Effect of ingesting a meal and orthostasis on the regulation of splanchnic and systemic hemodynamics and the responsiveness of cardiovascular α1-adrenoceptors.

Postprandial orthostasis activates mechanisms of cardiovascular homeostasis to maintain normal blood pressure (BP) and adequate blood flow to vital organs. The underlying mechanisms of cardiovascular homeostasis in postprandial orthostasis still require elucidation. Fourteen healthy volunteers were recruited to investigate the effect of an orthostatic challenge (60°-head-up-tilt for 20 min) on splanchnic and systemic hemodynamics before and after ingesting an 800-kcal composite meal. The splanchnic circulation was assessed by ultrasonography of the superior mesenteric and hepatic arteries and portal vein. Systemic hemodynamics were assessed noninvasively by continuous monitoring of BP, heart rate (HR), cardiac output (CO), and the pressor response to an intravenous infusion on increasing doses of phenylephrine, an α1-adrenoceptor agonist. Neurohumoral regulation was assessed by spectral analysis of HR and BP, plasma catecholamine and aldosterone levels and plasma renin activity. Postprandial mesenteric hyperemia was associated with an increase in CO, a decrease in SVR and cardiac vagal tone, and reduction in baroreflex sensitivity with no change in sympathetic tone. Arterial α1-adrenoceptor responsiveness was preserved and reduced in hepatic sinusoids. Postprandial orthostasis was associated with a shift of 500 mL of blood from mesenteric to systemic circulation with preserved sympathetic-mediated vasoconstriction. Meal ingestion provokes cardiovascular hyperdynamism, cardiac vagolysis, and resetting of the baroreflex without activation of the sympathetic nervous system. Meal ingestion also alters α1-adrenoceptor responsiveness in the hepatic sinusoids and participates in the redistribution of blood volume from the mesenteric to the systemic circulation to maintain a normal BP during orthostasis.NEW & NOTEWORTHY A unique integrated investigation on the effect of meal on neurohumoral mechanisms and blood flow redistribution of the mesenteric circulation during orthostasis was investigated. Food ingestion results in cardiovascular hyperdynamism, reduction in cardiac vagal tone, and baroreflex sensitivity and causes a decrease in α1-adrenoceptor responsiveness only in the venous intrahepatic sinusoids. About 500-mL blood shifts from the mesenteric to the systemic circulation during orthostasis. Accordingly, the orthostatic homeostatic mechanisms are better understood.

Ultra-processed food is associated with features of metabolic syndrome and non-alcoholic fatty liver disease.

BACKGROUND & AIMS: High consumption of ultra-processed food (UPF) is associated with mortality and chronic morbidity but has not been studied concerning to non-alcoholic fatty liver disease (NAFLD). We aimed to test the association of UPF consumption with metabolic syndrome, NAFLD and related-liver damage. METHODS: A cross-sectional study among volunteers who underwent abdominal ultrasound (AUS), anthropometrics, blood pressure measurements, and fasting blood tests including FibroMax for non-invasive assessment of NASH and significant fibrosis. A food-frequency questionnaire was used to evaluate UPF consumption using the NOVA classification. RESULTS: A total of 789 subjects were included in the total sample (mean age 58.83 ± 6.58 years, 52.60% men), a reliable FibroMax test was obtained from 714 subjects, 305 subjects were diagnosed with NAFLD. High consumption of UPF was associated with higher odds for metabolic syndrome (OR = 1.88, 95% CI 1.31-2.71, P = .001) and its components; hypertension, hypertriglyceridemia, and low HDL, among the entire sample (OR = 1.53, 1.07-2.19, P = .026; OR = 1.51, 1.08-2.11, P = .017; OR = 1.55, 1.05-2.29, P = .028). In addition, it was associated with higher odds for NASH and hypertension (OR = 1.89, 1.07-3.38, P = .030; OR = 2.26, 1.20-4.26, P = .012 respectively) among subjects with NAFLD. Stratification by smoking status revealed an association between high UPF consumption and significant fibrosis among ever smokers in the entire sample and among subjects with NAFLD (OR = 1.89, 95% CI 1.03-3.45, P = .039; OR = 2.85, 1.14-7.14, P = .026 respectively). CONCLUSIONS: High UPF consumption is associated with metabolic syndrome in the general population, and among those with NAFLD it is associated with NASH marker. Ever-smoking may act synergistically with UPF to amplify the risk for fibrosis.

