Neurocognitive disorders in patients with chronic hepatitis C: effects of extrahepatic viral replication and immune activation

Hepatitis C virus (HCV) infection is widespread in the world - the number of infected people is estimated at 170 million. About 50% of infected people complain of chronic fatigue, depression, difficulties with concentration, and impaired neurocognitive function. These symptoms are independent of both the degree of liver damage and the level of viral replication. HCV was long considered an exclusively hepatotropic virus, but there is now strong evidence that it is also lymphotropic and that it grows in peripheral blood mononuclear cells (PBMCs), among others. Posthepatic HCV replication can have serious clinical implications: infected leukocytes that cross the blood-brain barrier transmit the infection to the central nervous system (CNS). Hypothesis. Our general hypothesis is that HCV infects PBMCs, particularly monocytes / macrophages, and that infected cells cross the blood-brain barrier. Being in the CNS, they release pro-inflammatory cytokines that cause functional changes manifested by depression and neurocognitive disorders. The hypothesis predicts that the immune activation state of PBMCs correlates with the severity of these disorders. Moreover, the mere presence of HCV replication in PBMCs may indicate possible brain infection and may correlate with neurocognitive disorders and depression. The current project aims to investigate the relationship between HCV replication in PBMC and the activation status of these cells, and neurocognitive disorders in patients with chronic hepatitis C.