Non-alcoholic fatty liver disease (NAFLD) affects up to nearly a third of the Western population and has been inconsistently associated with cardiovascular diseases (CVDs). Therefore, we conducted a comprehensive meta-analysis to quantify the correlation of NAFLD with all major vascular diseases, acute coronary syndrome (ACS), subclinical atherosclerosis and endothelial dysfunction.

We searched PubMed and Embase for studies looking at the relationship between NAFLD and cardiovascular diseases published through September 2023. The parameters we used to assess cardiovascular diseases include acute coronary syndrome, brachial flow-mediated dilatation (FMD), serum asymmetric dimethylarginine (ADMA), carotid intima-media thickness (CIMT), and carotid stenosis (>50%). Data from these studies were then collected and meta-analysis was performed using the random effects model. RevMan v5.4 was used for statistical analysis.

We interrogated a total of 114 publications which met our inclusion criteria. NAFLD patients showed statistically significant reduction in FMD% [MD: -4.83 (95% CI: -5.84 to 3.81, p < .00001)] and increased serum ADMA [MD: 0.08 (95% CI: 0.05-0.11, p < .00001)]. Mean CIMT was also increased in NAFLD patients [MD 0.13 (95% CI: 0.12-0.14, p < .00001)]. NAFLD showed a higher prevalence of pathological CIMT [MD: 0.11 (95% CI: 0.10-0.12, p < .00001)] and increased carotid plaques [OR: 2.08 (95% CI: 1.52-2.86, p < .00001)]. Furthermore, we demonstrated statistically significant increase in cardiovascular diseases among NAFLD patients compared to controls [OR: 1.92 (95% CI: 1.53-2.41, p < .00001)].

NAFLD is a strong predictor for endothelial dysfunction, subclinical atherosclerosis and cardiovascular disease. Further studies are required to determine whether incidental findings of fatty liver on abdominal ultrasonography should prompt the need for detailed assessment of other CVD risk factors.

Evidence has demonstrated that visceral fat area (VFA) and subcutaneous fat area (SFA) have different influences on cardiovascular disease (CVD) risk in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the relationship between the visceral fat area (VFA), the subcutaneous fat area (SFA) ratio (V/S), and carotid atherosclerosis (CAS) in patients with T2DM.

From January 2018 to May 2023, 1838 patients with T2DM admitted to the National Metabolic Management Centre in our hospital were assigned to two groups based on comorbid CAS. Dual bioelectrical impedance analysis was used to measure the VAF and SFA, and the V/S was calculated. Patient characteristics and serum biochemical indices were compared between groups. Factors influencing comorbid CAS were determined, and correlations between V/S and other clinical indices were analyzed.

The group with comorbid CAS included 858 individuals and 980 without comorbid CAS. Those with comorbid CAS were older and had a longer disease duration, more significant systolic blood pressure, and greater V/S. The proportions of patients with comorbid hypertension increased significantly with the V/S ratio. The V/S ratio positively correlated with triglyceride (TG), low-density lipoprotein cholesterol levels, and waist circumference. According to binary logistic regression analysis, V/S was an independent risk factor for CAS.

Elevated V/S is an independent risk factor for CAS in patients with T2DM.

Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis without heavy alcohol consumption or other chronic conditions, encompasses a spectrum from non-alcoholic fatty liver to non-alcoholic steatohepatitis leading to cirrhosis. This analysis aimed to investigate the correlation between NAFLD and carotid intimal media thickness (C-IMT), a non-invasive surrogate for atherosclerosis.

Database searches, including PubMed, EMBASE and Cochrane Library, yielded studies up to April 2023. Included were studies exploring the NAFLD-C-IMT relationship in populations aged >18 years. Exclusions comprised non-English papers, those involving animals or pediatric populations and studies lacking control groups.

