The relationship between cardiovascular disorders and nonalcoholic fatty liver disease (NAFLD) has been extensively studied. To better pool this data and make a more definite conclusion, we performed a meta-analysis to evaluate the association between NAFLD and the thickness of media and intima of carotid artery (CIMT) and cardiovascular disorders.

We searched PubMed, Ovid, Scopus, ProQuest, Web of Science, and the Cochrane Library, and analyzed the pooled data using R studio and the "metafor" package.

The final analysis included a total of 59 studies with 16,179 cases and 26,120 control individuals. NAFLD was shown to be associated with an increase of 0.1231 mm (20.6%) in carotid artery intima-media thickness (CIMT) (p = 0.002, 95% confidence interval [CI]: 0.0462-0.2000) in individuals with NAFLD. The prevalence of atherosclerotic plaques in the carotid arteries and the occurrence of NAFLD are significantly correlated, according to a meta-analysis based on 17 distinct studies (p = 0.001, 1.28-1.43, 95% CI, odds ratio = 1.356).

Patients with increased CIMT are considerably more likely to have NAFLD. Large prospective investigations are required to corroborate these findings and their prognostic significance, along with the effectiveness of the available interventions.

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent disease and has been repeatedly associated with an increased risk of cardiovascular disease. However, the extent of such association is unclear. We conducted a systematic review and meta-analysis of the literature to evaluate the risk of myocardial infarction (MI), ischaemic stroke (IS), atrial fibrillation (AF), and heart failure (HF) in NAFLD patients.

According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed and EMBASE, from inception to 6 March 2021, and included all studies reporting the incidence of MI, IS, AF, and HF in patients with and without NAFLD. Random-effect fmodels were used to estimate pooled odds ratio (OR), 95% confidence intervals (CI), and 95% prediction intervals (PI); subgroup analyses, meta-regressions, and sensitivity analyses were additionally performed. Among 3254 records retrieved from literature, 20 studies were included. Non-alcoholic fatty liver disease was associated with an increased risk of MI (OR: 1.66, 95% CI: 1.39-1.99, 95% PI: 0.84-3.30), IS (OR: 1.41, 95% CI: 1.29-1.55, 95% PI 1.03-1.93), AF (OR: 1.27, 95% CI: 1.18-1.37, 95% PI: 1.07-1.52), and HF (OR: 1.62, 95% CI: 1.43-1.84, 95% CI: 1.04-2.51). We identified significant subgroup differences according to geographical location, study design, NAFLD definition, and risk of bias; meta-regressions identified mean age, male sex, and study-level characteristics as potential moderators of the risk of MI and IS.

Non-alcoholic fatty liver disease was associated with increased risk of MI, IS, AF, and HF. Age, sex, and study characteristics may moderate the strength of this association. Further studies are required to evaluate specific cardiovascular prevention strategies in patients with NAFLD.

The formation of advanced plaques, which is characterized by the uninterrupted aggregation of macrophages with high expression of folate receptor-β (FR-β), is observed in several concomitant metabolic syndromes. The objective of this study was to develop a novel FR-β-targeted single-photon emission computed tomography (SPECT) radiotracer and validate its application to the noninvasive detection of atherosclerosis (AS) plaque and non-alcoholic fatty liver (NAFL).

Two radioiodinated probes, [¹³¹I]IPBF and [¹³¹I]IBF, were developed, and cell uptake studies were used to identify their specific targets for activated macrophages. Biodistribution in normal mice was performed to obtain the pharmacokinetic information of the probes. Apolipoprotein E knockout (ApoE^-/-) mice with atherosclerotic aortas were induced by a high-fat and high-cholesterol (HFHC) diet. To investigate the affinity of radiotracers to FR-β, K_d values were determined using in vitro assays. In addition, the assessments of the aorta in the ApoE^-/- mice at different stages were performed using in vivo SPECT/CT imaging, and the findings were compared by histology.

Both [¹³¹I]IPBF and [¹³¹I]IBF were synthesized with > 95% radiochemical purity and up to 3 MBq/nmol molar activity. In vitro assay of [¹³¹I]IPBF showed a moderate binding affinity to plasma proteins and specific uptake in activated macrophages. The prolonged blood elimination half-life (t_1/2z) of [¹³¹I]IPBF (8.14 h) was observed in a pharmacokinetic study of normal mice, which was significantly longer than that of [¹³¹I]IBF (t_1/2z = 2.95 h). As expected, the K_d values of [¹³¹I]IPBF and [¹³¹I]IBF in the Raw 264.7 cells were 43.94 ± 9.83 nM and 61.69 ± 15.19 nM, respectively. SPECT imaging with [¹³¹I]IPBF showed a high uptake in advanced plaques and NAFL. Radioactivity in excised aortas examined by ex vivo autoradiography further confirmed the specific uptake of [¹³¹I]IPBF in high-risk AS plaques.

In summary, we reported a proof-of-concept study of an albumin-binding folate derivative for macrophage imaging. The FR-β-targeted probe, [¹³¹I]IPBF, significantly prolongs the plasma elimination half-life and has the potential for the monitoring of AS plaques and concomitant fatty liver.

Dipeptidyl peptidase 4 (DPP-4) inhibitors have anti-inflammatory and atheroprotective effects. We evaluated the effects of the DPP-4 inhibitor linagliptin on atherosclerotic plaque and hepatic inflammation using histology and 2-deoxy-2-[¹⁸F]-fluoro-d-glucose (¹⁸F-FDG), a positron emission tomography tracer of inflammation, in a mouse model of hypercholesterolemia and type 2 diabetes.

