Cerebral Effects of Pegylated Interferon in Hepatitis C Positive Subjects

Subjects with non-cirrhotic hepatitis C will have a magnetic resonance imaging (MRI)/magnetic
resonance (MR) spectroscopy and neuropsychological testing prior to starting interferon.
Subjects will have repeat testing following 12 weeks of interferon therapy and again at 12
weeks post interferon therapy.

MR spectroscopy (MRS) will measure the cerebral metabolites, NAA (N-acetyl aspartate), Cho
(choline), MI (myoinositol) and Cr (creatine) at 3 distinct brain regions, i.e. basal ganglia
and 2 locations within the frontal cortex.

Neuropsychological testing will include tests of the following cognitive domains: executive
functioning, memory, language, motor skills and will also include questionnaires pertaining
to quality of life (SF-36), mood (Beck's depression inventory) and a self-rating cognitive
questionnaire (Conners' Adult Attention Deficit Hyperactivity Disorder Rating Scales
[CAARS]).

Control subjects will include non-cirrhotic HCV subjects who are not taking interferon
therapy.

Inclusion Criteria:

- Adults (>18 years old) of both sexes with chronic HCV infection (all genotypes).

- Subjects due to start treatment with pegylated interferon-alpha (IFN-a) for HCV
eradication.

- Subjects with chronic hepatitis C who have elected not to be treated with
pegylated-IFN-a

- Subjects with mild fibrosis on liver biopsy (stage 0-III/IV fibrosis)

- Subjects able to give informed consent.

- Subjects with controlled depression currently taking anti-depressant medication.

Exclusion Criteria:

- Subjects with cirrhosis on liver biopsy.

- Subjects with active alcohol or drug abuse.

- Subjects co-infected with human immunodeficiency virus (HIV).

- Subjects with structural brain abnormality, past history of cerebrovascular accident
(CVA) or serious head trauma.

- Subjects with seizure disorder.

- Subjects with any contraindication to IFN therapy.

- Subjects with a poor command of the English language.

- Subjects with a contraindication to MRI, e.g. pacemaker, claustrophobia.