No statistical significance was noted between mild and moderate NAFLD compared to the control group regarding C-IMT [95% confidence intervals (CI): -0.03, 0.12] and (95% CI: -0.03, 0.21), respectively. There was a statistically significant difference only in the Severe NAFLD group ( P value 0.03). NAFLD with and without metabolic syndrome showed statistically significant differences compared to control regarding C-IMT (95% CI: 0.04, 0.12) and (95% CI: 0.01, 0.07), respectively. Fifty-nine studies were mentioned without classification of NAFLD severity and revealed a high statistically significant difference between NAFLD and controls regarding C-IMT with (95% CI: 0.09, 0.12, P < 0.00001). Stratified analysis according to sex was done in two studies and revealed statistical differences between NAFLD and control regarding C-IMT in both groups.

This meta-analysis underscores a significant association between NAFLD and increased C-IMT, emphasizing the importance of assessing C-IMT in NAFLD patients to identify cardiovascular risk and tailor therapeutic interventions for improved patient outcomes.

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.

Hepatic steatosis is a condition frequently encountered in clinical practice, with potential progression towards fibrosis, cirrhosis, and hepatocellular carcinoma. Detection and staging of hepatic steatosis are of most importance in nonalcoholic fatty liver disease (NAFLD), a disease with a high prevalence of more than 1 billion individuals affected. Ultrasound (US) is one of the most used noninvasive imaging techniques used in the diagnosis of hepatic steatosis. Detection of hepatic steatosis with US relies on several conventional US parameters, which will be described. US is the first-choice imaging in adults at risk for hepatic steatosis. The use of some scoring systems may add additional accuracy especially in assessing the severity of hepatic steatosis.

In the presented paper, we discuss screening and risk stratification, ultrasound features for diagnosing hepatic steatosis, B-mode criteria, focal fatty patterns and Doppler features of the hepatic vessels, and the value of the different US signs for the diagnosis of liver steatosis including classifying the severity of steatosis using different US scores. Limitations of conventional B-mode and Doppler features in the evaluation of hepatic steatosis are also discussed, including those in grading and assessing the complications of steatosis, namely fibrosis and nonalcoholic steatohepatitis.

Ultrasound is the first-line imaging examination for the screening and follow-up of patients with liver steatosis. The use of some scoring systems may add additional accuracy in assessing the severity of steatosis. Conventional B-mode and Doppler ultrasound have limitations in grading and assessing the complications of steatosis.

Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD.

Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD.

From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36-43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37-4.32; P<0.0001). Pooled analysis of 25,839 patients with NAFLD found the prevalence of stroke to be 5.04% (95% CI, 2.74-9.09%) with an odds ratio of 1.88 (95% CI, 1.23-2.88; P=0.02) compared to non-NAFLD. The degree of steatosis assessed by ultrasonography in NAFLD was closely associated with risk of carotid atherosclerosis and stroke. Older age significantly increased the risk of developing carotid atherosclerosis, but not stroke in NAFLD.

This meta-analysis shows that a stepwise increment of steatosis of NAFLD can significantly increase the risk of carotid atherosclerosis and stroke development in NAFLD. Patients more than a third sufferred from carotid atherosclerosis and routine assessment of carotid atherosclerosis is quintessential in NAFLD.

The association between nonalcoholic fatty liver disease (NAFLD) and carotid atherosclerosis is still controversial. The present study was designed to assess the relationship between left ventricular systolic mechanics, noninvasively assessed by two-dimensional (2D) speckle-tracking echocardiography (STE) and common carotid artery (CCA) intima-media thickness (IMT), in patients with nonadvanced NAFLD.

All consecutive NAFLD patients diagnosed with liver stiffness measurement (LSM) <12.5 kPa on transient elastography between September 2021 and December 2021 were prospectively enrolled. All participants underwent blood tests, transient elastography, 2D transthoracic echocardiography (TTE) implemented with 2D-STE analysis of left ventricular (LV) global longitudinal strain (GLS) and finally carotid ultrasonography. Main independent predictors of subclinical atherosclerosis, defined as CCA-IMT >0. 9 mm, were evaluated.

