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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.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.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.Our findings support the robustness, generalizability and clinical applicability of the END-PAC model.

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.

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)

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.

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 ± 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.

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 α

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.

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.

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. 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. 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

Longitudinal assessment of body composition following bariatric surgery allows monitoring of health status. Our aim was to elucidate trends of anthropometric and clinical outcomes 3 years following sleeve gastrectomy (SG). A prospective cohort study of 60 patients who underwent SG. Anthropometrics including body composition analysis measured by multi-frequency bioelectrical impedance analysis, blood tests, liver fat content measured by abdominal ultrasound and habitual physical activity were evaluated at baseline and at 6 (M6), 12 (M12), and 36 (M36) months post-surgery. Sixty patients (55% women, age 44.7 ± 8.7 years) who completed the entire follow-up were included. Fat mass (FM) was reduced significantly 1 year post-surgery (55.8 ± 11.3 to 26.7 ± 8.3 kg; P

BackgroundNon-alcoholic fatty liver disease (NAFLD) can range from simple steatosis to steatohepatitis with or without fibrosis. The predictors for liver fibrosis, so as 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.MethodsCross-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.ResultsFifty-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 P = 0.001).ConclusionPediatric 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 pediatric population.

Background: Budd-Chiari syndrome (BCS) is a rare disease defined as hepatic venous outflow obstruction at any level from the hepatic venules up to the cavo-atrial junction. Transjugular Intrahepatic Portosystemic Shunt (TIPS) is performed as a decompressive treatment in some patients.Aim: To evaluate the potential role of Transient Elastography (TE) in assessing liver stiffness in patients with primary BCS.Methods: Twenty one BCS patients and 10 patients with liver cirrhosis with different underlying etiologies underwent abdominal ultrasound and TE.Results: Ninety-five percent of BCS patients had liver stiffness compatible with F4 with a median of 21 kPa, values which are usually obtained in patients with liver cirrhosis. Ten BCS and 10 cirrhotic patients underwent repeated TE with a median of 320 days between exams for BCS and 4.5 years for cirrhotic patients. The change of liver stiffness in BCS patients was 5.75 kPa (range − 0.4 to 26.6), compared with − 4.85 kPa (range − 15.6 to 15.0) in cirrhotic patients (p-value = 0.0029). Change in liver stiffness from baseline to follow-up in BCS patients who underwent TIPS (n = 4) was 0.2 kPa (range − 0.4 to 15.3), whereas in patients without intervention (n = 6) it was 6.75 kPa (range 1.3 to 26.6). The difference was not statistically significant.Conclusion: Liver stiffness in BCS patients is a dynamic progressive process with parameters of TE resembling liver cirrhosis. Even if TIPS seem to slow down the increment of liver stiffness, because of decreased liver congestion, it kept most patients with high score. The TE in BCS patients may be considered for monitoring for stable or upfront disease deterioration.

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&ndash, 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&ndash, 5.07, P = 0.005, OR = 2.04, 1.02&ndash, 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&ndash, 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.

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., Graphical abstract, Highlights • High intake of total phenolic acids is associated with a lower prevalence of NAFLD and insulin resistance. • High intake of hydroxybenzoic acids is associated with a lower prevalence of steatosis and fibrosis. • High intake of hydroxycinnamic acids is associated with lower prevalence of 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.

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. 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). 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

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 p0.0001 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.

Soluble receptor for advanced glycation end-products (sRAGE) exerts protective metabolic effects.To identify if sRAGE plays a protective role in NAFLD.sRAGE (n=55) and Nε-(Carboxymethyl) lysine (CML) (n=36) serum levels were measured in NAFLD patients. Liver steatosis and fibrosis were non-invasively quantified by the hepatorenal index and the NAFLD fibrosis score (NFS).sRAGE levels were lower in NAFLD patients compared to controls (1207±439 vs. 1596±562ng/l, P0.001) and were lower among subjects with moderate-severe steatosis compared with mild (1043±287 vs. 1378±506, P=0.005). Higher sRAGE was associated with lower steatosis with adjustment for age, gender, BMI and fasting insulin (OR=0.998, 0.996-0.999 95%CI, P=0.018). CML was not correlated with liver steatosis (r=0.07, P=0.683), but was positively correlated with AST (r=0.34, P=0.04), GGT (r=0.38, P=0.023) and HbA1C (r=0.37, P=0.027). sRAGE tended to be higher in subjects with NFS-1.455 compared with NFS-1.455 (1287±450 n=36 vs. 1051±364 n=13, P=0.08). While sRAGE was positively correlated with vegetables consumption (r=0.268, P=0.05), CML levels were not associated with sRAGE or dietary intake. sRAGE increased following a 3 month-lifestyle intervention (1194±446 vs. 1367±440 n=31, P0.001) and change in sRAGE levels was negatively correlated with change in ALT levels (r=-0.37, P=0.041).sRAGE plays a protective role in NAFLD and it is influenced by lifestyle.

