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Nonalcoholic fatty liver disease (NAFLD) can progress to advanced fibrosis, which, in the nonsurgical population, is associated with poor hepatic and extrahepatic outcomes. Despite its high prevalence, NAFLD and related liver fibrosis may be overlooked during the preoperative evaluation, and the role of liver fibrosis as an independent risk factor for surgical-related mortality has yet to be tested. The aim of this study was to assess whether fibrosis-4 (FIB-4), which consists of age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelets, a validated marker of liver fibrosis, is associated with postoperative mortality in the general surgical population.A historical cohort of patients undergoing general anesthesia at an academic medical center between 2014 and 2018 was analyzed. Exclusion criteria included known liver disease, acute liver disease or hepatic failure, and alcohol use disorder. FIB-4 score was categorized into 3 validated predefined categories: FIB-4 ≤1.3, ruling out advanced fibrosis;1.3 and2.67, inconclusive; and ≥2.67, suggesting advanced fibrosis. The primary analytic method was propensity score matching (FIB-4 was dichotomized to indicate advanced fibrosis), and a secondary analysis included a multivariable logistic regression.Of 19,861 included subjects, 1995 (10%) had advanced fibrosis per FIB-4 criteria. Mortality occurred intraoperatively in 15 patients (0.1%), during hospitalization in 272 patients (1.4%), and within 30 days of surgery in 417 patients (2.1%). FIB-4 ≥2.67 was associated with increased intraoperative mortality (odds ratio [OR], 3.63; 95% confidence interval [CI], 1.25-10.58), mortality during hospitalization (OR, 3.14; 95% CI, 2.37-4.16), and within 30 days from surgery (OR, 2.46; 95% CI, 1.95-3.10), after adjusting for other risk factors. FIB-4 was related to increased mortality in a dose-dependent manner for the 3 FIB-4 categories ≤1.3 (reference),1.3 and2.67, and ≥2.67, respectively; during hospitalization (OR, 1.89; 95% CI, 1.34-2.65 and OR, 4.70; 95% CI, 3.27-6.76) and within 30 days from surgery (OR, 1.77; 95% CI, 1.36-2.31 and OR, 3.55; 95% CI, 2.65-4.77). In a 1:1 propensity-matched sample (N = 1994 per group), the differences in mortality remained. Comparing the FIB-4 ≥2.67 versus the FIB-42.67 groups, respectively, mortality during hospitalization was 5.1% vs 2.2% (OR, 2.70; 95% CI, 1.81-4.02), and 30-day mortality was 6.6% vs 3.4% (OR, 2.26; 95% CI, 1.62-3.14).A simple liver fibrosis marker is strongly associated with perioperative mortality in a population without apparent liver disease, and may aid in future surgical risk stratification and preoperative optimization.

Background Ultra-processed food (UPF) consumption is related to increased morbidity and mortality. However, knowledge on its association with cognitive function is lacking. In this longitudinal study, we examined the associations between UPF intake and cognitive decline in older adults with type-2 diabetes (T2D). Methods The sample included initially nondemented T2D older adults (≥65 years), from the Israel Diabetes and Cognitive Decline study, who had complete information on nutrition at baseline and at least 3 cognitive assessments (mean follow-up 5.3 ± 1.5 years). Nutritional intake was evaluated by a validated Food-Frequency Questionnaire, and foods were categorized as UPF based on NOVA classification. Percent of calories from UPF were calculated from total caloric consumption in total and specific food groups. Mixed effect models were used to examine the link between UPF intake (top vs bottom quartiles) and change in cognitive function overall and in specific domains, adjusting for potential confounders. Results Of the total sample (N = 568; mean age 71.3 ± 4.5 years, 60% men), 141 consumed >31% kcal from UPF (top quartile). Greater intake of ultra-processed meat was associated with a faster decline in executive functions and global cognition (β = −0.041 ± 0.013; p = .002 and β = −0.026 ± 0.010; p = .011, respectively). Additionally, consumption of ultra-processed oils/spreads was associated with faster decline in executive functions and global cognition (β = −0.037 ± 0.014; p = .006 and β = −0.028 ± 0.010; p = .009, respectively). Total UPF consumption and UPF-derived from dairy products and bread/pastries/starch were not associated with cognitive change. Conclusion This study suggests that a high intake of ultra-processed meat and oils/spreads may be associated with accelerated cognitive decline in older individuals with T2D.

