Search

Background & Aims: The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing. This study explores the association of food insecurity with MASLD prevalence and liver-related mortality (LRM) across the globe., Methods: The study combines United Nations' country-level food security data with the MASLD data from the Global Burden of Disease study 2021. Mixed-effects linear regression models, accounting for country-level random effects, were used to assess associations of food security indicators with MASLD prevalence and LRM. The analyses were performed according to each country's socio-demographic index (SDI) status., Results: In 2021, the median MASLD prevalence and liver-related mortality (MASLD-LRM) across 204 countries was 21.77% (14.14%-48.18%) and 2.92 per 100,000 (0.42-10.79) with the highest MASLD prevalence located in North Africa & Middle East (41.70%) and the lowest prevalence in high-income countries (17.31%). After adjustments for age, gender and SDI, higher MASLD prevalence was associated with increasing rates of obesity, type 2 diabetes and low physical activity (p <0.001). When analyses were performed based on SDI status, divergent patterns of MASLD prevalence were observed. In high SDI countries (socioeconomically more developed), MASLD prevalence was significantly higher in those in the top tertile of food insecurity compared to the bottom tertile (mean, 26.73% vs. 18.87%, p = 0.0001). In contrast, in low SDI countries (socioeconomically less developed), the opposite was true (19.45% vs. 24.96%, p = 0.0008). MASLD-LRM was associated with older age, obesity, and metabolic risks (p <0.001)., Conclusions: MASLD prevalence and MASLD-LRM exhibit significant geographical variability, which is influenced by clinicodemographic factors, and food insecurity. Targeted public health strategies which consider the socio-economic realities of each region are essential for mitigating the global burden of MASLD., Impact and Implications: Metabolic dysfunction-associated steatotic liver disease (MASLD) burden varies by region, influenced by food insecurity and healthcare access. In high socio-demographic index (SDI) countries, higher MASLD prevalence is linked to the consumption of low-quality, ultra-processed foods. Public health policies should focus on improving food quality, reducing unhealthy food consumption, and enhancing healthcare access. Conversely, in low SDI countries, while food insecurity can lead to outright deficiencies, the observed lower MASLD prevalence may also be partly attributable to underdiagnosis. In this context, limited healthcare access may have contributed to underestimation of the prevalence of MASLD. Therefore, country-specific policies should address both the issues related to poverty, as well as improving access to diagnostic modalities and healthcare infrastructure to ensure more accurate estimates of cases of MASLD in the specific country. Promoting physical activity is crucial in both high and low SDI countries to manage metabolic conditions associated with MASLD., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Competing Interests: AB reports unrelated research grants from Boehringer Ingelheim and Astra Zeneca, consulting fees paid to her institution from Boehringer Ingelheim, speaker fees paid to her institution from Hologic and General Electrics Healthcare, and is an advisory board member for Inventiva. PB reports speaker fees from Chiesi Farmaceutici and is a member of advisory boards for Sandoz, Biotest, and Kedrion. MB reports unrelated research grants from Gilead, consulting fees from Gilead, GSK, AbbVie, and Altimmune and speaker fees from Gilead, AbbVie, and Altimmune. PC reports unrelated research grants from Intercept and ANRS/MIE and INCA. PG reports unrelated grants from Gilead and Grifols, consulting fees from Gilead, RallyBio, SeaBeLife, MSD, Ocelot Bio, and Behring, and lecture fees from Pfizer. SH reports research grants from the National Institute for Health and Care Research, UK, and Public Health Scotland, NHS Scotland, and meeting support from EASL. THK reports consulting fees from MSD, Falk Pharma, and Albireo, speaker fees from Gilead, and he has owned stocks in Ultimovacs (unrelated to this topic). AK reports unrelated research grants from Novo Nordisk Foundation, Astra Zeneca, EU Horizon 2020, Innovationfund Denmark, Danish National Research Foundation, and Region of Southern Denmark, consulting fees from Resalis Therapeutics, AlphaSights, Takeda, and Zealand Pharma, royalties from Gyldendal, patents from Region of Southern Denmark and University of Southern Denmark, speaker fees from Norgine, Siemens, Novo Nordisk, and Nordic Bioscience, is an advisory board member for Norgine, Novo Nordisk, Boehringer Ingelheim, and Siemens, is a board member and co-founder of Evido (a