Two main causes for nutrient deficiencies following bariatric surgery (BS) are pre-operative deficiencies and favoring foods with high-energy density and poor micronutrient content. The aims of this study were to evaluate nutritional status and gender differences and the prevalence of nutritional deficiencies among candidates for laparoscopic sleeve gastrectomy (LSG) surgery. A cross-sectional analysis of pre-surgery data collected as part of a randomized clinical trial on 100 morbidly obese patients with non-alcoholic fatty liver disease (NAFLD) admitted to LSG surgery at Assuta Medical Center between February 2014 and January 2015. Anthropometrics, food intake, and fasting blood tests were evaluated during the baseline visit. One-hundred patients completed the pre-operative measurements (60 % female) with a mean age of 41.9 ± 9.8 years and a mean BMI of 42.3 ± 4.7 kg/m2. Pre-operatively, deficiencies for iron, ferritin, folic acid, vitamin B1, vitamin B12, vitamin D, and hemoglobin were 6, 1, 1, 6, 0, 22, and 6 %, respectively. Pre-surgery, mean energy, protein, fat, and carbohydrate intake were 2710.7 ± 1275.7 kcal/day, 114.2 ± 48.5, 110.6 ± 54.5, and 321.6 ± 176.1 gr/day, respectively. The intakes for iron, calcium, folic acid, vitamin B12, and vitamin B1 were below the Dietary Reference Intake (DRI) recommendations for 46, 48, 58, 14, and 34 % of the study population, respectively. We found a low prevalence of nutritional deficiencies pre-operatively except for vitamin D. Most micronutrient intake did not reach the DRI recommendations, despite high-caloric and macronutrient intake indicating a poor dietary quality.

The endocannabinoid (eCB) system plays a key role in the development of obesity and its comorbidities. Limited information exists on the changes in circulating eCBs following bariatric surgery. This study aims to (i) assess the circulating levels of eCBs and related molecules and (ii) examine the association between their levels and numerous clinical/metabolic features pre- and post-operatively. Sixty-five morbidly obese patients (age 42.78 ± 9.27 years; BMI 42.00 ± 5.01 kg/m2) underwent laparoscopic sleeve gastrectomy (LSG) surgery, and were followed up for 12 months. Data collected included anthropometrics and metabolic parameters. The serum levels of the eCBs, 2-arachidonoylglycerol (2-AG), anandamide (AEA); and their related molecules, arachidonic acid (AA) and oleoylethanolamine (OEA) were measured by liquid chromatography-mass spectrometry. Levels of 2-AG, AEA, and AA were reduced post operatively with no differences in serum OEA levels. The delta changes in eCB levels between pre- and post-operation were correlated with the delta of different metabolic parameters. Positive correlations were found between delta AA and waist circumference (WC) (r = 0.28, P