Higher BMI predicts liver fibrosis among obese children and adolescents with NAFLD - an interventional pilot study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) can range from simple steatosis to steatohepatitis with or without fibrosis. The predictors for liver fibrosis and the effect of nutritional intervention on hepatic fibrosis in pediatric population are not well established. We aimed to investigate the predictors for liver fibrosis and the effects of short-term nutritional intervention on steatosis and fibrosis among obese adolescents with NAFLD. METHODS: Cross-sectional study among obese adolescents. Sociodemographic and clinical data were collected. Liver fibrosis was estimated by Shearwave elastography. All participants were recommended to consume a low carbohydrate diet and were followed biweekly. Blood tests and elastography were performed upon admission and repeated after 3 months. RESULTS: Fifty-seven pediatric patients were recruited (35 males, mean age 13.5±2.9 years, mean body mass index [BMI] 38.8±9.7). Liver fibrosis was diagnosed in 34 (60%) subjects, which was moderate/severe (F≥2) in 24 (70%). A higher BMI Z score and moderate/severe steatosis correlated with moderate/severe fibrosis (P < 0.05). Seventeen patients completed 3 months of follow-up and displayed a decrease in BMI Z score (from BMI Z score 2.6±0.5 before intervention to 2.4±0.5 after intervention), with a significant decrease in liver fibrosis (P = 0.001). CONCLUSION: Pediatric patients with high BMIs and severe liver steatosis are at risk for severe liver fibrosis. Nutritional intervention with minimal weight loss may improves hepatic fibrosis among the pediatric population. TRIAL REGISTRATION: TRN NCT04561804 (9/17/2020).

Identification and Characterization of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is characterized by substantial diagnostic and evaluation gaps with no systematic screening. Even recognized cases are undercoded because of the perceived benign nature of disease and current absence of approved pharmacologic treatment. NAFLD is often detected incidentally, particularly in the asymptomatic early phase. We doubled NAFLD detection via natural language processing of 1 million imaging reports combined with laboratory data from an unselected population. We describe NAFLD comorbidities and health care utilization as compared with age, sex, and body mass index matched control subjects.

Obesity-related acetylcholinesterase elevation is reversed following laparoscopic sleeve gastrectomy.

BACKGROUND: Impaired sympathetic/parasympathetic response, expressed by elevated Acetylcholinesterase (AChE) is associated with obesity, metabolic syndrome and inflammation. However, the association between morbid obesity and AChE and the changes in cholinergic tone following bariatric laparoscopic sleeve gastrectomy (LSG) surgery-induced weight reduction were never analyzed. METHODS: Two studies are presented; the first (the "apparently healthy cohort") was a cross-sectional study and the second (the "LSG cohort") was a prospective-cohort study with 12 months of follow-up. The "apparently healthy cohort" included 1450 apparently healthy participants who volunteered to the Tel-Aviv Medical Center Inflammation Survey (TAMCIS) during a routine annual checkup visit. The "LSG cohort" included 77 morbid obese patients before and at 3, 6, and 12 months following LSG surgery. Main outcomes included anthropometric measurements, Hemoglobin A1c (HbA1C), serum AChE, insulin test and Homeostasis Model Assessment (HOMA). RESULTS: Among the TAMCIS participants, serum AChE activity increased with BMI in a dose-dependent manner until it reached a peak level at BMI of 30-35 kg/m², followed by a plateau. Following LSG, a significant decrease in AChE activity between baseline and 12 months post-surgery was found for men, but not for women (-122.2 ± 135.3, P < 0.001 vs. -21.8 ± 120.5, P = 0.258 nmol substrate hydrolyzed/min per ml, respectively). The reduction in AChE activity was negatively correlated with %excess weight loss (EWL) and positively correlated with %body fat reduction at 12 months post-surgery among women (r = -0.329, P = 0.034 and r = 0.350, P = 0.023, respectively). In men, AChE activity reduction was positively correlated with the HOMA reduction (r = 0.358, P = 0.048). CONCLUSIONS: Obesity-related AChE resistance phenotype may be reversed following LSG and correlates with metabolic outcomes. Further long-term studies will be needed to validate and evaluate the beneficial effect of AChE reduction post bariatric surgery.

