Does Acute Hepatitis C Infection Affect the Central Nervous System in HIV-1 Infected Individuals?

A. Winston; L. Garvey; E. Scotney; D. Yerrakalva; J. M. Allsop; E. C. Thomson; V. P. B. Grover; J. Main; J. I. Cox; M. Wylezinska; S. D. Taylor-Robinson


J Viral Hepat. 2010;17(6):419-426. 

In This Article


The study protocol was approved by the Wandsworth Ethics Committee, UK (07/H0803/128), and all subjects involved in the study provided written informed consent.

Patient Selection and Study Procedures

Patients attending St. Mary's Hospital, London, UK, for HIV care were eligible for inclusion in the study. Subjects were assigned as cases (chronic HIV and acute HCV, group 1) or HIV-infected controls (chronic HIV infection with no evidence of hepatitis C infection, group 2). Chronic HIV-1 infection was defined as HIV-1 antibody positive for at least 6 months. Acute HCV infection was defined as a positive HCV-RNA by polymerase chain reaction (PCR) testing, with either a previously negative HCV-RNA PCR test or a previous negative HCV antibody and normal liver function tests within the past 8 months. A further control group of hospital staff without evidence of HIV or HCV infection was also recruited (group 3).

Exclusion criteria for all subjects included: commencing or undergoing any changes to ART in the past 3 months, current or recent use of antidepressant or antipsychotic therapies (past 12 weeks), hepatitis B infection (hepatitis B surface antigen positive), recent significant head injury, established dementia, current or recent history of alcohol or recreational drug dependence, active opportunistic infections, untreated early syphilis, or evidence of established chronic liver disease, cirrhosis or hepatic encephalopathy. Furthermore, in the 48-h period prior to the start of study investigations, consumption of alcohol or caffeine was not permitted.

Study procedure involved undergoing neurocognitive testing (group 1) and cerebral MRS (all groups) on one occasion.

Cognitive Testing

A computerized cognitive test battery (CogState™, Melbourne, Australia) which has been previously validated in HIV-1 infected subjects[24] was undertaken. Group 1 participants completed one full practice test before undertaking the study examination to obtain optimal performance at baseline.[25] The following domains were assessed: associate learning, detection identification, congruent reaction, monitoring and one card learning.

Control data for cognitive testing were obtained from a separate cohort of HIV-1 infected, age-matched subjects with no evidence of HCV infection, who were on stable ART and had undergone identical neurocognitive testing previously.

Cerebral 1H Magnetic Resonance Spectroscopy

Proton magnetic resonance spectroscopy (1 H-MRS) was performed on an Achieva™ 1.5 Tesla scanner (Phillips, MR Systems, Best, the Netherlands) at the Robert Steiner Magnetic Resonance Unit, Hammersmith Hospital, London, UK. Examination began with sagittal, coronal and axial T1-weighted MR images of the brain to enable accurate positioning of the voxels, and T2-weighted axial double spin echo images to exclude any visible cerebral pathology.

The proton magnetic resonance spectroscopy (1 H-MRS) was performed in three voxel locations: right FWM, mid-frontal grey matter (FGM) and the right basal ganglia (RBG) (Fig. 1). MRS data were acquired by single voxel examination in the three areas using a double spin echo point resolved spectroscopy sequence with the following settings: echo time, 36 ms; repetition time, 3000 ms; 2048 data points; spectral width of 2500 Hz and 128 data acquisitions. Spectra were post-processed using the MRI machine manufacturer's software for automated water signal suppression and water shimming. Each examination lasted approximately 35 min. The magnetic resonance images were studied and reported by an experienced neuroradiologist.

Figure 1.

Volumes of interest: (a) right frontal white matter; (b) mid-frontal grey matter; (c) right basal ganglia.

All spectra were analysed and quantified by one observer (ES) using a Java-based version of the magnetic resonance user interface package (jMRUI Version Number: 3.0),[26] incorporating the AMARES algorithm[27] and expressing metabolites as ratios to cerebral creatine (Cr).

Statistical Methods

All statistical calculations were performed using SPSS (version 12.0; SPSS Inc., Chicago, IL, USA). Between-group differences in cerebral metabolite ratios were evaluated in a univariate model by linear regression (study group 1 vs 2 vs 3). Where significant associations were observed, factors associated with these ratios were also assessed in univariate models. Potential factors included patient baseline characteristics such as age (years), current and nadir CD4+ lymphocyte count, plasma HIV RNA (detectable vs undetectable), time since HIV diagnosis (years), alanine aminotransferase (IU) and plasma HCV viral load (copies/mL).

Between-group differences in the five neurocognitive domains tested were assessed as described above, with calculation of effect size.[28] Where significant associations were observed, potential associated factors were assessed with respect to cerebral metabolite ratios, using the statistical methodologies described above.

Variables with a skewed distribution were logarithm transformed and parameters with a P-value below 0.05 were considered significant.


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