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.

Biliatresone: progress in biliary atresia study

“…These toxins eventually affect the normal biliary system development of the fetus or newborn through the placenta or breast milk and ultimately lead to the occurrence of BA alone or accompanied by other environmental factors, such as CMV infection, which was verified to exist in 48%–50% of Chinese BA patients and is much higher than that of the European group (approximately 10%) [ 62 ]. In recent years, BA has been hypothesized to have begun as early as in utero, and syndromic BA is presumed to be an embryonic defect due to its unique visceral anomalies, such as polysplenia or situs inversus, although the actual genes involved are inconclusive [ 63 ]. Approximately 22.2% of fetuses diagnosed with hilar hepatic cysts develop cystic BA after birth, but it is not usually accompanied by organ abnormalities other than liver and gall [ 64 , 65 ].…”

Matrix Metalloproteinase-7 and Osteopontin Serum Levels as Biomarkers for Biliary Atresia

“…This etiological heterogeneity of BA is readily observed in the distinct clinical variants (syndromic, cytomegalovirus-associated, cystic and isolated BA). The prevalence could also vary between different ethnic or racial groups (28,29,48). The clinical heterogeneity of BA is reduced in the Far-East, as the overwhelming majority of infants have the isolated variant.…”

“…It is noteworthy that all published literature on the diagnostic value of MMP-7 in BA have been based on Asian series. The incidence, clinical phenotype, and pathogenesis of BA from such cohorts can be markedly different from that in Europe and North America (27)(28)(29). The aims of this study were validation of serum MMP-7 and OPN levels as diagnostic tools, and their assessment as prognostic markers in a Western single-center BA series.…”

Rare spontaneous monochorionic dizygotic twins: a case report and a systematic review

“…Patients with BASM could have polysplenia, asplenia or double spleen, situs inversus with and without malrotation; preduodenal portal vein, a complete absence of intrahepatic vena cava and cardiac anomalies. According to some researchers [27,28] the association between BA and laterality defects of the abdominal viscera may suggest a defect in the embryonic development to explain the etiology of BASM. The bile duct development begins at 4 gestational weeks and ends at about 13 weeks; in the same period laterality defects, such as development of left-right axis reversal (GA 2-3 weeks), splenic malformations (GA 3-6 weeks), preduodenal portal vein (GA 4-8 weeks), and interrupted vena cava (GA 6-8 weeks) are thought to occur [27].…”