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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2015; 21(36): 10299-10313
Published online Sep 28, 2015. doi: 10.3748/wjg.v21.i36.10299
Chronic hepatitis C virus infection and lipoprotein metabolism
Yoshio Aizawa, Nobuyoshi Seki, Tomohisa Nagano, Hiroshi Abe
Yoshio Aizawa, Nobuyoshi Seki, Tomohisa Nagano, Hiroshi Abe, Department of Internal Medicine, The Jikei University Katsushika Medical Center, Tokyo 125-8506, Japan
Author contributions: Aizawa Y, Seki N, Nagano T and Abe H equally contributed to this work.
Conflict-of-interest statement: There are no conflicts of interest to be declared.
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: Yoshio Aizawa, MD, PhD, Professor, Department of Internal Medicine, The Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan.
Telephone: +83-33-6032111 Fax: +83-33-8389944
Received: April 20, 2015
Peer-review started: April 21, 2015
First decision: May 18, 2015
Revised: July 11, 2015
Accepted: August 30, 2015
Article in press: August 31, 2015
Published online: September 28, 2015

Hepatitis C virus (HCV) is a hepatotrophic virus and a major cause of chronic liver disease, including hepatocellular carcinoma, worldwide. The life cycle of HCV is closely associated with the metabolism of lipids and lipoproteins. The main function of lipoproteins is transporting lipids throughout the body. Triglycerides, free cholesterol, cholesteryl esters, and phospholipids are the major components of the transported lipids. The pathway of HCV assembly and secretion is closely linked to lipoprotein production and secretion, and the infectivity of HCV particles largely depends on the interaction of lipoproteins. Moreover, HCV entry into hepatocytes is strongly influenced by lipoproteins. The key lipoprotein molecules mediating these interactions are apolipoproteins. Apolipoproteins are amphipathic proteins on the surface of a lipoprotein particle, which help stabilize lipoprotein structure. They perform a key role in lipoprotein metabolism by serving as receptor ligands, enzyme co-factors, and lipid transport carriers. Understanding the association between the life cycle of HCV and lipoprotein metabolism is important because each step of the life cycle of HCV that is associated with lipoprotein metabolism is a potential target for anti-HCV therapy. In this article, we first concisely review the nature of lipoprotein and its metabolism to better understand the complicated interaction of HCV with lipoprotein. Then, we review the outline of the processes of HCV assembly, secretion, and entry into hepatocytes, focusing on the association with lipoproteins. Finally, we discuss the clinical aspects of disturbed lipid/lipoprotein metabolism and the significance of dyslipoproteinemia in chronic HCV infection with regard to abnormal apolipoproteins.

Keywords: Hepatitis C virus, Apolipoprotein, Lipo-viral particle, Dyslipoproteinemia, Lipoprotein

Core tip: Hepatitis C virus (HCV) and lipids interact closely at multiple stages in the HCV life cycle. HCV infection may have a profound influence on lipid metabolism, while lipids can regulate HCV replication. Infectious HCV forms lipo-viral particles that possess the features of lipoproteins. Examination of lipoprotein sub-fractions and apolipoproteins is inevitable for evaluating the nature of disturbed lipid metabolism. Among apolipoproteins, apolipoprotein E is a key molecule required for HCV entry, and is one of the possible therapeutic targets for interrupting HCV infection. Understanding the disturbed lipid metabolism may shed light on the pathophysiology of HCV infection and help develop novel therapeutics.