Researchers identified a 14-gene expression pattern that predicted transplant-free survival for 2 years in pediatric patients with biliary atresia, according to a study published in Gastroenterology.
Zhenhua Luo, from the University of Cincinnati College of Medicine, and colleagues explained that, while there have been advances in understanding the key factors relevant to etiology and pathogenesis of biliary atresia, the only treatment is hepatoportoenterostomy. This treatment may restore bile drainage in some patients but does not stop fibrosis progression.
“Despite the association of young age with treatment response, age alone does not predict clinical outcome nor correlates reliably with liver histological scoring or transcriptional profiles,” they wrote. “With substantial variability in clinical course, the discovery of predictive biomarkers at the time of diagnosis would be invaluable to the field by enabling the customization of treatment protocols and the stratification of patients into clinical trials.”
In search of predictive biomarkers, Luo and colleagues analyzed liver biopsies from 171 patients aged 2 years, who were either a part of a discovery cohort (n = 121) or validation cohort (n = 50).
The 14-gene pattern that correlated with survival in the discovery group was reproducible in the validation cohort. After patients were further separated into low survival and high survival groups, analyses showed younger patients in both the high survival discovery (P = .0001) and validation groups (P = .034) and a higher degree of fibrosis in the low survival discovery (P = .0039) and validation groups (P = .016).
Multivariate analysis confirmed that the 14-gene signature (HR = 2.2; 95% CI, 1.4-3.6) along with persistent elevation of TB at 3 months after HPE (HR = 1.2; 95% CI, 1.12-1.29) were risk factors for low survival in the discovery group with similar findings in the validation group.
“In these patients, fibrosis may represent a later stage of liver disease that may not be uniformly correlated with the age at diagnosis, or it may represent a rapid fibrosis program that is poorly understood and limited to a subgroup of patients,” the researchers wrote. “A potential application of the 14-gene signature is to guide clinical trials or the development of new care protocols that take into account the most prominent biological processes at the time of diagnosis.” – by Talitha Bennett
Disclosure: The authors report no relevant financial disclosures.