Search

BACKGROUND: We assessed the relationship of liver fibrosis score with incident dementia in a large, national sample. METHODS: For this retrospective cohort study, data of dementia‐free individuals aged 40‐69 years were derived from electronic records of the largest healthcare provider in Israel. The association between liver fibrosis score (FIB‐4), assessed from routine laboratory measurements, and incident dementia was explored through multivariate cox regression models. RESULTS: Of the total sample (N = 826,578, mean age 55 ± 8 years at baseline), 636,967 (77%) had no fibrosis, 180,114 (21.8%) had inconclusive fibrosis status and 9497 (1.2%) had high risk for advanced fibrosis. Over a median follow‐up of 17 years, 41,089 dementia cases were recorded. Inconclusive liver fibrosis and advanced fibrosis were associated with increased dementia risk (HR = 1.09, 95%CI: 1.07–1.11 and HR = 1.18, 95%CI: 1.10–1.27, respectively). This association remained robust through seven sensitivity analyses. CONCLUSIONS: Liver fibrosis assessed through a serum‐based algorithm may serve as a risk factor for dementia in the general population. Highlights: Liver fibrosis may predict dementia diagnosis in the general population.Inconclusive liver fibrosis was associated with 9% increased dementia risk.Advanced liver fibrosis was associated with 18% increased dementia risk.Findings remained robust in sensitivity analyses and after adjustments. [ABSTRACT FROM AUTHOR]

Non‐alcoholic fatty liver disease (NAFLD) affects at least 25% of the general population and is an increasingly important cause of cirrhosis and hepatocellular carcinoma. Although it is the research focus of the hepatology field, it is clear that primary care physicians are seeing the majority of NAFLD patients and are in a pivotal position to provide quality care. In this article, we review the role of primary care in the management of NAFLD. NAFLD is common in patients with diabetes, obesity and other metabolic risk factors. Abdominal ultrasonography is the most commonly used method to diagnose fatty liver. Simple fibrosis scores have high negative predictive values in excluding advanced liver fibrosis and future liver‐related events and can be used in primary care as initial evaluation. An abnormal result should be followed by subsequent workup or specialist referral. Primary care is the ideal setting to institute multidisciplinary care, especially the involvement of dietitians and physical activity trainers in lifestyle intervention, as well as initiating the discussion of bariatric surgery in patients with severe obesity. Although specific drug treatment for steatohepatitis would require a more precise diagnosis, metabolic drugs that improve both steatohepatitis and cardiovascular outcomes (e.g. glucagon‐like peptide‐1 receptor agonists) may be considered in patients with NAFLD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Background: Non‐alcoholic fatty liver disease (NAFLD) is a highly prevalent condition that requires a comprehensive and coordinated response across sectors and disciplines. Aims: In the absence of a multisectoral framework to tackle this condition, we developed one using the sustainable development goals (SDGs) as the basis for converging thinking about the design and delivery of public health responses. Methods: A multidisciplinary group identified the SDG targets and indicators for inclusion in the new framework through a two‐stage process. Firstly, a core team of three researchers independently reviewed the 169 targets and 231 indicators of the SDGs to select a shortlist. Over two Delphi rounds, a multidisciplinary group of 12 experts selected which of the shortlisted targets and indicators to include. Respondents also provided written feedback on their selection. Targets and indicators with 75% or greater agreement were included in the final framework. Results: The final framework comprises 16 targets—representing 9% of all targets and 62% (16/26) of the shortlisted targets—and seven indicators, accounting for 50% (7/14) of the shortlisted indicators and 3% of all indicators. The selected targets and indicators cover a broad range of factors, from health, food and nutrition to education, the economy, and the built environment. Conclusions: Addressing the challenge of NAFLD will require a re‐envisioning of the liver health landscape, with greater focus on joined‐up systems thinking and action. This new framework can help guide this process, including by outlining the stakeholders with whom the liver health community needs to engage. