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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Naïve hepatitis B e antigen-negative chronic hepatitis B patients are at risk of carotid atherosclerosis: A prospective study
Mar Riveiro-Barciela, Cristina Marcos-Fosch, Fernando Martinez-Valle, Fabrizio Bronte, Olimpia Orozco, Isidro Sanz-Pérez, Daniele Torres, Maria-Teresa Salcedo, Salvatore Petta, Rafael Esteban, Antonio Craxi, Maria Buti
Mar Riveiro-Barciela, Cristina Marcos-Fosch, Rafael Esteban, Maria Buti, Department of Medicine of the UAB, Hospital Universitari Vall d’Hebron, Barcelona 08035, Spain
Mar Riveiro-Barciela, Rafael Esteban, Maria Buti, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid 28029, Spain
Fernando Martinez-Valle, Olimpia Orozco, Isidro Sanz-Pérez, Systemic Autoimmune Diseases Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain
Fabrizio Bronte, Daniele Torres, Salvatore Petta, Antonio Craxi, Sezione di Gastroenterologia, Di.Bi.M.I.S, University of Palermo, Palermo 90133, Italy
Maria-Teresa Salcedo, Pathology Department, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain
Author contributions: Buti M acts as guarantor of this article; Riveiro-Barciela M, Marcos-Fosch C, Martinez-Valle F, Craxi A and Buti M drafted the manuscript; Riveiro-Barciela M, Marcos-Fosch C, Martinez-Valle F, Bronte F, OrozcoO, Sanz-Pérez I, Torres D and Salcedo MT acquired the data; Riveiro-Barciela M, Marcos-Fosch C, Bronte F and Petta S analyzed the data; All authors approved the final version of the article.
Supported by IV Fellowship Gilead-Research projects in HIV and hepatitisfunded by Gilead Science, No. GLD16_00057.
Institutional review board statement: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. It was approved by the Ethics Committee of both hospitals (PR(AG)245/2015).
Informed consent statement: Informed verbal consent was obtained from all individual participants included in the study and recorded at the medical records.
Conflict-of-interest statement: Riveiro-Barciela M has received research grants from Gilead and served as speaker for Gilead and Grifols. Esteban R has received research grants from Gilead and has served as advisors for Gilead, Bristol-Myers Squibb and Novartis. Buti M has received research grants from Gilead and has served as advisors for Gilead, Bristol-Myers Squibb and Novartis. The rest of authors have no personal or financial conflicts of interest.
Data sharing statement: Technical appendix, and dataset available from the corresponding author at [mbuti@vhebron.net]. Participants gave informed verbal consent for data sharing.
Open-Access: This article is an open-access article that 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: Maria Buti, MD, PhD, Chief Doctor, Full Professor, Senior Scientist, Department of Medicine of the UAB, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebrón 119-129, General Hospital Building, Hepatology Unit, Barcelona 08035, Spain. mbuti@vhebron.net
Received: February 16, 2021
Peer-review started: February 16, 2021
First decision: May 1, 2021
Revised: May 13, 2021
Accepted: July 9, 2021
Article in press: July 9, 2021
Published online: August 14, 2021
BACKGROUND
There is an increased risk of atherosclerosis in patients with chronic hepatitis C or human immunodeficiency virus, but there is scarce data on hepatitis B virus infection. The hypothesis of this study is that hepatitis B virus infection increases the risk of carotid plaques and subclinical atherosclerosis in naïve hepatitis B e antigen (HBeAg) negative subjects.
AIM
To assess the rate of carotid plaques and subclinical atherosclerosis in naïve HBeAg negative subjects in comparison with a cohort of healthy controls.
METHODS
Prospective case-control collaborative study conducted in two tertiary hospitals. Four hundred and two subjects prospectively recruited at the outpatient clinic were included from May 2016 to April 2017: 201 naïve HBeAg-negative hepatitis B virus-infected [49 chronic hepatitis B (CHB) and 152 inactive carriers(ICs)] and 201 healthy controls. Anthropomorphic and metabolic measures, liver stiffness and carotid Doppler ultrasound were performed. Subclinical atherosclerosis was established on an intima-media thickness increase of ≥1.2 mm and/or the presence of carotid plaques. Normally distributed quantitative variables were compared with the Student t test and those with a non-normal distribution with the Mann-Whitney U test. Categorical variables were compared between groups using the χ2 or Fisher exact test.
RESULTS
Carotid plaques were found more often in CHB (32.7%) than ICs (17.1%) or controls (18.4%) (P = 0.048). Subclinical atherosclerosis was also increased in CHB (40.8%) vsICs (19.1%) or controls (19.4%) (P = 0.003). No differences in the risk of atherosclerosis were observed between controls and ICs. The factors independently associated with the presence of carotid plaques were age [odds ratio(OR) 1.43, P < 0.001] and CHB (OR 1.18, P = 0.004) and for subclinical atherosclerosis, age (OR 1.45, P < 0.001), CHB (OR 1.23, P < 0.001) and diabetes (OR 1.13, P = 0.028). In the subset of young subjects (< 50 years), carotid plaques (12.5% vs 1.1%, P = 0.027) and subclinical atherosclerosis (12.5% vs 2.2%, P = 0.058) were more frequent among CHB than ICs.
CONCLUSION
Untreated HBeAg-negative CHB is an independent risk factor for carotid plaques and subclinical atherosclerosis, while ICs present a similar risk to controls.
Core Tip: This prospective case-control collaborative study aimed to assess whether chronic infection by hepatitis B was associated with risk of carotid plaques and subclinical atherosclerosis. Overall, 402 subjects were recruited, 201 naïve hepatitis B e antigen-negative hepatitis B virus-infected and 201 healthy controls Patients with hepatitis B e antigen-negative chronic hepatitis B presented a higher rate of carotid plaques than non-infected controls,but no differences were observed between controls and hepatitis B inactive carriers. These results suggest that hepatitis B infection may have a role as a cardiovascular risk factor in patients with chronic hepatitis B.
