Published online Nov 14, 2015. doi: 10.3748/wjg.v21.i42.11974
Peer-review started: June 6, 2015
First decision: August 31, 2015
Revised: September 11, 2015
Accepted: September 30, 2015
Article in press: September 30, 2015
Published online: November 14, 2015
Since its identification in 1989, hepatitis C virus (HCV) has emerged as a worldwide health problem with roughly 185 million chronic infections, representing individuals at high risk of developing cirrhosis and liver cancer. In addition to being a frequent cause of morbidity and mortality due to liver disease, HCV has emerged as an important trigger of lymphoproliferative disorders, owing to its lymphotropism, and of a wide spectrum of extra-hepatic manifestations (HCV-EHMs) affecting different organ systems. The most frequently observed HCV-EHMs include mixed cryoglobulinemia and cryoglobulinemic vasculitis, B-cell non-Hodgkin’s lymphoma, nephropathies, thyreopathies, type 2 diabetes mellitus, cardiovascular diseases, and several neurological conditions. In addition, neuropsychiatric disorders and neurocognitive dysfunction are reported in nearly 50% of patients with chronic HCV infection, which are independent of the severity of liver disease or HCV replication rates. Fatigue, sleep disturbance, depression and reduced quality of life are commonly associated with neurocognitive alterations in patients with non-cirrhotic chronic HCV infection, regardless of the stage of liver fibrosis and the infecting genotype. These manifestations, which are the topic of this review, typically occur in the absence of structural brain damage or signal abnormalities on conventional brain magnetic resonance imaging (MRI), although metabolic and microstructural changes can be detected by in vivo proton magnetic resonance spectroscopy, perfusion-weighted and diffusion tensor MRI, and neurophysiological tests of cognitive processing. Several lines of evidence, including comparative and longitudinal neuropsychological assessments in patients achieving spontaneous or treatment-induced viral clearance, support a major pathogenic role for HCV in neuropsychiatric and neurocognitive disorders.
Core tip: Neurocognitive dysfunction, sleep disturbance, depression, fatigue and reduced quality of life are common manifestations of chronic hepatitis C virus (HCV) infection. Neuropsychological performance is impaired in HCV patients, in the absence of structural brain alterations on conventional magnetic resonance imaging (MRI). Brain metabolic and microstructural changes are easily detected by in vivo proton magnetic resonance spectroscopy and perfusion-weighted/diffusion tensor MRI, enabling detection of brain dysfunction in clinically asymptomatic subjects. The regional distribution of metabolic changes indicates an exclusive involvement of telencephalic areas, but not the diencephalon or brainstem. HCV is likely to play a major pathogenic role in these disorders.