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Background: Hepatitis C Virus (HCV) is widely prevalent in Egypt. There is an evidence of neurocognitive dysfunction even in the absence of advanced liver disease in patients with chronic HCV infection. The patients are more likely to manifest impairments in the quality of life, fatigue, and depression than patients with liver disease of other etiology. Objective: The work aimed to study the impact of HCV infection on cerebral functions using cerebral Magnetic-Resonance Spectroscopy (MRS). Patients and Methods: The study included two groups; A patients' group composed of 20 chronic, drug-naïve HCV patients and a control group composed of 20 healthy subjects. MRS and Psychometric assessment were done including Mini-Mental State Examination (MMSE), Fatigue Severity Scale (FSS) and 17-Item Hamilton Depression Rating Scale (HDRS). Results: Chronic HCV patients scored worse on both FSS and 17- Item HDRS than Controls, and showed an altered spectroscopic metabolic ratio along white matter at the level of the centrum semiovale bilaterally. The choline/creatine, ratios and N-acetyl aspartate/creatine ratios were significantly higher in the white matter of the patients compared to healthy volunteers. There was a positive correlation between abnormal spectroscopic findings and the severity of fatigue and depression. Conclusion: The altered cerebral metabolism in patients with chronic hepatitis C infection (with preserved liver functions) suggested that HCV may exert a direct effect on brain function. [ABSTRACT FROM AUTHOR]