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      Exploring Biomarkers in Nonalcoholic Fatty Liver Disease Among Individuals With Type 2 Diabetes Mellitus

      research-article
      , PharmD, PhD * , , , , , MD, MPH §
      Journal of Clinical Gastroenterology
      Lippincott Williams & Wilkins
      biomarkers, MASLD, NAFLD, omics, type 2 diabetes mellitus

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          Abstract

          Integrating biomarkers into a comprehensive strategy is crucial for precise patient management, especially considering the significant healthcare costs associated with diseases. Current studies emphasize the urgent need for a paradigm shift in conceptualizing nonalcoholic fatty liver disease (NAFLD), now renamed metabolic dysfunction–associated steatotic liver disease (MASLD). Biomarkers are emerging as indispensable tools for accurate diagnosis, risk stratification, and monitoring disease progression. This review classifies biomarkers into conventional and novel categories, such as lipids, insulin resistance, hepatic function, and cutting-edge imaging/omics, and evaluates their potential to transform the approach to MASLD among individuals with type 2 diabetes mellitus (T2D). It focuses on the critical role of biomarkers in early MASLD detection, enhancing predictive accuracy, and discerning responses to interventions (pharmacological or lifestyle modifications). Amid this discussion, the complexities of the relationship between T2D and MASLD are explored, considering factors like age, gender, genetics, ethnicity, and socioeconomic background. Biomarkers enhance the effectiveness of interventions and support global initiatives to reduce the burden of MASLD, thereby improving public health outcomes. This review recognizes the promising potential of biomarkers for diagnostic precision while candidly addressing the challenges in implementing these advancements in clinical practice. The transformative role of biomarkers emerges as a central theme, promising to reshape our understanding of disease trajectories, prognosis, and the customization of personalized therapeutic strategies for improved patient outcomes. From a future perspective, identifying early-stage biomarkers, understanding environmental impact through exposomes, and applying a multiomics approach may reveal additional insight into MASLD development.

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          Most cited references89

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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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              The Global Epidemiology of NAFLD and NASH in Patients with type 2 diabetes: A Systematic Review and Meta-analysis

              Although non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and NASH with advanced fibrosis are closely associated with type 2 diabetes mellitus (T2DM), their global prevalence rates have not been well described. Our aim was to estimate the prevalence of NAFLD, NASH, and advanced fibrosis among patients with T2DM, by regions of the world.
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                Author and article information

                Contributors
                Journal
                J Clin Gastroenterol
                J Clin Gastroenterol
                MCG
                Journal of Clinical Gastroenterology
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0192-0790
                1539-2031
                January 2025
                01 October 2024
                : 59
                : 1
                : 36-46
                Affiliations
                [* ]Data Science and Biostatistics Department, Julius Global Health, University Medical Center Utrecht, Utrecht, The Netherlands
                []Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
                []Beatty Liver and Obesity Research Program Center for Liver Diseases, Inova Health System, Falls Church, VA
                [§ ]The Global NASH Council, Center for Outcomes Research in Liver Disease, Washington, DC
                Author notes
                Address correspondence to: Fariba Ahmadizar, PharmD, PhD, Data Science and Biostatistics Department, Julius Global Health, University Medical Center Utrecht, Utrecht, The Netherlands (e-mail: f.ahmadizar@ 123456umcutrecht.nl ).
                Author information
                https://orcid.org/0000-0002-6261-9445
                Article
                JCG-D-24-00234 00006
                10.1097/MCG.0000000000002079
                11630663
                39352015
                b95f6246-c7f4-4000-bb30-a519ab6705a8
                Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/

                History
                : 27 March 2024
                : 2 September 2024
                Categories
                Clinical Reviews
                Custom metadata
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                biomarkers,masld,nafld,omics,type 2 diabetes mellitus
                biomarkers, masld, nafld, omics, type 2 diabetes mellitus

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