For Health Care Professionals

Living With Alagille Syndrome

The Impact of Alagille Syndrome

The symptoms and severity of Alagille syndrome can vary greatly from one person to another. For most families affected by Alagille syndrome, life can feel uncertain.

Pruritus affects up to 88% of children with Alagille syndrome. It is also among the most severe pruritus in any chronic liver disease, negatively impacting quality of life, physical health, and psychosocial health.1,2

The Burden of Alagille Syndrome

This Alagille Syndrome Comprehensive Brochure can help you learn more about the impact of this rare liver disease.

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The Impact of Alagille Syndrome

Poor Quality of Life

Alagille syndrome is more than an insufferable itch.

Parents and caregivers of children with Alagille syndrome describe pruritus as the most challenging symptom, citing the anxiety, sleep deprivation, fatigue, and emotional distress associated with unrelenting itching and scratching.2-4

In addition to unrelenting itching and scratching, cholestatic pruritus leads to skin damage, bleeding, scarring, cutaneous mutilation, sleep disturbances, disrupted school activities, and more.1-4

Furthermore, many children with Alagille syndrome encounter significant growth deficits and a failure to thrive.2,4,5

We end up with bloody bed sheets, wounds on his face, and him wanting to tear his skin off. –Robigaile B.

While pruritus is considered the most unbearable symptom associated with cholestatic liver disease in Alagille syndrome, xanthomas are also common, affecting 30% to 42% of patients and usually appearing at a median of 20 months to 48 months of age. In patients with a native liver, the presence of xanthomas is associated with a worse 10-year survival rate than in those without.2,6

Out of a group of children with Alagille syndrome who had xanthomas (36%)3:

12% had restrictions in physical activity

61% felt their physical appearance was affected

46% felt distraught

Xanthomas are also associated with poor long-term hepatic outcomes.7

Failure to Thrive

Malnutrition and growth deficiencies are common in Alagille syndrome, and these may be related to the impaired absorption of fat and fat‑soluble vitamins. Children may have growth hormone resistance, and their short stature may be because of cholestasis, cardiovascular abnormality, and/or defective bone development.7,8

Limited Treatment Options

Previously, treatment options were very limited.1 Therapy was focused on the consequences of liver disease, as well as the surgical and medical treatment of congenital heart defects.9 While several off-label, unapproved medications are frequently used to treat cholestatic pruritus or other symptoms of cholestatic liver disease, including rifampin, ursodiol, cholestyramine, naltrexone, and antihistamines, these approaches may not be entirely effective.1,9

We run 14 syringes of medication through his G-tube every morning, night, and midnight. Still, he itches and scratches all the time. –Chad H.
Lack of Effective Noninvasive Treatments

Surgical Interventions

As a result of medical management shortcomings, surgery becomes the only viable option to treat the signs and symptoms of cholestatic pruritus in Alagille syndrome.

Indications for liver transplant include1,10,11:

  • Intractable pruritus
  • Growth failure
  • Xanthomas
  • Metabolic bone disease
  • Fat-soluble vitamin deficiency
  • Poor quality of life

Therefore, there is a high unmet need in Alagille syndrome for more pharmacologic strategies to limit the progression of liver disease and need for surgical interventions, including liver transplant.1

...Knowing our son might one day need a liver transplant, we worried and had many questions. –Maribel V.
Surgical Interventions
References: 1. Kamath BM, Stein P, Houwen RHJ, Verkade HJ. Potential of ileal bile acid transporter inhibition as a therapeutic target in Alagille syndrome and progressive familial intrahepatic cholestasis. Liver Int. 2020;40(8):1812-1822. doi:10.1111/liv.14553 2. Kamath BM, Baker A, Houwen R, Todorova L, Kerkar N. Systematic review: the epidemiology, natural history, and burden of Alagille syndrome. J Pediatr Gastroenterol Nutr. 2018;67(2):148-156. doi:10.1097/MPG.0000000000001958 3. Elisofon SA, Emerick KM, Sinacore JM, Alonso EM. Health status of patients with Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010;51(6):759-765. doi:10.1097/MPG.0b013e3181ef3771 4. Kamath BM, Abetz-Webb L, Kennedy C, et al. Development of a novel tool to assess the impact of itching in pediatric cholestasis. Patient. 2018;11(1):69-82. doi:10.1007/s40271-017-0266-4 5. Quiros-Tejeira RE, Ament ME, Heyman MB, et al. Does liver transplantation affect growth pattern in Alagille syndrome? Liver Transpl. 2000;6(5):582-587. doi:10.1053/jlts.2000.9739 6. Lykavieris P, Hadchouel M, Chardot C, Bernard O. Outcome of liver disease in children with Alagille syndrome: a study of 163 patients. Gut. 2001;49(3):431-435. doi:10.1136/gut.49.3.431 7. Saleh M, Kamath BM, Chitayat D. Alagille syndrome: clinical perspectives. Appl Clin Genet. 2016;9:75-82. doi:10.2147/TACG.S86420 8. Singh SP, Pati GK. Alagille syndrome and the liver: current insights. Euroasian J Hepatogastroenterol. 2018;8(2):140-147. doi:10.5005/jp-journals-10018-1280 9. Turnpenny PD, Ellard S. Alagille syndrome: pathogenesis, diagnosis and management. Eur J Hum Genet. 2012;20(3):251-257. doi:10.1038/ejhg.2011.181 10. Verkade HJ, Bezerra JA, Davenport M, et al. Biliary atresia and other cholestatic childhood diseases: advances and future challenges. J Hepatol. 2016;65(3):631-642. doi:10.1016/j.jhep.2016.04.032 11. Vandriel SM, Li L-T, She H, et al. Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study. Hepatology. In press.