AIM To evaluate the association between the Mediterranean diet (MD) pattern and its components, and advanced colorectal polyps (adenoma and serrated adenoma). METHODS A case-control study among patients undergoing screening, diagnostic or surveillance colonoscopies during 2010-2015 at the Tel-Aviv Medical Center, Gastroenterology Department. Cases with advanced polyps were defined as: Advanced adenoma [> 10 mm, with features of high grade dysplasia (HGD) or villous histology], advanced serrated adenoma (> 10 mm or with dysplasia) or multiple (≥ 3) non-advanced adenomas or serrated adenomas. Cases of non-advanced adenomas were defined as adenomas < 10 mm, without features of HGD or villous histology. Controls were defined as those without polyps at the current colonoscopy and without a history of colorectal polyps. Data collection included: anthropometrics measured according to a standardized protocol, fasting blood tests performed at the same lab, medical history recorded by a structured interview and dietary intake evaluated by a 116-item food frequency questionnaire. Adherence to the MD components was evaluated according to intake above/below the sample median, for potentially beneficial/detrimental components respectively, as accepted. RESULTS We recruited 206 cases with advanced polyps, 192 cases with non-advanced adenoma and 385 controls. The number of adhered MD components was inversely associated with a diagnosis of advanced polyps in a dose-response manner (OR = 0.34, 95%CI: 0.17-0.65; OR = 0.22, 95%CI: 0.11-0.43; and OR = 0.18, 95%CI: 0.07-0.47 for 3-4, 5-7 and 8-10 components, respectively), but not with non-advanced adenomas (OR = 0.54, 95%CI: 0.25-1.13; OR = 0.48, 95%CI: 0.23-0.99; and OR = 0.43, 95%CI: 0.16-1.12 for 3-4, 5-7 and 8-10 components, respectively). Low intake of sugar-sweetened beverages and red meat, as well as high intake of fish, were inversely associated with advanced polyps (OR = 0.56, 95%CI: 0.36-0.87; OR = 0.63, 95%CI: 0.42-0.95; and OR = 0.66, 95%CI: 0.44-0.99, respectively), while only low intake of red meat was inversely associated with non-advanced adenomas (OR = 0.71, 95%CI: 0.49-0.97). CONCLUSION A better adherence to the MD, specifically low intake of sugar-sweetened beverages and red meat as well as high intake of fish, is related to lower odds for advanced polyps.

The goal of this study is to test the association between lifetime smoking habits and colorectal polyps of different classifications.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.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.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.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.

Liver stiffness and spleen stiffness in patients with myelofibrosis have traditionally been assessed through manual palpation and thus influenced by interobserver variability. In this article, for the first time, liver stiffness and spleen stiffness of patients with myelofibrosis were evaluated through FibroScan and shear wave elastography (SWE). Nine patients with myelofibrosis comprised the study group. They were compared with 11 patients with liver cirrhosis and 8 healthy volunteers. Before the FibroScan study, all patients underwent ultrasound study to delineate the left intercostal space for validated measurements. In patients with myelofibrosis, the mean stiffness of the spleen was 41.3 and 32.9 kilopascals (kPa) through FibroScan and SWE, respectively. The mean stiffness of the liver was 7.8 kPa through FibroScan and 10.4 kPa through SWE. The stiffness of the spleen in patients with cirrhosis was even higher, reaching a mean of 58.5 kPa through FibroScan and 40.5 kPa through SWE. The means were considerably lower among the healthy controls (13.5 and 18.1 kPa, respectively). The correlation between spleen stiffness among the patients with cirrhosis is negative and opposite in direction (r = -0.35) in comparison with the patients with myelofibrosis (r = 0.78). Among the patients with liver cirrhosis and myelofibrosis, spleen size was weakly related to spleen stiffness as assessed through SWE (r = 0.49) but had almost no relation to the FibroScan measure (r = 0.13). The FibroScan and SWE of the spleen have little ability to distinguish between the patients with myelofibrosis and cirrhosis, but they do differentiate both patient groups from the healthy controls. The stiffness of spleen and liver as measured through FibroScan and SWE was not correlated to the longevity of myelofibrosis.

