Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Oct 27, 2020; 12(10): 850-862
Published online Oct 27, 2020. doi: 10.4254/wjh.v12.i10.850
Novel markers of endothelial dysfunction in hepatitis C virus-related cirrhosis: More than a mere prediction of esophageal varices
Amr Shaaban Hanafy, Mohamed Abdel Khalik Basha, Fady Maher Wadea
Amr Shaaban Hanafy, Fady Maher Wadea, Department of Internal Medicine, Gastroenterology and Hepatology Division, Zagazig University Hospital, Zagazig 44519, Egypt
Mohamed Abdel Khalik Basha, Department of Diagnostic Radiology, Zagazig University, Zagazig 44519, Egypt
Author contributions: Hanafy AS was the guarantor; Hanafy AS, and Wadea FM were involved in the study concept and design; Hanafy AS, Basha MAK, and Wadea FM participated in the acquisition, analysis, and interpretation of the data, and drafted the initial manuscript; Hanafy AS performed the statistical analysis; Basha MAK was responsible for radiological investigations; all authors revised the article critically for important intellectual content.
Institutional review board statement: The study was reviewed and approved by Zagazig Faculty of Medicine Ethical Committee.
Informed consent statement: All study participants, or their legal guardian, provided written informed consent before study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—a checklist of items.
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 NonCommercial (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: Amr Shaaban Hanafy, MD, Assistant Professor, Department of Internal Medicine, Gastroenterology and Hepatology Division, Zagazig University Hospital, 40- Elzohour treet, Zagazig 44519, Egypt. amrhanafy@zu.edu.eg
Received: April 29, 2020
Peer-review started: April 29, 2020
First decision: July 5, 2020
Revised: July 15, 2020
Accepted: August 24, 2020
Article in press: August 24, 2020
Published online: October 27, 2020

Hepatitis C virus (HCV) infection may affect lipid metabolism by enhancing the circulating levels of inflammatory cytokines, together with its impact on endothelial function.


To evaluate the potential correlation of changes in lipid profile, carotid intima-media thickness (CIMT), and ankle-brachial index with the severity of fibrosis, grades of esophageal varices (EVs), and fibrosis indices.


The study included 240 subjects who were divided into 3 groups; group 1 (n = 90, HCV-related cirrhotic patients with EVs), group 2 (n = 90, HCV-related cirrhotic patients without EVs), and group 3 (n = 60, served as the healthy control group). All patients underwent routine laboratory tests, including a lipid profile assay. Low-density lipoproteins (LDL)/platelet count and platelet/splenic diameter ratios were calculated. Abdominal ultrasonography, CIMT by carotid Doppler, bedside ankle-brachial index (ABI), liver stiffness measurement, and upper gastrointestinal endoscopy were performed.


Multivariate logistic regression revealed that very-low-density lipoprotein (VLDL) (β = 0.988, odds ratio 2.5, P = 0.001), LDL/platelet count ratio (β = 1.178, odds ratio 3.24, P = 0.001), CIMT (β = 1.37, odds ratio 3.9, P = 0.001), and ABI (β = 2.3, odds ratio 5.9, P = 0.001) were the key variables associated with significant fibrosis, EVs and endothelial dysfunction. CIMT and LDL/platelet count ratio were predictive of advanced fibrosis and EVs at cutoff values of 1.1 mm and 1 mm, respectively, with an area under the curve (AUC) of 0.966 and 0.960 (P = 0.001), while VLDL and ABI at a cutoff of 16.5 mg/dL and 0.94 were predictive of advanced fibrosis and EVs with an AUC of 0.891 and 0.823, respectively (P = 0.001).


CIMT, ABI, VLDL, LDL/platelet count ratio are good non-invasive predictors of advanced fibrosis, presence of EVs, and endothelial dysfunction in liver cirrhosis.

Keywords: Lipid profile, Liver cirrhosis, Esophageal varices, Carotid-intima media thickness, Ankle-brachial index

Core Tip: Hepatitis C virus (HCV) infection may affect lipid metabolism by enhancing the circulating levels of inflammatory cytokines. HCV may induce endothelial dysfunction. Carotid intima-media thickness, low-density lipoproteins (LDL)/platelet count ratio, ankle-brachial index, and very LDL were predictive of advanced fibrosis, esophageal varices, and endothelial dysfunction at cutoff values of 1.1 mm, 1, 0.94, and 16.5 mg/dL, respectively. Novel markers provide information beyond the previous traditional markers such as platelet count, FIB-4, and platelet/splenic diameter ratio with additional data regarding endothelial dysfunction and subclinical atherosclerosis.