{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:10:47Z","timestamp":1786122647234,"version":"build-2736575974"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Fulminant viral hepatitis (FVH) in children is a rare but often fatal form of acute liver failure occurring in the absence of preexisting liver disease. Its exceptional incidence during otherwise common viral infections, including hepatitis A virus (HAV), hepatitis B virus (HBV), and herpes simplex virus (HSV), supports a decisive role for host susceptibility. Recent advances in human immunogenetics delineate two major, mechanistically distinct pathways to pediatric FVH. The first reflects failure of immune regulation, culminating in excessive IFN-\u03b3\u2013driven inflammation and immune-mediated hepatocellular necrosis. Autosomal recessive IL-18BP and IL-10RB deficiencies exemplify this mechanism, in which disruption of key regulatory checkpoints permits uncontrolled activation of cytotoxic lymphocytes and macrophage-dependent immunopathology, particularly in the context of HAV infection. The second pathway involves impaired intrinsic antiviral defense, most prominently through neutralizing autoantibodies against type I interferons, which phenocopy genetic defects of IFN-I signaling and are strongly associated with HSV-triggered FVH; in this setting, inadequate early antiviral control enables unchecked hepatic replication with extensive cytopathic damage. Finally, syndromic hyperinflammatory disorders, including familial hemophagocytic lymphohistiocytosis and X-linked lymphoproliferative disease, broaden the spectrum of immune predisposition in which fulminant hepatitis may arise. Together, these discoveries redefine pediatric FVH as an immunopathological syndrome and provide a framework for targeted genetic and serologic diagnosis and for mechanism-based interventions aimed at improving survival.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1858895","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T11:16:37Z","timestamp":1786101397000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic and autoimmune predispositions to fulminant viral hepatitis in children"],"prefix":"10.3389","volume":"17","author":[{"given":"Mohamed","family":"Bousfiha","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Immunology, Infection and Autoimmunity, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University of Casablanca","place":["Casablanca, Morocco"]},{"name":"Department of Clinical Immunology and Pediatrics Infectious Diseases, Abderrahim El Harouchi 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