Neurological and psychiatric effects of hepatitis C virus infection

Hepatitis C virus (HCV) infection is widespread and affects 71 million people worldwide. Although hepatic manifestations are the most frequent, ranging from chronic hepatitis to cirrhosis and hepatocellular carcinoma, it is also associated with several extrahepatic manifestations. Infected patients may present nonspecific neurological symptoms, regardless of the presence of liver cirrhosis. Several pathogenetic mechanisms underlying neurological symptoms have been hypothesized: Neuroinvasion, immune-mediated damage, neurotransmitter alterations and cryoglobulinemia. Alterations of the central nervous system include cerebral vasculopathy, acute or subacute encephalopathy and inflammatory disorders. HCV infection may be responsible for neuropathies, of which the most frequent form is symmetrical axonal sensory or sensory-motor polyneuropathy which causes loss of leg sensitivity and weakness. Up to 50% of patients with HCV infection may experience cognitive decline and psychological disorders, such as depression and fatigue. HCV associated neurocognitive disorder is independent of the presence of liver cirrhosis and affects different domains than in patients with hepatic encephalopathy. It can be studied using specific tests that mainly explore executive functions, verbal learning and verbal recall. These disorders significantly reduce the quality of life. The new antiviral therapies improve the extrahepatic symptoms of HCV infection and their success depends on the achievement of sustained virological response. However, the effect of therapy may differ depending on the type of organ involved; neurological symptoms can be irreversible if there is organic liver damage. The aim of this review is to provide a critical overview of physiopathological mechanisms, diagnostic and therapeutic strategies of the neurological and psychiatric effects of HCV infection.