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      Screening for undiagnosed non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH): A population-based risk factor assessment using vibration controlled transient elastography (VCTE)

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          Abstract

          The screening for undiagnosed non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (SUNN) study was a population-based screening study that aimed to provide proof of concept to encourage community-level screening and detection for this non-communicable disease. Current screening guidelines do not recommend the routine screening of nonalcoholic fatty liver disease (NAFLD) for asymptomatic populations, so providers are not encouraged to actively seek disease, even in high-risk patients. This study sought to determine whether a self-selecting cohort of asymptomatic individuals would have scores based on vibration controlled transient elastography (VCTE) and controlled attenuation parameter (CAP) significantly correlated to risk factors to suggest that routine screening for high-risk patients should be recommended. The study recruited 1,070 self-selected participants in Houston and Galveston County, Texas, 940 of which were included in final analysis. A pre-screening survey was used to determine eligibility. VCTE-based scores analyzed steatosis and fibrosis levels. Fifty-seven percent of the study population demonstrated steatosis without fibrosis, suggesting NAFLD, while 16% demonstrated both steatosis and fibrosis, suggesting NASH. Statistically significant risk factors included factors related to metabolic syndrome, race, and age, while statistically significant protective factors included consumption of certain foods and exercise. The findings of this study suggest that high-risk individuals should be screened for NAFLD even in the absence of symptoms and that community-based screenings are an effective tool, particularly in the absence of proactive guidelines for providers.

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          Most cited references39

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          Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.

          Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression, and outcomes of NAFLD and nonalcoholic steatohepatitis (NASH). PubMed/MEDLINE were searched from 1989 to 2015 for terms involving epidemiology and progression of NAFLD. Exclusions included selected groups (studies that exclusively enrolled morbidly obese or diabetics or pediatric) and no data on alcohol consumption or other liver diseases. Incidence of hepatocellular carcinoma (HCC), cirrhosis, overall mortality, and liver-related mortality were determined. NASH required histological diagnosis. All studies were reviewed by three independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication, and study population. We used random-effects models to provide point estimates (95% confidence interval [CI]) of prevalence, incidence, mortality and incidence rate ratios, and metaregression with subgroup analysis to account for heterogeneity. Of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. Global prevalence of NAFLD is 25.24% (95% CI: 22.10-28.65) with highest prevalence in the Middle East and South America and lowest in Africa. Metabolic comorbidities associated with NAFLD included obesity (51.34%; 95% CI: 41.38-61.20), type 2 diabetes (22.51%; 95% CI: 17.92-27.89), hyperlipidemia (69.16%; 95% CI: 49.91-83.46%), hypertension (39.34%; 95% CI: 33.15-45.88), and metabolic syndrome (42.54%; 95% CI: 30.06-56.05). Fibrosis progression proportion, and mean annual rate of progression in NASH were 40.76% (95% CI: 34.69-47.13) and 0.09 (95% CI: 0.06-0.12). HCC incidence among NAFLD patients was 0.44 per 1,000 person-years (range, 0.29-0.66). Liver-specific mortality and overall mortality among NAFLD and NASH were 0.77 per 1,000 (range, 0.33-1.77) and 11.77 per 1,000 person-years (range, 7.10-19.53) and 15.44 per 1,000 (range, 11.72-20.34) and 25.56 per 1,000 person-years (range, 6.29-103.80). Incidence risk ratios for liver-specific and overall mortality for NAFLD were 1.94 (range, 1.28-2.92) and 1.05 (range, 0.70-1.56).
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            The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases.

