The intertwisted correlations among non-alcoholic fatty liver disease, atherosclerosis, and metabolic syndrome

Abstract

Non-alcoholic fatty liver disease (NAFLD) refers to a spectrum of disorders from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), steatohepatitis with inflammation and fibrosis, which can progress to cirrhosis, and hepatocellular carcinoma. NAFLD is the most common cause of abnormal liver function tests. The prevalence of NAFLD is approximately between 10 and 30% of the general population in various countries and considered to be increasing [1–3]. Previous studies have shown that NAFLD is strongly associated with obesity, type 2 diabetes mellitus, dyslipidemia and insulin resistance, which are all features of the metabolic syndrome [4, 5]. Accordingly, NAFLD is considered the hepatic manifestation of the metabolic syndrome [6, 7]. The metabolic syndrome is a risk factor for the development of cardiovascular disease and a predictor of type 2 diabetes mellitus [8–10]. A large number of studies have demonstrated that metabolic syndrome apparently associates with cardiovascular disease [11]. In view of several lines of evidence, NAFLD would relate to cardiovascular disease and might play a role in the development of atherosclerosis. Recently, the importance of the association between NAFLD and cardiovascular disease has been focused, and several studies have revealed that NAFLD is related to carotid artery intima-media thickness (IMT), a marker of subclinical atherosclerosis, independent of insulin resistance, metabolic syndrome components, and the traditional risk factors for cardiovascular disease [12, 13]. Carotid IMT, as measured noninvasively by ultrasonography, is directly associated with increased risk of cardiovascular disease. In addition, carotid IMT has been shown to be an independent predictor of cardiovascular disease after adjustment for traditional risk factors, and the only noninvasive imaging test recommended by the American Heart Association for inclusion in the evaluation of risk [14, 15]. Brea et al. [12] reported that patients with NAFLD have significantly greater carotid IMT than age and sex matched patients without NAFLD, independent of the classical risk factor of the metabolic syndrome, in a hospital-based case– control study. NAFLD is suggested to be a strong risk factor for carotid atherosclerosis beyond its association with metabolic syndrome. Furthermore, Targher et al. [16] showed that NAFLD is independently associated with an increased incidence of cardiovascular events in type 2 diabetic patients. Interestingly, the severity of liver histopathology among NAFLD patients is strongly associated with early carotid atherosclerosis, independent of classical risk factors and the presence of metabolic syndrome [17]. The relation between NAFLD and carotid IMT was investigated by several hospital-based or population-based case control studies [18]. However, some studies examined the association in a small population, or utilized mainly diabetic individuals, although a German study investigated a random large population sample [19]. In this issue of the Journal of Gastroenterology, Carallo et al. [20] studied a large population mainly consisting of nondiabetic patients but with cardiovascular or metabolic risk factors in a hospital-based case–control study, and demonstrated that hepatic steatosis was associated with cardio atherosclerosis, independent of metabolic syndrome, cardiovascular diseases, diabetes mellitus, and/or insulin resistance, as well as previous reports in diabetic patients. The online version of the article referred to in this editorial can be found under doi: 10.1007/s00535-009-0125-8.