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

Background & Aims ABCB11 deficiency presenting in infancy is believed generally to manifest as persistent/progressive cholestasis. We describe a group of patients with biallelicABCB11variants whose disorder manifested as transient neonatal cholestasis (TNC). Methods Neonatal intrahepatic cholestasis in 68 children (31 males) with biallelic predictedly pathogenic variants (PPV) inABCB11was 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. Results 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. Conclusions Neonatal cholestasis associated with biallelic PPV inABCB11can 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.