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              Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention

              NAFLD is one of the most important causes of liver disease worldwide and will probably emerge as the leading cause of end-stage liver disease in the coming decades, with the disease affecting both adults and children. The epidemiology and demographic characteristics of NAFLD vary worldwide, usually parallel to the prevalence of obesity, but a substantial proportion of patients are lean. The large number of patients with NAFLD with potential for progressive liver disease creates challenges for screening, as the diagnosis of NASH necessitates invasive liver biopsy. Furthermore, individuals with NAFLD have a high frequency of metabolic comorbidities and could place a growing strain on health-care systems from their need for management. While awaiting the development effective therapies, this disease warrants the attention of primary care physicians, specialists and health policy makers.
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                Author and article information

                Contributors
                Role: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: ResourcesRole: Supervision
                Role: Formal analysisRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Formal analysisRole: SoftwareRole: VisualizationRole: Writing – original draft
                Role: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                30 November 2021
                2021
                : 16
                : 11
                : e0260320
                Affiliations
                [1 ] Fatty Liver Foundation, Boise, Idaho, United States of America
                [2 ] Section of Gastroenterology and Hepatology and Division of Abdominal Transplantation, Departments of Medicine and Surgery, Baylor College of Medicine, Houston, Texas, United States of America
                [3 ] Link2Labs, Houston, Texas, United States of America
                Osaka City University Graduate School of Medicine, JAPAN
                Author notes

                Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: WE, GAW, MLH, and HEC are employees of FLF, which reports program support and educational grants from Allergan, Amazon, Bristol-Myers Squibb, Celgene, Clinical Care Options, Continuum Clinical, Echosens, Eskridge Family Trust, Fibronostics, First Line Creative, Gilead Sciences, Global Engage, Google, Health Business Solutions, Intercept Pharmaceuticals, Madrigal Pharmaceuticals, Meetrix, Merck & Co., Inc. NetNoggin, Prosciento, Pfizer, Terns Pharmaceuticals and various private and philanthropic individual donors. JMV reports relevant research and grant support from Allergan, Alnylam, 89Bio, Bristol-Myers Squibb, Celgene, CymaBay, Exalenz, Galectin, Galmed, Genfit, Gilead, Hanmi, Immuron, Intercept, Madrigal, Merck, Mochida, Molecular Stethoscope, Novartis, NovoNordisk, Pliant, Sagimet, Tobira Therapeutics, and Zydus; advisor or consultant fees from Allergan, Blade Pharmaceuticals, Bristol-Myers Squibb, Conatus, CymaBay, Exalenz, Fractyl, Intercept, Novartis; and is on the Data Safety and Management Boards for NIH NIDDK Drug-Induced Liver Injury Network (DILIN) and Fractyl. WG reports grant support from AbbVie and Gilead Sciences. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                https://orcid.org/0000-0002-9717-5194
                https://orcid.org/0000-0001-5547-6020
                Article
                PONE-D-21-19005
                10.1371/journal.pone.0260320
                8631660
                34847156
                95f14d8f-b0ae-42f6-aea2-5aaf12661088
                © 2021 Eskridge et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 9 June 2021
                : 7 November 2021
                Page count
                Figures: 1, Tables: 7, Pages: 17
                Funding
                Funded by: Health Business Solutions
                Award Recipient :
                Funded by: Intercept Pharmaceuticals (US)
                Award Recipient :
                Funded by: Eskridge Family Trust (US)
                Award Recipient :
                We received study grants from Intercept Pharmaceuticals ( https://www.interceptpharma.com/) and the Eskridge Family Trust. In-kind contributions were made by Health Business Solutions. The opinions, results and conclusions reported in this paper are those of the authors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Anatomical Pathology
                Cytopathology
                Steatosis
                Biology and Life Sciences
                Developmental Biology
                Fibrosis
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Liver Diseases
                Fatty Liver
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Biology and Life Sciences
                Biochemistry
                Lipids
                Fats
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Medical Conditions
                Metabolic Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Medical Conditions
                Cardiovascular Diseases
                Cardiovascular Disease Risk
                Medicine and Health Sciences
                Cardiology
                Cardiovascular Medicine
                Cardiovascular Diseases
                Cardiovascular Disease Risk
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized
                Uncategorized

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