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Li W, Wang F, Li Z, Feng W, Huang H, Kwan MP, Tse LA. Lipid profile and non-alcoholic fatty liver disease detected by ultrasonography: is systemic inflammation a necessary mediator? Ann Med 2025; 57:2480250. [PMID: 40098359 PMCID: PMC11921154 DOI: 10.1080/07853890.2025.2480250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 02/11/2025] [Accepted: 03/05/2025] [Indexed: 03/19/2025] Open
Abstract
AIMS To examine the relationship between lipid profile and non-alcoholic fatty liver (NAFL), compare the predictive strengths of different lipid indicators to NAFL, and explore the possible mechanisms. METHODS Male workers from a baseline survey of a cohort of workers in southern China were included. Basic information was collected through face-to-face interviews. Plasma concentrations of fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined using a blood biochemical analyzer. Liver sonography was used to identify NAFL cases. Regression models were used to calculate ORs, and examine the association between C-reactive protein (CRP) levels and lipid profiles. Restricted cubic spline regression with four knots was used to examine the dose-response relationship, and mediation analysis was employed to examine the mediation effect. RESULTS h Among the 4016 male workers, 829 (20.64%) were diagnosed with NAFL. Compared with normal lipid profile, individuals with abnormal lipid profile had higher prevalence of NAFL (OR=2.27, 95%CI: 1.85-2.79 for TG; OR=1.45, 95%CI: 1.03-2.04 for TC; OR=1.56, 95%CI: 1.21-2.02 for HDL; OR=1.65, 95%CI: 1.25-2.18 for LDL; OR=2.28, 95%CI: 1.87-2.77 for dyslipidaemia) after adjusting for potential confounders. Dose-response relationships were observed among TG, HDL, and NAFL. In addition, no significant mediation effect of C-reactive protein (CRP) was found in the association between lipid profiles and NAFL. CONCLUSIONS Abnormal TG, TC, HDL, and LDL levels were all positively associated with NAFL, while CRP has no mediating effect, and TG tended to be a better predictor of NAFL.
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Affiliation(s)
- Wenzhen Li
- Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong SAR, China
- CUHK Centre for Public Health and Primary Care (Shenzhen), Shenzhen Municipal Key Laboratory for Health Risk Analysis, Shenzhen Research Institute of the Chinese University of Hong Kong, Shenzhen, China
| | - Feng Wang
- Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong SAR, China
| | - Zhimin Li
- Institute of Occupational Medicine, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, China
| | - Wenting Feng
- Institute of Occupational Medicine, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, China
| | - Hongying Huang
- Institute of Occupational Medicine, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, China
| | - Mei-Po Kwan
- Department of Geography and Resource Management, The Chinese University of Hong Kong, Hong Kong SAS, China
- Institute of Space and Earth Information Science, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Lap Ah Tse
- Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong SAR, China
- CUHK Centre for Public Health and Primary Care (Shenzhen), Shenzhen Municipal Key Laboratory for Health Risk Analysis, Shenzhen Research Institute of the Chinese University of Hong Kong, Shenzhen, China
- Institute of Space and Earth Information Science, The Chinese University of Hong Kong, Hong Kong SAR, China
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Chen Y, Wang Y, Shen T, Wang N, Bai X, Li Q, Fang S, He Z, Sun C, Feng R. Serum metabolic signatures and MetalnFF diagnostic score for mild and moderate metabolic dysfunction-associated steatotic liver disease. J Pharm Biomed Anal 2025; 260:116772. [PMID: 40048991 DOI: 10.1016/j.jpba.2025.116772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 02/20/2025] [Accepted: 02/23/2025] [Indexed: 04/01/2025]
Abstract
To explore serum metabolic changes in metabolic dysfunction-associated steatotic liver disease (MASLD) with mild or moderate steatosis and develop a diagnostic index based on liver fat content to differentiate these stages. A total of 149 participants were enrolled from the Nutrition Health Atlas Project in 2019 (Stage 1, n = 92) and 2022 (Stage 2, n = 57). Serum levels of amino acids, free fatty acids (FFAs) and other organic acids were quantified using liquid or gas chromatography-mass spectrometry. The relationships between serum metabolites and magnetic resonance imaging proton density hepatic fat fraction were analyzed and a predictive model fitting fat fraction was constructed in Stage 1 and validated in Stage 2. Patients with moderate MASLD had significantly higher pyruvic acid, 2-ketoglutaric acid, malic acid, 2-hydroxyisocaproic acid and FFA(C14:0) than mild MASLD. Pathway analysis indicated that liver fat accumulation is associated with alterations in amino acid, FFA metabolism and tricarboxylic acid cycle (TCA). The MetalnFF score was developed to discriminate among three groups, achieving an area under the curve (AUC) of 0.956 (95 %CI:0.905, 1.00) for MASLD and 0.857 (95 %CI:0.745, 0.968) for moderate MASLD in Stage 1, and was further validated in Stage 2 with an AUC of 0.986 (95 %CI: 0.951, 1.00) and 0.759 (95 %CI:0.607, 0.921), respectively. In the early stages of MASLD, disrupted amino acid, FFAs metabolism and TCA cycle have occurred. As the disease progresses, metabolic disturbances in pyruvate metabolism become more severe. These findings enhance a deeper understanding of pathogenesis and propose MetalnFF score as a potential diagnostic tool.