High red and processed meat consumption is associated with non-alcoholic fatty liver disease and insulin resistance.

BACKGROUND & AIMS: High red and processed meat consumption is related to type 2 diabetes. In addition, cooking meat at high temperatures for a long duration forms heterocyclic amines (HCAs), which are related to oxidative stress. However, the association between meat consumption and non-alcoholic fatty liver disease (NAFLD) is yet to be thoroughly tested. Therefore, we aimed to test the association of meat type and cooking method with NAFLD and insulin resistance (IR). METHODS: This was a cross-sectional study in individuals who were 40-70 years old and underwent screening colonoscopy between 2013 and 2015 in a single center in Israel. NAFLD and IR were evaluated by ultrasonography and homeostasis model assessment. Meat type and cooking method were measured by a food frequency questionnaire (FFQ) and a detailed meat questionnaire. Unhealthy cooking methods were considered as frying and grilling to a level of well done and very well done. Dietary HCA intake was calculated. RESULTS: A total of 789 individuals had a valid FFQ and 357 had a valid meat questionnaire. High consumption of total meat (portions/day above the median) (odds ratio [OR] 1.49; 95% CI 1.05-2.13; p = 0.028; OR 1.63; 1.12-2.37; p = 0.011), red and/or processed meat (OR1.47; 95% CI 1.04-2.09; p = 0.031; OR1.55; 1.07-2.23; p = 0.020) was independently associated with higher odds of NAFLD and IR, respectively, when adjusted for: body mass index, physical activity, smoking, alcohol, energy, saturated fat and cholesterol intake. High intake of meat cooked using unhealthy methods (OR1.92; 95% CI 1.12-3.30; p = 0.018) and HCAs (OR2.22; 95% CI 1.28-3.86; p = 0.005) were independently associated with higher odds of IR. CONCLUSION: High consumption of red and/or processed meat is associated with both NAFLD and IR. High HCA intake is associated with IR. If confirmed in prospective studies, limiting the consumption of unhealthy meat types and improving preparation methods may be considered as part of NAFLD lifestyle treatment. LAY SUMMARY: High red and processed meat consumption is related to several diseases. In addition, cooking meat at high temperatures for a long duration forms heterocyclic amines, which have harmful health effects. Non-alcoholic fatty liver disease is a significant public health burden and its formation is strongly related to insulin resistance. In this study, both were found to be more frequent in people who consume relatively high quantities of red and processed meat. In addition, a high intake of heterocyclic amines was associated with insulin resistance.

Are transient and shear wave elastography useful tools in Gaucher disease?

Up to now, there are no reliable biochemical markers or imaging that could reveal early tissue damage in Gaucher disease. Therefore, we addressed whether elastography technique can serve as a tool for evaluating patients with Gaucher disease. The study included 42 patients with Gaucher disease type I and 33 patients with liver cirrhosis as well as 22 healthy volunteers. Ultrasound and Doppler examination was performed on each participant prior to apply transient and 2D shear wave elastography. In Gaucher disease the median stiffness of the spleen as assessed by transient elastography (TE) and shear wave elastography (SWE) was 35KPa and 22KPa respectively in contrast to the median stiffness of healthy controls (16.95 and 17.5KPa, p=0.0028 and p=0.0002, respectively) and of patients with cirrhosis (45KPa and 34.5KPa, p=0.015 and p<0.0001 respectively). The liver stiffness in GD as measured by TE and SWE had median values of 7.1KPa and 7KPa respectively, slightly higher than in the healthy controls, but much smaller than for the cirrhotic patients (medians of 24.2KPa and 21KPa). In conclusion, a transient and shear wave elastography show a significant promise as noninvasive and reproducible tools to differentiate Gaucher disease from healthy controls and among those with splenomegaly from cirrhotic patients.

Smoking Habits are Strongly Associated With Colorectal Polyps in a Population-based Case-control Study.