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: People with non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH) are stigmatized, partly since 'non‐alcoholic' is in the name, but also because of obesity, which is a common condition in this group. Stigma is pervasive in social media and can contribute to poorer health outcomes. We examine how stigma and negative feelings concerning NAFLD/NASH and obesity manifest on Twitter. Methods: Using a self‐developed search terms index, we collected NAFLD/NASH tweets from May to October 2019 (Phase I). Because stigmatizing NAFLD/NASH tweets were limited, Phase II focused on obesity (November‐December 2019). Via sentiment analysis, >5000 tweets were annotated as positive, neutral or negative and used to train machine learning–based Natural Language Processing software, applied to 193 747 randomly sampled tweets. All tweets collected were analysed. Results: In Phase I, 16 835 tweets for NAFLD and 2376 for NASH were retrieved. Of the annotated NAFLD/NASH tweets, 97/1130 (8.6%) and 63/535 (11.8%), respectively, related to obesity and 13/1130 (1.2%) and 5/535 (0.9%), to stigma; they primarily focused on scientific discourse and unverified information. Of the 193 747 non‐annotated obesity tweets (Phase II), the algorithm classified 40.0% as related to obesity, of which 85.2% were negative, 1.0% positive and 13.7% neutral. Conclusions: NAFLD/NASH tweets mostly indicated an unmet information need and showed no clear signs of stigma. However, the negative content of obesity tweets was recurrent. As obesity‐related stigma is associated with reduced care engagement and lifestyle modification, the main NAFLD/NASH treatment, stigma‐reducing interventions in social media should be included in the liver health agenda. [ABSTRACT FROM AUTHOR]

Background and aims: Effective therapy for clinically significant fibrosis in nonalcoholic fatty liver disease (NAFLD) is an unmet need. Data on the effectiveness of endoscopic placement of intragastric balloon (IGB) in patients with NAFLD are limited. In this study, we evaluated the impact of IGB placement in NAFLD patients with advanced fibrosis. Methods: We retrospectively assessed the effects of the Orbera™ fluid‐filled IGB in a cohort of obese patients with liver stiffness ≥9.7 kPa (corresponding to F3‐F4). Patients with endoscopic signs of portal hypertension were excluded. Changes in metabolic and liver parameters from baseline to follow‐up (6 mo) were assessed. Results: A total of 26 obese patients, aged 53 [44 ‐ 62] years, with BMI 35.1 ± 4.7 kg/m2 were included. All patients achieved a significant body weight loss (106 ± 19.7 vs. 92 ± 18.3 kg, P <.001) and waist circumference reduction (116 ± 13.3 vs. 104 ± 13.4 kg, P <.001) at 6‐month follow‐up after IGB placement. Weight loss induced by IGB lowered blood glucose (140 [112; 169] vs. 118 [94; 144] mg/dl, P <.01), glycated hemoglobin (7.5 ± 1.3 vs. 6.6 ± 1.2%, P <.001), FIB‐4 (3.2 ± 0.7 vs. 2.7 ± 0.8, P <.001), liver stiffness (13.3 ± 3.2 vs. 11.3 ± 2.8 kPa, P <.001) and controlled attenuation parameter (355 [298‐400] vs. 296 [255‐352] dB/m, P <.01). Gastroesophageal reflux symptoms were common, but no severe adverse event was observed. Conclusion: Obese patients with advanced liver fibrosis, treated with 6‐month IGB, can achieve regression of fibrosis as assessed by reduction of liver stiffness and FIB‐4. Randomized controlled trials are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition. Accumulating evidence points to an association of NAFLD with cognitive impairment, brain aging and decreased brain activity, yet the association with Alzheimer's disease is unclear. Evidence suggests that liver fibrosis, rather than the existence of hepatic steatosis per se, is a strong prognostic factor for long‐term extra‐hepatic complications. We examined whether NAFLD and risk for advanced fibrosis assessed using a non‐invasive index, are associated with in vivo quantification of brain amyloid and tau pathology. Method: The study sample included participants from the Offspring and Third generation of the Framingham Study. We included participants who underwent positron emission tomography (PET) imaging for assessment