Diagnostic approaches for infants with cholestatic liver diseases: Position paper and perspectives of the Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition

Abstract

Cholestasis in infancy is the most common manifestation of liver disease in children, with some patients progressing to cirrhosis or liver failure necessitating transplantation. Neonatal cholestasis remains a diagnostic challenge, as it requires differentiation of cholestatic infants from a large number of jaundiced newborns with benign causes. The first step is to diagnose patients with biliary atresia (BA) as early as possible to ensure timely surgery-Kasai portoenterostomy (KPE). Universal newborn screening using stool color cards or direct bilirubin measurements have been shown to identify patients before the onset of symptoms. Multiple diagnostic modalities, including clinical history, physical examination, laboratory tests, emerging biomarkers, imaging studies, and liver histopathology, can facilitate the decision for intraoperative cholangiography and potential corrective surgery. Advances in diagnostic testing, particularly genetic sequencing, have greatly enhanced our ability to evaluate and manage infants with cholestasis. Given highly variable resources and access to these new diagnostic modalities, local flexibility and adaptability should be implemented within each institution and medical care system to foster seamless collaboration between primary care physicians and specialized centers with expertise in genetic diagnosis, KPE, and liver transplantation. This report provides updates on the evaluation of neonatal cholestasis, including insights into screening, diagnosis, and genetic testing, along with future perspectives.