Occult HCV

General Characteristics of Occult HCV Persistence

"Individuals with occult HCV infection usually have normal serum liver enzymes and most of them are reactive for anti-HCV antibodies. These individuals could have a history of resolved CHC due to antiviral therapy, spontaneous recovery from hepatitis C or asymptomatic exposure to HCV. Low levels of HCV RNA have also been detected in a significant portion of patients with persistently elevated liver enzymes of unknown etiology who were anti-HCV antibody nonreactive.[43,58] The data gathered using highly sensitive assays show serum HCV-RNA positivity in the majority of persons with an SVR or after spontaneous recovery from hepatitis C in those who were repeatedly negative for HCV RNA by standard clinical assays. In our studies applying nested RT-PCR/NAH, more than 80% of these individuals followed for up to 7 years were serum HCV-RNA-positive, usually at levels not exceeding 102 vge/ml. Also, on average, approximately 30% of these people carried HCV RNA in naive (mitogen unstimulated) peripheral lymphoid cells at levels between 10 and 104 vge/107 cells.[6,10] However, when the same cells, including those apparently negative for HCV RNA, were treated ex vivo with mitogens, HCV RNA was detected in essentially all of the individuals.[6,9,10] Expression of HCV-RNA-negative strand was detected in up to 60 and 75%, of naive and mitogen-treated PBMCs reactive for the virus-positive strand, respectively.[10] Furthermore, the most recent investigation of six individuals with occult HCV infection documented HCV replication in isolated, mitogen-stimulated CD4+ and CD8+ T cells and/or in untreated B cells or monocytes from all individuals [Pham et al., Unpublished Data]. Interestingly, CD4+ T cells most frequently expressed HCV-RNA-negative strand.

In addition to consistent identification of HCV-RNA in lymphoid cells, HCV-RNA has also been detected in the liver tissue of individuals with occult infection with an SVR.[7,8,59] These individuals generally exhibit histologically evident improvement after IFN-α/ribavirin therapy, including partial regression of fibrosis. Nonetheless, liver biopsies from some of these patients show evidence of persistent minimal to moderate inflammation and even occasional, active mild chronic hepatitis.[7,8,59]

It has been shown that occult HCV infection is frequently accompanied by HCV-specific T-cell proliferative reactivity[60] and that individuals convalescent from hepatitis C demonstrate vigorous and multispecific T-cell proliferative and cytotoxic responses against HCV antigenic epitopes for decades after recovery .[61,62] It has been hypothesized that, as in occult HBV infection,[2,63] the presence of low amounts of the replicating virus could provide continuous antigenic stimuli beneficial to immunocompetent individuals in maintaining an active antiviral immune response and keeping the occult infection under control. This response, albeit seemingly sufficient to defend the host against severe pathological consequences, is not able to completely eradicate the virus. This could be a consequence of the fact that the virus replicating in the cells of the immune system is largely shielded from immune elimination."

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See:  Molecular Diagnosis of Occult HCV and HBV Infection @
http://www.medscape.com/viewarticle/563337_1

Mike