Abstract
Aim of studyThe diagnosis of biliary atresia (BA) remains challenging and delay can lead to significant morbidity with time to surgery a key factor in determining outcome. Prematurity may impact on outcome potentially delaying diagnosis. We sought to assess whether the premature BA infants (PBA) have a delayed time to surgery and as such, worse outcomes?MethodsReview of a single-centre prospectively maintained database. Prematurity was defined as delivery < 37/40 gestation. PBA was compared with date-matched term biliary atresia controls on a 2:1 basis. Primary outcomes were clearance of jaundice (< 20 μmol/L) and native liver survival. A retrospective assessment of liver fibrosis was made on biopsies at diagnosis and at Kasai portoenterostomy (KPE) in both premature and term cohorts. Data are quoted as median (range) unless indicated. A P value of ≤ 0.05 was considered statistically significant.Results21 (female n = 14, 67%) premature infants with BA were treated in the period Jan. 1988–Dec. 2016 and compared with 41 contemporaneous term BA controls. Median gestation was 33 (29–36) weeks and birth weight 1930 (948–4230)g. Twin pregnancy (n = 10) was the leading cause for prematurity and significantly higher than the controls (48 vs. 0%; P < 0.0001). Maternal co-morbidity was high (n = 10, 48%) including pre-eclampsia (19%) and diabetes (14%). Liver biopsy was performed in 19 (90%) patients (all diagnostic) at a median of 57 (4–266) days. Delayed diagnosis (> 50 days) was seen in n = 13 but not associated with parenteral nutrition use (46 vs. 33%, P = 0.59) or phototherapy (50 vs. 83%, P = 0.19). Both BASM (33 vs. 7.5%; P = 0.01) and duodenal atresia (19 vs. 0%; P = 0.01) were seen more frequently in the PBA cohort. Mean fibrosis scores (Ishak) from diagnostic biopsies were lower in the premature group than the control group (2.71 vs. 3.53, P = 0.043) indicating less fibrosis but this equalized by time of subsequent KPE (P = 0.17). Primary surgery was Kasai portoenterostomy (n = 20) at an older median age than controls (65 vs. 56 days; P = 0.06). Liver transplantation was the primary procedure in one late-presenting child. There was an increased but non-significant clearance of jaundice in the PBA group [n = 12/20 (60%) vs 20/41 (48%); P = 0.23] post-KPE. Native liver survival and true survival were not different (P = 0.58 and 0.23).ConclusionsPBA infants have similar outcomes to term infants, despite delayed diagnosis and higher frequency of the syndromic form. The high incidence of discordant twins supports the theory that epigenetic modifications could contribute to the pathogenesis of BA.Level of evidenceIIIc Retrospective Matched Cohort Study.
Highlights
Biliary atresia is an obstructive cholangiopathy of essentially unknown aetiology which, left untreated, is a potent cause of liver fibrosis and secondary biliary cirrhosis [1]
There are three large-scale studies from Sweden [18], Taiwan [19] and, most recently, The Netherlands [20] in which the incidence of biliary atresia (BA) was reportedly higher in the premature population than in term infants with an odds ratio of 2.9 and 1.65 in the first two studies, respectively. Despite this reported increased incidence, outcomes and characteristics have been rarely reported, consisting largely of case reports [21,22,23]. Features such as diagnostic delay, single cases of twins, maternal morbidity and BASM have been mentioned as possible associations but not substantiated
Our cohort was characterized by an increased proportion of twinning which had not been identified in this Taiwanese study
Summary
Biliary atresia is an obstructive cholangiopathy of essentially unknown aetiology which, left untreated, is a potent cause of liver fibrosis and secondary biliary cirrhosis [1]. Possible causes include a developmental disorder of the bile ducts either in isolation or in association with other anomalies [2], bile duct ischaemia, or acquired bile duct injury secondary to a viral-mediated or triggered immune response [3, 4]. The onset of the injury may vary from early in the first trimester during embryonic organogenesis (e.g., Biliary Atresia Splenic Malformation (BASM)) to perhaps the perinatal period (e.g., CMV IgM+ve associated BA). Recent evidence from incidental blood sampling on day 1 or day 2 of life suggest that most if not all have a demonstrable conjugated hyperbilirubinaemia which implies that at the time of birth there is already established biliary obstruction [10]
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