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

Area of Science:

• Genetics
• Hepatology
• Pediatrics

Background:

• ABCB11 deficiency typically presents as persistent/progressive cholestasis in infancy.
• This study identifies a subset of patients with biallelic ABCB11 variants presenting with transient neonatal cholestasis (TNC).

Purpose of the Study:

• To classify neonatal intrahepatic cholestasis in children with biallelic ABCB11 variants.
• To correlate clinical, genetic, and bile salt export pump (BSEP) expression with cholestasis outcomes.
• To investigate the characteristics of TNC in ABCB11 deficiency.

Main Methods:

• Retrospective classification of 68 children with biallelic ABCB11 predictedly pathogenic variants (PPV) into TNC, intermittent (BRIC), or persistent/progressive (PFIC) groups.
• Correlation of clinical data, genetic variants (biallelic non-null vs. null), and liver BSEP expression with patient outcomes.
• Statistical analysis including Kaplan-Meier survival analysis.

Main Results:

• The TNC group (n=23) had a significantly earlier median onset of jaundice compared to the PFIC group (n=42).
• TNC patients more frequently harbored biallelic non-null ABCB11 variants and showed higher rates of detectable liver BSEP expression.
• Detectable BSEP expression was associated with a better prognosis.

Conclusions:

• Neonatal cholestasis due to biallelic ABCB11 PPV can be transient in about one-third of cases.
• Resolution of cholestasis is more probable in patients with biallelic non-null ABCB11 variants or with detectable liver BSEP expression.