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Bilirubin (BR), the final breakdown product of heme, is primarily considered to be a toxic waste product but has recently been considered to be an immunomodulatory metabolite. Through mechanisms that include intracellular signaling and transcriptional control, BR affects those immune cell functions that regulate cell proliferation, differentiation and apoptosis. During the pathogenesis of viral hepatitis, the heme degradation pathway is disrupted, resulting in changes to normal BR concentrations. These alterations have been previously studied mainly as a consequence of the infection. However, little is known about the potential immunomodulatory role played by BR in the development of infectious hepatocellular diseases. Differences in BR levels in the context of viral hepatitis are likely to provide important insights into the metabolite\u2010mediated mechanisms controlling the immune responses underlying both the long\u2010term persistence of hepatitis C virus (HCV) infection and the resolution of hepatitis A virus (HAV) infection during the acute phase. In this review, the cross\u2010talk between heme catabolism and immune function is described in detail. Special emphasis is given to discoveries that hold promise for identifying immunologic features of metabolic products in the resolution of viral diseases.<\/jats:p>","DOI":"10.1038\/cti.2015.37","type":"journal-article","created":{"date-parts":[[2015,12,11]],"date-time":"2015-12-11T08:21:24Z","timestamp":1449822084000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Rethinking the immune properties of bilirubin in viral hepatitis: from bench to bedside"],"prefix":"10.1002","volume":"4","author":[{"given":"Karla F","family":"Corral\u2010Jara","sequence":"first","affiliation":[{"name":"Unidad de Inmunovirolog\u00eda, Servicio de Biolog\u00eda Molecular en Medicina, Hospital Civil de Guadalajara \u2018Fray Antonio Alcalde\u2019  Guadalajara Mexico"},{"name":"Departamento de Biolog\u00eda Molecular, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara  Guadalajara 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