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      The association between nonalcoholic fatty liver disease and esophageal, stomach, or colorectal cancer: National population-based cohort study

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          Abstract

          We investigated the association between nonalcoholic fatty liver disease (NAFLD) and gastrointestinal tract cancer in the general population. Retrospective data on individuals aged ≥20 years who received healthcare checkups from January 1, 2009 to December 31, 2009 were analyzed using the National Health Insurance Database in Korea. NAFLD was defined based on the fatty liver index (FLI ≥60). The primary outcome was newly diagnosed esophageal, stomach, or colorectal cancer using ICD-10 codes during follow-up until 31 December 2017. Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Among 8,120,674 subjects, 936,159 adults (11.5%) were identified as having NAFLD. Their mean age was 46.7 ± 14.1 years, and 52.1% were male. During the follow-up period (7.2 years), 3,792 esophageal, 57,292 stomach and 68,769 colorectal cancer cases were identified. FLI ≥60 was significantly associated with the development of esophageal (HR 2.10, 95% CI 1.88–2.35), stomach (HR 1.18, 95% CI 1.14–1.22), and colon cancer (HR, 1.23, 95% CI 1.19–1.26) after multivariable adjustment. Compared to subjects without NAFLD, all-cause mortality in patients with esophageal (HR 1.46, 95% CI 1.28–1.67), stomach (HR 1.26, 95% CI 1.18–1.34), and colorectal cancer (HR 1.16, 95% CI 1.10–1.22) was significantly increased in subjects with NAFLD (FLI ≥60). NAFLD defined using FLI was a good predictive indicator for GI tract malignancy and all-cause mortality in the general population. Subjects with NAFLD are needed for active surveillance of esophageal, stomach, and colorectal cancers.

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          Non alcoholic fatty liver disease and metabolic syndrome.

          Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic entity increasingly recognized as a major health burden in developed countries. It includes a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and rarely, progression to cirrhosis. Recent studies emphasize the role of insulin resistance, oxidative stress and subsequent lipid peroxidation, proinflammatory cytokines, adipokines and mitochondrial dysfunction in the development and progression of NAFLD. Furthermore, accumulating evidence supports an association between NAFLD and metabolic syndrome. Although the data are mainly epidemiological, the pathogenesis of NAFLD and metabolic syndrome seems to have common pathophysiological mechanisms, with focus on insulin resistance as a key factor. This review summarizes the current knowledge on the epidemiology, pathophysiology and diagnosis of both NAFLD and metabolic syndrome and the findings that strongly support the association of nonalcoholic fatty liver disease as a possible component in the cluster of metabolic syndrome.
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            Data Analytic Process of a Nationwide Population-Based Study Using National Health Information Database Established by National Health Insurance Service

            In 2014, the National Health Insurance Service (NHIS) signed a memorandum of understanding with the Korean Diabetes Association to provide limited open access to its databases for investigating the past and current status of diabetes and its management. NHIS databases include the entire Korean population; therefore, it can be used as a population-based nationwide study for various diseases, including diabetes and its complications. This report presents how we established the analytic system of nation-wide population-based studies using the NHIS database as follows: the selection of database study population and its distribution and operational definition of diabetes and patients of currently ongoing collaboration projects.
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              Sarcopenia is associated with significant liver fibrosis independently of obesity and insulin resistance in nonalcoholic fatty liver disease: Nationwide surveys (KNHANES 2008-2011).

              Sarcopenia is associated with nonalcoholic fatty liver disease (NAFLD). This study investigated whether sarcopenia is associated with significant liver fibrosis in subjects with NAFLD. Data from the Korean National Health and Nutrition Examination Surveys 2008-2011 database were analyzed. NALFD was defined by NAFLD liver fat score, comprehensive NAFLD score, or hepatic steatosis index. Degree of liver fibrosis was assessed by NAFLD fibrosis score (NFS), FIB-4, and Forns index. Significant liver fibrosis was defined as FIB-4 ≥2.67 and the highest quartile values of NFS and Forns index. Sarcopenia index (= total appendicular skeletal muscle mass [kg]/body mass index (kg/m(2) ]) was calculated using dual-energy X-ray absorptiometry. Using the NAFLD liver fat score, NAFLD was identified in 2761 (28.5%) of 9676 subjects. Of subjects with NAFLD, sarcopenia was identified in 337 (12.2%). Sarcopenia was significantly associated with significant liver fibrosis assessed in fibrosis prediction models (all P < 0.05). In subgroups stratified according to body mass index and homeostasis model assessment of insulin resistance, a significant association between sarcopenia and significant liver fibrosis by NFS was consistently present (odds ratio = 1.76-2.68 depending on the subgroup, all P < 0.05). Multivariate logistic regression analysis demonstrated an independent association between SI and significant liver fibrosis by NFS after adjusting for other confounders (odds ratio = 0.52-0.67, all P < 0.01). Other NAFLD (comprehensive NAFLD score, hepatic steatosis index) and fibrosis prediction models (FIB-4 and Forns index) produced similar results.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: Writing – review & editing
                Role: Methodology
                Role: MethodologyRole: Writing – review & editing
                Role: InvestigationRole: Supervision
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                24 January 2020
                2020
                : 15
                : 1
                : e0226351
                Affiliations
                [1 ] Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
                [2 ] Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, United States of America
                [3 ] Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
                [4 ] Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
                Kaohsiung Medical University Chung Ho Memorial Hospital, TAIWAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-3703-1479
                Article
                PONE-D-19-22169
                10.1371/journal.pone.0226351
                6980645
                31978054
                7631ccde-f673-4e4e-ae68-cda14e672dae
                © 2020 Lee 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
                : 6 August 2019
                : 25 November 2019
                Page count
                Figures: 3, Tables: 4, Pages: 16
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003710, Korea Health Industry Development Institute;
                Award ID: HI18C0275
                Award Recipient :
                This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea, grant number HI18C0275. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Stomach
                Medicine and Health Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Stomach
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Colorectal Cancer
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Liver Diseases
                Fatty Liver
                Medicine and Health Sciences
                Urology
                Genitourinary Cancers
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Body Mass Index
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Body Mass Index
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Biology and Life Sciences
                Population Biology
                Population Metrics
                Death Rates
                Custom metadata
                All relevant data are publicly available from the Health Insurance Data Sharing Service: https://nhiss.nhis.or.kr/bd/ay/bdaya001iv.do. The authors confirm they had no special privileges or access to the data.

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                Uncategorized

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