A total of 92 NAFLD patients (54.0 ± 11.1 years, 50% males) were prospectively analyzed. Mean LSM was 6.2 ± 2.4 kPa. FibroScan results revealed that 76.1% of patients had F0-F1, 5.4% F2 and 18.5% F3 liver fibrosis. Despite normal biventricular systolic function on 2D-TTE, LV-GLS was reduced (less negative than -20%) in 64.1% of patients. However, 62.0% of NAFLD patients were found with CCA-IMT >0. 9 mm. Age [odds ratio (OR),1.19; 95% confidence interval (CI), 1.05-1.36], hypertension (OR, 3.73; 95% CI, 1.53-9.11), LSM (OR, 4.83; 95% CI, 2.43-9.59), LV-GLS (OR, 0.49; 95% CI, 0.36-0.68) and statin therapy (OR, 0.10; 95% CI, 0.02-0.60) were independently associated with subclinical atherosclerosis. Age ≥51 years, LSM ≥5.5 kPa and LV-GLS less negative than -20% were the best cutoff values for predicting subclinical atherosclerosis.

Subclinical myocardial dysfunction and subclinical atherosclerosis are simultaneously present in patients with nonadvanced NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease. In our meta-analysis, we aimed to assess the correlation of NAFLD and four surrogate markers of subclinical atherosclerosis. PubMed, Embase, and the Cochrane Library were searched up until April 2017. Original studies investigating the association between NAFLD and subclinical atherosclerosis were included. The outcome data were extracted and pooled for the effect estimate by using a random-effects model. We used the Newcastle-Ottawa Quality Assessment Scale to assess the quality of the included studies. Of the 434 initially retrieved studies, 26 studies involving a total of 85,395 participants (including 29,493 patients with NAFLD) were included in this meta-analysis. The Newcastle-Ottawa Quality Assessment Scale scores suggested the included studies were of high quality. The pooled effects estimate showed that subjects with NAFLD exhibited a significant independent association with subclinical atherosclerosis compared to the non-NAFLD group (odds ratio, 1.60; 95% confidence interval, 1.45-1.78). Subgroup analysis suggested that the presence of NAFLD yielded a remarkable higher risk of increased carotid artery intima-media thickness/plaques, arterial stiffness, coronary artery calcification, and endothelial dysfunction with odds ratios (95% confidence interval) of 1.74 (1.47-2.06), 1.56 (1.24-1.96), 1.40 (1.22-1.60), and 3.73 (0.99-14.09), respectively. Conclusion: Our meta-analysis revealed a close link between NAFLD and subclinical atherosclerosis in light of four different indices. Patients with NAFLD might benefit from screening and surveillance of early atherosclerosis, which would facilitate the prediction of potential cardiovascular disease burden, risk stratification, and appropriate intervention in the long term. (Hepatology Communications 2018;2:376-392).

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.

Nonalcoholic fatty liver disease (NAFLD) is independently associated with atherosclerosis in nondiabetic individuals. In type 2 diabetic patients, the link between fatty liver and atherosclerosis is less clear. Here, we assessed whether liver fat content evaluated using (1)H-magnetic resonance spectroscopy ((1)H-MRS) was independently associated with prevalent carotid plaque as a marker of atherosclerosis in type 2 diabetic patients.

One hundred and forty-four prospectively enrolled patients with type 2 diabetes underwent liver fat content measurement using (1)H-MRS and carotid plaque assessment using ultrasound. Multiple logistic regressions were used to identify factors associated with carotid plaque.

Mean ± SD liver fat content was 9.86±8.12%. Carotid plaque prevalence was 52.1% (75/144). Patients without plaque were younger (P=0.006) and had a smaller visceral fat area (P=0.015), lower reported prevalence of previous cardiovascular events or current statin therapy (P=0.002), and higher liver fat content than those with plaque (P=0.009). By multivariable logistic regression, increased liver fat content independently predicted the absence of carotid plaque [odds ratios (ORs), 0.94; 95% confidence intervals (CIs), 0.89-0.99; P=0.017].

Liver fat content measured by (1)H-MRS is higher in type 2 diabetic patients without carotid plaque compared to those with plaque. This study suggests that increased liver fat content could be associated with a relative protection against carotid atherosclerosis in patients with type 2 diabetes mellitus.

