Background: Alagille syndrome (ALGS) is characterized by cholestatic pruritus and poor quality of life (QOL) leading to liver transplant in 60-75% of patients. Pruritus is the leading indication among transplant recipients. Maralixibat, an IBAT inhibitor, is approved for the treatment of cholestatic pruritus in patients with ALGS ≥3 months of age in the US and ≥2 months of age in the EU. We report real-world experience of delaying the need for liver transplant following treatment with maralixibat in two children with ALGS.

Methods: Chart reviews were performed for two patients with ALGS listed for liver transplant due to cholestatic pruritus and subsequently treated with maralixibat.

Results: Case 1 is a 2-year old male diagnosed with ALGS at 3 months. He had growth failure, fat-soluble vitamin deficiency, and severe pruritus for which he received UDCA, hydroxyzine, and rifampin. Due to these complications and subsequent poor QOL, the patient was referred for liver transplant. Five months later, he was started on maralixibat for persistent pruritus. The patient had complete pruritus resolution and maralixibat was well-tolerated with no reported diarrhea. Given response to maralixibat, transplant evaluation was postponed. Case 2 is a 7-year old female diagnosed with ALGS at ~3 weeks old. At 4 years, she was evaluated for liver transplant due to refractory pruritus despite multiple anti-pruritic medications. These interventions did not improve her QOL and her severe pruritus continued to impact her sleep; thus, she was evaluated and listed for liver transplant. She was started on maralixibat at 6 years and significant improvements in pruritus and sleep quality were observed by Week 4. There were no reported side effects with maralixibat and she was made inactive on the transplant waitlist.

Conclusions: These two cases provide real-world evidence of the effectiveness of maralixibat in delaying the need for liver transplant in ALGS patients due to the significant and rapid improvements in pruritus and QOL after treatment.