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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2015; 21(22): 6820-6834
Published online Jun 14, 2015. doi: 10.3748/wjg.v21.i22.6820
Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease: An update
Vasilios G Athyros, Konstantinos Tziomalos, Niki Katsiki, Michael Doumas, Asterios Karagiannis, Dimitri P Mikhailidis
Vasilios G Athyros, Niki Katsiki, Michael Doumas, Asterios Karagiannis, Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, 55132 Thessaloniki, Greece
Konstantinos Tziomalos, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 55132 Thessaloniki, Greece
Dimitri P Mikhailidis, Department of Clinical Biochemistry (Vascular Prevention Clinic), Royal Free Hospital Campus, University College London Medical School, University College London, London NW3 2QG, United Kingdom
Author contributions: Athyros VG designed the review and wrote the paper; Tziomalos K selected relevant papers; Kastiki N selected relevant papers, and edited the original paper; Doumas M wrote the paper; Karagiannis A designed the review outline and added-set key points to review; and Mikhailidis DP wrote the original paper and edited the final version.
Conflict-of-interest: This review was written independently. The authors did not receive financial or professional help with the preparation of the manuscript. The authors have given talks, attended conferences and participated in advisory boards and trials sponsored by various pharmaceutical companies. DPM has given talks and attended conferences sponsored by Merck, Sharp and Dohme, AstraZeneca and Genzyme.
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: Dimitri P Mikhailidis, MD, FFPM, FRCP, FRCPath, Academic Head, Department of Clinical Biochemistry (Vascular Prevention Clinic), Royal Free Hospital Campus, University College London Medical School, University College London, Pond Street, London NW3 2QG, United Kingdom. mikhailidis@aol.com
Telephone: +44-20-78302258 Fax: +44-20-78302235
Received: January 21, 2015
Peer-review started: January 22, 2015
First decision: March 10, 2015
Revised: March 31, 2015
Accepted: May 7, 2015
Article in press: May 7, 2015
Published online: June 14, 2015
Processing time: 148 Days and 0.9 Hours
Abstract

Non-alcoholic fatty liver disease (NAFLD) is considered to be an independent cardiovascular disease (CVD) risk factor. However, simple steatosis has a benign clinical course without excess mortality. In contrast, the advanced form of NAFLD, non-alcoholic steatohepatitis (NASH) with liver fibrosis increases mortality by approximately 70%, due to an increase in CVD mortality by approximately 300%. Chronic kidney disease (CKD) may be caused by NAFLD/NASH and it substantially increases CVD risk, especially in the presence of type 2 diabetes mellitus. Moreover, CKD may trigger NAFLD/NASH deterioration in a vicious cycle. NAFLD/NASH is also related to increased arterial stiffness (AS), an independent CVD risk factor that further raises CVD risk. Diagnosis of advanced liver fibrosis (mainly by simple non-invasive tests), CKD, and increased AS should be made early in the course of NAFLD and treated appropriately. Lifestyle measures and statin treatment may help resolve NAFLD/NASH and beneficially affect the CVD risk factors mentioned above.

Keywords: Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Cardiovascular disease; Liver fibrosis; Statins; Chronic kidney disease; Arterial stiffness; Inflammation

Core tip: Non-alcoholic fatty liver disease (NAFLD) is an independent cardiovascular disease (CVD) risk factor. However, simple steatosis has a rather benign clinical course, while its advanced form, non-alcoholic steatohepatitis (NASH) substantially increases total mortality, mainly due to increased CVD events. In this review we propose the use of statin treatment for NASH, given its beneficial effect on NAFLD/NASH and CVD risk. There are data suggesting biopsy proven amelioration of NASH and normalization in liver ultrasonography and enzyme values as well as improvement of chronic kidney disease and arterial stiffness that usually accompany NASH and exacerbate CVD risk.