GOALS: The goal of this study is to test the association between lifetime smoking habits and colorectal polyps of different classifications. BACKGROUND: Smoking is an established risk factor for several cancers, including colorectal cancer. However, the association between lifetime smoking habits including intensity, duration, and cessation, and premalignant colorectal polyps is yet to be established. STUDY: A case-control study among 828 consecutive subjects aged 40 to 70 years, undergoing screening or diagnostic colonoscopy. Exclusion criteria were: medically treated diabetes, colectomy, and belonging to colorectal cancer high risk group. Polyps were stratified according to histology (serrated or adenomatous polyp) and location. All participants underwent anthropometric measurements and a structured medical and lifestyle interview. RESULTS: Current-smoking was more strongly associated with increased odds for distal rather than proximal polyps [odds ratio (OR), 4.00; 95% confidence interval (CI), 2.40-6.68 and OR, 2.52; 95% CI, 1.46-4.36, respectively], with serrated-polyps rather than adenomas (OR, 6.36; 95% CI, 2.77-14.57 and OR, 3.01; 1.90-4.74, respectively). All levels of smoking intensity (daily cigarettes) were associated with colorectal polyps. A dose-response association was seen between smoking duration and colorectal polyps. Smoking duration of ≥20 years was strongly associated with distal polyps (OR, 4.01; 95% CI, 1.62-9.84), independently of potential confounders, smoking intensity and years since smoking cessation. All associations were stronger for distal serrated polyps. CONCLUSIONS: Smoking duration is associated with colorectal plyps, independently of other potential confounders, smoking intensity, and cessation. The association is stronger with distal rather than proximal polyps, and with serrated polyps rather than adenomas.

Non-high-density lipoprotein cholesterol independently predicts new onset of non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular disease (CVD) risk. Non-high-density lipoprotein cholesterol (non-HDL-C), i.e. total cholesterol minus HDL, is a well-established risk factor for CVD; however, its association with NAFLD development has not been established. Our aim was to test whether non-HDL-C is an independent predictor of new onset of NAFLD. METHODS: A prospective cohort study of 213 subjects from the general population, without liver disease, was studied. Evaluation of medical history, dietary and physical activity habits, fasting blood tests and ultrasonographic evidence of NAFLD was performed at baseline and after a 7-year follow-up by identical protocols. RESULTS: From 147 patients that did not have NAFLD at baseline, 28 (19%) developed NAFLD at the 7-year follow-up. The baseline levels of non-HDL-C were higher among subjects who developed NAFLD (179.5 ± 37.1 vs. 157.3 ± 35.1 mg/dl, P = 0.003). Non-HDL-C independently predicted new onset of NAFLD adjusting for age, gender, BMI or waist circumference, lifestyle and serum insulin (OR = 1.02 for every mg/dl increment, 1.01-1.04 95% CI, P = 0.008). Non-HDL-C was a stronger predictor for NAFLD than total cholesterol, low-density lipoprotein cholesterol, triglycerides and HDL. No patients with non-HDL-C < 130 mg/dl developed NAFLD, whereas 20.8% of those with values between 130 to 160 and 24.6% of those with values >160 mg/dl developed NAFLD (P for trend = 0.015). CONCLUSIONS: Non-HDL-C is an independent predictor for NAFLD and a stronger predictor than other lipoproteins. This association may stem from the combined hepato-toxic effect of non-HDL-C and may explain the association between NAFLD and CVD.

Non-alcoholic fatty liver disease independently predicts prediabetes during a 7-year prospective follow-up.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is suspected to confer an increased risk for developing type 2 diabetes (DM). However, only a few prospective studies evaluated NAFLD as a predictor for DM, most did not adjust for the full range of potential cofounders and none used an objectively quantified degree of steatosis. Our aim was to evaluate the independent role of NAFLD in predicting the development of pre-DM in a 7-year prospective follow-up of healthy volunteers. METHODS: A prospective cohort of a subsample of the Israeli National Health Survey evaluated at baseline and after 7 years by identical protocols. Metabolic parameters and ultrasonographic evidence of NAFLD were evaluated in 213 subjects, without known liver disease or history of alcohol abuse. Exclusion criteria were pre-DM at the baseline survey. Steatosis was quantified by ultrasound with the hepato-renal ultrasound index (HRI). RESULTS: The study included 141 volunteers (mean age 48.78 ± 9.68, 24.82% with NAFLD) without pre-DM/DM at baseline. Both NAFLD on regular US (OR=2.93, 1.02-8.41 95%CI) and HRI (OR=7.87, 1.83-33.82) were independent predictors for the development of pre-DM, adjusting for age, gender, BMI, family history of DM, baseline insulin, adiponectin and glucose. Further adjustment for physical activity and dietary intake did not weaken the association. Furthermore, NAFLD was a stronger predictor for pre-DM than the metabolic syndrome. Subjects with both NAFLD and glucose ≥89 had 93.3% incidence rate of pre-DM. CONCLUSION: Non-alcoholic fatty liver disease is a strong and independent risk factor for pre-DM in the general adult population; thus, NAFLD patients should be classified as a population at risk.

