Researchers reported that the use of whole-exome sequencing/next-generation sequencing can yield an actionable diagnosis in pediatric patients with unexplained liver disease, according to an abstract presented at the 54th Annual Meeting of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition in Copenhagen, Denmark. 

Pediatric liver diseases often present with vague symptoms such as jaundice, coagulopathy, hepatosplenomegaly, and failure to thrive. The problem is that many liver diseases share these characteristic features, making it a challenge for physicians to accurately associate these symptoms with a particular diagnosis.

“Despite the several laboratory tools, the rate of indeterminant cases remains approximately 30 percent,” the authors of the study wrote.

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This can be regrettable, considering that an accurate diagnosis is often the catalyst for the prescription of a treatment regime tailored according to the patients’ needs. A proposed method to diagnose vague liver presentations is to employ the use of genetic analysis.

The research team collected data from patients with liver disease who were followed up at a pediatric gastrointestinal and hepatology clinic between 2018 and 2021 (n=81). Genetic data were investigated using either whole-exome sequencing or targeted gene sequencing.

Of the 81 patients recruited for this study, the genetic diagnosis was possible in 64 (79%) of them. A total of 48 patients underwent whole-exome sequencing and 33 had targeted gene sequencing.

“In general, the most common mutations causing liver diseases were linked with familial progressive intrahepatic cholestasis (PFIC), Alagille syndrome, and [neuroblastoma amplified sequence gene mutations],” the authors said. 

Read more about Alagille syndrome overview

The researchers proposed that further studies include a larger cohort of patients and investigate the possibility of establishing a molecular diagnostic flowchart for genetic liver diseases. A molecular diagnostic flowchart for this purpose may eliminate the need for unnecessary laboratory investigations and liver transplantations and make healthcare for patients with liver pathology more streamlined and efficient.


Naomi F, Mizikoğlu O, Ceylaner S, Arikan C. Diagnosing yielding of genetic testing in children with undetermined liver disease. Poster presented at: 54th Annual Meeting of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition: June 22-25, 2022; Copenhagen, Denmark.