Retrospective studies suggest that coffee consumption may exert beneficial effects in patients with nonalcoholic fatty liver; however, prospective data supporting a protective role on liver steatosis development are lacking. In this study, we aimed to evaluate the association between coffee consumption and fatty liver onset in the general population. The analysis was performed both in a cross-sectional cohort (n = 347) and, prospectively, in a subcohort of patients without fatty liver at baseline and followed-up for 7 years (n = 147). Fatty liver was diagnosed with abdominal ultrasound and liver steatosis was quantified noninvasively by hepatorenal index (HRI) and SteatoTest, whereas FibroTest was used to assess fibrosis degree. A structured questionnaire on coffee consumption was administrated during a face-to-face interview. Neither the incidence nor the prevalence of fatty liver according to ultrasonography, SteatoTest, and the HRI was associated with coffee consumption. In the cross-sectional study, high coffee consumption was associated with a lower proportion of clinically significant fibrosis ≥F2 (8.8% vs 16.3%; P = 0.038); consistently, in multivariate logistic regression analysis, high coffee consumption was associated with lower odds for significant fibrosis (odds ratio = 0.49, 95% confidence interval, 0.25–0.97; P = 0.041) and was the strongest predictor for significant fibrosis. No association was demonstrated between coffee consumption and the new onset of nonalcoholic fatty liver, but coffee intake may exert beneficial effects on fibrosis progression.

Objective Prevention of colorectal cancer (CRC) by colonoscopy is recommended according to age and personal/familial history. Metabolic alterations are associated with colorectal adenomas, but data are scarce regarding serrated polyps and advanced polyps. The aim of this study was to evaluate the association between metabolic alterations and colorectal polyp type and advanced polyps. Methods A case-control study was conducted among consecutive subjects, 40 to 70 years old, who underwent screening/diagnostic colonoscopy from 2010 to 2015. Subjects who were treated for diabetes, who had a family/personal history of CRC, and who were at high risk for CRC were excluded. Participants underwent anthropometric, laboratory, and ultrasonographic evaluations and a medical and lifestyle interview. Polyps were histologically classified as adenomatous or serrated polyps and divided into advanced and non-advanced categories. Results The study included 828 participants (58.4 ± 6.6 years, 50.4% men). Abdominal obesity (odds ratio [OR] = 1.67, 95% CI: 1.20-2.30), hypertension (OR = 1.47, 95% CI: 1.03-2.09), and a high glycosylated hemoglobin percentage (HbA1c%) (OR = 1.57, 95% CI: 1.06-2.34) were independently associated with colorectal adenomas, whereas a high triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio was independently associated with serrated polyps (OR = 2.31, 95% CI: 1.32-4.03). A combination of three metabolic alterations was strongly associated with colorectal polyps. Conclusions Abdominal obesity, hypertension, and a high HbA1c% are independently associated with adenomas, whereas a high TG/HDL ratio is associated with serrated polyps. These parameters are easily accessible in clinical practice and may help define high-risk groups for CRC.

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.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).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).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.

Probiotics are commonly used after bariatric surgery; however, uncertainty remains regarding their efficacy. Our aim was to compare the effect of probiotics vs placebo on hepatic, inflammatory and clinical outcomes following laparoscopic sleeve gastrectomy (LSG). This randomized, double-blind, placebo-controlled, trial of 6-month treatment with probiotics (Bio-25; Supherb) vs placebo and 6 months of additional follow-up was conducted among 100 morbidly obese nonalcoholic fatty liver disease (NAFLD) patients who underwent LSG surgery. The primary outcome was a reduction in liver fat content, measured by abdominal ultrasound, and secondary outcomes were improvement of fibrosis, measured by shear-wave elastography, metabolic and inflammatory parameters, anthropometrics and quality of life (QOL). Fecal samples were collected and analyzed for microbial composition. One hundred patients (60% women, mean age of 41.9±9.8 years and body mass index of 42.3±4.7 kg m−2) were randomized, 80% attended the 6-month visit and 77% completed the 12-month follow-up. Fat content and NAFLD remission rate were similarly reduced in the probiotics and placebo groups at 6 months postsurgery (−0.9±0.5 vs −0.7±0.4 score; P=0.059 and 52.5 vs 40%; P=0.262, respectively) and at 12 months postsurgery. Fibrosis, liver-enzymes, C-reactive protein (CRP), leptin and cytokeratin-18 levels were significantly reduced and QOL significantly improved within groups (P⩽0.014 for all), but not between groups (P⩾0.173 for all) at 6 and 12 months postsurgery. Within-sample microbiota diversity (alpha-diversity) increased at 6-month postsurgery compared with baseline in both study arms (P⩽0.008) and decreased again at 12 months postsurgery compared with 6 months postsurgery (P⩽0.004) but did not reach baseline values. Probiotics administration does not improve hepatic, inflammatory and clinical outcomes 6- and 12 months post-LSG.

