Hepatitis C virus infection and the brain

Abstract

There is growing evidence that hepatitis C virus (HCV)-infection may affect the brain. About half of the HCV-infected patients complain of chronic fatigue irrespective of their stage of liver disease or virus replication rate. Even after successful antiviral therapy fatigue persists in about one third of the patients. Many patients, in addition, report of deficits in attention, concentration and memory, some also of depression. Psychometric testing revealed deficits in attention and verbal learning ability as characteristic for HCV-afflicted patients with normal liver function. Magnetic resonance spectroscopic studies showed alterations of the cerebral choline, N-acetyl-aspartate, and creatine content in the basal ganglia, white matter and frontal cortex, respectively. Recently, pathologic cerebral serotonin and dopamine transporter binding and regional alterations of the cerebral glucose utilisation compatible with alterations of the dopaminergic attentional system were observed. Several studies detected HCV in brain samples or cerebro-spinal fluid. Interestingly, viral sequences in the brain often differed from those in the liver, but were closely related to those found in lymphoid tissue. Therefore, the Trojan horse hypothesis emerged: HCV-infected mononuclear blood cells enter the brain, enabling the virus to reside within the brain (probably in microglia) and to infect brain cells, especially astrocytes.

Hepatitis C virus and neurological damage

“…Further findings have shown [60] a lower level of NAA/Cr ratio in the frontal grey matter of HCVpatients without any change in the Cho/Cr ratio. Both findings have suggested the occurrence of an increased cell membrane turnover and reduced neuronal function [27] . Use of ondansetron which is a competitive antagonist of serotonin receptors has ameliorated fatigue in HCV infected patient.…”

“…In a study on 37 HCV infected patients without other complications by McAndrews et al [26] , verbal learning impairment and lack of attention were observed. A correlation of cognitive impairment and fatigue with HCV infection was observed in half of the patients observed in a study conducted by Weissenborn et al [27] , comparing neuropsychological functioning of HCV positive patients with normal liver function; though in another study by Montagnese et al [28] , an exceptionally high incidence of fast (βdominated) electroencephalograms was documented.…”

“…HCV, though primarily infecting the liver, is frequently associated with CNS abnormalities [27] . Neurocogni tive defects in chronic HCV infection independent of hepatic encephalopathy is increasingly reported in several studies [10,26,29] .…”

Improvement of Central Nervous System Vasculitis in a Patient with Chronic Hepatitis C Virus Infection after Treatment with an Interferon-Free Regimen

“…There are several studies demonstrating the presence of the HCV virons both in the CSF and brain tissue of patients with HCV infection [5]. Nonetheless, the link between direct central nervous system infection and the development of vasculitic lesions of the brain is weak.…”

Challenges in Diagnosing Hepatic Encephalopathy

“…Further factors that may impact the results of neuropsychological or neurophysiological methods used for diagnosing minimal HE are the disorders underlying liver cirrhosis such as alcoholism [35], hepatitis C virus infection [36] or primary biliary cirrhosis, for example [37].…”