The article details a study on the pathogenesis of systemic rotavirus (RV) infection and biliary atresia (BA) in neonates, highlighting a critical role for the hepcidin-iron axis. The authors, Xu et al., explain that RV infection triggers persistent Type I Interferon (IFN-I) signaling, which upregulates hepcidin in liver macrophages (specifically TREM2+ macrophages) and hepatocytes. This dysregulation impairs iron export, leading to systemic iron overload and subsequent ferroptosis-mediated tissue damage in the liver and intestines. Critically, the study demonstrates that folic acid (FA) supplementation targets this pathway, mitigating liver injury in RV-infected mice and showing promising clinical results—including reduced cholangitis and lower liver transplantation rates—in a clinical trial involving infants with BA.

References:

• Xu Y, Chen X, Fang R, et al. A dysregulated hepcidin-iron axis impairs antiviral immunity and induces lethal liver pathology in neonates[J]. Immunity, 2025.