S5533 Novel Use of Ileal Bile Acid Transport Inhibitor in Benign Recurrent Intrahepatic Cholestasis Refractory to Conventional Therapy

Introduction: Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive disorder characterized by impaired bile salt transport resulting in intermittent cholestasis with recurrent episodes of jaundice and intense pruritus, with significant impact on quality of life. Conventional treatment options often provide only incomplete symptom control with an unmet need for more effective treatment options. We report the first case of BRIC treated successfully using ileal bile acid transporter (IBAT) inhibitor. Case Description/Methods: A 40-year-old man was diagnosed with BRIC type 1 due to ATP8B1 mutation after extensive evaluation of recurrent episodes of severe pruritus with elevated liver enzymes in the absence of biliary obstruction. Even though he responded well initially to pharmacotherapy including cholestyramine, ursodeoxycholic acid and rifampin, he subsequently required placement of nasobiliary drain during these episodes for symptom control. Subsequent clinical course was characterized by refractoriness to both conventional pharmacotherapy and nasobiliary drainage. He was then treated off-label with IBAT inhibitor odevixibat at a dose of 2400 mcg daily starting at onset of pruritic episodes with prompt and complete symptom relief and normalization of liver biochemical tests and serum bile acid levels. Over the course of the past 20 months, he has had 4 such episodes that have responded dramatically to IBAT inhibitor therapy, thereby obviating the need for nasobiliary drain placement. We continued therapy for a week after complete symptom resolution, with total treatment duration ranging from 9-11 days during these episodes. Discussion: BRIC and progressive familial intrahepatic cholestasis (PFIC) share mutations in similar genes contributing to intrahepatic cholestasis with shared pathophysiologic mechanisms. While BRIC generally has a more favorable prognosis, repetitive cholestatic episodes can significantly impact quality of life. IBAT inhibitors are a novel class of drugs approved recently for the treatment of pruritus in patients 3 months of age and older with PFIC and Alagille’s syndrome. Our case illustrates the potential role of IBAT inhibitors as a safe, effective and well-tolerated treatment option in aborting pruritic episodes in patients with BRIC unresponsive to conventional therapy, highlighting the potential applicability of this class of medications in a wider spectrum of genetic cholestatic disorders.