Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2017; 23(37): 6777-6787
Published online Oct 7, 2017. doi: 10.3748/wjg.v23.i37.6777
Intrahepatic vascular changes in non-alcoholic fatty liver disease: Potential role of insulin-resistance and endothelial dysfunction
Marcos Pasarín, Juan G Abraldes, Eleonora Liguori, Beverley Kok, Vincenzo La Mura
Marcos Pasarín, Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, IDIBAPS (Institut d’Investigacions Biomèdiques August Pi i Sunyer), University of Barcelona, 08036 Barcelona, Spain
Juan G Abraldes, Beverley Kok, Cirrhosis Care Clinic, Division of Gastroenterology (Liver Unit), CEGIIR, University of Alberta, AB T6G 2R3 Edmonton, Canada
Eleonora Liguori, Vincenzo La Mura, Internal Medicine, IRCCS San Donato, Department of Biomedical Sciences for Health, University of Milan, 20097 San Donato Milanese, Italy
Author contributions: Pasarín M and La Mura V contributed to systematic review of literature, design and writing of the manuscript; Abraldes JG contributed to revision of the major intellectual contents; Kok B contributed to edition of the language (as mother tongue), revision of the major intellectual contents; Liguori E contributed to edition of the paper, figures and systematic review of literature; and La Mura V contributed to supervision of the manuscript edition.
Conflict-of-interest statement: No potential conflicts of interest.
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: Vincenzo La Mura, MD, PhD, Assistant Professor, Internal Medicine, IRCCS San Donato, Department of Biomedical Sciences for Health, University of Milan, p.zza Edmondo Malan, 1, 20097 San Donato Milanese, Italy.
Telephone: +39-02-52774317
Received: May 14, 2017
Peer-review started: May 19, 2017
First decision: June 22, 2017
Revised: August 31, 2017
Accepted: September 20, 2017
Article in press: September 19, 2017
Published online: October 7, 2017

Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and insulin resistance can be a frequent comorbidity in several chronic liver diseases, in particular hepatitis C virus infection and/or cirrhosis. Several studies have demonstrated that insulin action is not only relevant for glucose control, but also for vascular homeostasis. Insulin regulates nitric oxide production, which mediates to a large degree the vasodilating, anti-inflammatory and antithrombotic properties of a healthy endothelium, guaranteeing organ perfusion. The effects of insulin on the liver microvasculature and the effects of IR on sinusoidal endothelial cells have been studied in animal models of non-alcoholic fatty liver disease. The hypotheses derived from these studies and the potential translation of these results into humans are critically discussed in this review.

Keywords: Non-alcoholic fatty liver disease, Endothelial dysfunction, Insulin resistance, Metabolic syndrome

Core tip: Insulin-resistance participates in the development of endothelial dysfunction and interferes with vascular homeostasis in patients with metabolic syndrome. This has been demonstrated in large conductance vessels, promoting atherosclerosis, but also occurs at a microcirculation level, suggesting an important role for Insulin in controlling vascular resistance and, finally, organ perfusion. We offer an overview of those pre-clinical and clinical studies exploring the liver microcirculation, and discuss the importance of early vascular changes induced by insulin-resistance in non-alcoholic fatty liver disease and in the most common chronic hepatitis in which Insulin-Resistance is a comorbidity.