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Infection with hepatitis C virus (HCV) is a global health problem with more than 80% of those infected developing chronic hepatitis C (CHC) that tends to advance to liver cirrhosis and hepatocellular carcinoma. It is estimated that up to three-quarters of HCV-infected individuals are neither diagnosed nor aware that they are infected, and symptomatic liver damage may not appear for years or decades in many patients following virus exposure. The pathogenic and epidemiological significance of HCV could be further magnified by the existence of occult HCV infection (OCI), evidenced by small quantities of HCV RNA in plasma (usually below 100 virus genome copies/ml), liver and/or peripheral blood mononuclear cells (PBMCs), continuing in the context of essentially normal liver function tests after self-limited or therapeutically induced resolution of hepatitis C and OCI in which carriage of HCV RNA traces coincide with moderately elevated liver enzymes of unclear aetiology.1 Although HCV is conventionally known to target hepatocytes, a large and increasing body of experimental and clinical data provides cumulative, hence not yet commonly acknowledged evidence that HCV also propagates at extrahepatic locations, particularly in cells of the immune system.2 3
HCV is a positive single-stranded RNA virus of the Flaviviridae family that demonstrates remarkable genetic variability and typically exists in an infected host as a heterologous population of closely related quasispecies resulting from virus rapid replication driven by …