Igf2/Ldlr^-/-Apob^100/100 mice were fed a high-fat diet (HFD) for 8 weeks and then randomly allocated to receive HFD (n = 14), or HFD with added linagliptin (n = 15) for additional 12 weeks. Five mice fed a chow diet were studied as an additional control. At the end of the study, glucose tolerance, aortic and liver uptake of ¹⁸F-FDG, and histology were studied.

Mice in linagliptin and HFD groups had similar fasting glucose concentrations, but linagliptin improved glucose tolerance. Aortas of linagliptin and HFD groups showed advanced atherosclerotic plaques with no difference in the mean intima-to-media ratio or number of macrophages in the plaques. Autoradiography showed similar ¹⁸F-FDG uptake by atherosclerotic plaques in linagliptin and HFD groups (plaque-to-wall ratio: 1.7 ± 0.25 vs. 1.6 ± 0.21; p = 0.24). In the liver, linagliptin reduced the histologic inflammation score but had no effect on ¹⁸F-FDG uptake. Compared with chow diet, uptake of ¹⁸F-FDG was similar in the aorta, but higher in the liver after HFD.

Linagliptin therapy improved glucose tolerance and reduced hepatic inflammation but had no effect on plaque burden or atherosclerotic inflammation, as determined by histology and ¹⁸F-FDG uptake, in atherosclerotic mice with type 2 diabetes.

The rapidly growing field of functional, molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a "digital biopsy" for in vivo study of liver pathophysiology. To foster the application of bio-imaging in clinical and translational research, there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver. It can be hoped that the combination of digital, liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer. A group of experts of different disciplines (Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver, Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure) discussed criteria, methods and guidelines for facilitating the requisite application of data collection. This manuscript provides a multi-Author review of the issue with special focus on fatty liver.

Several original articles and editorials have been published in the Journal of Nuclear Cardiology in 2017. It has become a tradition at the beginning of each year to summarize some of these key articles in 2 sister reviews. In this first part one, we will discuss some of the progress made in the field of heart failure (cardio-oncology, myocardial blood flow, viability, dyssynchrony, and risk stratification), inflammation, molecular and hybrid imaging using advancement in positron emission tomography, computed tomography, and magnetic resonance imaging.

Non-alcoholic fatty liver disease is the most common cause of chronic liver disease and affects nearly one-third of US population. With the increasing trend of obesity in the population, associated fatty change in the liver will be a common feature observed in imaging studies. Fatty liver causes changes in liver parenchyma appearance on imaging modalities including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) and may affect the imaging characteristics of focal liver lesions (FLLs). The imaging characteristics of FLLs were classically described in a non-fatty liver. In addition, focal fatty change and focal fat sparing may also simulate FLLs. Knowledge of characteristic patterns of fatty change in the liver (diffuse, geographical, focal, subcapsular, and perivascular) and their impact on the detection and characterization of FLL is therefore important. In general, fatty change may improve detection of FLLs on MRI using fat suppression sequences, but may reduce sensitivity on a single-phase (portal venous) CT and conventional ultrasound. In patients with fatty liver, MRI is generally superior to ultrasound and CT for detection and characterization of FLL. In this pictorial essay, we describe the imaging patterns of fatty change in the liver and its effect on detection and characterization of FLLs on ultrasound, CT, MRI, and PET.

Fatty liver, which frequently coexists with necro-inflammatory and fibrotic changes, may occur in the setting of nonalcoholic fatty liver disease (NAFLD) and chronic infections due to either hepatitis C virus (HCV) or human immunodeficiency virus (HIV). These three pathologic conditions are associated with an increased prevalence and incidence of cardiovascular disease (CVD) and type 2 diabetes (T2D). In this multidisciplinary clinical review, we aim to discuss the ever-expanding wealth of clinical and epidemiological evidence supporting a key role of fatty liver in the development of T2D and CVD in patients with NAFLD and in those with HCV or HIV infections. For each of these three common diseases, the epidemiological features, pathophysiologic mechanisms and clinical implications of the presence of fatty liver in predicting the risk of incident T2D and CVD are examined in depth. Collectively, the data discussed in this updated review, which follows an innovative comparative approach, further reinforce the conclusion that the presence of fatty/inflamed/fibrotic liver might be a shared important determinant for the development of T2D and CVD in patients with NAFLD, HCV or HIV. This review may also open new avenues in the clinical and research arenas and paves the way for the planning of future, well-designed prospective and intervention studies.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in many developed countries, affecting an estimated 30 % of the adult population. In this updated clinical review, we summarize the current knowledge regarding the strong association between NAFLD and the risk of coronary heart disease (CHD) and other functional, structural, and arrhythmic cardiac complications (e.g., left ventricular dysfunction, heart valve diseases and atrial fibrillation). We also briefly discuss the putative biological mechanisms linking NAFLD with these important extra-hepatic complications. To date, a large body of evidence has suggested that NAFLD is not simply a marker of CHD and other functional, structural, and arrhythmic cardiac complications, but also may play a part in the development and progression of these cardiac complications. The clinical implication of these findings is that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions aimed at decreasing the risk of CHD and other cardiac and arrhythmic complications.