of amyloid and tau deposition who do not consume excessive amount of alcohol. Additionally, we included those with information on NAFLD from CT imaging (n=169) or those with all components of the FIB‐4 index (i.e. age, platelets count, aspartate aminotransferase and alanine aminotransferase; n=177). Linear regression models were performed to assess the relationship of NAFLD and risk of advanced fibrosis with amyloid FLR and amyloid and tau regional measures, adjusting for age, sex, time between exposure and PET, and camera, and additionally for body mass index, alcohol consumption, systolic blood pressure, smoking, cardiovascular disease, physical activity, C‐reactive protein, cholesterol, insulin resistance, diabetes, hypertension and visceral adipose tissue. Result: Of the subsample with NAFLD information (mean age 52±9y; 57% males), 57 (34%) had NAFLD. Prevalent NAFLD was not associated with PET amyloid and tau. Of the subsample with information on liver fibrosis (mean age 50±10y; 51% males), 34 (19%) had increased risk of advanced fibrosis (FIB4>1.3). One unit increment of FIB‐4 index (but not advanced fibrosis) was significantly associated with increased tau in the inferior temporal, parahippocampal, entorhinal and rhinal brain regions (table 1). Among individuals with prevalent NAFLD (n=57), liver fibrosis (both continuous and using the 1.3 cutoff) was related to all amyloid and tau measures except for entorhinal amyloid (table 2). Conclusion: This pioneering study suggests a possible association between liver fibrosis and early Alzheimer's disease markers, independently of vascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Non‐alcoholic fatty liver disease (NAFLD) is common and has been recently related to brain health. We aimed to assess the relationships of NAFLD and its severity, using the NAFLD fibrosis score (NFS), with cognitive performance. Methods: Framingham study Offspring and 3rd generation participants were included if they attended exams 9 (2002‐2008) and 2 (2008‐2011), respectively, were free of dementia and stroke, and did not have excessive alcohol intake. Between 2008 and 2011, participants underwent Multi‐detector computed tomography scans of the abdomen to determine NAFLD diagnosis and the NFS was used to categorize the severity of fibrosis. Cross‐sectional relationships of NAFLD and the NFS with cognitive testing of memory, abstract reasoning, visual perception, attention and executive function were assessed, while adjusting for multiple cardiometabolic variables including visceral adipose tissue, diabetes and insulin resistance. Results: Of the 1287 participants (mean age = 61±12 years, 48% men), 378 (29%) had NAFLD. The presence of NAFLD was not associated with cognitive function. However, among those with NAFLD (mean age = 61±12 years; 58% men), high compared to low risk of advanced fibrosis was associated with poorer performance on similarities (β = −2.22 ± 0.83; P = 0.009) and trail‐making B minus A (β = −0.11 ± 0.05; P = 0.028), independently of potential confounders. Conclusions: Participants with high risk of advanced fibrosis may have poorer cognitive function compared to those with low risk, particularly in executive function and abstract reasoning. Future findings are necessary to evaluate the value of the NFS as a biomarker that predicts cognitive impairment and dementia and to explore the role of hepatic fibrosis in brain health. [ABSTRACT FROM AUTHOR]

The prevalence of cardiovascular disease (CVD) death in Israel, a high‐income country that provides universal healthcare, is ~25 percent lower than in the United States. Is better disease management a factor? Primary care physicians answered a web‐based survey asking how they manage patients with CVD risk factors and about the health‐care system at the macro level. Most physicians (53.6 percent) spent 5–10  minutes managing CVD risks; 39.3 percent spent 10–20  minutes. Over 40 percent of physicians scheduled return visits in  less than  3 months. Their emphasis was on either balanced lifestyle and medication management or lifestyle (91 percent), while only 9 percent emphasized medication management. They believe that universal coverage and the motivation of both the doctor and patient are key in the successful outcomes. Israeli physicians provide resource‐intensive disease management, committing time, providing frequently repeated visits, and focusing on a balance of lifestyle and medication management. These practices may provide good chronic disease management and could contribute to reduced cardiovascular death. [ABSTRACT FROM AUTHOR]