Predictors for incidence and remission of NAFLD in the general population during a seven-year prospective follow-up.

BACKGROUND & AIMS: Data on the incidence and remission rates of non-alcoholic fatty liver disease (NAFLD) as well as predictive factors are scant. This study aims at evaluating NAFLD's epidemiology in prospective follow-up of individuals sampled from the general population. METHODS: Evaluation of metabolic parameters and ultrasonographic evidence of NAFLD was performed in 213 subjects, with no known liver disease or history of alcohol abuse. The evaluation was performed at baseline and after a 7-year period by identical protocols. RESULTS: Of the 147 patients who did not have NAFLD at baseline, 28 (19%) were found to have NAFLD at a 7-year follow-up. Baseline BMI, HOMA score, blood cholesterol, triglycerides, leptin levels, and weight gain (5.8±6.1 vs. 1.4±5.5kg, p<0.001) were significantly higher and adiponectin was lower among those who developed NAFLD at 7-year follow-up, compared with those who remained NAFLD-free. However, only weight gain and baseline HOMA were independent predictors for the development of NAFLD. Of the 66 patients who were found to have NAFLD at baseline, as many as 24 patients (36.4%) had no evidence of NAFLD at 7years. Weight loss of 2.7±5.0kg was significantly associated with NAFLD remission. Moreover, there was a 75% remission rate among NAFLD patients who lost 5% or more from their baseline weight. CONCLUSIONS: Among the general population, weight gain, and baseline insulin resistance are predictors for NAFLD incidence. One third of NAFLD patients may have remission of disease within a 7-year follow-up, mostly depending on modest weight reduction.

Validation of the Enriching New-Onset Diabetes for Pancreatic Cancer Model: A Retrospective Cohort Study Using Real-World Data.

OBJECTIVES: The Enriching New-onset Diabetes for Pancreatic Cancer (END-PAC) model identified patients at high-risk for pancreatic ductal adenocarcinoma (PDAC) more than 6 months before diagnosis. The current study aimed to validate the END-PAC model using a large, state-mandated health care provider database. METHODS: A retrospective cohort study of patients older than 50 years that had a diagnosis of new-onset diabetes (NOD) between 2006 and 2015. A risk score was assigned according to the END-PAC model. Patients who developed PDAC over the 3-year period after NOD diagnosis were identified using the Israeli National Cancer Registry. RESULTS: Twenty-three percent (1245/5408) of NOD patients were classified as high-risk, of them 32 (2.6%) developed PDAC. Median follow-up time from NOD detection to PDAC diagnosis was 609 days (interquartile range, 367-997). The hazard ratio for PDAC diagnosis among individuals at the high-risk group compared with the low-risk group was 5.70 (95% confidence interval, 2.93-11.06). Using the high-risk group as the screening threshold, the sensitivity, specificity, positive predictive value and negative predictive value of the model were 54.2%, 76.98%, 2.57%, and 99.4%, respectively. Area under the curve of the model was 0.69. CONCLUSIONS: Our findings support the robustness, generalizability and clinical applicability of the END-PAC model.

High Meat Consumption Is Prospectively Associated with the Risk of Non-Alcoholic Fatty Liver Disease and Presumed Significant Fibrosis.

