Fewer than half of children with Alagille syndrome reach adulthood with the liver they were born with, a large international cohort study found. Researchers also found that total bilirubin levels of less than 5 mg/dL in patients aged 6 months to 1 year are associated with better hepatic outcomes. 

In the study, published in Hepatology, a team of researchers from the Global ALagille Alliance (GALA) Study Group explored the natural history of liver disease in a cohort of children with the disease. Most of the data regarding outcomes in Alagille syndrome are derived from tertiary centers, and real-world data are scarce. 

The researchers retrospectively analyzed the native liver survival and event-free survival rates of 1433 children with clinically and/or genetically confirmed Alagille syndrome who were born between January 1997 and August 2019.


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They reported that the 10- and 18-year native liver survival rates of the patients were 54.4% and 40.3%, respectively.

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By the age of 10 years, 51.5% of the children had experienced at least 1 adverse liver-related event such as clinically evident portal hypertension, liver transplant, or death. By the age of 18 years, this ratio was 66%.

Children who had median total bilirubin levels between 5 and 10 mg/dL when aged 6 months to 1 year had a 4.1-fold increase in the risk of developing clinically evident portal hypertension compared to those with median total bilirubin levels below 5 mg/dL. The risk increased 8-fold if the levels were 10 mg/dL or higher.

These thresholds were also associated with 4.8- and 15.6-fold increased risks of liver transplantation, respectively.

Finally, median total bilirubin levels of less than 5 mg/dL were associated with higher native liver survival rates than median total bilirubin levels of 5 mg/dL or more.

“These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of novel therapies,” the authors of the study wrote.

Reference

Vandriel SM, Li LT, She H, et al; Global ALagille Alliance (GALA) Study Group. Natural history of liver disease in a large international cohort of children with Alagille syndrome: results from the GALA study. Hepatology. Published online August 29, 2022. doi:10.1002/hep.32761