AIM: To examine the association between non-alcoholic fatty liver disease (NAFLD) and general health perception. METHODS: This cross sectional and prospective follow-up study was performed on a cohort of a sub-sample of the first Israeli national health and nutrition examination survey, with no secondary liver disease or history of alcohol abuse. On the first survey, in 2003-2004, 349 participants were included. In 2009-2010 participants from the baseline survey were invited to participate in a follow-up survey. On both baseline and follow-up surveys the data collected included: self-reported general health perception, physical activity habits, frequency of physician's visits, fatigue impact scale and abdominal ultrasound. Fatty liver was diagnosed by abdominal ultrasonography using standardized criteria and the ratio between the median brightness level of the liver and the right kidney was calculated to determine the Hepato-Renal Index. RESULTS: Out of 349 eligible participants in the first survey, 213 volunteers participated in the follow-up cohort and were included in the current analysis, NAFLD was diagnosed in 70/213 (32.9%). The prevalence of "very good" self-reported health perception was lower among participants diagnosed with NAFLD compared to those without NAFLD. However, adjustment for BMI attenuated the association (OR = 0.73, 95%CI: 0.36-1.50, P = 0.392). Similar results were observed for the hepato-renal index; it was inversely associated with "very good" health perception but adjustment for BMI attenuated the association. In a full model of multivariate analysis, that included all potential predictors for health perception, NAFLD was not associated with the self-reported general health perception (OR = 0.86, 95%CI: 0.40-1.86, P = 0.704). The odds for "very good" self-reported general health perception (compared to "else") increased among men (OR = 2.42, 95%CI: 1.26-4.66, P = 0.008) and those with higher performance of leisure time physical activity (OR = 1.01, 95%CI: 1.00-1.01, P < 0.001, per every minute/week) and decreased with increasing level of BMI (OR = 0.91, 95%CI: 0.84-0.99, P = 0.028, per every kg/m2) and older age (OR = 0.96, 95%CI: 0.93-0.99, P = 0.033, per one year). Current smoking was not associated with health perception (OR = 1.31, 95%CI: 0.54-3.16, P = 0.552). Newly diagnosed (naive) and previously diagnosed (at the first survey, not naive) NAFLD patients did not differ in their self-health perception. The presence of NAFLD at the first survey as compared to normal liver did not predict health perception deterioration at the 7 years follow-up. In terms of health-services utilization, subjects diagnosed with NAFLD had a similar number of physician’s visits (general physicians and specialty consultants) as in the normal liver group. Parameters in the fatigue impact scale were equivalent between the NAFLD and the normal liver groups. CONCLUSION: Fatty liver without clinically significant liver disease does not have independent impact on self-health perception.

