Case Control Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2016; 22(29): 6716-6725
Published online Aug 7, 2016. doi: 10.3748/wjg.v22.i29.6716
Hepatitis C virus G1b infection decreases the number of small low-density lipoprotein particles
Chika Kinoshita, Tomohisa Nagano, Nobuyoshi Seki, Yoichi Tomita, Tomonori Sugita, Yuta Aida, Munenori Itagaki, Kenichi Satoh, Satoshi Sutoh, Hiroshi Abe, Akihito Tsubota, Yoshio Aizawa
Chika Kinoshita, Tomohisa Nagano, Nobuyoshi Seki, Yoichi Tomita, Tomonori Sugita, Yuta Aida, Munenori Itagaki, Kenichi Satoh, Satoshi Sutoh, Hiroshi Abe, Yoshio Aizawa, Department of Gastroenterology and Hepatology Internal Medicine of Jikei University Katsushika Medical Center, Tokyo 125-8506, Japan
Akihito Tsubota, Core Research Facilities for Basic Science, Research Center for Medical Science, Jikei University School of Medicine, Tokyo 105-8461, Japan
Author contributions: Aizawa Y and Seki N designed research; Kinoshita C, Nagano T, Seki N, Tomita Y, Sugita T, Aida Y, Itagaki M, Satoh K, Sutoh S, Abe H and Aizawa Y treated patients and collected materials and clinical data; Nagano T, Seki N and Aizawa Y analyzed data; Kinoshita C and Aizawa Y wrote the paper.
Supported by Shionogi Pharmaceutical KK.
Institutional review board statement: The study was approved by the ethics committee of Jikei University School of Medicine (Tokyo, Japan). The protocol for this trans-sectional study was approved by the human ethics review committee of the Jikei University School of Medicine (21-032 5610, February 1, 2010, a study of the association between lipoprotein metabolism and pathology in patients with CHC).
Informed consent statement: Written informed consent was obtained from all patients enrolled in this study.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: Technical appendix, statistical code, and dataset are available from the corresponding author at c.kinoshita.3678@gmail.com. No additional data are available.
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: Chika Kinoshita, MD, Department of Gastroenterology and Hepatology, Internal Medicine of Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushikaku, Tokyo 125-8506, Japan. c.kinoshita.3678@gmail.com
Telephone: +81-3-360321111 Fax: +81-3-38389944
Received: March 30, 2016
Peer-review started: April 6, 2016
First decision: May 30, 2016
Revised: June 11, 2016
Accepted: July 6, 2016
Article in press: July 6, 2016
Published online: August 7, 2016
Processing time: 121 Days and 2 Hours
Abstract

AIM: To investigate how hepatitis C virus (HCV) G1b infection influences the particle number of lipoproteins.

METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1b infection (active HCV group) and 91 with cleared HCV infection (SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using LipoSEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1b infection and the lipoprotein particle number was determined by multiple linear regression analysis.

RESULTS: The median number of low-density lipoprotein (LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range (IQR): 444 nmol/L] than in the SVR group (1363 nmol/L, IQR: 472 nmol/L, P < 0.001), as was that of high-density lipoprotein (HDL) particles (14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein (VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium (median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P < 0.001), small (median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P < 0.001), and very small LDL particles (median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P < 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL particles or any sub-fractions of VLDL and HDL particles.

CONCLUSION: HCV G1b infection decreases the numbers of medium, small, and very small LDL particles.

Keywords: Chronic hepatitis C; Lipoprotein particles; Low-density lipoproteins; Very low-density lipoproteins; Triglycerides; Cholesterol; Regression analysis

Core tip: Hepatitis C virus (HCV) infection was previously reported to alter the serum lipid and lipoprotein profiles. However, the effect of HCV on the number of lipoprotein particles was not previously examined because counting the number of lipoprotein particles is challenging. In this report, we investigated how HCV infection changes the particle number of lipoproteins and demonstrated that HCV infection independently decreased the numbers of medium, small, and very small low-density lipoprotein particles. This finding may provide a new perspective on the association between HCV infection and atherosclerosis.