ABCB11 deficiency presenting as transient neonatal cholestasis: Correlation with genotypes and BSEP expression

• DOI: 10.1111/liv.14642
• Publication Date: 2020-08-28T03:13:18Z
• Authors: Li‐Ting Li; Zhong‐Die Li; Ye Yang; Yi Lu; Xin‐Bao Xie; Lian Chen; Jia‐Yan Feng; A. S. Knisely; Jian‐She Wang
• Keywords: Male; 0303 health sciences; Cholestasis; Genotype; Infant, Newborn; Infant; Cholestasis, Intrahepatic; 3. Good health; 03 medical and health sciences; Mutation; Humans; ATP-Binding Cassette Transporters; Child; ATP Binding Cassette Transporter, Subfamily B, Member 11

AbstractBackground & AimsABCB11 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).MethodsNeonatal 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.ResultsThe 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.ConclusionsNeonatal 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.