Abstract: There are inconsistent data on mortality rates in patients with bullous pemphigoid (BP). Trends in mortality in BP throughout the years are yet to be established. The aim of the present study was to study the mortality in BP patients relative to the general population and to estimate trends in standardized mortality over the past 30 years. We performed a systematic review and meta‐analysis of observational studies in Medline, Embase and Scopus (1823–2017). Reference lists of included studies were also searched for eligible studies. Quality of evidence was assessed using the Newcastle–Ottawa Scale (NOS). A meta‐analysis was performed using random‐effects models to estimate pooled standardized mortality ratios (SMR) with 95% confidence intervals (CI). Meta‐regression models were used to investigate the secular trends in SMR. Ten studies were included covering the period 1960–2015 (1736 patients, 746 deaths). Pooled all‐cause SMR was 3.6 (95% CI, 2.6–5.0). There was no trend in all‐cause SMR across the last three decades (regression coefficient 0.02 [change in logSMR/year]; 95% CI, 0.04–0.08; P = 0.545). In conclusion, there is a 3.6‐fold increased mortality among patients with BP as compared with the age‐matched general population. The excess mortality in BP has not changed significantly over the past 30 years. [ABSTRACT FROM AUTHOR]

Abstract: Background: There is growing evidence linking nonalcoholic fatty liver disease (NAFLD) with reduced glomerular filtration rate (GFR). Living kidney donors do not have underlying kidney disease, but have reduced GFR as a result of nephrectomy. Whether kidney donation is associated with a higher risk for development or progression of NAFLD is currently unknown. Methods: Retrospective evaluation of metabolic parameters and sonographic evidence of NAFLD were performed in 232 living kidney donors and 162 healthy controls. Results: A total of 25 donors and 44 controls had NAFLD at baseline. During a mean follow‐up of 6.8 years, 6 donors (24%) and 17 controls (38.6%) (P = .29) had a remission of NAFLD, related with decreased body mass index (BMI). The progression of NAFLD fibrosis score was similar in both groups. New onset of NAFLD was observed in 14 (6.8%) donors and 13 (11.01%) controls (P = .211), and was related to increased BMI and a higher baseline Fatty Liver Index score. Neither eGFR nor urine albumin excretion in the donors were related to new onset or progression of NAFLD. Conclusions: Reduced kidney function secondary to kidney donation is not associated with increased incidence or progression of NAFLD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease ( NAFLD) has become a major global health burden, leading to increased risk for cirrhosis, hepatocellular carcinoma, type-2 diabetes and cardiovascular disease. Lifestyle intervention aiming at weight reduction is the most established treatment. However, changing the dietary composition even without weight loss can also reduce steatosis and improve metabolic alterations as insulin resistance and lipid profile. The Mediterranean diet ( MD) pattern has been proposed as appropriate for this goal, and was recommended as the diet of choice for the treatment of NAFLD by the EASL- EASD- EASO Clinical Practice Guidelines. The MD has an established superiority in long term weight reduction over low fat diet, but it improves metabolic status and steatosis even without it. However, the effect on liver inflammation and fibrosis was tested only in few observational studies with positive results. Furthermore, considering the strong association between NAFLD and diabetes and CVD, the MD has a highly established advantage in prevention of these diseases, demonstrated in randomized clinical trials. The individual components of the MD such as olive oil, fish, nuts, whole grains, fruits, and vegetables, have been shown to beneficially effect or negatively correlate with NAFLD, while consumption of components that characterize a Western dietary pattern as soft drinks, fructose, meat and saturated fatty acids have been shown to have detrimental association with NAFLD. In this review we will cover the epidemiological evidence and the plausible molecular mechanisms by which the MD as a whole and each of its components can be of benefit in NAFLD. [ABSTRACT FROM AUTHOR]

