Supplementary file 1_Integrative transcriptomic and single-cell analysis reveals a convergent cholangiocyte-associated host inflammatory program in biliary atresia and SARS-CoV-2-associated hepatobiliary injury.docx

STAT1, ISG15, and CXCL10 were retained in the stringent core and remained central components of the interaction network. In COVID-19 liver single-nucleus data, donor-level analysis showed preferential localization of the shared signature to cholangiocytes, whose mean scores were significantly higher than those of all other hepatic cells combined (P = 0.00368). A similar pattern was observed descriptively in our BA single-nucleus dataset and further supported by an independent BA single-cell cohort.

Tissue immunofluorescence spatially associated pSTAT1, total STAT1, and ISG15 signals with KRT19-positive ductular structures, whereas CXCL10 was predominantly periductal. Poly(I:C) stimulation induced representative components of the program in cultured cholangiocytes. Computational analyses retained mefloquine among the top-ranked exploratory candidates.

Collectively, these findings support a convergent cholangiocyte-associated interferon/inflammatory host-response program in BA and SARS-CoV-2-associated hepatobiliary injury. They indicate molecular association rather than a common etiology or causal relationship and provide testable hypotheses for further investigation of biliary epithelial inflammatory responses.</p>