Occult Hepatitis C Virus Infection: A Narrative Review

Hepatitis C virus (HCV) infections occur worldwide. Approximately 75% of these acute infections lead to chronic hepatitis C with few symptoms, at least during the initial phase of infection. Occult hepatitis C develops in some infected patients. These infections are defined by the presence of HCV RNA in hepatocytes and peripheral blood mononuclear cells (PBMCs) but not in the serum. Some of these patients have negative tests for anti-HCV antibodies, which make them very difficult to detect. These patients have been identified throughout the world. Occult infections have been found more frequently in patients with hepatitis B infection, HIV infection, cryptogenic liver disease/cirrhosis, renal failure on haemodialysis and lymphoproliferative disorders. These infections have also been identified in blood donors who have negative HCV antibodies. Low-level viral replication in the liver likely contributes to ongoing liver damage and the release of infectious virions that potentially infect adjacent hepatocytes and extrahepatic sites, such as PBMCs. Studies indicate that occult HCV infection may contribute to the pathogenesis of cryptogenic liver disease, steatotic liver disease, cirrhosis and hepatocellular carcinoma and could cause relapses following either a spontaneous clearance of the virus or treatment-induced clearance of the virus. These infections present diagnostic difficulties. This virus is present in the liver; however, that would require a liver biopsy to demonstrate this. It is also present in PBMCs, but these cells are not usually used during routine patient evaluation. The development of quasispecies, which can be identified in PBMCs by specialised labs, helps explain ineffective host defence responses and antiviral drug treatment in some patients. There is no specific therapy for the treatment of this sub-group of HCV-infected patients, and treatment should start with direct-acting antiviral drugs with careful follow-up and serial testing for viral clearance. In summary, patients with occult HCV need more study to determine the role of these infections in the progression of liver disease, to improve diagnostic algorithms and to determine treatment protocols that can eliminate these low-level infections.