AIM To describe the relationships between non-alcoholic fatty-liver disease (NAFLD) patient’s disease consequences and treatment perceptions, self-efficacy, and healthy lifestyle maintenance. METHODS A cross-sectional study among 146 ultrasound diagnosed NAFLD patients who visited the fatty liver clinic at the Tel-Aviv Medical Center. Eighty-seven of these individuals, participated in a clinical trial of physical activity and underwent fasting blood tests, analyzed at the same lab. Exclusion criteria included positivity for serum HBsAg or anti-HCV antibodies; fatty liver suspected to be secondary to hepatotoxic drugs; excessive alcohol consumption (≥ 30 g/d in men or ≥ 20 g/d in women) and positive markers of genetic or immune-mediated liver diseases. Patients were asked to complete a self-report structured questionnaire, assembled by the Israeli Center for Disease Control. Nutrition habits were measured using six yes/no questions (0 = no, 1 = yes) adopted from the national survey questionnaire. Participants in the clinical trial completed a detailed semi-quantitative food frequency questionnaire (FFQ) reporting their habitual nutritional intake during the past year. Self-efficacy was assessed by the Self-Efficacy Scale questionnaire, emotional representation, degree of illness understanding, timeline perception, treatment perception and symptoms were measured by the Brief Illness Perception questionnaire. Illness consequences were measured by the Personal Models of Diabetes Interview questionnaire. A path analysis was performed to describe the interrelationships between the patients’ illness perceptions, and assess the extent to which the data fit a prediction of nutritional habits. RESULTS The study sample included 54.1% men, with a mean age of 47.76 ± 11.68 years (range: 20-60) and mean body mass index of 31.56 ± 4.6. The average perceived nutrition habits score was 4.73 ± 1.45 on a scale between 0-6, where 6 represents the healthiest eating habits. Most of the study participants (57.2%) did not feel they fully understood what NAFLD is. Better nutritional habits were positively predicted by the degree of illness understanding (β = 0.26; P = 0.002) and self-efficacy (β = 0.25; P = 0.003). Perceptions of more severe illness consequences were related with higher emotional representation (β = 0.55; P < 0.001), which was related with lower self-efficacy (β = -0.17; P = 0.034). The perception of treatment effectiveness was positively related with self-efficacy (β = 0.32; P < 0.001). In accordance with the correlation between self-efficacy and the perceived nutrition habits score, self-efficacy was also correlated with nutrient intake evaluated by the FFQ; negatively with saturated fat (percent of saturated fat calories from total calories) (r = -0.28, P = 0.010) and positively with fiber (r = 0.22, P = 0.047) and vitamin C intake (r = 0.34, P = 0.002). In a sub analysis of the clinical trial participants, objectively measured compliance to physical activity regimen was positively correlated with the self-efficacy level (r = 0.34, P = 0.046). CONCLUSION Self-efficacy and illness understanding are major determinants of lifestyle-modification among NAFLD patients. This information can assist clinicians in improving compliance with lifestyle changes among these patients.

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.

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 hepatorenal 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.

To evaluate the association between circulating levels of endocannabinoids (eCBs) and non-alcoholic fatty liver disease (NAFLD).The serum levels of the main eCBs, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their endogenous precursor and breakdown product, arachidonic acid (AA), were analyzed by liquid chromatography/tandem mass spectrometry in 105 volunteers screened for NAFLD. Hepatic ultrasound, fasting blood tests, and anthropometrics were assessed. Liver fat was quantified by the hepato-renal-ultrasound index representing the ratio between the brightness level of the liver and the kidney.Patients with NAFLD had higher levels (pmol/mL) of AA (2,721 ± 1,112 vs. 2,248 ± 977, P = 0.022) and 2-AG (46.5 ± 25.8 vs. 33.5 ± 13.6, P = 0.003), but not AEA. The trend for higher levels of AA and 2-AG in the presence of NAFLD was observed in both genders and within subgroups of overweight and obesity. The association of AA and 2-AG with NAFLD was maintained with adjustment for age, gender, and BMI (OR = 1.001, 1.000-1.001 95% CI, P = 0.008 and OR = 1.05, 1.01-1.09, P = 0.006, respectively) or waist circumference.This study is the first to show high circulating levels of 2-AG and AA in NAFLD patients compared with controls, independent of obesity. The findings may suggest an independent role of eCBs in the pathogenesis of NAFLD.

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.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.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, p0.001) 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.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.

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.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.A significant correlation was found between histologic steatosis and the hepatorenal sonographic index (r = 0.82, p0.001). The validity of the hepatorenal sonographic index for the diagnosis of fatty liver was compared with liver biopsies with a steatosis level5%. 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 steatosis5% 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%.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.

Background There is little information on the relationship between growth hormone/insulin-like growth factor-I (GH/IGF-I) deficiency or IGF-I treatment on nonalcoholic fatty liver disease (NAFLD) a disorder linked to obesity and insulin resistance. Objective To find out whether the markedly obese patients with Laron syndrome (LS) and GH gene deletion have fatty livers. Subjects We studied 11 untreated adult patients with LS (5M, 6F), five girls with LS treated by IGF-I and five adult patients with GH gene deletion (3M, 3F), four previously treated by hGH in childhood. Methods Fatty liver was quantitatively evaluated by ultrasonography using a phase array US system (HITACHI 6500, Japan). Body adiposity was determined by DEXA, and insulin resistance was estimated by HOMA-IR using the fasting serum glucose and insulin values. Results Six out of 11 adult patients with LS, two out of the five IGF-I treated girls with LS and three out of five adult hGH gene deletion patients were found to have NAFLD (nonalcoholic fatty liver disease). Conclusion NAFLD is a frequent complication in untreated and treated congenital IGF-I deficiency. No correlation between NAFLD and age, sex, degree of obesity, blood lipids, or degree of insulin resistance was observed.

