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      Nonalcoholic Fatty Liver Disease and Cardiovascular Disease: a Review of Shared Cardiometabolic Risk Factors

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          Abstract

          The prevalence of nonalcoholic fatty liver disease (NAFLD) is rising. NAFLD/nonalcoholic steatohepatitis (NASH) is associated not only with hepatic morbidity and mortality but also with an increased cardiovascular risk. NAFLD and cardiovascular disease (CVD) share several risk factors, such as obesity, metabolic syndrome, hypertension, dyslipidemia, type 2 diabetes, and chronic kidney disease. This review summarizes the evidence linking cardiometabolic risk factors and NAFLD in the context of risk for CVD. The cause of NAFLD/NASH is complex, involving a range of factors from genetics to lifestyle and energy balance. Genetically driven high liver fat content does not appear to be causally associated with increased CVD risk. In contrast, metabolic dysfunction not only predisposes to liver pathology but also leads to a significantly higher CVD risk. Given that NAFLD pathophysiology is influenced by multiple factors, each patient is unique as to their risk of developing CVD and liver pathology. At the same time, the rising burden of NAFLD/NASH is closely linked with the global increase in metabolic disorders, including obesity and type 2 diabetes. Therefore, both personalized therapeutic approaches that recognize individual pathophysiology, as well as public health policies that address the root causes of cardiometabolic risk factors for NAFLD may be needed to effectively address the NAFLD/NASH epidemic.

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          Most cited references94

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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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            A new definition for metabolic associated fatty liver disease: an international expert consensus statement

            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.
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              MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease

              Fatty liver associated with metabolic dysfunction is common, affects a quarter of the population, and has no approved drug therapy. Although pharmacotherapies are in development, response rates appear modest. The heterogeneous pathogenesis of metabolic fatty liver diseases and inaccuracies in terminology and definitions necessitate a reappraisal of nomenclature to inform clinical trial design and drug development. A group of experts sought to integrate current understanding of patient heterogeneity captured under the acronym nonalcoholic fatty liver disease (NAFLD) and provide suggestions on terminology that more accurately reflects pathogenesis and can help in patient stratification for management. Experts reached consensus that NAFLD does not reflect current knowledge, and metabolic (dysfunction) associated fatty liver disease "MAFLD" was suggested as a more appropriate overarching term. This opens the door for efforts from the research community to update the nomenclature and subphenotype the disease to accelerate the translational path to new treatments.
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                Author and article information

                Contributors
                (View ORCID Profile)
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                Journal
                Hypertension
                Hypertension
                Ovid Technologies (Wolters Kluwer Health)
                0194-911X
                1524-4563
                July 2022
                July 2022
                : 79
                : 7
                : 1319-1326
                Affiliations
                [1 ]Department of Internal Medicine, Endocrinology Section, Clinical Centre of Montenegro, Podgorica (E.M.).
                [2 ]Faculty of Medicine, University of Montenegro, Podgorica, Montenegro (E.M.).
                [3 ]Section of Endocrinology, Diabetes, Nutrition & Weight Management, Boston University School of Medicine, Boston, MA (C.C.-H.P.).
                [4 ]Northeast Medical Group, Yale New Haven Health, New Haven, CT (M.J.B.).
                [5 ]Clinical Genomics and Pharmacogenomics Unit, 4th Department of Internal Medicine, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Greece (D.S.).
                [6 ]Biomedical Research Foundation of the Academy of Athens, Greece (D.S.).
                [7 ]Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London, Medical School, University College London (UCL), United Kingdom (D.P.M.).
                [8 ]Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai (D.P.M.).
                [9 ]Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.S.M.).
                Article
                10.1161/HYPERTENSIONAHA.122.17982
                35465684
                1d5de994-4401-44c4-be67-46c2451ea92d
                © 2022
                History

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