Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2019; 25(38): 5826-5837
Published online Oct 14, 2019. doi: 10.3748/wjg.v25.i38.5826
Hepatitis C virus clearance and less liver damage in patients with high cholesterol, low-density lipoprotein cholesterol and APOE ε4 allele
Karina Gonzalez-Aldaco, Sonia Roman, Rafael Torres-Valadez, Claudia Ojeda-Granados, Luis A Torres-Reyes, Arturo Panduro
Karina Gonzalez-Aldaco, Sonia Roman, Rafael Torres-Valadez, Claudia Ojeda-Granados, Luis A Torres-Reyes, Arturo Panduro, Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara “Fray Antonio Alcalde” and Health Sciences Center, University of Guadalajara, Guadalajara 44280, Jalisco, Mexico
Author contributions: Panduro A conceived the study and clinically evaluated all patients. Gonzalez-Aldaco K carried out experimental work, statistical analysis, and drafted the manuscript. Roman S revised all experimental data and copyedited the English version. Torres-Valadez R carried out clinical and laboratory work. Ojeda-Granados C performed the clinical nutrition evaluation, and Torres-Reyes LA revised all biostatistical analysis. All authors contributed intelligently, critically revised, and approved the final version of the manuscript.
Supported by Programa para el Desarrollo Profesional Docente (PRODEP) to Gonzalez-Aldaco K, No. UDG-PTC-1422; and Consejo Nacional de Ciencia y Tecnologí a (CONACYT) to Panduro A, No. 2017-01-5254.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board, Health Sciences Center, University of Guadalajara, Certificate #CI-00612.
Informed consent statement: All participants signed an informed consent before participating in the study.
Conflict-of-interest statement: The authors have no conflict of interest to declare.
Data sharing statement: 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/
Corresponding author: Arturo Panduro, MD, PhD, FAASLD, Professor, Department of Molecular Biology in Medicine Civil Hospital of Guadalajara “Fray Antonio Alcalde”, Hospital 278, Guadalajara 44280, Jalisco, Mexico. biomomed@cencar.udg.mx
Telephone: +52-33-36147743 Fax: +52-33-36147743
Received: June 18, 2019
Peer-review started: June 20, 2019
First decision: August 28, 2019
Revised: September 9, 2019
Accepted: September 27, 2019
Article in press: September 27, 2019
Published online: October 14, 2019
Abstract
BACKGROUND

Cholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus (HCV). APOE gene polymorphisms regulate cholesterol levels modifying the course of the HCV infection. The relationship between cholesterol, APOE alleles, and the outcome of HCV infection has not been evaluated in the admixed population of Mexico.

AIM

To investigate the role of APOE -ε2, -ε3, and -ε4 alleles and the metabolic profile in the outcome of HCV infection.

METHODS

A total of 299 treatment-naïve HCV patients were included in this retrospective study. Patients were stratified in chronic hepatitis C (CHC) (n = 206) and spontaneous clearance (SC) (n = 93). A clinical record was registered. Biochemical tests were assessed by dry chemistry assay. APOE genotypes were determined using a Real-Time polymerase chain reaction assay.

RESULTS

Total cholesterol, low-density lipoprotein cholesterol (LDL-c), triglycerides, and hypercholesterolemia were higher in SC than CHC patients as well as the frequency of the APOE ε4 allele (12.4% vs 7.3%). SC patients were overweight (54.8%). The ε4 allele was associated with SC (OR = 0.55, 95%CI: 0.31-0.98, P = 0.042) and mild fibrosis (F1-F2) in CHC patients (OR 0.091, 95%CI 0.01-0.75, P = 0.020). LDL-c ≥ 101.5 mg/dL (OR = 0.20, 95%CI: 0.10-0.41, P < 0.001) and BMI ≥ 26.6 kg/m2 (OR= 0.37, 95%CI: 0.18-0.76, P < 0.001) were associated with SC status; while ALT ≥ 50.5 IU/L was negatively associated (OR = 5.67, 95%CI: 2.69-11.97, P < 0.001).

CONCLUSION

In SC patients, the APOE ε4 allele and LDL-c conferred a protective effect in the course of the HCV infection in the context of excess body weight.

Keywords: Liver damage, Body mass index, Spontaneous hepatitis C virus clearance, Low-density lipoprotein, Cholesterol

Core tip: Cholesterol is a metabolic regulator of the hepatitis C virus (HCV) life cycle. Genetic polymorphisms in the APOE gene can regulate cholesterol and modify the outcome of the HCV infection. Our findings suggest that APOE ε4 allele and low-density lipoprotein cholesterol (LDL-c) confer a protective effect in the course of the HCV infection in the context of high body mass index (BMI). Levels of LDL-c, BMI, and ALT may estimate the risk of chronicity in HCV-infected patients. An individualized therapy accounting the host´s genetic, environmental, and metabolic factors could aid in the clinical management of HCV infection, especially in populations with a high prevalence of overweight and obesity.