Studies suggest that HCV may be able to replicate in the brain, and HCV has been associated with cognitive impairment independently of hepatic compromise. HCV viral load can be measured in the blood and CSF. HCV can cause cognitive impairment in the absence of systemic illness, elevated liver enzymes, or liver failure, and there appears to be an additive effect of HCV and HIV on cognitive dysfunction (86–88). Several studies have shown HCV infection to be a predictor of impairments in learning, abstraction, and motor skills in the HIV-negative population as well (77, 89, 90). In one study, 46% of HIV-positive/HCV-positive patients met criteria for HIV-associated dementia, as opposed to 10% of HIV-positive/HCV-negative patients; however, 45% of HIV-positive/HCV-negative patients met criteria for minor cognitive-motor disorder, as opposed to 23% of HIV-positive/HCV-positive patients (30). In advanced HCV disease, increasing ammonia levels can also lead to CNS impairment, usually reversible with appropriate treatment (77, 91).

Psychiatrists are often asked to evaluate patients who have a current episode or history of mood disorders before the initiation of treatment for HCV. Depression is the most common side effect of interferon treatment with ribavirin for HCV infection. Current evidence of the value of antidepressant treatment in the non-HIV population suggests that antidepressant medication should be continued in those already being treated for depression and should be considered as prophylaxis in those with a prior history of depression (92, 93). A double-blind, randomized, controlled trial of 40 patients with malignant melanoma who received interferon treatment suggested that prophylactic treatment with paroxetine is an effective strategy for minimizing depression induced by interferon (94). A small open-label study suggested citalopram may be effective for depression in patients with HCV infection (95).