small university spinout company developing data models for detection of chronic liver disease in primary care; he has no revenue in the company and receives no payment), and declares receipt of drugs, equipment, or services from Norgine, Siemens, Echosense, and Nordic Bioscience. MPM reports consulting fees from Assembly Bio, Bristol Myers Squibb, Falk Pharma, Gilead, GSK, Inventiva, MSD, Novartis, Otsuka/Visterra, Precision Biosciences, and Preglem/Gedeon Richter, speaker fees from AbbVie, Bristol Myers Squibb, Falk Pharma, Gilead, and MSD, unrelated travel support from AbbVie, Bristol Myers Squibb, Falk Pharma, Gilead, Merck (MSD), and Novartis, and is an advisory board member for Falk Pharma, Gilead, MSD, and Novartis. GS reports lecture fees from Otsuka Lundbeck. SZ-S reports consulting fees from Siemens and unrelated travel support from AbbVie. SK is the Deputy Editor of The Lancet. All other authors declare no competing interests. AK is Secretary General, MB is Public Health Councillor, and SZ-S is Public Health Councillor elect of EASL. The Commissioners are Harry Rutter, Patrizia Carrieri, Shira Zelber-Sagi, Eivind Engebretsen, Sharon Hutchinson, Kristin Voigt, Neil Guha, Annalisa Berzigotti, Georg Schomerus, Pere Gines, Maria Buti, Patrizia Burra, Michael P Manns, Aleksander Krag, Phil Newsome, Vlad Ratziu, Philippe Mathurin, Nuria Fabrellas, Michele Cecchini, Erika Duffell, Volkan Yomuk, Thomas Berg, Achim Kautz, Marcelo Naveira, Liana Gheorghe, and Tom H Karlsen. A Steering Committee governs the work of the Commission, formed by Aleksander Krag, Sabine Kleinert, Patrizia Burra, Michael P Manns, Maria Buti, and Shira-Zelber Sagi, and chaired by Tom H Karlsen.

Background & Aims: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers., Methods: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey., Results: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%)., Conclusions: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties., Impact and Implications: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma., Competing Interests: Conflict of interest ZMY: research funding or consultation fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cymabay, GlaxoSmithKline, Intercept, Novo Nordisk, Siemens, Madrigal, Merck; VWSW: served as a consultant or advisory board member for AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, Visirna, speaker for Abbott, AbbVie, Gilead Sciences, Novo Nordisk, Unilab, received a research grant from Gilead Sciences, co-founder of Illuminatio Medical Technology Limited; AMA: grant funding from NIH, Novo Nordisk, Target Pharma, consulting/advisory board for Novo Nordisk; JMS: consultant for Astra Zeneca, Apollo Endosurgery, Bayer, Boehringer Ingelheim, BMS, Gilead Sciences, GSK, Intercept Pharmaceuticals, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Siemens Healthineers, receives research funding from Gilead Sciences, Boehringer Ingelheim, Siemens Healthcare GmbH, has stock options of AGED diagnostics, Hepta Bio, received speaker honorarium from Boehringer Ingelheim, Echosens, MedPublico GmbH, Novo Nordisk, Madrigal Pharmaceuticals, Histoindex, MedPublico GmbH; CWS: speaker bureau fees from Gilead Sciences, Abbott; RL: receives funding support from NCATS, NIDDK, NHLBI, serves as a consultant to Aardvark Therapeutics, Altimmune, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Eli Lilly, Gilead, Glympse bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Takeda, Terns Pharmaceuticals and Viking Therapeutics. In addition, his institution received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes, Terns Pharmaceuticals, co-founder of LipoNexus Inc; PC: received research grants by MSD and Intercept. Other coauthors report no conflicts of interest related to this study. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community., Methods: Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy., Results: The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of 'agree' responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement ('agree' + 'somewhat agree'); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% 'agree'), 13 priorities had <80% 'agree', with greater reliance on 'somewhat agree' to achieve >90% combined agreement., Conclusions: Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community's efforts to advance and accelerate responses to this widespread and fast-growing public health threat., Impact and Implications: An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent, yet largely underappreciated liver condition which is closely associated with obesity and metabolic disease. Despite affecting an estimated 1 in 4 adults globally, NAFLD is largely absent on national and global health agendas., Methods: We collected data from 102 countries, accounting for 