The Burden of Pruritus in Pediatric Cholestatic Liver Disease, with Mercedes Martinez, MD

Pruritus is a distressing and often debilitating symptom of pediatric cholestatic liver disease, significantly impacting both affected children and their families.

Typically seen in children with Alagille syndrome and progressive familial intrahepatic cholestasis (PFIC), the severity of pruritus can vary from patient to patient—while some children experience mild discomfort, others scratch to the point of skin damage, bleeding, and severe sleep disturbances.

In an interview with HCPLive, Mercedes Martinez, MD, a professor of pediatrics and medicine, medical director of the intestinal transplant program at the Center for Liver Disease and Abdominal Organ Transplantation, and medical director of the pediatric abdominal organ transplantation program at NewYork-Presbyterian, explains the pathophysiology and clinical presentation of pruritus in children with cholestatic liver disease.

She notes that although pruritus is not exclusive to liver disease—it can also occur in conditions like kidney disease and lymphoma—it is particularly severe in certain pediatric liver disorders, including Alagille syndrome and PFIC.

“The severity [of pruritus] varies,” Martinez explained. “Some patients just scratch here and there. Other patients might bleed from the intensity of the scratch and have scratch marks.”

She goes on to outline treatment strategies, including warm or cold baths and topical treatments, and pharmacologic therapies targeting bile acid accumulation, as bile acids are key pruritogens in cholestatic liver disease.

Next, Martinez discusses systemic therapies aimed at altering bile acid metabolism and pruritogen processing. Rifampin, an antibiotic originally developed for tuberculosis, is used for pruritus management due to its effects on bile acid metabolism. Other medications, such as hydroxyzine, naltrexone, and sertraline, act on the central nervous system to modify the sensation of itching.

She also describes more invasive interventions, including nasogastric bile drainage, extracorporeal filtration, and biliary diversion surgeries, which redirect bile away from the intestine to reduce systemic pruritogens. In severe cases, liver transplantation is considered.

Finally, she highlights a major advancement in pruritus management: ileal bile acid transporter (IBAT) inhibitors.

In 2021, the FDA approved odevixibat (Bylvay) for the treatment of pruritius in patients ≥ 3 months of age with PFIC and maralixibat (Livmarli) oral solution for the treatment of cholestatic pruritus in patients with Alagille syndrome ≥ 1 year of age.1,2

In 2023, odevixibat gained an additional indication for cholestatic pruritus in patients ≥12 months of age with Alagille syndrome. A year later, maralixibat was approved for the treatment of cholestatic pruritus in patients ≥ 5 years of age with PFIC.3,4

“We have these beautiful new medications that are called IBAT inhibitors, and they have been approved for certain pediatric conditions,” Martinez said. “They are wonderful for most patients. The improvement of the pruritus is significant.”

Editors’ note: Martinez has no relevant disclosures.

Reference

1. Walter K. FDA Approves Odevixibat for PFIC. HCPLive. July 20, 2021. Accessed March 21, 2025. https://www.hcplive.com/view/fda-approves-odevixibat-pfic

2. Walter K. FDA Approves First Treatment for Rare Pediatric Liver Disease. HCPLive. September 29, 2021. Accessed March 21, 2025. https://www.hcplive.com/view/fda-approves-first-treatment-rare-pediatric-liver-disease

3. Kunzmann K. FDA Approves Odevixibat for Cholestatic Pruritus in Alagille Syndrome. HCPLive. June 13, 2023. Accessed March 21, 2025. https://www.hcplive.com/view/fda-approves-odevixibat-cholestatic-pruritus-alagille-syndrome

4. Brooks A. FDA Approval of Maralixibat for Cholestatic Pruritus in PFIC Signals New Frontier for IBAT Inhibitor. HCPLive. March 13, 2024. Accessed March 21, 2025. https://www.hcplive.com/view/fda-approval-of-maralixibat-for-pfic-ibat-inhibitors