Hepatic FDG uptake in patients with NAFLD: An important prognostic factor for cardio-cerebrovascular events?

Non-alcoholic fatty liver disease (NAFLD) encompasses the often benign non-alcoholic fatty liver (NAFL) characterized by hepatic steatosis with or without mild inflammation and the more complicated non-alcoholic steatohepatitis (NASH) with lobular inflammation and hepatocellular ballooning which can be complicated by fibrosis. Independent associates for the presence of liver fibrosis in patients with NASH are diabetes mellitus (DM), insulin resistance, hypertension, weight gain, and increased serum alanine and aspartate aminotransferase. NAFLD patients with fibrosis are at increased risk for liver cirrhosis. The estimated risks to develop liver cirrhosis are for patients with NASH and patients with NAFL, 22% and 4%, respectively. In the last decade, the prevalence of NAFLD has tremendously increased as a result of the world-wide raise of patients with DM and obesity (i.e., metabolic syndrome). This has led to a fivefold increase of NAFLDrelated liver transplantation. Moreover, NAFLD is considered to be the hepatic expression of the metabolic syndrome with augmented atherogenesis expressed by increased carotid intima-media thickness (CIMT), endothelial dysfunction, arterial stiffness, impaired left ventricular function, and coronary calcification. As a result, patients with NAFLD have an increased risk for cardiovascular (CV) disease and mortality. Among others, Adams et al demonstrated that the 10year survival of patients with NAFLD was significantly lower compared with the general population (77 vs 87%, P[log-rank] = 0.005), due to higher frequency of fatal CV disease and malignancy. In addition, Targher et al demonstrated that the presence ofNAFLD in asymptomatic patients with DM type 2 was independently associated with an increased risk for myocardial infarction, coronary revascularization procedures, ischemic stroke, and/or CV death (odds ratio 1.84, 95% CI 1.4;2.1, P\0.001). Currently, the diagnostic reference standard to diagnose NAFLD is a liver biopsy. However, in an asymptomatic population this invasive technique is not practical as a screening method and not without hazards. Therefore, as an alternative technique, positron emission tomography (PET)/computed tomography (CT) can be used to detect hepatic inflammation by means of the glucose tracer fluorine-18 fluoro-2-deoxyglucose (18FFDG). 18F-FDG visualizes the importance and utilization of glucose (metabolic activity) of the cells and is expected to be higher in inflammatory cells. The major drawback of this method is that 18F-FDG PET/CT cannot differentiate between hepatic histologic subtypes. Results of studies evaluating the hepatic uptake of 18F-FDG measured with PET or PET/CT in NAFLD patients are controversial. Abikhzer et al demonstrated in patients with hepatic steatosis a small global decrease in hepatic metabolic activity corrected for lean body mass in comparison with controls. However, there was no difference when the hepatic standard uptake value (SUV) of 18F-FDG was corrected for body weight. In addition, Lin et al demonstrated a significantly negative correlation in the degree of fatty liver and the maximum hepatic SUV of 18F-FDG on PET. In contrast, Bural et al showed higher maximum hepatic SUVs on PET in subjects with diffuse hepatic steatosis compared to those in the control group. A part of the Reprint requests: Arthur J. H. A. Scholte, MD, PhD, Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, Postal zone 2300 RC, 2333 ZA, Leiden, The Netherlands; [email protected] J Nucl Cardiol 2017;24:900–2. 1071-3581/$34.00 Copyright 2016 The Author(s). This article is published with open access at Springerlink.com