86% of the world population, on NAFLD policies, guidelines, civil society engagement, clinical management, and epidemiologic data. A preparedness index was developed by coding questions into 6 domains (policies, guidelines, civil awareness, epidemiology and data, NAFLD detection, and NAFLD care management) and categorising the responses as high, medium, and low; a multiple correspondence analysis was then applied., Results: The highest scoring countries were India (42.7) and the United Kingdom (40.0), with 32 countries (31%) scoring zero out of 100. For 5 of the domains a minority of countries were categorised as high-level while the majority were categorised as low-level. No country had a national or sub-national strategy for NAFLD and <2% of the different strategies for related conditions included any mention of NAFLD. National NAFLD clinical guidelines were present in only 32 countries., Conclusions: Although NAFLD is a pressing public health problem, no country was found to be well prepared to address it. There is a pressing need for strategies to address NAFLD at national and global levels., Lay Summary: Around a third of the countries scored a zero on the NAFLD policy preparedness index, with no country scoring over 50/100. Although NAFLD is a pressing public health problem, a comprehensive public health response is lacking in all 102 countries. Policies and strategies to address NAFLD at the national and global levels are urgently needed., Competing Interests: Conflict of interest HEM, MV-R, and AP report receiving consulting fees from the EASL International Liver Foundation related to this work. The EASL International Liver Foundation received grants from Intercept, Bristol-Myers-Squibb Company, Genfit, and MSD to support this study. The funders played no role in the conceptualisation, design, data collection, analysis, decision to publish, or preparation of the manuscript. All other authors declare no relevant completing interests. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the population worldwide, and its prevalence is anticipated to increase globally. While most NAFLD patients are asymptomatic, NAFLD may progress to fibrosis, cirrhosis, cardiovascular disease, and diabetes. Research reports, with daunting results, show the challenge that NAFLD's burden causes to global population health. The current process for identifying fibrosis risk levels is inefficient, expensive, does not cover all potential populations, and does not identify the risk in time. Instead of invasive liver biopsies, we implemented a non-invasive fibrosis assessment process calculated from clinical data (accessed via EMRs/EHRs). We stratified patients' risks for fibrosis from 2007 to 2017 by modeling the risk in 5579 individuals. The process involved time-series machine learning models (Hidden Markov Models and Group-Based Trajectory Models) profiled fibrosis risk by modeling patients' latent medical status resulted in three groups. The high-risk group had abnormal lab test values and a higher prevalence of chronic conditions. This study can help overcome the inefficient, traditional process of detecting fibrosis via biopsies (that are also medically unfeasible due to their invasive nature, the medical resources involved, and costs) at early stages. Thus longitudinal risk assessment may be used to make population-specific medical recommendations targeting early detection of high risk patients, to avoid the development of fibrosis disease and its complications as well as decrease healthcare costs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: Declarations of interests IG received support from Fundacion de Investigacion sanitaria and was cofunded by Instituto Carlos III for the present manuscript; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead Sciences, Intercept, and AbbVie; and support for attending meetings or travel from Intercept and Gilead Sciences. EB received grants or contracts from Gilead Sciences; received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead Sciences and Novo Nordisk; and participated on Data Safety Monitoring Boards or advisory boards for Bristol Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Intercept, Inventiva, and Novo Nordisk. MC received grants or contracts and support for attending meetings or travel from the OECD programme of work for public health. RF received grants or contracts from Gilead Sciences, AbbVie, Roche, and Merck Sharp & Dohme; consulting fees from Gilead Sciences, AbbVie, Janssen, and Pfizer; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead Sciences, AbbVie, Merck Sharp & Dohme, and AdamedPG; and support for attending meetings or travel from Gilead Sciences, AbbVie, and Merck Sharp & Dohme. JVL received grants or contracts from AbbVie, Gilead Sciences, Merck Sharp & Dohme; and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AbbVie, Gilead Sciences, Intercept, Janssen, and Merck Sharp & Dohme. AL received grants or contracts from the OECD programme of work for public health, which is supported by Ministries of Health, National Governmental Institutions, and intergovernmental organisations, as well as support to present results from OECD analyses to meetings, seminars, and workshops. CL received grants or contracts from the University of Oxford, UK National Centre for Smoking Cessation and Training, and Horizon 2020 of the European Commission; received royalties or licenses from and has patents planned, issued, or pending with Olvos Science (Cretan Iama); received payment for expert testimony from WHO and the European Commission; and participated on Data Safety Monitoring Boards or advisory boards for Merck Sharp & Dohme, Pfizer Hellas, Vianex. MPM received grants or contracts from AbbVie, Eiger BioPharmaceuticals, Bristol Myers Squibb, Dr Falk Pharma, Gilead Sciences, Intercept, Merck Sharp & Dohme, and Roche; received consulting fees from AbbVie, Bristol Myers Squibb, Dr Falk Pharma, Gilead Sciences, Intercept, Merck Sharp & Dohme, Novartis, and Roche; received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AbbVie, Bristol Myers Squibb, Dr Falk Pharma, Gilead Sciences, Merck Sharp & Dohme, and Roche; received support for attending meetings or travel from AbbVie, Bristol Myers Squibb, Dr Falk Pharma, Gilead Sciences, Merck Sharp & Dohme, and Roche; participated on Data Safety Monitoring Boards or advisory boards for Eiger, Dr Falk Pharma, Gilead Sciences, and Roche; and is Associate Editor for Clinical Gastroenterology and Hepatology. NKM received grants or contracts from Merck Sharp & Dohme and Gilead Sciences. MN received grants or contracts from Gilead Sciences, Merck Sharp & Dohme, AbbVie, and Janssen; and was President of the World Hepatitis Alliance (2018–20). CYP received grants or contracts from Takeda, Pliant, and Gilead Sciences; consulting fees from Pliant and Shire (Takeda); and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Takeda, Tillotts Pharma, and Pfizer. BSa received grants or contracts from Bristol Myers Squibb and Sirtex Medical; received consulting fees from Adaptimmune, AstraZeneca, Bayer, Bristol Myers Squibb, BTG, Sirtex Medical, TERUMO, H3 Biomedicine, Incyte, Ipsen, Lilly, and Roche; received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Bayer, Bristol Myers Squibb, Sirtex Medical, TERUMO, Incyte, and Ipsen; and participated on Data Safety Monitoring Boards or advisory boards for Adaptimmune, AstraZeneca, Bayer, Bristol Myers Squibb, BTG, Sirtex Medical, TERUMO, H3 Biomedicine, Incyte, Ipsen, Lilly, and Roche. CS received grants or contracts from BiomX and Galapagos; consulting fees from BiomX; and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Falk Foundation. NSc received grants or contracts from Gilead Sciences. MS-B received grants or contracts from the European Commission. CT received grants or contracts from Merck Sharp & Dohme; and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead Sciences and AbbVie. RB received consulting fees from WHO. HC-P received consulting fees from Orphalan; and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Orphalan, Novo Nordisk, GENFIT, Promethera Biosciences, and Intercept. GD received consulting fees from Aligos Therapeutics, Roche, Arbutus Biopharma, Gilead Sciences, Shionogi, Antios Therapeutics; received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead Sciences; and participated on Data Safety Monitoring Boards or advisory boards for Janssen, Pharmaceuticals, GlaxoSmithKline, and Aligos Therapeutics. THK received consulting fees from Engitix and Intercept; has stock or stock options in Ultimovacs; received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead Sciences, Novartis, and AlfaSigma; and is on the board of the Biomedical Alliance in Europe. ES received consulting fees from Albireo, Mirum, and Alexion; received support for attending meetings or travel from Astellas; participated on Data Safety Monitoring Boards or advisory boards for Albireo, Alexion, and Mirum; and received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Albireo. PB received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Kedrion Biopharma, Biotest, and Chiesi Farmaceutici. MB received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead Sciences and AbbVie. SJH received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Gilead Sciences. NF participated on Data Safety Monitoring Boards or advisory boards for Intercept in relation to NAFLD. GM participated on Data Safety Monitoring Boards or advisory boards for Gilead Sciences, Novartis, Pfizer, and AstraZeneca. All other authors declare no competing interests.

