ABCB4 Mutations in Adults Cause a Spectrum Cholestatic Disorder Histologically Distinct from Other Biliary Disease

Area of Science:

• Hepatology
• Genetics
• Histopathology

Background:

• ABCB4 gene mutations disrupt bile acid emulsification, leading to cholestatic liver disease.
• Disease presentations vary from childhood PFIC3 to milder adult forms.

Observation:

• Studied four unrelated adults and three sisters with adult-onset cholestatic liver disease and ABCB4 variants.
• Performed clinical review and detailed histopathological analysis.

Findings:

• Identified two novel pathogenic ABCB4 variants: c.620 T>G, p.(Ile207Arg) and c.2301dupT, p.(Thr768TyrfsTer26).
• Observed diverse phenotypes including LPAC, ICP, drug-induced cholestasis, ductopenia, and adult PFIC3.
• Histology showed ductopenia, mild portal inflammation, bilirubinostasis, copper deposition, and fibrosis.

Implications:

• Adult ABCB4 mutations present a spectrum of cholestatic phenotypes, potentially requiring liver transplantation.
• A distinct histological pattern aids diagnosis, differentiating from classical biliary diseases.
• ABCB4 sequencing is recommended for patients with suggestive phenotypes or histology for timely intervention and family screening.