Non-alcoholic fatty liver disease (NAFLD) has been associated with meat consumption in cross-sectional studies. However, only a few prospective studies have been conducted, and they did not test for liver fibrosis. We aimed to assess the association between meat consumption changes and the incidence and remission of NAFLD and significant liver fibrosis. We used a prospective cohort study design, including 316 subjects aged 40-70 years, participating in baseline and follow-up evaluations at Tel-Aviv Medical Center. NAFLD was determined by liver ultrasound or controlled attenuation parameter (CAP), and liver fibrosis was determined by FibroScan. Meat consumption (g/day) was assessed by a food frequency questionnaire (FFQ). In multivariable-adjusted analyses, high consumption of red and/or processed meat (≥gender-specific median) was associated with a higher risk of NAFLD with elevated alanine aminotransferase (ALT) (OR = 3.75, 1.21-11.62, p = 0.022). Consistently high (in both baseline and follow-up evaluations) total meat consumption was associated with 2.55-fold (95% CI 1.27-5.12, p = 0.009) greater odds for new onset and/or persistence of NAFLD compared to consistently low meat consumption. A similar association was shown for consistently high consumption of red and/or processed meat (OR = 2.12, 95% CI 1.11-4.05, p = 0.022). Consistently high red and/or processed meat consumption was associated with 4.77-fold (95% CI 1.36-16.69, p = 0.014) greater odds for significant fibrosis compared to consistently low consumption. Minimizing the consumption of red and/or processed meat may help prevent NAFLD and significant fibrosis.

Serum Malondialdehyde is Associated with Non-Alcoholic Fatty Liver and Related Liver Damage Differentially in Men and Women.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are associated with increased oxidative stress and lipid peroxidation, but large studies are lacking. The aim was to test the association of malondialdehyde (MDA), as a marker of oxidative damage of lipids, with NAFLD and liver damage markers, and to test the association between dietary vitamins E and C intake and MDA levels. METHODS: A cross-sectional study was carried out among subjects who underwent blood tests including FibroMax for non-invasive assessment of NASH and fibrosis. MDA was evaluated by reaction with Thiobarbituric acid and HPLC-fluorescence detection method. NAFLD was diagnosed by abdominal ultrasound. FINDINGS: MDA measurements were available for 394 subjects. In multivariate analysis, the odds for NAFLD were higher with the rise of MDA levels in a dose-response manner, adjusting for age, gender, BMI, and lifestyle factors. Only among men, higher serum MDA was associated of higher odds for NAFLD and NASH and/or fibrosis (OR = 2.59, 95% CI 1.33-5.07, P = 0.005; OR = 2.04, 1.02-4.06, P = 0.043, respectively). Higher vitamin E intake was associated with lower odds of high serum MDA level (OR = 0.28 95% CI 0.13-0.62, P = 0.002). In conclusion, serum MDA is associated with NAFLD and markers of NASH or fibrosis among men. Dietary vitamin E may be protective among women.

A healthy lifestyle pattern has a protective association with colorectal polyps.

BACKGROUND: Colorectal cancer is associated with lifestyle characteristics such as diet, physical inactivity, obesity, and smoking, but these are not incorporated in screening recommendations. Moreover, the joint association of these factors with various colorectal polyps is not established. METHODS: A case-control study, among consecutive subjects aged 40-70 years, undergoing colonoscopy. Cases with colorectal polyps were compared with controls. Detailed information was gathered regarding polyp histology and anatomic location, demographics, medical history, anthropometrics, and lifestyle. The healthy lifestyle index was estimated as the sum of: non-smoking, maintaining a healthy weight, healthy diet, and physical activity. RESULTS: A total of 788 participants were included (cases n = 403, controls n = 385). The healthy lifestyle index had a negative association with colorectal polyps (OR = 0.72, 95% CI 0.62-0.85, P < 0.001), both adenomas and serrated polyps (OR = 0.75, 0.64-0.89, and OR = 0.59, 0.44-0.79, respectively), and both proximal and distal adenomas (OR = 0.77, 0.62-0.95, and OR = 0.73, 0.59-0.90, respectively). Adherence to ≥ 2 healthy lifestyle components was strongly related with colorectal polyps (OR = 0.50, 0.34-0.75, P = 0.001). Abstinence from smoking, and a healthy diet were the factors most strongly associated with lower odds of colorectal polyps (OR = 0.58, 0.42-0.79, and OR = 0.61, 0.44-0.85, respectively). CONCLUSIONS: Adherence to a healthy lifestyle (≥2 healthy lifestyle components) is inversely associated with colorectal polyps, especially serrated and distal polyps, with no dose-response association. Components most strongly associated with lower odds of colorectal polyps were maintaining a healthy diet and abstinence from smoking. Lifestyle-related characteristics may assist in risk stratification and are potential goals for colorectal neoplasia prevention.