Observational studies suggest that nonalcoholic fatty liver disease (NAFLD) is associated with increased carotid intimal medial thickness (C-IMT) and carotid plaques in both children and adults. We carried out a meta-analysis to evaluate the relationship between NAFLD and carotid atherosclerosis measured as C-IMT and carotid plaque prevalence. Medline (Ovid), PubMed, Web of Science, and CINAHL databases were searched from 1946 to September 2014, complemented with a manual review of references of the published articles for studies that compared C-IMT or carotid plaque prevalence in adults and children. Results were pooled using both fixed and random effects models. Of the studies identified, 20 were suitable for testing the effect of NAFLD on C-IMT in adults, 13 for testing the effect of NAFLD on carotid plaque prevalence in adults, and five for testing the effect of NAFLD on C-IMT in the pediatric population. The pooled data from 20 studies (19,274 adult participants: NAFLD=8652, controls=10,622) showed significantly increased C-IMT in patients with NAFLD, compared with controls without NAFLD, according to both fixed [standardized mean difference (SMD)=0.251, 95% confidence interval (CI): 0.220-0.282, P<0.001] and random effects models (SMD=0.944, 95% CI: 0.728-1.160, P<0.001). NAFLD was also found to be associated with a higher carotid artery plaque prevalence when compared with controls, according to both fixed (OR=1.273, 95% CI=1.162-1.394, P<0.001) and random effects models (OR=1.769, 95% CI: 1.213-2.581, P=0.003), on pooling of 13 studies (14,445 adult participants: NAFLD=5399 and controls=9046). Analysis of pooled data from five studies in the pediatric population (1121 pediatric participants: NAFLD=312 and controls=809) also found NAFLD to be associated with significantly increased C-IMT according to fixed (SMD=0.995, 95% CI: 0.840-1.150, P<0.001) and random effects models (1.083, 95% CI: 0.457-1.709, P=0.001). NAFLD is associated with increased C-IMT in both children and adults, and with increased carotid plaque prevalence in adults. Individuals identified with carotid disease should be evaluated for NAFLD and vice versa.

Hyperhomocysteinemia is considered an independent risk factor for cardiovascular disease. Oxidative stress is one of the major pathogenic mechanisms in non-alcoholic fatty liver disease and atherosclerosis.

Our study aimed to evaluate serum homocysteine levels and oxidative stress in patients with biopsy-proven non-alcoholic steatohepatitis and possible association with cardiovascular risk measured by carotid artery intima-media thickness (c-IMT).

50 patients with non-alcoholic steatohepatitis and 30 healthy controls, age and gender matched, were recruited. Lipid profile, liver biochemical markers, serum homocysteine, vitamins B6 and B12, folic acid, glutathione (reduced and total), erythrocyte superoxide dismutase, whole blood glutathione peroxidase, malondialdehyde and carotid intima-media thickness were assayed.

Patients had an altered lipid profile and liver biochemical markers; carotid intima-media thickness and serum homocysteine levels were significantly higher compared to controls, but there were no differences in folate, B12 and B6 vitamins levels. Patients had significantly lower levels of glutathione peroxidase activity, total and reduced glutathione and higher levels of malondialdehyde, but unchanged superoxide dismutase activity compared to control group. Also, serum homocysteine level showed significant positive correlation with waist circumference, body mass index, free cholesterol, triglycerides, LDL-cholesterol, amino transferases and negative correlation with reduced and total glutathione, superoxide dismutase and γ-GT.

Non-alcoholic steatohepatitis is an independent cardiovascular risk factor, associated with elevated homocysteine levels, oxidative stress and c-IMT. c-IMT could be used as an indicator of early atherosclerotic changes initiated by dyslipidemia and oxidative stress, while higher level of homocysteine might be an effect of liver damage.