Aim We sought to determine the extent to which higher lean and fat mass as measured by dual X-ray absorptiometry in older adults with frailty are related to total hip bone mass density (BMD) index and the rate of hip fractures. Methods The data are from the Women's Health Initiative Observational Study. We identified 872 participants aged ≥65 years with body composition measures and positive frailty. Frailty was determined using modified Fried's criteria. Linear and Cox regressions were used to model study outcomes. Results During the follow-up period, 5.6% patients ( n = 49) had sustained a hip fracture. Body composition indexes were associated with total hip BMD ( P < 0.001 for all). In models adjusted for age, ethnicity, smoking, history of fractures, recurrent falls, number of frailty criteria and corresponding lean mass, the hazard ratio for hip fracture per 1 kg/m2 increase in fat mass was 0.73 (95% confidence interval 0.60-0.88) for appendicular compartment, 0.76 (95% confidence interval 0.65-0.89) for trunk and 0.84 (95% confidence interval 0.77-0.93) for whole-body fat mass. The hazard ratio for hip fracture per 1 kg/m2 increase in appendicular lean mass was 0.63 (95% confidence interval 0.46-0.88). However, after final adjustment for total hip BMD, the only index that remained statistically significant was whole-body fat mass ( P for trend = 0.04). Conclusions We showed that in frail older women, higher fat and lean mass was associated with reduced hip-fracture rates. Higher whole-body adiposity, however, was also associated with lower hip-fracture rate independent of total hip BMD. The present results confirm the importance of weight maintenance in frail populations. Geriatr Gerontol Int 2017; 17: 898-904. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between circulating levels of endocannabinoids (eCBs) and non-alcoholic fatty liver disease (NAFLD).Methods: 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.Results: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objectives To compare the ability of the commonly used Women's Health Initiative ( WHI) and Cardiovascular Health Study ( CHS) frailty phenotypes to predict falls, hip fracture, and death in WHI Clinical Trial participants aged 65 and older. Design Longitudinal cohort study. Setting WHI Clinical Trial. Participants Participants with data for WHI and CHS frailty phenotypes (N = 3,558). Measurements Frailty was operationally defined in the CHS as the presence of three or more of weight loss, poor energy, weakness, slowness, and low physical activity. WHI operationalized frailty similarly but with the RAND-36 physical function scale substituted for slowness and weakness ( RAND-36 physical function scale score <13 = 2 points, 13-78 = 1 point, >78 = 0 points). Frailty was defined as a summary score of 3 or greater, prefrailty as a score of 2 or 1, and nonfrailty as a score of 0. Outcomes were modeled using Cox regression. Harrell C-statistics were compared for models containing alternative instruments. Results Approximately 5% of participants were frail based on the CHS or WHI phenotype. The WHI frailty phenotype was associated with higher rates of falls (hazard ratio ( HR) = 1.48, P = .003), hip fracture ( HR = 1.87, P = .04), and death ( HR = 2.32, P < .001). Comparable HRs in CHS-phenotype frail women were 1.32 ( P = .04), 1.08 ( P = .83), and 1.91 ( P < .001), respectively. Harrell C-statistics revealed marked but insignificant differences in predicting abilities between CHS and WHI phenotype models ( P > .50 for all). Conclusion The WHI phenotype, which does not require direct measurements of physical performance, might offer a practical advantage for epidemiological and clinical needs. