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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2015; 21(42): 11974-11983
Published online Nov 14, 2015. doi: 10.3748/wjg.v21.i42.11974
Hepatitis C virus-associated neurocognitive and neuropsychiatric disorders: Advances in 2015
Salvatore Monaco, Sara Mariotto, Sergio Ferrari, Massimiliano Calabrese, Gianluigi Zanusso, Alberto Gajofatto, Domenico Sansonno, Franco Dammacco
Salvatore Monaco, Sara Mariotto, Sergio Ferrari, Massimiliano Calabrese, Gianluigi Zanusso, Alberto Gaiofatto, Department of Neurological and Movement Sciences, University of Verona, 37134 Verona, Italy
Salvatore Monaco, Sara Mariotto, Sergio Ferrari, Massimiliano Calabrese, Gianluigi Zanusso, Alberto Gajofatto, Neurologia B, Azienda Ospedaliera Universitaria Integrata, 37134 Verona, Italy
Domenico Sansonno, Franco Dammacco, Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, 70124 Bari, Italy
Author contributions: Monaco S, Mariotto S, Sansonno D and Dammacco F conceived and designed the manuscript; Ferrari S, Calabrese M, Zanusso G and Gajofatto A performed the literature review; all authors wrote and approved the final version of the manuscript.
Supported by Ministero della Salute, Italy, No. RF-2011-02347955 to Monaco S.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Salvatore Monaco, MD, Professor, Department of Neurological and Movement Sciences, University of Verona, Policlinico “G.B. Rossi”, Piazzale L.A. Scuro 10, 37134 Verona, Italy.
Telephone: +39-45-8124768 Fax: +39-45-8027492
Received: June 3, 2015
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.

Keywords: Extra-hepatic manifestations, Hepatitis C virus syndrome, Hepatitis C virus, Neurocognitive impairment, Neuropsychiatric disorders, Proton magnetic resonance spectroscopy, Sleep disorder

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.