Published online Feb 27, 2020. doi: 10.4254/wjh.v12.i2.64
Peer-review started: November 14, 2019
First decision: December 12, 2019
Revised: December 19, 2019
Accepted: January 1, 2020
Article in press: January 1, 2020
Published online: February 27, 2020
Benign recurrent intrahepatic cholestasis is a genetic disorder with recurrent cholestatic jaundice due to ATP8B1 and ABCB11 gene mutations encoding for hepato-canalicular transporters. Herein, we firstly provide the evidence that a nonsense variant of ATP8B1 gene (c.1558A>T) in heterozygous form is involved in BRIC pathogenesis.
A 29-year-old male showed severe jaundice and laboratory tests consistent with intrahepatic cholestasis despite normal gamma-glutamyltranspeptidase. Acute and chronic liver diseases with viral, metabolic and autoimmune etiology were excluded. Normal intra/extra-hepatic bile ducts were demonstrated by magnetic resonance. Liver biopsy showed: Cholestasis in the centrilobular and intermediate zones with bile plugs and intra-hepatocyte pigment, Kupffer’s cell activation/hyperplasia and preserved biliary ducts. Being satisfied benign recurrent intrahepatic cholestasis diagnostic criteria, ATP8B1 and ABCB11 gene analysis was performed. Surprisingly, we found a novel nonsense variant of ATP8B1 gene (c.1558A>T) in heterozygosis. The variant was confirmed by Sanger sequencing following a standard protocol and tested for familial segregation, showing a maternal inheritance. Immunohistochemistry confirmed a significant reduction of mutated gene related protein (familial intrahepatic cholestasis 1). The patient was treated with ursodeoxycholic acid 15 mg/kg per day and colestyramine 8 g daily with total bilirubin decrease and normalization at the 6th and 12th mo.
A genetic abnormality, different from those already known, could be involved in familial intrahepatic cholestatic disorders and/or pro-cholestatic genetic predisposition, thus encouraging further mutation detection in this field.
Core tip: Benign recurrent intrahepatic cholestasis is a rare genetic disorder characterized by recurrent jaundice due to the mutation of the ATP8B1/ABCB11 genes encoding for hepato-canalicular transporters. The original finding, which characterizes the case we observed, is the association of a novel nonsense variant of ATP8B1 gene (c.1558A>T) in a heterozygous condition with hepato-canalicular transporter protein deficiency. Indeed, the disorder has been described until now as an autosomal recessive one, whereas, in this case, the patient expressed the disease despite having only one mutated allele of ATP8B1 gene.