Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2016; 22(43): 9488-9505
Published online Nov 21, 2016. doi: 10.3748/wjg.v22.i43.9488
Nonalcoholic fatty liver disease - A multisystem disease?
Ivana Mikolasevic, Sandra Milic, Tamara Turk Wensveen, Ivana Grgic, Ivan Jakopcic, Davor Stimac, Felix Wensveen, Lidija Orlic
Ivana Mikolasevic, Sandra Milic, Davor Stimac, Department of Gastroenterology, UHC Rijeka, 51000 Rijeka, Croatia
Tamara Turk Wensveen, Department of Endocrinology, Diabetes and Metabolic Diseases, UHC Rijeka, 51000 Rijeka, Croatia
Ivana Grgic, Department of Cardiology, UHC Rijeka, 51000 Rijeka, Croatia
Ivan Jakopcic, School of Medicine, 51000 Rijeka, Croatia
Felix Wensveen, Department of Histology and Embryology, School of Medicine, 51000 Rijeka, Croatia
Lidija Orlic, Department of Nephrology, Dialysis and Kidney Transplantation, UHC Rijeka, 51000 Rijeka, Croatia
Author contributions: Mikolasevic I researched the database, wrote the manuscript, and is the guarantor of this work; Milic S, Wensveen TT, Grgic I, Jakopcic I, Stimac D, Wensveen F and Orlic L contributed to the discussion and reviewed/edited the manuscript.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
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: Ivana Mikolasevic, MD, PhD, Department of Gastroenterology, UHC Rijeka, Kresimirova 42, 51000 Rijeka, Croatia.
Telephone: +38-551-658122
Received: June 28, 2016
Peer-review started: June 30, 2016
First decision: July 29, 2016
Revised: August 30, 2016
Accepted: October 19, 2016
Article in press: October 19, 2016
Published online: November 21, 2016

Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians.

Keywords: Nonalcoholic fatty liver disease, Metabolic syndrome, Diabetes mellitus type 2, Cardiovascular disease, Chronic kidney disease, Multisystem disease

Core tip: Given the increasing worldwide incidence of obesity and metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease. Recent developments in the field have shown that NAFLD not only is a “liver disease” but also is the underlying cause of an increasing number of extrahepatic manifestations; thus, it should be treated as a multisystem disease. NAFLD is most prominently linked to chronic kidney disease, mellitus type 2 and cardiovascular disease, as well as a number of other severe chronic diseases. These findings demonstrate that NAFLD ranks amongst the most serious public health problems of our time.