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Affiliation(s)
- Yang Chen
- Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Heilongjiang, China; Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, Heilongjiang, China; NHC Specialty Laboratory Cooperation Unit of Food Safety Risk Assessment and Standard Development, Heilongjiang, China
| | - Yiran Wang
- Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Heilongjiang, China; Institute of Cancer Prevention and Treatment, Harbin Medical University, Heilongjiang, China
| | - Tianjiao Shen
- Department of Epidemiology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, US
| | - Nan Wang
- Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Heilongjiang, China
| | - Xiao Bai
- Haxi New Area Community Health Service Center, Nangang District, Heilongjiang, China
| | - Qiyang Li
- Imaging Center, Harbin Medical University Cancer Hospital, Heilongjiang, China
| | - Siyue Fang
- Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Heilongjiang, China
| | - Zhe He
- Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Heilongjiang, China
| | - Changhao Sun
- Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Heilongjiang, China; Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, Heilongjiang, China; NHC Specialty Laboratory Cooperation Unit of Food Safety Risk Assessment and Standard Development, Heilongjiang, China.
| | - Rennan Feng
- Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Heilongjiang, China; Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, Heilongjiang, China; NHC Specialty Laboratory Cooperation Unit of Food Safety Risk Assessment and Standard Development, Heilongjiang, China.
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Liu Z, Huang J, Dai L, Yuan H, Jiang Y, Suo C, Jin L, Zhang T, Chen X. Steatotic Liver Disease Prevalence in China: A Population-Based Study and Meta-Analysis of 17.4 Million Individuals. Aliment Pharmacol Ther 2025; 61:1110-1122. [PMID: 40013739 DOI: 10.1111/apt.70051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 12/20/2024] [Accepted: 02/16/2025] [Indexed: 02/28/2025]
Abstract
BACKGROUND Steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD), has emerged as a leading cause of chronic liver disease in China. AIMS We aimed to provide a comprehensive and updated description of SLD prevalence in China. METHODS We described the prevalence, subgroup distribution, and clinical characteristics of SLD in the Taizhou Study of Liver Diseases (T-SOLID). Additionally, we searched for studies reporting SLD prevalence in five databases. Eligible data were analysed using a generalised linear mixed model. Linear regression was applied to estimate the annual average percentage change (AAPC). RESULTS Of the 28,623 participants in T-SOLID, 30.8% were diagnosed with SLD, among which 83.8% were classified as MASLD. Prevalence of SLD increased from 22.1% in 2018 to 36.7% in 2021. The meta-analysis included 792 publications and 17,404,296 subjects. Nationwide, the pooled SLD prevalence rose from 23.8% (95% CI 21.9%-25.9%) during 2001-2010 to 27.9% (26.0%-29.8%) during 2016-2023 in the general population (AAPC = 2.56, p < 0.0001), equating to approximately 402.0 million cases. An increase in SLD prevalence was observed in subpopulations by region, sex, and age, and in high-risk groups. Northeast China had the highest prevalence (35.0%). Males had a higher prevalence rate than females (35.0% vs. 20.6%). SLD prevalence increased with age, ranging from 8.1% in children and adolescents to 31.8% in the elderly. Meta-regression identified calendar period, age, sex, geographical area, and residence area as significant determinants of SLD prevalence. CONCLUSION The ubiquitously rising prevalence of SLD in Chinese populations underscores the urgent need for targeted public health interventions.
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Affiliation(s)
- Zhenqiu Liu
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Jiayi Huang
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Luojia Dai
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Huangbo Yuan
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Yanfeng Jiang
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Chen Suo
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Li Jin
- Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Tiejun Zhang
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Xingdong Chen
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- State Key Laboratory of Genetic Engineering and Human Phenome Institute, Fudan University, Shanghai, China
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Cannella R, Agnello F, Porrello G, Spinello AU, Infantino G, Pennisi G, Cabibi D, Petta S, Bartolotta TV. Performance of ultrasound-guided attenuation parameter and 2D shear wave elastography in patients with metabolic dysfunction-associated steatotic liver disease. Eur Radiol 2025; 35:2339-2350. [PMID: 39373742 PMCID: PMC11914239 DOI: 10.1007/s00330-024-11076-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 07/06/2024] [Accepted: 08/23/2024] [Indexed: 10/08/2024]
Abstract
