Li Li-Ting, Li Zhong-Die, Yang Ye, Lu Yi, Xie Xin-Bao, Chen Lian, Feng Jia-Yan, Knisely A S, Wang Jian-She
The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China.
Department of Pediatrics, Jinshan Hospital, Fudan University, Shanghai, China.
Liver Int. 2020 Nov;40(11):2788-2796. doi: 10.1111/liv.14642. Epub 2020 Oct 13.
BACKGROUND & AIMS: ABCB11 deficiency presenting in infancy is believed generally to manifest as persistent/progressive cholestasis. We describe a group of patients with biallelic ABCB11 variants whose disorder manifested as transient neonatal cholestasis (TNC).
Neonatal intrahepatic cholestasis in 68 children (31 males) with biallelic predictedly pathogenic variants (PPV) in ABCB11 was classified as transient (TNC group, n = 23, 11 males), intermittent (benign recurrent intrahepatic cholestasis [BRIC] group, n = 3, 1 male) or persistent/ progressive (progressive familial intrahepatic cholestasis [PFIC] group, n = 42, 19 males). Clinical, genetic and bile salt export pump (BSEP) expression information was correlated with outcomes.
The median onset age of jaundice was 3 days (birth to 2 months) for the TNC group and 10.5 days (birth to 3 months) for the PFIC group (P = .034). The median length of follow-up of TNC patients was 44 months (12 months-168 months). At presentation, hepatobiliary-injury biomarker values were similar between the groups (P > .05). TNC patients (17/23) more often than PFIC patients (20/42, P = .041) harboured biallelic non-null variants (predicted not to terminate translation prematurely). TNC patient livers (7/7) more often than PFIC patient livers (5/16, P = .005) expressed immunohistochemically detectable BSEP. Kaplan-Meier analysis showed better prognosis for patients with BSEP expression (P = .009). Too few BRIC patients were available for statistical study.
Neonatal cholestasis associated with biallelic PPV in ABCB11 can resolve temporarily or persistently in one third of cases. Resolution is more likely in patients with biallelic non-null PPV or with liver BSEP expression.
一般认为婴儿期出现的ABCB11缺乏通常表现为持续性/进行性胆汁淤积。我们描述了一组双等位基因ABCB11变异的患者，其疾病表现为短暂性新生儿胆汁淤积（TNC）。
对68例（31例男性）ABCB11双等位基因预测致病变异（PPV）的新生儿肝内胆汁淤积患者进行分类，分为短暂性（TNC组，n = 23，11例男性）、间歇性（良性复发性肝内胆汁淤积[BRIC]组，n = 3，1例男性）或持续性/进行性（进行性家族性肝内胆汁淤积[PFIC]组，n = 42，19例男性）。临床、遗传和胆盐输出泵（BSEP）表达信息与预后相关。
TNC组黄疸的中位发病年龄为3天（出生至2个月），PFIC组为10.5天（出生至3个月）（P = 0.034）。TNC患者的中位随访时间为44个月（12个月 - 168个月）。就诊时，各组间肝胆损伤生物标志物值相似（P > 0.05）。TNC患者（17/23）比PFIC患者（20/42，P = 0.041）更常携带双等位基因非无效变异（预测不会过早终止翻译）。TNC患者肝脏（7/7）比PFIC患者肝脏（5/16，P = 0.005）更常通过免疫组化检测到BSEP表达。Kaplan-Meier分析显示BSEP表达患者的预后更好（P = 0.009）。BRIC患者数量太少，无法进行统计学研究。
与ABCB11双等位基因PPV相关的新生儿胆汁淤积在三分之一的病例中可暂时或持续缓解。双等位基因非无效PPV或肝脏有BSEP表达的患者更有可能缓解。