Inflammation is a major contributor to the development of atherosclerotic plaque, yet the involvement of liver and visceral adipose tissue inflammatory status in atherosclerotic lesion development has yet to be fully elucidated. We hypothesized that an atherogenic diet would increase inflammatory response and lipid accumulation in the liver and gonadal adipose tissue (GAT) and would correlate with systemic inflammation and aortic lesion formation in low-density lipoprotein (LDL) receptor null (LDLr-/-) mice. For 32 weeks, LDLr-/- mice (n = 10/group) were fed either an atherogenic (high saturated fat and cholesterol) or control (low fat and cholesterol) diet. Hepatic and GAT lipid content and expression of inflammatory factors were measured using standard procedures. Compared with the control diet, the atherogenic diet significantly increased hepatic triglyceride and total cholesterol (TC), primarily esterified cholesterol, and GAT triglyceride content. These changes were accompanied by increased expression of acyl-CoA synthetase long-chain family member 5, CD36, ATP-binding cassette, subfamily A, member 1 and scavenger receptor B class 1, and they decreased the expression of cytochrome P450, family 7 and subfamily a, polypeptide 1 in GAT. Aortic TC content was positively associated with hepatic TC, triglyceride, and GAT triglyceride contents as well as plasma interleukin 6 and monocyte chemoattractant protein-1 concentrations. Although when compared with the control diet, the atherogenic diet increased hepatic tumor necrosis factor α production, they were not associated with aortic TC content. These data suggest that the LDLr-/- mice responded to the atherogenic diet by increasing lipid accumulation in the liver and GAT, which may have increased inflammatory response. Aortic TC content was positively associated with systemic inflammation but not hepatic and GAT inflammatory status.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in adults and children. A number of genetic and environmental factors are known to predispose individuals to NAFLD. Certain dietary sugars, particularly fructose, are suspected to contribute to the development of NAFLD and its progression. The increasing quantity of fructose in the diet comes from sugar additives (most commonly sucrose and high fructose corn syrup) in beverages and processed foods. Substantial links have been demonstrated between increased fructose consumption and obesity, dyslipidemia, and insulin resistance. Growing evidence suggests that fructose contributes to the development and severity of NAFLD. In human studies, fructose is associated with increasing hepatic fat, inflammation, and possibly fibrosis. Whether fructose alone can cause NAFLD or if it serves only as a contributor when consumed excessively in the setting of insulin resistance, positive energy balance, and sedentary lifestyle is unknown. Sufficient evidence exists to support clinical recommendations that fructose intake be limited through decreasing foods and drinks high in added (fructose-containing) sugars.

Abdominal ultrasonography (US) represents the first-line imaging examination in chronic liver diseases; in most cases, US, laboratory findings and the clinical context are generally sufficient to guide the diagnosis. Thanks to the considerable diffusion of US, we have seen an increased diagnosis of NAFLD in recent years, although this condition is generally silent from a clinical point of view. We have to identify the metabolic syndrome in the general population and to promptly recognize NAFLD to prevent its development into non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. Among the non-invasive diagnostic techniques for NAFLD and for early vascular damage, ultrasonography represents the method of choice. In fact, besides the traditional semiotics of fundamental US of the liver, new US techniques have recently been proposed (contrast enhancement US, acoustic structure characterization), with respect to serum biomarkers and Fibroscan, for the study of liver fibrosis. Similarly, also as concerns the US measurement of carotid intima-media thickness, new automated methods with sophisticated software and radio-frequency signal have recently been introduced. Finally, we report the preliminary results of a personal experience on liver and carotid US in the epidemiology of the metabolic syndrome.

Non-alcoholic fatty liver disease (NAFLD) has been linked to increased cardiovascular morbidity. However, genetic factors have an unclear role in this condition.

To analyse heritability of NAFLD and its association with abnormal vascular parameters in a large twin cohort.

Anthropometric and lipid metabolic parameters were obtained from 208 adult Hungarian twins (63 monozygotic and 41 dizygotic pairs; 58 men and 150 women; age 43.7 ± 16.7 years). B-mode ultrasonography was performed to detect steatosis and categorize severity. Brachial and aortic augmentation indices and aortic pulse wave velocity were assessed using oscillometry (TensioMed Arteriograph). Carotid intima media thickness (IMT) was measured using ultrasonography on the proximal common, distal common and internal carotid arteries.

