Introduction

Cerebral dysfunction in HCV positive patients treated with pegyalated IFN (PIFN) has not been well characterized.

Aim

The aim of this study was to determine the cerebral metabolic and neuropsychiatric effects of PIFN in HCV positive subjects.

Materials and Methods

HCV positive subjects due to start a course of PIFN underwent an MRI and ¹H“MRS (spectroscopy) of the brain in addition to neuropsychological evaluation (neuropsychometric tests, Beck™s depression inventory, quality of life and self-reported cognitive dysfunction questionnaires), prior to, and 12 weeks following initiation of PIFN. MR studies were performed on a 3.0-T scanner (Signa, GE). MR spectra were acquired from the basal ganglia (caudate nucleus) and from the frontal gray and white matter. Concentrations of the neuronal metabolite N-acetyl aspartate (NAA), and the glial metabolites choline (CHO) and myoinositol (MI) were measured and expressed as a ratio of the control metabolite, creatine (Cr). Major exclusion criteria were cirrhosis, HIV co-infection, active alcohol or drug abuse, and gross white matter changes on baseline MRI.

Results

10 subjects have been enrolled in the study to date. Baseline NAA and MI were similar in all subjects, mean 1.45 (SD,0.27), and 0.72 (SD,0.15). Baseline CHO was higher in the basal ganglia and frontal cortex of subjects with a high viral load > 2 million IU/ml (0.95, 0.64) than in those with a low viral load < 2 million IU/ml (0.46, 0.23). NAA and MI remained relatively unchanged after 12 weeks of PIFN when compared to baseline values, whereas CHO concentration decreased after 12 weeks of PIFN and HCV viral clearance (mean change in basal ganglia 0.99 to 0.24, frontal cortex 0.64 to 0.25) Subjects demonstrated impairments in the cognitive domains of executive functioning, language skills and fine motor co-ordination but not attention and memory. Depression scores increased, QOL was reduced and all patients reported subjective complaints of cognitive difficulties (CAARS).

Conclusion

This study demonstrates neuronal preservation and reduced glial activation following 12 weeks of successful PIFN therapy and increases the evidence for HCV cerebral infection. However, HCV clearance is offset by cognitive decline and reduced QOL. Novel and neuroprotective agents may play a future role in preventing cognitive dysfunction during treatment with Pegulated Interferon.