Hepatitis C Virus and the Brain
Hepatitis C Virus and the Brain
Recent studies have suggested that HCV infection is associated with inflammatory responses in the brain. The brain metabolites choline, creatine and inositol were significantly increased in HCV-infected patients compared with healthy controls, yet those patients with low levels of fatigue had higher levels of choline than those with severe fatigue. Nevertheless, these results suggest activation of microglia and possibly astrocytes in HCV-infected patients with fatigue. A recent study of treatment-naïve subjects with mild chronic HCV infection revealed microglial and brain macrophage activation using a combination of proton magnetic resonance spectroscopy and positron emission tomography (PET) with a ligand for neuroinflammation, which was not observed in HCV seronegative subjects. This immune activation was associated with HCV viraemia and altered cerebral metabolism, demonstrating altered basal ganglia myoinositol/creatinine and choline/creatine ratios in HCV-infected patients, putative biomarkers of glial cell inflammation and activation. This observation was reported in a group of 22 HCV-infected patients, of which 15 were treated with pegylated interferon and ribavirin, and seven were untreated HCV-positive controls. In the treated group, the patients who responded to therapy had lower cerebral metabolite measurements (reductions in choline and myoinositol) than non-responders or untreated controls, and the reduction in metabolites associated with improved neurocognitive performance. A further study of postmortem tissue demonstrated that brain tissue from HCV-infected subjects expressed significantly increased levels of proinflammatory cytokines IL-1, TNF-α, IL-12, and IL-18, which could explain glial cell activation reported in several studies. Astrogliosis and demyelination were reported in rare cases of HCV infection with severe neuropathology; however, this is not observed in the majority of patients. These results demonstrate that higher viral load and lower neurocognitive performance correlate with increased immune activation in the CNS of HCV-infected individuals; further large-scale studies are required to ascertain the extent to which this phenomenon occurs in chronic hepatitis C.
HCV Infection is Associated With Immune Responses in the Brain
Recent studies have suggested that HCV infection is associated with inflammatory responses in the brain. The brain metabolites choline, creatine and inositol were significantly increased in HCV-infected patients compared with healthy controls, yet those patients with low levels of fatigue had higher levels of choline than those with severe fatigue. Nevertheless, these results suggest activation of microglia and possibly astrocytes in HCV-infected patients with fatigue. A recent study of treatment-naïve subjects with mild chronic HCV infection revealed microglial and brain macrophage activation using a combination of proton magnetic resonance spectroscopy and positron emission tomography (PET) with a ligand for neuroinflammation, which was not observed in HCV seronegative subjects. This immune activation was associated with HCV viraemia and altered cerebral metabolism, demonstrating altered basal ganglia myoinositol/creatinine and choline/creatine ratios in HCV-infected patients, putative biomarkers of glial cell inflammation and activation. This observation was reported in a group of 22 HCV-infected patients, of which 15 were treated with pegylated interferon and ribavirin, and seven were untreated HCV-positive controls. In the treated group, the patients who responded to therapy had lower cerebral metabolite measurements (reductions in choline and myoinositol) than non-responders or untreated controls, and the reduction in metabolites associated with improved neurocognitive performance. A further study of postmortem tissue demonstrated that brain tissue from HCV-infected subjects expressed significantly increased levels of proinflammatory cytokines IL-1, TNF-α, IL-12, and IL-18, which could explain glial cell activation reported in several studies. Astrogliosis and demyelination were reported in rare cases of HCV infection with severe neuropathology; however, this is not observed in the majority of patients. These results demonstrate that higher viral load and lower neurocognitive performance correlate with increased immune activation in the CNS of HCV-infected individuals; further large-scale studies are required to ascertain the extent to which this phenomenon occurs in chronic hepatitis C.
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