Chronic hepatitis C virus infection and neurological and psychiatric disorders: An overview

Abstract

Hepatitis C virus (HCV) infection is considered a systemic disease because of involvement of other organs and tissues concomitantly with liver disease. Among the extrahepatic manifestations, neuropsychiatric disorders have been reported in up to 50% of chronic HCV infected patients. Both the central and peripheral nervous system may be involved with a wide variety of clinical manifestations. Main HCV-associated neurological conditions include cerebrovascular events, encephalopathy, myelitis, encephalomyelitis, and cognitive impairment, whereas "brain fog", depression, anxiety, and fatigue are at the top of the list of psychiatric disorders. Moreover, HCV infection is known to cause both motor and sensory peripheral neuropathy in the context of mixed cryoglobulinemia, and has also been recently recognized as an independent risk factor for stroke. These extrahepatic manifestations are independent of severity of the underlying chronic liver disease and hepatic encephalopathy. The brain is a suitable site for HCV replication, where the virus may directly exert neurotoxicity; other mechanisms proposed to explain the pathogenesis of neuropsychiatric disorders in chronic HCV infection include derangement of metabolic pathways of infected cells, alterations in neurotransmitter circuits, autoimmune disorders, and cerebral or systemic inflammation. A pathogenic role for HCV is also suggested by improvement of neurological and psychiatric symptoms in patients achieving a sustained virologic response following interferon treatment; however, further ad hoc trials are needed to fully assess the impact of HCV infection and specific antiviral treatments on associated neuropsychiatric disorders.

Hepatitis C virus and neurological damage

“…HCV has been proposed to prompt demyelination via an immunemediated response. These findings proposed that in cases with acute disseminated encephalomyelitis the likelihood of HCV infection in creases [11] .…”

“…It is reported that chronic HCV infection has been associated with neurological as well as psychiatric conditions in upto about 50% of the cases [11] . Major HCV related neurological ailments comprise of autoimmune disorders, cerebrovascular events, myelitis, encephalopathy, encephalomyelitis, and cognitive impair ment; psychiatric disorders include, anxiety depression, and fatigue [12,13] .…”

Interactions between neurotropic pathogens, neuroinflammatory pathways, and autophagic neural cell death

“…Transcription factor NF-κB is reported to be involved in cytokine gene expression. Therefore, blocking NF-κB can be a therapeutic approach to controlling HCV mediated neuroinflammation [52] . According to the above study, viral core proteins have been observed to activate microglial cells, astrocytes, and macrophages of patients infected with HCV.…”

Hepatitis C infection: A multi-faceted systemic disease with clinical, patient reported and economic consequences

“…Along with the increased risk of vascular disease in HCV positive patients, evidence has also shown an increased cardiovascular mortality risk [57,58]. Finally, the mechanism of the neuropsychiatric manifestation (depression and brain fog) of HCV may be related to the virus invading both the white brain matter and brain stem, as well as the impact of circulating HCV-related cytokines on the brain [59][60][61][62][63]. Furthermore, the cause of chronic fatigue (both peripheral and central fatigue) observed during HCV infection is unknown but is also thought to be a result of the disruption in cellular activity caused by the effects of circulating inflammatory cytokines and chemokines [60,62].…”