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the association between currently recommended guidelines and commonly used clinical criteria for body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) and all-cause mortality in frail older women. Design Longitudinal prospective cohort study. Setting Women's Health Initiative (WHI)-Observational Study. Participants A sample of women aged 65-84 with complete data to characterize frailty in the third year of WHI follow-up (N = 11,070). Measurements Frailty phenotype was determined using the modified Fried criteria. Information on anthropometric measures (BMI, WC, WHR) was collected in clinical examinations. Cox proportional hazards models were used to estimate the effect of BMI, WC, and WHR on mortality adjusted for demographic characteristics and health behaviors. Results Over a mean follow-up of 11.5 years, there were 2,911 (26%) deaths in the sample. Women with a BMI from 25.0 to 29.9 kg/m2 (hazard rate ratio ( HR) = 0.80, 95% confidence interval ( CI) = 0.73-0.88) and those with a BMI from 30.0 to 34.9 kg/m2 ( HR = 0.79, 95% CI = 0.71-0.88) had lower mortality than those with a BMI from 18.5 to 24.9 kg/m2. Women with a WHR greater than 0.8 had higher mortality (HR = 1.16, 95% CI = 1.07-1.26) than those with a WHR of 0.8 or less. No difference in mortality was observed according to WC. Stratifying according to chronic morbidity or smoking status or excluding women with early death and unintentional weight loss did not substantially change these findings. Conclusion In frail, older women, having a BMI between 25.0 and 34.9 kg/m2 or a WHR of 0.8 or less was associated with lower mortality. Currently recommended healthy BMI guidelines should be reevaluated for frail older women. [ABSTRACT FROM AUTHOR]

Non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), is emerging as a main health problem in industrialized countries. Lifestyle modifications are effective in the treatment of NAFLD; however, the long-term compliance is low. Therefore, several pharmacological treatments have been proposed but none has shown significant efficacy or long-term safety. Natural polyphenols are a heterogeneous class of polyphenolic compounds contained in vegetables, which are being proposed for the treatment of different metabolic disorders. Although the beneficial effect of these compounds has traditionally related to their antioxidant properties, they also exert several beneficial effects on hepatic and extra-hepatic glucose and lipid homeostasis. Furthermore, natural polyphenols exert antifibrogenic and antitumoural effects in animal models, which appear relevant from a clinical point of view because of the association of NASH with cirrhosis and hepatocellular carcinoma. Several polyphenols, such anthocyanins, curcumin and resveratrol and those present in coffee, tea, soy are available in the diet and their consumption can be proposed as part of a healthy diet for the treatment of NAFLD. Other phenolic compounds, such as silymarin, are commonly consumed worldwide as nutraceuticals or food supplements. Natural antioxidants are reported to have beneficial effects in preclinical models of NAFLD and in pilot clinical trials, and thus need clinical evaluation. In this review, we summarize the existing evidence regarding the potential role of natural antioxidants in the treatment of NAFLD and examine possible future clinical applications. [ABSTRACT FROM AUTHOR]

Background & Aims Elevated serum uric acid levels reflect and also cause both oxidative stress and insulin resistance and are frequently observed in patients with the metabolic syndrome. A strong association exists between the metabolic syndrome and non-alcoholic fatty liver disease ( NAFLD). Therefore, we aimed to test the association between uric acid and elevated alanine aminotransferase ( ALT), as a surrogate for NAFLD, using real-world data. Methods Data used for the cross-sectional study were obtained from Maccabi Healthcare System, a 2-million member health maintenance organization in Israel. The population consisted of individuals aged 20-60 years who underwent blood tests for ALT and uric acid between 1997 and 2012. Individuals with secondary liver disease, celiac, and inflammatory bowel-disease were excluded. Subgroup analysis was performed in subjects who were given the diagnosis of fatty liver in their medical records ( n = 2628). Results The study population included 82 608 people (32.5% men, mean age 43.91 ± 10.15 years). There was a significant positive dose-response association between serum uric acid levels and the rate of elevated serum ALT ( P for trend <0.001). In multivariable model, controlling for potential confounders, the association between uric acid and elevated ALT persisted ( OR = 2.10, 95% CI 1.93-2.29, for the fourth quartile vs. the first). This association was maintained in all categories of gender and BMI. Similar results were