis which will then be anastomosed to the Roux jejunal loop.