The effects of hepatitis C, HIV, and methamphetamine dependence on neuropsychological performance: biological correlates of disease

Letendre, Scott La; Cherner, Marianab; Ellis, Ronald Jc; Marquie-Beck, Jenniferc; Gragg, Bryanb; Marcotte, Thomasb; Heaton, Robert Kb; McCutchan, J Allena; Grant, Igorb; the HNRC Group

Section II: Neurocognitive and neuropsychological studies

Objective: To determine the effects of hepatitis C virus (HCV) infection on neuropsychological (NP) performance.

Design: Cross-sectional analysis of a prospectively enrolled cohort.

Methods: A total of 239 HIV-seropositive and 287 HIV-seronegative subjects enrolled in prospective cohort studies at a single center. Subjects underwent standardized assessments, including comprehensive neuropsychological testing, substance use inventory neuromedical examination, venipuncture, and lumbar puncture. HCV antibody was measured in serum. In seropositive individuals, HCV RNA was measured in plasma and cerebrospinal fluid (CSF).

Results: HCV-seropositive subjects performed worse on neuropsychological testing and were almost twice as likely to be diagnosed as globally impaired, compared with those who were HCV seronegative. In a multivariate analysis, HCV, HIV, and methamphetamine dependence were independently associated with worse performance, even after adjusting for Centers for Disease Control stage and antiretroviral use. HCV-RNA levels in plasma were higher in those with memory, but not global, impairment. In cerebrospinal fluid, HCV RNA was below 100 copies/ml in all specimens. In HIV-infected subjects, HCV was associated with higher levels of HIV RNA in CSF, but not in plasma. HCV was also associated with higher levels of monocyte chemotactic protein 1, TNF-α, and soluble TNF receptor II. HCV-seropositive subjects did not appear to have advanced liver disease.

Conclusions: HIV, HCV, and methamphetamine independently injure the central nervous system, leading to global neuropsychological impairment. HCV may injure the brain by viral or immune-mediated mechanisms. HCV-associated brain injury may be preventable or reversible because HCV infection is potentially curable.

From the aDepartments of Medicine


cNeurosciences, University of California San Diego, San Diego, CA, USA.

Correspondence to Scott Letendre, MD, University of California San Diego, 150 West Washington Street, San Diego, CA 92103, USA. fax: +1 619 543 1235; e-mail:

© 2005 Lippincott Williams & Wilkins, Inc.