Recent updates on the diagnosis and treatment of cholestatic etiologies such as Alagille syndrome (ALGS) could help prevent complications and disease progression, according to a study recently published in Current Opinion in Pediatrics.

This literature review aimed to group and correlate the most recent findings and consensus regarding screening, diagnosis, and management of children with cholestatic disease, including congenital, genetic, and infectious causes.

“Once an infant is found to be cholestatic, the goal is to evaluate for biliary atresia and to rule out other common causes of cholestasis prior to invasive testing,” the authors wrote.

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In the case of ALGS, diagnosis remains challenging. This limitation also occurs in other hereditary causes, such as cystic fibrosis, alpha-1 antitrypsin deficiency, and progressive familial intrahepatic cholestasis, to name a few. Regardless, monogenic mutations may account for up to half of neonatal cholestasis cases.

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Important advances in this topic include a wider availability and lower cost of next-generation sequencing tests. Some guidelines now recommend performing this genetic testing after ruling out biliary atresia. In a cohort of 2171 individuals, including 863 infants under 3 months of age, ALGS was the most frequent genetic diagnosis, identified by JAG1/NOTCH2 mutations.

Perhaps the area that showcases the most promising advances is the therapeutic management of children with ALGS.

“In the treatment of pruritus in Alagille syndrome and progressive familial intrahepatic cholestasis the clinical studies of two newly Food and Drug Administration approved ileal bile acid transport inhibitors are discussed,” Wehrman and Lee wrote.

Maralixibat (Livmarli®), an ileal bile acid transport inhibitor that impairs the reabsorption of bile acids and limits their enterohepatic circulation, can decrease bile acid levels in the blood. It was approved last year as a symptomatic treatment for children aged 1 year and above with ALGS, as it decreases the characteristic pruritus and prevents liver damage.


Wehrman A, Lee CK. The cholestatic infant: updates on diagnosis and genetics. Curr Opin Pediatr. Published online August 4, 2022. doi:10.1097/mop.0000000000001156