Cholestatic Pruritus in Children: Signs, Burden, and Treatment Gaps

Pruritus in children with cholestatic liver diseases can look like colic, reflux, or attention problems, delaying recognition.

In an interview with HCPLive, Jennifer Vittorio, MD, associate professor of pediatrics and medical director of pediatric liver transplantation at NYU Langone Health, described how cholestatic pruritus presents across ages, how it affects families, and why it has historically been so difficult to treat.

“In young children or infants, pruritus can often be described as an irritability or fussiness with disturbed sleep, rather than a clearly articulated complaint,” Vittorio said. “Far too often, I hear families come to me and say that their child’s been diagnosed with something like reflux, or even colic, when really this is just a manifestation of pruritus.”

Signs of Cholestatic Pruritus by Age

In school-age children, Vittorio said, pruritus may present as fatigue, daytime sleepiness, or difficulty concentrating. Teachers sometimes raise concerns about ADHD in children who cannot sit still in class because of itch.

In adolescents, scratching and the distress it brings can contribute to social isolation, withdrawal, and depression. Vittorio described cholestatic pruritus as a persistent, debilitating symptom that affects sleep, mood, energy, and participation in everyday activities.

Pruritus Burden on Caregivers and Families

The impact extends beyond the patient. Caregivers who are up at night with their child face chronic sleep deprivation, and siblings and extended family are affected as well.

Vittorio noted that pruritus is well recognized in Alagille syndrome and progressive familial intrahepatic cholestasis (PFIC) but is often unrecognized in other conditions, including biliary atresia. She said clinicians should routinely ask patients and caregivers how itch is affecting daily life.

Off-Label Therapies Used for Cholestatic Pruritus

Historically, treatment relied on off-label therapies, including ursodeoxycholic acid, rifampicin, bile acid sequestrants, antihistamines, and selective serotonin reuptake inhibitors. Vittorio said these were often ineffective or only partially effective, added to pill burden, and carried unwanted effects such as daytime fatigue with antihistamines.

When pruritus remained severe despite medical therapy, clinicians began discussing surgical biliary diversion or liver transplantation.

“Once you start to gain more and more experience with these patients, and you’re seeing them in your office, and you’re witnessing firsthand what’s going on, you have a better understanding of why we would turn to something like liver transplant, just because the quality of life is so compromised,” Vittorio said.

IBAT Inhibitors and the EXPAND Trial

Maralixibat (Livmarli), an ileal bile acid transporter (IBAT) inhibitor, is approved by the US Food and Drug Administration (FDA) for cholestatic pruritus in Alagille syndrome and PFIC.² In the phase 3 EXPAND trial, maralixibat reduced itch severity vs placebo in patients with ultra-rare cholestatic liver diseases, including biliary atresia, with a placebo adjusted improvement of 0.98 points on a 0 to 4 scale (P = .0004).¹ The results are topline and have not been peer reviewed.

Editor’s Note: Vittorio reports relevant disclosures with Mirum Pharmaceuticals.

References

1. Mirum Pharmaceuticals announces primary endpoint met in phase 3 EXPAND study of Livmarli (maralixibat) in ultra-rare cholestatic liver diseases. News release. Mirum Pharmaceuticals. October 12, 2026. Accessed October 16, 2026. https://ir.mirumpharma.com/news/news-details/2026/Mirum-Pharmaceuticals-Announces-Primary-Endpoint-Met-in-Phase-3-EXPAND-Study-of-LIVMARLI-maralixibat-in-Ultra-Rare-Cholestatic-Liver-Diseases/default.aspx

2. Livmarli (maralixibat). Prescribing information. Mirum Pharmaceuticals. Accessed October 16, 2026. https://files.mirumpharma.com/livmarli/livmarli-prescribinginformation.pdf