Occult infection with hepatitis C virus: friend or foe?

Hepatitis C virus (HCV) infection is a global pandemic associated with a growing disease burden due to cirrhosis and the consequent morbidity and mortality. Transmission is largely via blood-to-blood contact. Following primary infection, a minority of individuals clear the infection predominantly via cellular immune mechanisms, whereas the majority become chronically infected. Recent data suggest that a third outcome may also be possible, termed 'occult' infection in which subjects who are known, or suspected to have previously been infected with HCV, no longer have viral RNA in their serum at levels detectable by sensitive commercial assays, but do have virus detected by ultra-sensitive techniques. Occult infection has also been detected in peripheral blood mononuclear cells, which may indicate an extra-hepatic reservoir of the virus. Although the clinical significance of occult infection remains unknown, most authors have raised concerns of recrudescent infection. Here we critically review the published literature, suggest further avenues of investigation and propose that occult infection may be beneficial to the host by maintaining immunological memory to protect against reinfection. Immunology and Cell Biology (2012) 90, 763-773; doi:10.1038/icb.2012.20; published online 1 May 2012