Different dietary regimens for weight loss have developed over the years. Since the most evidenced treatment for non-alcoholic fatty liver disease (NAFLD) is weight reduction, it is not surprising that more diets targeting obesity are also utilized for NAFLD treatment. However, beyond the desired weight loss effects, one should not ignore the dietary composition of each diet, which may not necessarily be healthy or safe over the long term for hepatic and extrahepatic outcomes, especially cardiometabolic outcomes. Some of these diets are rich in saturated fat and red meat, are very strict, and require close medical supervision. Some may also be very difficult to adhere to for long periods, thus reducing the patient's motivation. The evidence for a direct benefit to NAFLD by restrictive diets such as very-low-carb, ketogenic, very-low-calorie diets, and intermittent fasting is scarce, and the long-term safety has not been tested. Nowadays, the approach is that the diet should be tailored to the patient's cultural and personal preferences. There is strong evidence for the independent protective association of NAFLD with a diet based on healthy eating patterns of minimally-processed foods, low in sugar and saturated fat, high in polyphenols, and healthy types of fats. This leads to the conclusion that a Mediterranean diet should serve as a basis that can be restructured into other kinds of diets. This review will elaborate on the different diets and their role in NAFLD. It will provide a practical guide to tailor the diet to the patients without compromising its composition and safety.

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.

Several studies have demonstrated that curcumin can cause the regression of polyps in familial adenomatous polyposis (FAP), while others have shown negative results. Wholistic turmeric (WT) containing curcumin and additional bioactive compounds may contribute to this effect. We performed a double-blinded, randomized, controlled trial to assess the efficacy of WT in FAP patients. Ten FAP patients were randomly assigned to receive either WT or placebo for 6 months. Colonoscopies were performed at baseline and after 6 months. The polyp number and size, as well as the cumulative polyp burden, were assessed. No differences were noted between the groups in terms of changes from the baseline’s polyp number, size, or burden. However, stratifying the data according to the right vs. left colon indicated a decrease in the median polyp number (from 5.5 to 1.5, p = 0.06) and polyp burden (from 24.25 mm to 11.5 mm, p = 0.028) in the left colon of the patients in the WT group. The adjusted left polyp number and burden in the WT arm were lower by 5.39 (p = 0.034) and 14.68 mm (p = 0.059), respectively. Whether WT can be used to reduce the polyp burden of patients with predominantly left-sided polyps remains to be seen; thus, further larger prospective trials are required.

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.

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

Malnutrition and sarcopenia that lead to functional deterioration, frailty, and increased risk for complications and mortality are common in cirrhosis. Sarcopenic obesity, which is associated with worse outcomes than either condition alone, may be overlooked. Lifestyle intervention aiming for moderate weight reduction can be offered to obese compensated cirrhotic patients, with diet consisting of reduced caloric intake, achieved by reduction of carbohydrate and fat intake, while maintaining high protein intake. Dietary and moderate exercise interventions in patients with cirrhosis are beneficial. Cirrhotic patients with malnutrition should have nutritional counseling, and all patients should be encouraged to avoid a sedentary lifestyle.

Smoking and ultra-processed foods (UPFs), a substantial part of the western diet, have been suggested to have a potential carcinogenic effect, though epidemiologic data are lacking. We aimed to examine the association between high UPF intake and colorectal adenomas, and to test the interaction with smoking. In a case-control study among consecutive subjects undergoing colonoscopy in a tertiary center during 2010–2015, UPF intake and smoking were compared between cases with colorectal adenomas and controls. Within 652 participants (cases, n = 294 and controls, n = 358), high UPF intake (defined as percent of kcal from UPF above the study sample upper tertile) was positively associated with adenomas (Odds ratio (OR) = 1.75, 95% Confidence interval (CI) 1.14–2.68), advanced and proximal adenomas (OR = 2.17, 1.29–3.65 and OR = 2.38, 1.37–4.11) among the whole study sample, and with adenomas (OR = 3.54, 1.90–6.61), non-advanced adenomas (OR = 2.60, 1.20–5.63), advanced adenomas (OR = 4.76, 2.20–10.30), proximal adenomas (OR = 6.23, 2.67–14.52), and distal adenomas (OR = 2.49, 1.21–5.13) among smokers. Additionally, a dose-dependent association was observed between tertiles of UPF intake and adenomas only among smokers (p for trend &lt, 0.001). A significant interaction between smoking and high UPF intake was detected (p for interaction = 0.004). High intake of UPFs is strongly and independently associated with colorectal adenomas, especially advanced and proximal adenoma, and interacts with smoking. Results highlight smokers as more susceptible to the negative health effects of UPF consumption on colorectal neoplasia.

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.

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.