Odevixibat improves pruritus and bile acid level in Alagille syndrome: A case report

Alagille syndrome (ALGS) is a rare genetic disorder that affects the liver causing, cholestasis, jaundice and intractable pruritus which can significantly impair health-related quality of life (QoL). The treatment of liver involvement is mainly supportive with the majority eventually requiring liver transplant. Ileal bile acid transporter inhibition is a novel therapeutic concept for cholestatic pruritus and cholestatic liver disease. We report the effects of odevixibat treatment in a patient ALGS over 12 months.

A male patient presented with jaundice at 3 months. ALGS was suspected clinically and genetic testing identified JAG1 mutation. Mother reported severe pruritus since the age of 18 months disrupting the child's daily activity including sleeping. He was treated with ursodiol at 10 mg/kg three times a day, rifampin at 5 mg/kg twice daily, cholestyramine at 4 g twice daily and cetirizine 5 mg once daily. The patient continued to have persistent itching affecting the QoL, with abnormal liver enzymes and bile acid level. The patient pediatric end-stage liver disease score was 15. Abdominal ultrasound (June 2023) showed enlarged coarse liver, normal portal vein flow and massive splenomegaly measuring 14 cm in sagittal span (spleen size was 11.2 cm on previous scan 6 months earlier). Odevixibat was administered to the patient at initial dose 40 μg/kg/day increasing up to 120 μg/kg/day to ameliorate gastrointestinal side effects. The patient itching improved very shortly after initiating treatment and was able to sleep overnight for the very first time. The patients' serum bile acids, bilirubin and alanine transferase improved up to 12 months after treatment. There was no reported side effect.

This case demonstrates the use of ileal bile acid transporter inhibitors treating pruritus and improving patient QoL. It has potential to delay the need for liver transplantation. However more long-term studies are needed to help clinicians better understand the benefit of this new treatment.