Higher phenolic acid intake independently associates with lower prevalence of insulin resistance and non-alcoholic fatty liver disease.

BACKGROUND & AIMS: The inverse association between non-alcoholic fatty liver disease (NAFLD) and diets rich in fruit and vegetables has been demonstrated, but the specific compounds that may be responsible for this association need to be elucidated. The aim of this study was to test the association between phenolic acid consumption, NAFLD, and insulin resistance (IR). METHODS: A cross-sectional cohort of individuals included in a metabolic screening program was studied. Liver steatosis was evaluated by ultrasonography and quantified by the hepatorenal index (HRI); fibrosis was assessed by FibroTest; IR by the sample upper quartile of the homeostatic model assessment score. Dietary intake was measured by a food frequency questionnaire. The phenolic acid content of food was calculated according to Phenol-Explorer. RESULTS: A total of 789 individuals were included (52.6% men, age 58.83 ± 6.58 years). Higher (above the upper median) phenolic acid intake was inversely associated with the presence of NAFLD (odds ratio [OR] 0.69; 95% CI 0.49-0.98; p = 0.036), higher HRI (OR 0.64; 95% CI 0.45-0.91; p = 0.013) and higher IR (OR 0.61; 95% CI 0.42-0.87; p = 0.007), when adjusted for age, gender, body mass index, and lifestyle factors. Considering specific classes of phenolic acids, higher hydroxybenzoic acid intake was independently associated with lower odds of NAFLD, higher HRI and fibrosis. Higher hydroxycinnamic acid intake was independently associated with lower odds of IR. CONCLUSION: A higher intake of phenolic acids is associated with a lower prevalence of liver steatosis and IR in a cross-sectional study, suggesting a possible protective effect that requires confirmation in prospective studies. LAY SUMMARY: High dietary intake of total phenolic acids is associated with a lower prevalence of non-alcoholic fatty liver disease and insulin resistance. A high intake of hydroxybenzoic acids, a class of phenolic acids, is associated with a lower prevalence of steatosis and clinically significant fibrosis, while a high intake of hydroxycinnamic acids, another class of phenolic acids, is associated with a lower prevalence of insulin resistance.

Role of leisure-time physical activity in nonalcoholic fatty liver disease: a population-based study.

UNLABELLED: Physical activity (PA) is commonly recommended for nonalchoholic fatty liver disease (NAFLD) patients. However, there is limited evidence on the independent role of PA in NAFLD. The aim of this study was to examine the association between PA and NAFLD. We conducted a cross-sectional study of a subsample (n = 375) of the Israeli National Health and Nutrition Survey. Exclusion criteria were any known etiology for liver disease. Participants underwent an abdominal ultrasound examination; biochemical tests, including leptin, adiponectin, and resistin; and the noninvasive biomarker SteatoTest and anthropometric evaluations. A semiquantitative food frequency questionnaire and a detailed PA questionnaire were administered. Three hundred forty-nine patients (52.7% men, 30.9% primary NAFLD) were included. The NAFLD group engaged in less aerobic, resistance, or other kinds of PA (P

Diagnostic value of a computerized hepatorenal index for sonographic quantification of liver steatosis.

OBJECTIVE: Quantification of liver steatosis is clinically relevant in various liver diseases but cannot be done by conventional sonography, which only provides a qualitative assessment with significant observer variability. The aim of this study was to assess sonography as an objective tool for the quantification of liver steatosis. MATERIALS AND METHODS: Files of 111 patients with chronic liver disease who were referred for sonographically guided liver biopsy were collected. A hepatorenal sonographic index was calculated on the basis of the ratio between the echogenicity of the liver and that of the right kidney cortex using histogram echo intensity. Liver steatosis was graded by histology. RESULTS: A significant correlation was found between histologic steatosis and the hepatorenal sonographic index (r = 0.82, p < 0.001). The validity of the hepatorenal sonographic index for the diagnosis of fatty liver was compared with liver biopsies with a steatosis level > 5%. The area under the receiver operating characteristic curve was 99.2% (95% CI, 98-100%). The optimal hepatorenal sonographic index cutoff point for the prediction of steatosis > 5% was 1.49, with sensitivity of 100% and specificity of 91%. The optimal hepatorenal sonographic index cutoff point for the prediction of steatosis >/= 25% was 1.86, with sensitivity of 90% and specificity of 90%. The optimal hepatorenal sonographic index cutoff point for the prediction of steatosis >/= 60% was 2.23, with sensitivity of 90% and specificity of 93%. CONCLUSION: The hepatorenal sonographic index is a sensitive noninvasive method for steatosis quantification. It can diagnose small amounts of liver fat that would be missed by conventional sonography. It is reproducible and operator independent and can serve as an efficient tool to follow patients with steatosis and evaluate the efficacy of new treatment techniques.