NAFLD was identified in 47 subjects (22.6%), of which 44 (93.6%) had mild and 3 (6.4%) had moderate steatosis. These subjects were older (age: 50.9 ± 14.3 vs. 41.5 ± 16.7 years, P < 0.001) and had a higher body mass index (BMI; 30.1 ± 5.2 vs. 24.6 ± 4.1 km/m(2) , P < 0.001) than non-NAFLD twins. Based on 91 same-sex twin pairs, heritability analysis indicated no discernible role for genetic components in the presence of NAFLD (95% confidence interval, 0.0-36.0%), while shared and unshared environmental effects accounted for 74.2% and 25.8% of variations adjusted for age and BMI. Augmentation indices and carotid IMT in twins with NAFLD were increased at most examined locations (P < 0.05-P < 0.001).

These findings do not support heritability of NAFLD, although it coexists with vascular parameters linked to increased cardiovascular risk, underscoring the importance and value of prevention in this very common disorder.

Non-alcoholic fatty liver disease is now recognized as the hepatic component of the metabolic syndrome. Non-alcoholic fatty liver disease is a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in non-alcoholic fatty liver disease and may progress to non-alcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. Prevalence estimates for non-alcoholic fatty liver disease range from 17 to 33% in the general populations and it has been estimated that non-alcoholic fatty liver disease exists in up to 70% of people with Type 2 diabetes. Non-alcoholic fatty liver disease increases risk of Type 2 diabetes and cardiovascular disease. In people with Type 2 diabetes, non-alcoholic fatty liver disease is the most frequent cause (∼80%) of fatty liver diagnosed by ultrasound. As non-alcoholic fatty liver disease is strongly associated with insulin resistance, the presence of non-alcoholic fatty liver disease with diabetes often contributes to poor glycaemic control. Consequently, strategies that decrease liver fat and improve whole-body insulin sensitivity may both contribute to prevention of Type 2 diabetes and to better glycaemic control in people who already have developed diabetes. This review summarizes the Dorothy Hodgkin lecture given by the author at the 2012 Diabetes UK annual scientific conference, proposing that fatty acid fluxes through the liver are crucial for the pathogenesis of non-alcoholic fatty liver disease and for increasing insulin resistance.

Dietary fructose induces unfavorable lipid alterations in animal models and adult studies. Little is known regarding metabolic tolerance of dietary fructose in children.

The aim of the study was to evaluate whether dietary fructose alters plasma lipids in children with nonalcoholic fatty liver disease (NAFLD) and in healthy children.

We performed a 2-d, crossover feeding study at the Inpatient Clinical Interaction Site of the Atlanta Clinical and Translational Science Institute at Emory University Hospital.

Nine children with NAFLD and 10 matched controls without NAFLD completed the study. We assessed plasma lipid levels over two nonconsecutive, randomly assigned, 24-h periods under isocaloric, isonitrogenous conditions with three macronutrient-balanced, consecutive meals and either: 1) a fructose-sweetened beverage (FB); or 2) a glucose beverage (GB) being consumed with each meal.

Differences in plasma glucose, insulin, triglyceride, apolipoprotein B, high-density lipoprotein cholesterol, and nonesterified free fatty acid levels were assessed using mixed models and 24-h incremental areas under the time-concentration curve.

After FB, triglyceride incremental area under the curve was higher vs. after GB both in children with NAFLD (P = 0.011) and those without NAFLD (P = 0.027); however, incremental response to FB was greater in children with NAFLD than those without NAFLD (P = 0.019). For all subjects, high-density lipoprotein cholesterol declined in the postprandial and overnight hours with FB, but not with GB (P = 0.0006). Nonesterified fatty acids were not impacted by sugar but were significantly higher in NAFLD.

The dyslipidemic effect of dietary fructose occurred in both healthy children and those with NAFLD; however, children with NAFLD demonstrated increased sensitivity to the impact of dietary fructose.

Nonalcoholic fatty liver disease (NAFLD) is a feature of metabolic syndrome and has a high prevalence in the general population.

To determine the severity of atherosclerotic finding in various grade of NAFLD.

