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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 28, 2016; 8(12): 545-556
Published online Apr 28, 2016. doi: 10.4254/wjh.v8.i12.545
Hepatitis C virus and neurological damage
Shilu Mathew, Muhammed Faheem, Sara M Ibrahim, Waqas Iqbal, Bisma Rauff, Kaneez Fatima, Ishtiaq Qadri
Shilu Mathew, Muhammed Faheem, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Muhammed Faheem, Department of Biosciences, Faculty of Sciences, COMSATS Institute of Information Technology, Islamabad 45550, Pakistan
Sara M Ibrahim, Waqas Iqbal, Department of Biochemistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Bisma Rauff, Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, NSW 2006, Australia
Kaneez Fatima, IQ Institute of Infection and Immunity, Lahore 54000, Pakistan
Ishtiaq Qadri, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Author contributions: Mathew S and Faheem M contributed equally to this manuscript; Qadri I conceived and designed the topic; Mathew S, Faheem M, Ibrahim SM, Iqbal W and Rauff B contributed to materials and wrote the paper; Faheem M, Ibrahim SM, Iqbal W, Rauff B, Fatima K and Qadri I contributed to proof reading of the manuscript.
Supported by KACST large R and D grant to Ishtiaq Qadri (#162-34).
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
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: Ishtiaq Qadri, Professor, King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80200, Jeddah 21589, Saudi Arabia. ishtiaq80262@yahoo.com
Received: August 27, 2015
Peer-review started: August 31, 2015
First decision: October 8, 2015
Revised: March 19, 2016
Accepted: April 7, 2016
Article in press: April 11, 2016
Published online: April 28, 2016
Abstract

Chronic hepatitis C virus (HCV) infection exhibits a wide range of extrahepatic complications, affecting various organs in the human body. Numerous HCV patients suffer neurological manifestations, ranging from cognitive impairment to peripheral neuropathy. Overexpression of the host immune response leads to the production of immune complexes, cryoglobulins, as well as autoantibodies, which is a major pathogenic mechanism responsible for nervous system dysfunction. Alternatively circulating inflammatory cytokines and chemokines and HCV replication in neurons is another factor that severely affects the nervous system. Furthermore, HCV infection causes both sensory and motor peripheral neuropathy in the mixed cryoglobulinemia as well as known as an important risk aspect for stroke. These extrahepatic manifestations are the reason behind underlying hepatic encephalopathy and chronic liver disease. The brain is an apt location for HCV replication, where the HCV virus may directly wield neurotoxicity. Other mechanisms that takes place by chronic HCV infection due the pathogenesis of neuropsychiatric disorders includes derangement of metabolic pathways of infected cells, autoimmune disorders, systemic or cerebral inflammation and alterations in neurotransmitter circuits. HCV and its pathogenic role is suggested by enhancement of psychiatric and neurological symptoms in patients attaining a sustained virologic response followed by treatment with interferon; however, further studies are required to fully assess the impact of HCV infection and its specific antiviral targets associated with neuropsychiatric disorders.

Keywords: Hepatitis C virus, Neuro disorders, Blood brain barrier, Nervous system, Inflammation

Core tip: There is high prevalence rate of neuropsychiatric ailments with respect to patients infected with chronic hepatitis C virus (HCV). Brain inflammatory disorders, cerebrovascular disease peripheral neuropathy, psychiatric disturbs and cognitive symptoms are the complex clinical signs which occurs when infected by chronic HCV infection. HCV prompts psychiatric and neurological symptoms through numerous pathways with imprecise mechanisms, which includes neurotransmitter and metabolic pathway imbalance, immune-mediated responses and direct brain neurotoxicity inflammation. Awareness of HCV-associated neuropsychiatric disorders and its pathogenic mechanisms is vital to understand the clinical manifestations and to introduce an applicable treatment.