Dietary vitamin E and C intake is inversely associated with the severity of nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Although antioxidants have a protective potential in nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), there is limited evidence regarding the role of dietary intake of antioxidants. The aim was to test the association between dietary vitamins E and C intake and NAFLD, NASH and fibrosis markers. METHODS: Cross-sectional study of a large cohort of subjects undergoing colonoscopy. The presence of NAFLD was evaluated by ultrasonography. The level of steatosis was defined using SteatoTest, moderate-severe NASH using new quantitative NashTest and borderline-significant fibrosis ≥ F1-F2 using FibroTest. Nutritional intake was measured by food frequency questionnaire (FFQ). RESULTS: Overall, 789 subjects were included (52.6% men, age 58.83 ±â€¯6.58 years), 714 had reliable FibroMax. Adjusting for BMI, dietary and lifestyle factors, the upper tertile of vitamin E intake/1000 Kcal was associated with lower odds of NASH (OR = 0.64, 0.43-0.94, P = 0.024). There was an inverse association between reaching the recommended vitamin E intake and NASH (OR = 0.48, 0.30-0.77, P = 0.002). The upper tertile of vitamin C intake/1000 Kcal was associated with lower odds of NAFLD and NASH (OR = 0.68, 0.47-0.99, P = 0.045; OR = 0.57, 0.38-0.84, P = 0.004, respectively). Both vitamins were related with the level of steatosis according to SteatoTest. CONCLUSION: Vitamin E and C intake may be protective from NAFLD-related liver damage.

Serum Soluble Receptor for AGE (sRAGE) Levels Are Associated With Unhealthy Lifestyle and Nonalcoholic Fatty Liver Disease.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) has been demonstrated to be positively associated with serum advanced glycation end products (AGEs) and negatively with soluble receptor for AGE (sRAGE) in a few small studies. We aimed to test the association between lifestyle and sRAGE levels and the association between sRAGE levels or AGEs intake and NAFLD, insulin resistance (IR), and elevated alanine aminotransferase (ALT). METHODS: Cross-sectional analysis among participants of a screening study. Fasting blood tests and serum sRAGE levels were obtained. NAFLD and insulin resistance were evaluated by ultrasonography and homeostasis model assessment, respectively. Nutritional intake was measured by food frequency questionnaire, and the intake of dietary AGEs was calculated. RESULTS: A total of 743 subjects were included (52.6% men, mean age 58.83 ± 6.58 years, 38.7% NAFLD). Exercise was independently protective from low sRAGE levels (odds ratio [OR] = 0.71, 95% confidence interval 0.52-0.97, P = 0.031). Pack-years, working time, and sedentary time (OR = 1.51, 1.03-2.22, P = 0.036; OR = 1.66, 1.18-2.35, P = 0.004; OR = 1.64, 1.18-2.29, P = 0.004, respectively), and intake of red and/or processed meat or processed meat alone (OR = 1.01, 1.04-2.21, P = 0.045; OR = 1.49, 1.00-2.21, P = 0.048, respectively) were associated with increased odds for low sRAGE levels. Low sRAGE levels were independently associated with elevated ALT (OR = 1.69, 1.11-2.57, P = 0.014) and NAFLD with elevated ALT (OR = 2.17, 1.23-3.83, P = 0.007). High intake of dietary AGEs was associated with IR (OR = 2.04, 1.25-3.34 P = 0.004). DISCUSSION: Lifestyle is associated with sRAGE levels and, in turn, low levels of sRAGE are associated with NAFLD and elevated ALT.