We examined 250 consecutive patients with various grade of NAFLD and 85 control subjects matched for age, gender, to determine carotid intima-media thickness (CIMT) in each groups.

The mean CIMT in patients with G1, G2 and G3 NAFLD were 0.78±0.15 mm, 0.82±0.11mm and 0.85±0.16mm respectively. The differences in CIMT between the various grades of NAFLD were statistically significant (p=0.01).

According to our study results the presence of NAFLD; severity of atherosclerosis will be higher parallel with severity of fatty liver infiltration. Therefore, Patients with NAFLD especially high-grade fatty liver may be candidate to be investigated for the presence CAD.

Nonalcoholic fatty liver disease (NAFLD) is prevalent in people with the metabolic syndrome and type 2 diabetes and is present in up to one-third of the general population. Evidence is now accumulating that NAFLD is associated with obesity and diabetes and may serve as a predictor of cardiovascular disease (CVD). The possible mechanisms linking NAFLD and CVD include inflammation and oxidative stress, hyperlipidaemia, insulin resistance, and direct impact of NAFLD on coronary arteries and left ventricular dysfunction. In addition, several studies suggest that NAFLD is associated with high risk of CVD and atherosclerosis such as carotid artery wall thickness and lower endothelial flow-mediated vasodilation independently of classical risk factors and components of the metabolic syndrome. It is not yet clear how treatment of NAFLD will modulate the risk of CVD. Furthermore, studies are urgently needed to establish (i) the pathophysiology of CVD with NAFLD and (ii) the benefit of early diagnosis and treatment of CVD in patients with NAFLD. In the absence of biochemical markers, it is crucial that screening and surveillance strategies are adopted in clinical practice in the growing number of patients with NAFLD and at risk of developing CVD. Importantly, the current evidence suggest that statins are safe and effective treatment for CVD in individuals with NAFLD.

Nonalcoholic fatty liver disease (NAFLD), a highly prevalent condition, is a feature of metabolic syndrome and is characterized by excessive accumulation of fat in the liver cells. The purpose of this study was to investigate the association between NAFLD and carotid intima-media thickness (CIMT) as an independent risk factor for atherosclerosis.

We examined 250 consecutive patients with ultrasonographically confirmed NAFLD and 85 age-matched and gender-matched controls with normal parenchymal liver echogenicity for determination of CIMT and presence of carotid atherosclerotic plaque.

Compared with control subjects, patients with NAFLD showed an increased mean CIMT (0.81 ± 0.14 mm) compared with control subjects (0.58 ± 0.15 mm). This difference was statistically significant (P = 0.001). After performing multivariate analysis, the presence of NAFLD was associated with abnormal CIMT independent of other atherogenic risk factors or its association with metabolic syndrome.

NAFLD can be an independent risk factor for developing atherosclerosis. Therefore, NAFLD with and without metabolic syndrome can be associated with increased CIMT and increased risk of cardiovascular events in patients with NAFLD incidentally diagnosed on abdominal ultrasonography.

This review focuses on recent advances in the study of the epidemiology, pathogenesis, natural history and treatment of nonalcoholic fatty liver disease (NAFLD).

Study of hepatic lipid metabolism, insulin resistance, mitochondrial dysfunction and oxidative stress, genetic variants and predisposition to altered metabolism and cell injury have contributed to our current understanding of NAFLD. Differential expression of microRNA in fatty liver and its implication in disease pathogenesis and therapeutic potential have continued to advance over the year. The pathogenesis of hepatocellular carcinoma in steatohepatitis continues to be explored. The diagnostic utility of imaging and noninvasive markers seems promising in estimating the severity of steatosis and fibrosis. Liver biopsy remains the gold standard for accurately assessing NAFLD and steatohepatitis. Lifestyle modification and weight loss improve both metabolic profile and liver histology. Pharmacotherapy for the treatment of NAFLD remains lacking.

The underlying mechanism and pathogenesis of NAFLD remain elusive despite ongoing researches to make significant advances in the understanding of its natural history, pathogenesis and management. Pharmacotherapy has yet to indicate a promising therapeutic intervention. Current treatment focuses on managing underlying cardio-metabolic risks.