Hepatitis C virus infection is associated with reduced white matter N-acetylaspartate in abstinent methamphetamine users

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Abstract
Nearly 3,000,000 people in the United States, and over 100,000,000 people worldwide, are infected with hepatitis C virus (HCV), with an increasing trajectory for the foreseeable future (Alter et al., 1999). While hepatic encephalopathy has been long recognized as a disorder associated with cerebral structural, metabolic, and cognitive changes (e.g., Tarter et al., 1989), HCV infection itself is increasingly associated with changes in the brain, even in the absence of hyperammonemia. Specifically, HCV-infected individuals may have deficits in cognitive functions such as attention, working memory, and speed of information processing (Forton et al., 2002; Hilsabeck et al., 2002). They may also have abnormalities on magnetic resonance spectroscopy (MRS), a non-invasive method to measure cerebral metabolites. The most reliably measured compounds using a standard 1.5 Tesla MRI scanner are N-acetylaspartate (NAA), a marker of neuronal integrity; choline and choline-containing compounds (Cho), a measure of cell membrane turnover and lipid changes; myo-Inositol (Ins), a possible indicator of glial proliferation and/or osmolar changes; and creatine+phosphocreatine (Cr), an indicator of high energy stores that is often used as a relative standard for other metabolites. In the first studies of HCV using MRS, Forton et al. (2001; 2002) found elevated Cho/Cr in the frontal white matter and basal ganglia in patients with HCV. In addition patients with two or more impaired neuropsychological test performances had higher Cho/Cr compared to those with less than two impaired test performances.Dr. Erin D. Bigler served as Action Editor during the course of this review.