Researchers identified fibrogenesis-associated proteins and molecular pathways that could be potential biomarkers for pediatric cholestatic liver diseases such as Alagille syndrome (ALGS), alpha-1 antitrypsin deficiency (AATD), and biliary atresia.

“These proteins have predicted origins and hallmarks that suggest the importance of epithelial to mesenchymal transition possibly implicating the relevance of mesothelial cells in the fibrogenesis of pediatric cholestasis,” the researchers wrote in the abstract. The study will be presented at this year’s The Liver Meeting® in November.

Proteome analysis of plasma samples from pediatric patients with cholestatic liver diseases revealed many proteins correlated to liver stiffness, including 6000 in ALGS, 600 in AATD, and 3000 in biliary atresia. ALGS exhibited the most distinct proteome, while the overall composition of the AATD and biliary atresia proteome was similar.

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Bioinformatic analysis identified the epithelial-to-mesenchymal transition as a central pathway for pediatric cholestatic liver diseases, being the most enriched pathway of the 3 diseases. Complement and apical junction pathways were also correlated with liver stiffness in biliary atresia.

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Median areas under the curve (AUCs) for predicting liver stiffness measurement less than 7 kPa were 0.67 in ALGS, 0.50 in AATD, and 0.76 in biliary atresia, whereas median AUCs for predicting liver stiffness measurement greater than 12 kPa were 0.71 in ALGS, 1.0 in AATD, and 0.95 in biliary atresia.

Moreover, the researchers identified a module of 92 proteins that were highly correlated with liver stiffness in biliary atresia. Relevant proteins associated with biliary atresia were inferred to have mesenchymal, endothelial, and mesothelial origin.

The study included 46 participants with ALGS, 31 with AATD, and 93 with biliary atresia who were enrolled in another study evaluating the role of a noninvasive technology in detecting and quantifying liver fibrosis (FORCE, NCT02922751). These patients generally had compensated liver disease, and about 20% had thrombocytopenia. Mean liver stiffness measurement was 14 kPa.


Shneider BL, Kanchi R, Grimm SL, et al. The plasma proteome in pediatric cholestasis reveals biomarkers of liver stiffness and suggests a role for epithelial-to-mesenchymal transition in fibrinogenesis. Hepatology. 2022;76(S1):S202-S203.