observed among patients diagnosed with fatty liver ( OR = 1.77, 1.22-2.57). Conclusions Serum uric acid is independently associated with elevated ALT, as a surrogate for NAFLD, and thus may serve as a serum marker for liver damage and should be further investigated as a risk factor for NAFLD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Only a few studies have assessed the epidemiology of non-alcoholic fatty liver disease (NAFLD). The aim was to evaluate the prevalence of primary NAFLD in a population-based study in Israel and to determine independent risk factors. Methods: A cross-sectional study of a subsample of the Israeli national health survey ( n=352). Individuals with a known etiology for secondary NAFLD were excluded. Each participant underwent an abdominal ultrasound, biochemical tests and an anthropometric evaluation. Results: Three hundred and twenty-six subjects (53.4% male, mean age 50.5±10.3 standard deviaton [SD]) met the inclusion criteria. The prevalence of primary NAFLD was 30% (25–35% 95% confidence intervals [CI]). NAFLD was more prevalent in men than women (38% vs. 21%; P=0.001). Compared with ultrasonography, the sensitivity of serum alanine transaminase (ALT) for the diagnosis of primary NAFLD was 8.2%. Risk factors independently associated with NAFLD included male gender (odds ratios (OR)=2.8, 95% CI 1.5–5.3), abdominal obesity (OR=2.9, 95% CI 1.3–6.4), homeostasis model assessment (OR=5.8, 95% CI 2.0–17.2), hyperinsulinemia (OR=2.3, 95% CI 1.2–4.3, P=0.01) and hypertriglyceridemia (OR=2.4, 95% CI 1.3–4.5). Conclusions: NAFLD is prevalent in the general Israeli population and closely related to the metabolic syndrome. The use of ALT as a marker for NAFLD seriously underestimates its prevalence. [ABSTRACT FROM AUTHOR]

Background: Ultra‐processed foods (UPF) are ready‐to‐eat/heat foods that derive from a series of industrial processes. These products constitute a large and increasing amount of the food supply in high and middle‐income countries. Accumulating evidence point to an association of UPF intake with increased mortality and adverse health outcomes, including cardiovascular and metabolic diseases. However, whether UPF consumption is associated with cognitive function is not clear. We investigated the associations between UPF intake and cognitive decline, in a cohort of older adults at high‐risk for dementia due to type‐2 diabetes (T2D). Method: The study sample included initially non‐demented T2D older adults (≥65y), from the Israel Diabetes and Cognitive Decline (IDCD) study, who had complete information on nutrition at baseline and at least three cognitive assessments (mean follow‐up 5.3±1.5y). 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, first as overall UPF intake and then for specific food groups. Global cognitive functioning and four cognitive domains (episodic memory, working memory/attention, semantic categorization, and executive functions) were assessed. Mixed effect models were used to examine the link between UPF intake (top vs. bottom quartiles) and change in cognitive function while adjusting for age, sex, education, smoking, physical activity, BMI, HbA1C, duration of diabetes, total cholesterol and blood pressure. Result: Of the total sample (N=578; mean age at baseline 71.3±4.5y, 61% men), 144 (top quartile) consumed >31% kcal from UPF out of total kcal. Total UPF consumption was not related to cognitive function. However, consumption of ultra‐processed fat (e.g. mayonnaise) was associated with faster decline in global cognition, executive function and memory (ß=‐0.028±0.010; p=0.009, ß=‐0.031±0.014; p=0.022 and ß=‐0.035±0.017; p=0.046, respectively). Additionally, increased intake of ultra‐processed meat (e.g. sausages) was associated with a faster decline in executive functions (ß=‐0.029±0.013; p=0.031). UPF derived from dairy products and carbohydrates were not associated with cognitive change. Conclusion: This pioneering study suggests a possible association of ultra‐processed meat and fat intake with accelerated cognitive decline in older individuals with T2D, independently of sociodemographic, lifestyle, cardiovascular and T2D‐related factors. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented related to the article on relationship between serum uric acid levels and non-alcoholic fatty liver disease (NAFLD) by F. Ozcelik and colleagues, in a 2015 issue.