Background: A growing body of evidence suggests that Non-alcoholic fatty liver disease (NAFLD) and liver fibrosis are associated with cardiovascular disease (CVD). However, the independent role of liver fibrosis markers in the prediction of CVD in the general population is seldom tested., Aims: To assess whether a marker of liver fibrosis predicts the first occurrence of a CVD event in a large sample of community-based general population., Methods: Historical cohort using data from a large health provider that operates a centralized computerized medical record. The level of liver fibrosis was measured by the fibrosis-4 (FIB-4) score, and the association with CVD was adjusted for the European Systematic Coronary Risk Evaluation calculator (SCORE)., Results: The study included 8,511 individuals, 3,292 with inconclusive fibrosis and 195 with advanced fibrosis (FIB-4 ≥ 2.67). People with advanced fibrosis had higher risk for CVD, after adjustment for sociodemographic characteristics, the SCORE, use of statins and aspirin (HR [95%CI], 1.63 [1.29-2.06]). The association persisted in both women and men. Using age-specific cut-offs, there was a dose-response association between inconclusive and advanced fibrosis and CVD (HR [95%CI], 1.15 [1.01-1.31]) and HR [95%CI], 1.60 [1.27-2.01], respectively, P for trend<0.001)., Conclusions: A simple fibrosis score is independently associated with CVD, suggesting that fibrosis markers should be considered in primary-care risk assessment., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The exclusion of other chronic liver diseases including "excess" alcohol intake has until now been necessary to establish a diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD). However, given our current understanding of the pathogenesis of MAFLD and its rising prevalence, "positive criteria" to diagnose the disease are required. In this work, a panel of international experts from 22 countries propose a new definition for the diagnosis of MAFLD that is both comprehensive and simple, and is independent of other liver diseases. The criteria are based on evidence of hepatic steatosis, in addition to one of the following three criteria, namely overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation. We propose that disease assessment and stratification of severity should extend beyond a simple dichotomous classification to steatohepatitis vs. non-steatohepatitis. The group also suggests a set of criteria to define MAFLD-associated cirrhosis and proposes a conceptual framework to consider other causes of fatty liver disease. Finally, we bring clarity to the distinction between diagnostic criteria and inclusion criteria for research studies and clinical trials. Reaching consensus on the criteria for MAFLD will help unify the terminology (e.g. for ICD-coding), enhance the legitimacy of clinical practice and clinical trials, improve clinical care and move the clinical and scientific field of liver research forward., Competing Interests: Conflicts of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Lifestyle intervention can be effective when treating non-alcoholic fatty liver diseases (NAFLD) patients. Weight loss decreases cardiovascular and diabetes risk and can also regress liver disease. Weight reductions of ⩾10% can induce a near universal non-alcoholic steatohepatitis resolution and fibrosis improvement by at least one stage. However, modest weight loss (>5%) can also produce important benefits on the components of the NAFLD activity score (NAS). Additionally, we need to explore the role of total calories and type of weight loss diet, micro- and macronutrients, evidence-based benefits of physical activity and exercise and finally support these modifications through established behavioural change models and techniques for long-term maintenance of lifestyle modifications. Following a Mediterranean diet can reduce liver fat even without weight loss and is the most recommended dietary pattern for NAFLD. The Mediterranean diet is characterised by reduced carbohydrate intake, especially sugars and refined carbohydrates (40% of the calories vs. 50-60% in a typical low fat diet), and increased monounsaturated and omega-3 fatty acid intake (40% of the calories as fat vs. up-to 30% in a typical low fat diet). Both TV sitting (a reliable marker of overall sedentary behaviour) and physical activity are associated with cardio-metabolic health, NAFLD and overall mortality. A 'triple hit behavioural phenotype' of: i) sedentary behaviour, ii) low physical activity, and iii) poor diet have been defined. Clinical evidence strongly supports the role of lifestyle modification as a primary therapy for the management of NAFLD and NASH. This should be accompanied by the implementation of strategies to avoid relapse and weight regain., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Although