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 < 0.03). The SteatoTest was significantly lower among subjects engaging in any PA or resistance PA at least once a week (P < 0.01). PA at least once a week in all categories was associated with a reduced risk for abdominal obesity. Adjusting for sex, engaging in any kind of sports (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.440.96 per 1 standard deviation increment in PA score) and resistance exercise (OR 0.61, 95% CI 0.38-0.85) were inversely associated with NAFLD. These associations remained unchanged after adjusting for homeostasis model assessment, most nutritional factors, adiponectin, and resistin. Only the association with resistance PA remained significant with further adjustment for body mass index (OR 0.61, 95% CI 0.44-0.85). Adding leptin or waist circumference to the model eliminated the statistical significance. Conclusion: Habitual leisure-time PA, especially anaerobic, may play a protective role in NAFLD. This association appears to be mediated by a reduced rate of abdominal obesity. (HEPATOLOGY 2008;48: 000-000.)

Weight loss is considered therapeutic for patients with NAFLD. However, there is no epidemiological evidence that dietary habits are associated with NAFLD. Dietary patterns associated with primary NAFLD were investigated.A cross-sectional study of a sub-sample (n=375) of the Israeli National Health and Nutrition Survey. Exclusion criteria were any known etiology for secondary NAFLD. Participants underwent an abdominal ultrasound, biochemical tests, dietary and anthropometric evaluations. A semi-quantitative food-frequency questionnaire was administered.After exclusion, 349 volunteers (52.7% male, mean age 50.7+/-10.4, 30.9% primary NAFLD) were included. The NAFLD group consumed almost twice the amount of soft drinks (P=0.03) and 27% more meat (P0.001). In contrast, the NAFLD group consumed somewhat less fish rich in omega-3 (P=0.056). Adjusting for age, gender, BMI and total calories, intake of soft drinks and meat was significantly associated with an increased risk for NAFLD (OR=1.45, 1.13-1.85 95% CI and OR=1.37, 1.04-1.83 95% CI, respectively).NAFLD patients have a higher intake of soft drinks and meat and a tendency towards a lower intake of fish rich in omega-3. Moreover, a higher intake of soft drinks and meat is associated with an increased risk of NAFLD, independently of age, gender, BMI and total calories.

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.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.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 values160 mg/dl developed NAFLD (P for trend = 0.015).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.

The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this “gold-standard” is imperfect; even according to its proponents, it is only “the best” among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future.

Background & Aims: Few controlled studies have addressed the issue of effective medical treatment for nonalcoholic fatty liver disease (NAFLD). We herein assessed the effect of orlistat in patients with NAFLD. Methods: We performed a randomized, double-blind, placebo-controlled study on 52 patients with NAFLD diagnosed by ultrasound (US) and confirmed by liver biopsy (40 patients). The patients were randomized to receive either orlistat (120 mg 3 times daily for 6 months) or placebo. All patients participated in an identical behavioral weight loss program. All patients underwent monthly evaluation by abdominal US; liver enzyme levels, lipid profiles, insulin levels, and anthropometric parameters were monitored, and all patients underwent nutritional follow-up evaluation. Twenty-two patients underwent a second liver biopsy examination at the end of the study. Results: Fifty-two patients were recruited and 44 (mean age, 47.7 y; mean body mass index, 33) completed the study. Serum glucose and insulin levels (P < .03) were significantly higher in the orlistat group, which also presented a higher degree of fibrosis. Body mass index was reduced significantly in each group, with a nonsignificant difference between the groups. Serum alanine transaminase (ALT) levels decreased significantly in both groups, with an almost 2-fold reduction in the orlistat group (48% vs 26.4%). There was a statistically significant reversal of fatty liver by US only in the orlistat group (P < .05). Conclusions: Orlistat improves serum ALT levels and steatosis on US in NAFLD patients, beyond its effect on weight reduction.