736 EVIDENCE OF NEUROINFLAMMATION IN PATIENTS WITH CHRONIC HEPATITIS C: A CEREBRAL POSITRON EMISSION TOMOGRAPHY (PET) STUDY

Aims:We sought to determine whether the neuropsychological symptoms and cognitive impairment experienced by patients with chronic hepatitis C (HCV) are associated with cerebral neuroinflammation using a PET ligand for microglial activation, [11C](R)-PK11195.Methods: 11 subjects (6F; 5M, mean [range] age 52 [46-63] yr) with biopsy-proven mild HCV were studied using cerebral PET and MRI.Mode of HCV acquisition was intravenous drug use in 6 subjects, none had used illicit drugs within 10 years of the study.Patients were assessed with the fatigue impact score (FIS) and psychometric tests: conventional paperand-pencil and a computer-based Cognitive Drug Research (CDR) battery.For PET studies, a selective in vivo marker of activated microglia/brain macrophages, [11C](R)-PK11195, was used with 10 healthy volunteers as controls.Binding potentials (BP), measuring specific binding of the tracer (Bmax/Kd), were calculated on a voxel-by-voxel basis using a simplified tissue model.Cluster analysis was performed for extraction and identification of normal reference input functions.Volumes of interest within the basal ganglia and cerebral cortex were defined on MRI.BP values were extracted using ANALYZE software.Mann-Whitney test was used to define differences between patients and controls, Spearman's rank correlation to test for correlations, using SPSS.Results: There was a significant increase in the BP of [11C](R)-PK11195 in the caudate of mild HCV patients, compared to controls (0.12±0.013 versus 0.08±0.008,mean±SE, P = 0.03).The increase in BP was more significant in the subgroup of 8 patients with genotypes 1 and 4 HCV (0.13±0.03 versus 0.08±0.008,P = 0.01).The thalamic BP was also increased in this subgroup (0.41±0.03 vs 0.31±0.02,P = 0.03).However, there was no correlation with fatigue status or psychometric performance.Conclusions: Our study demonstrates microglial activation in the brains of patients with mild HCV.These findings provide further evidence for a direct neurotropic role for HCV, supported by previous studies isolating viral variants from post-mortem brains of HCV-infected patients.The basal ganglia are involved in learning and memory processing.Thus, some of the affective and cognitive abnormalities that HCV patients experience could be explained by our findings.