studies to date have confirmed the association between nutrition and frailty, the impact of dietary intake and dietary patterns on survivorship in those with frailty is yet to be examined in a well-powered cohort with validated frailty status. Moreover, previous studies were limited by measurement error from dietary self-reports. Objective: We derived biomarker-calibrated dietary energy and protein intakes to address dietary self-report error. Using these data, we then evaluated the association of mortality in older women with frailty and dietary intake and healthy diet indexes, such as the alternate Mediterranean Diet (aMED), the Dietary Approaches to Stop Hypertension (DASH) score, and the Dietary Inflammatory Index (DII). Design: The analytic sample included 10,034 women aged 65-84 y with frailty and complete dietary data from the Women's Health Initiative Observational Study. Frailty was assessed with modified Fried's criteria. Dietary data were collected by food-frequency questionnaire. Results: Over a mean follow-up period of 12.4 y, 3259 (31%) deaths occurred. The HRs showed progressively decreased rates of mortality in women with higher calibrated dietary energy intakes ( P- trend = 0.003), higher calibrated dietary protein intakes ( P- trend = 0.03), higher aMED scores ( P- trend = 0.006), and higher DASH scores ( P- trend = 0.02). Although the adjusted point estimates of HRs (95% CIs) for frail women scoring in the second, third, and fourth quartiles on DII measures were 1.15 (1.03, 1.27), 1.28 (1.15, 1.42), and 1.24 (1.12, 1.38), respectively, compared with women in the first quartile, no overall effect was observed across quartiles ( P- trend = 0.35). Subgroup analyses by chronic morbidity or smoking status or by excluding women with early death did not substantially change these findings. Conclusions: The current study highlights the importance of nutrition in older, frail women. Diet quality and quantity should be considered in managing persons with frailty., (© 2017 American Society for Nutrition.)

Background: Soluble receptor for advanced glycation end-products (sRAGE) exerts protective metabolic effects., Aims: To identify if sRAGE plays a protective role in NAFLD., Methods: 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)., Results: sRAGE levels were lower in NAFLD patients compared to controls (1207±439 vs. 1596±562ng/l, P<0.001) 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, P<0.001) and change in sRAGE levels was negatively correlated with change in ALT levels (r=-0.37, P=0.041)., Conclusion: sRAGE plays a protective role in NAFLD and it is influenced by lifestyle., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Low postoperative protein intake may represent a modifiable risk factor that leads to fat free mass (FFM) loss postlaparoscopic sleeve gastrectomy (LSG), but data concerning this phenomenon is scarce., Objectives: To evaluate the association between daily protein intake and relative FFM loss at 6 (M6) and 12 (M12) months after LSG surgery., Settings: Private hospital and university hospital., Methods: A prospective cohort study with 12 months follow-up of 77 patients who underwent LSG surgery. Anthropometrics including body composition analysis measured by multifrequency bioelectrical impedance analysis, 3-day food diaries, food intolerance, and habitual physical activity were evaluated at baseline and at M3, M6, and M12., Results: Repeated body composition measurements and food diary were available for 77 patients (45 women) at M6 and for 68 patients at M12. Mean age was 42.7±9.4 years and mean preoperative body mass index was 42.2±4.8 kg/m 2 . A protein intake of≥60 g/d was achieved in 13.3%, 32.5% and 39.7% of the study participants at M3, M6 and M12, respectively. FFM significantly decreased at M6 and stabilized at M12. Protein intake of≥60 g/d was associated with a significantly lower relative FFM loss at M6 among women (8.9±6.5% versus 12.4±4.1%; P = .039) and this trend was also reported among men (9.5±5.5% versus 13.4±6.0%; P = .068). A logistic regression for the prediction of FFM loss of≥10% at M6, indicated that protein intake≥60 g/d is a strong protective factor (odds ratio = 0.29, 95% confidence interval .09-.96, P = .043)., Conclusion: Our study supports the currently recommended protein intake goal of≥60 g/d as an efficient strategy for better preservation of FFM post-LSG., (Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: A growing number of patients have been undergoing bariatric surgery in recent years. The role of adherence with regular dietician follow-up in successful long-term weight reduction has yet to be determined, and there are no studies characterizing the utilization of nutritional services after bariatric surgery. The objective of this study was to determine