title: The effects of hepatitis C, HIV, and methamphetamine dependence on neuropsychological performance: biological correlates of disease.
abstract: OBJECTIVE
  To determine the effects of hepatitis C virus (HCV) infection on neuropsychological (NP) performance.
  
  
  METHODS
  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-alpha, 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.
authors.affiliation: Department of Medicine, University of California San Diego, CA 92103, USA. sletendre@ucsd.edu
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
authors.forename: Mariana
authors.initials: M
authors.lastname: Cherner
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: Jennifer
authors.initials: J
authors.lastname: Marquie-Beck
authors.forename: Bryan
authors.initials: B
authors.lastname: Gragg
authors.forename: Thomas
authors.initials: T
authors.lastname: Marcotte
authors.forename: Robert K
authors.initials: RK
authors.lastname: Heaton
authors.forename: J Allen
authors.initials: JA
authors.lastname: McCutchan
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
mesh_terms: D000328:Adult; D003072:Cognition Disorders / Q000209:etiology* / Q000276:immunology / Q000821:virology; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000523:psychology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D016174:Hepacivirus / Q000502:physiology; D006526:Hepatitis C / Q000150:complications / Q000276:immunology / Q000523:psychology* / Q000821:virology; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D008297:Male; D008694:Methamphetamine; D008875:Middle Aged; D009483:Neuropsychological Tests; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D019966:Substance-Related Disorders / Q000150:complications / Q000523:psychology*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D008694:Methamphetamine