Durkin Natalie, Deheragoda Maesha, Davenport Mark
Department of Paediatric Surgery, King's College Hospital, London, SE5 9RS, UK.
Institute of Liver Studies, King's College Hospital, London, SE5 9RS, UK.
Pediatr Surg Int. 2017 Dec;33(12):1355-1361. doi: 10.1007/s00383-017-4193-1. Epub 2017 Oct 13.
The 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?
Review 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.
21 (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).
PBA 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.
IIIc Retrospective Matched Cohort Study.
胆道闭锁（BA）的诊断仍然具有挑战性，诊断延迟会随着时间推移导致严重的发病率，手术时机是决定预后的关键因素。早产可能会影响预后，潜在地延迟诊断。我们试图评估早产BA婴儿（PBA）是否手术时间延迟，以及预后是否更差？
回顾一个单中心前瞻性维护的数据库。早产定义为妊娠<37/40周。PBA与按2:1比例匹配的足月儿BA对照进行比较。主要结局为黄疸清除（<20μmol/L）和自体肝存活。对早产和足月儿队列在诊断时及Kasai肠肝吻合术（KPE）时的活检组织进行肝纤维化的回顾性评估。数据以中位数（范围）表示，除非另有说明。P值≤0.05被认为具有统计学意义。
1988年1月至2016年12月期间，对21例（女性n = 14，67%）患有BA的早产婴儿进行了治疗，并与41例同期足月儿BA对照进行比较。中位妊娠周数为33（29 - 36）周，出生体重为1930（948 - 4230）g。双胎妊娠（n = 10）是早产的主要原因，且显著高于对照组（48% vs. 0%；P < 0.0001）。母亲合并症发生率较高（n = 10，48%），包括子痫前期（19%）和糖尿病（14%）。19例（90%）患者进行了肝活检（均为诊断性活检），中位时间为57（4 - 266）天。13例出现诊断延迟（>50天），但与肠外营养使用（46% vs. 33%，P = 0.59）或光疗（50% vs. 83%，P = 0.19）无关。PBA队列中BASM（33% vs. 7.5%；P = 0.01）和十二指肠闭锁（19% vs. 0%；P = 0.01）的发生率更高。早产组诊断性活检的平均纤维化评分（Ishak）低于对照组（2.71 vs. 3.53，P = 0.043），表明纤维化程度较低，但在随后的KPE时纤维化程度趋于相等（P = 0.17）。初次手术为Kasai肠肝吻合术（n = 20），中位年龄比对照组大（65天vs. 56天；P = 0.06）。一名就诊较晚的儿童以肝移植作为主要手术。PBA组KPE后黄疸清除率有所增加但无统计学意义[n = 12/20（60%）vs 20/41（48%）；P = 0.23]。自体肝存活率和实际存活率无差异（P = 0.58和0.23）。
尽管诊断延迟且综合征形式的发生率较高，但PBA婴儿的预后与足月儿相似。双卵双胎的高发生率支持了表观遗传修饰可能参与BA发病机制的理论。
IIIc级回顾性匹配队列研究。
