Occult hepatitis C virus infection: what does it mean?

Occult hepatitis C virus infection (OCI) is a recently identified entity of which the existence became evident when nucleic acid amplification assays of enhanced sensitivity were introduced for the detection of hepatitis C virus (HCV) genome and its replication. This form of HCV infection has been found to persist in the presence of antibodies against HCV and normal levels of liver enzymes for years after spontaneous or antiviral therapy-induced resolution of hepatitis C and, therefore, can be termed as secondary OCI. HCV RNA in OCI circulate at fluctuating levels normally not exceeding 200 genome copies per millilitre of serum or plasma, while low levels of virus genome and its replicative intermediate RNA-negative strand are detectable in the liver and, importantly, immune cells, which provide an opportunity to detect active virus replication without the need for acquiring a liver biopsy. In addition to secondary OCI, a form of OCI accompanied by persistently moderately elevated serum liver enzymes in the absence of antibodies to HCV, which can be termed as cryptogenic OCI, has also been described. The current understanding of the nature and characteristics of OCI, methods and pitfalls of its detection, as well as the documented and expected pathological consequences of OCI will be summarized in this review.