whether dietary counseling by a dietician can contribute to weight reduction after surgery in a follow-up of morbidly obese adult patients who underwent bariatric surgery., Methods: Inclusion criteria were age 20-70 at the time of the bariatric surgery and available body mass index (BMI) measurements before and at least 1 month after the surgery. Medical history and blood test results (triglycerides, cholesterol, and glucose) were recorded. Furthermore, data were collected on the utilization of healthcare services., Results: The final study sample consisted of 1680 patients. Only 681 (40.54%) patients in the cohort attended dietician counseling in Maccabi, and only 471 (28%) patients received such counseling at least twice. Patients attending significant diet counseling had significantly higher proportions of at least 5% reduction in BMI. Two or more visits to dietician counseling were significantly and independently associated (odds ratio = 1.56, 1.02-2.38, 95% CI, P = .04) with a BMI reduction of at least 5%, adjusting for age, gender, number of expert counseling sessions, additional surgery, type of operation, and the interval between BMI measurements., Conclusion: Structured nutritional counseling after bariatric surgery can help in achieving clinically significant weight reduction., (Copyright © 2013 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Data on the incidence and remission rates of non-alcoholic fatty liver disease (NAFLD) as well as predictive factors are scant. This study aims at evaluating NAFLD's epidemiology in prospective follow-up of individuals sampled from the general population., Methods: Evaluation of metabolic parameters and ultrasonographic evidence of NAFLD was performed in 213 subjects, with no known liver disease or history of alcohol abuse. The evaluation was performed at baseline and after a 7-year period by identical protocols., Results: Of the 147 patients who did not have NAFLD at baseline, 28 (19%) were found to have NAFLD at a 7-year follow-up. Baseline BMI, HOMA score, blood cholesterol, triglycerides, leptin levels, and weight gain (5.8±6.1 vs. 1.4±5.5kg, p<0.001) were significantly higher and adiponectin was lower among those who developed NAFLD at 7-year follow-up, compared with those who remained NAFLD-free. However, only weight gain and baseline HOMA were independent predictors for the development of NAFLD. Of the 66 patients who were found to have NAFLD at baseline, as many as 24 patients (36.4%) had no evidence of NAFLD at 7years. Weight loss of 2.7±5.0kg was significantly associated with NAFLD remission. Moreover, there was a 75% remission rate among NAFLD patients who lost 5% or more from their baseline weight., Conclusions: Among the general population, weight gain, and baseline insulin resistance are predictors for NAFLD incidence. One third of NAFLD patients may have remission of disease within a 7-year follow-up, mostly depending on modest weight reduction., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background/aims: 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., Methods: 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., Results: 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 (P<0.001). 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)., Conclusions: 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.

Background/aims: There is an increasing body of evidence that serum ferritin is associated with the metabolic syndrome. However, no study has tested for NAFLD. The aim was to test the assumption that the association between serum ferritin and the metabolic syndrome is mediated by NAFLD., Methods: A cross-sectional study of a sub-sample of the first Israeli national health survey. Exclusion criteria were any known etiology for secondary NAFLD. Participants underwent an abdominal ultrasound (US), biochemical tests, and dietary and anthropometric evaluations., Results: Three hundred and forty-nine subjects were included in the analysis. Serum ferritin was higher in the NAFLD group (92.4+/-63.1 vs. 65.1+/-58.0, P<0.001). After adjusting for age and gender, the following variables were significantly associated with increased ferritin levels: abdominal obesity, hyperglycemia, hyperinsulinemia, HOMA, hypertriglyceridemia and the metabolic syndrome itself. After further adjusting for NAFLD, only abdominal obesity [2.1 (1.1-3.9)] and hyperinsulinemia [2.3 (1.3-4.2)] were still significantly associated with ferritin. In a multivariate analysis the interaction between NAFLD and hyperinsulinemia was the second strongest predictor of serum ferritin (P=0.005)., Conclusions: The association between serum ferritin and the metabolic syndrome is mediated by undiagnosed NAFLD. The interaction between NAFLD and hyperinsulinemia is a major determinant of serum ferritin levels at the population level.