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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2015; 21(8): 2269-2280
Published online Feb 28, 2015. doi: 10.3748/wjg.v21.i8.2269
Chronic hepatitis C virus infection and neurological and psychiatric disorders: An overview
Luigi Elio Adinolfi, Riccardo Nevola, Giacomo Lus, Luciano Restivo, Barbara Guerrera, Ciro Romano, Rosa Zampino, Luca Rinaldi, Ausilia Sellitto, Mauro Giordano, Aldo Marrone
Luigi Elio Adinolfi, Clinical Hospital of Marcianise, Second University of Naples, 81025 Marcianise (CE), Italy
Luigi Elio Adinolfi, Riccardo Nevola, Luciano Restivo, Barbara Guerrera, Ciro Romano, Rosa Zampino, Luca Rinaldi, Ausilia Sellitto, Mauro Giordano, Aldo Marrone, Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, Second University of Naples, 80100 Naples, Italy
Giacomo Lus, Neurological Sciences, Second University of Naples, 80100 Naples, Italy
Author contributions: Adinolfi LE and Nevola R conceived, drafted the article, and approved the final version; Restivo L, Guerrera B, Romano C, Zampino R, Rinaldi L, Sellitto A and Marrone A conceived the paper, reviewed the literature, and approved the final version of this article; Lus G and Giordano M critically reviewed the manuscript and approved the final version of this article.
Supported by Research grant from Regione Campania, Italy.
Conflict-of-interest: All authors have no conflicts 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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Luigi Elio Adinolfi, MD, Professor, Director of Internal Medicine, Clinical Hospital of Marcianise, Second University of Naples, ASL Caserta, Rione Santella, 81025 Marcianise (CE), Italy. luigielio.adinolfi@unina2.it
Telephone: +39-823-690642 Fax: +39-823-690642
Received: October 1, 2014
Peer-review started: October 3, 2014
First decision: October 29, 2014
Revised: November 11, 2014
Accepted: January 8, 2015
Article in press: January 8, 2015
Published online: February 28, 2015
Processing time: 150 Days and 12.4 Hours
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.

Keywords: Hepatitis C virus; Neurological disorders; Psychiatric disorders; Stroke; Inflammation

Core tip: High prevalence of neuropsychiatric disorders has been reported in chronic hepatitis C virus (HCV) infected patients. Cerebrovascular disease, brain inflammatory disorders, cognitive symptoms, peripheral neuropathy, and psychiatric disturbs are among the multifaceted clinical manifestations occurring during chronic HCV infection. HCV induces neurological and psychiatric symptoms through several complex and as yet unclear mechanisms, including direct brain neurotoxicity, metabolic and neurotransmitter pathway derangement, inflammation, and immune-mediated responses. Knowledge of HCV-associated neuropsychiatric manifestations and pathogenic mechanisms is paramount to correctly understand the whole clinical picture and to institute an appropriate treatment. Evidence suggests improvement of neurological symptoms following specific antiviral therapy.