PURPOSE To assess the performance and the reproducibility of ultrasound-guided attenuation parameter (UGAP) and two-dimensional shear wave elastography (2D-SWE) in patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS This study included consecutive adult patients with MASLD who underwent ultrasound with UGAP, 2D-SWE and percutaneous liver biopsy. The median values of 12 consecutive UGAP measurements were acquired by two independent radiologists (R1 and R2). Hepatic steatosis was graded by liver biopsy as: (0) < 5%; (1) 5-33%; (2) > 33-66%; (3) > 66%. Areas under the curve (AUCs) were calculated to determine the diagnostic performance. Inter- and intra-observer reliability was assessed with intraclass correlation coefficient (ICC). RESULTS A hundred patients (median age 55.0 years old) with MASLD were prospectively enrolled. At histopathology, 70 and 42 patients had grade ≥ 2 and 3 steatosis, respectively. Median UGAP was 0.78 dB/cm/MHz (IQR/Med: 5.55%). For the diagnosis of grade ≥ 2 steatosis, the AUCs of UGAP were 0.828 (95% CI: 0.739, 0.896) for R1 and 0.779 (95% CI: 0.685, 0.856) for R2. The inter- and intra-operator reliability of UGAP were excellent, with an ICC of 0.92 (95% CI: 0.87-0.95) and 0.95 (95% CI: 0.92-0.96), respectively. The median liver stiffness was 6.76 kPa (IQR/Med: 16.30%). For the diagnosis of advanced fibrosis, 2D-SWE had an AUC of 0.862 (95% CI: 0.757, 0.934), and the optimal cutoff value was > 6.75 kPa with a sensitivity of 80.6% and a specificity of 75.7%. CONCLUSION UGAP and 2D-SWE provide a good performance for the staging of steatosis and fibrosis in patients with MASLD with an excellent intra-operator reliability of UGAP. KEY POINTS Question How well do ultrasound-guided attenuation parameter (UGAP) and two-dimensional shear wave elastography (2D-SWE) perform for quantifying hepatic steatosis and fibrosis? Findings UGAP had a maximum AUC of 0.828 for the diagnosis of grade ≥ 2 steatosis, and 2D-SWE had an AUC of 0.862 for diagnosing advanced fibrosis. Clinical relevance UGAP and 2D-SWE allow rapid, reproducible, and accurate quantification of hepatic steatosis and fibrosis that can be used for the noninvasive assessment of patients with metabolic dysfunction-associated steatotic liver disease.
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Affiliation(s)
- Roberto Cannella
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Via del Vespro 129, Palermo, 90127, Italy.
| | - Francesco Agnello
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Via del Vespro 129, Palermo, 90127, Italy
| | - Giorgia Porrello
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Via del Vespro 129, Palermo, 90127, Italy
| | - Alessandro Umberto Spinello
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Via del Vespro 129, Palermo, 90127, Italy
| | - Giuseppe Infantino
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Grazia Pennisi
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Daniela Cabibi
- Unit of Anatomic Pathology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Tommaso Vincenzo Bartolotta
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Via del Vespro 129, Palermo, 90127, Italy
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Daniels SJ, Nelander K, Eriksson J, Jermutus L, Saillard J, Oyesola S, Tavaglione F, Arrese M, Ladrón de Guevara AL, Vespasiani-Gentilucci U, Alkhouri N, Blau JE. Design and rationale for a global novel non-invasive screening observational study using genetics and non-invasive methodologies to identify at-risk MASLD participants: The ALIGN study. Contemp Clin Trials Commun 2025; 44:101437. [PMID: 39916681 PMCID: PMC11800087 DOI: 10.1016/j.conctc.2025.101437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 01/13/2025] [Accepted: 01/20/2025] [Indexed: 02/05/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disease that is heterogenous in nature with various drivers and modifiers such as metabolic dysfunction and genetic factors. MASLD and the progressive subtype, metabolic dysfunction-associated steatohepatitis (MASH) represent the most rapidly increasing cause of liver-related mortality. There are limited treatment options for patients living with MASLD and MASH, various treatments with an array of different targets are under investigation and one therapeutic has been approved since the initiation of this study. Clinical trials investigating treatments for MASLD and MASH are associated with a high screen failure rate, driven largely by the regulatory required histological inclusion criteria for clinical trial eligibility. Other available clinically utilized biomarkers, typically referred to as non-invasive tests (NITs), can assess both the presence of steatosis and the severity of liver fibrosis in patients with MASLD and MASH in the clinic but are not yet approved over histological changes as endpoints for pivotal trials. However, the use of NITs have been demonstrated to increase the likelihood of meeting clinical trial entry criteria. All-Liver Interventional Global Network (ALIGN) is the first described multi-centre global observational screening study aimed at identifying individuals with a high likelihood of MASLD/MASH interested in participating in therapeutic clinical trials using non-invasive methodologies and genetic testing. This study represents a valuable prototype for industry and academic groups looking to evaluate large populations for MASH eligibility and interest in clinical trial participation.
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Affiliation(s)
| | - Karin Nelander
- CVRM Biometrics, Late CVRM, AstraZeneca, Gothenburg, Sweden
| | - John Eriksson
- CVRM Biometrics, Late CVRM, AstraZeneca, Gothenburg, Sweden
| | - Lutz Jermutus
- Research, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK
| | - Jelena Saillard
- Clinical Operations CVRM, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, USA
| | - Stephanie Oyesola
- Clinical Operations CVRM, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK
| | - Federica Tavaglione
- Clinical Medicine and Hepatology, Fondazione Policlinico Universitario Campus Bio-Medico and Università Campus Bio-Medico di Roma, Rome, Italy
| | - Marco Arrese
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | - Umberto Vespasiani-Gentilucci
- Clinical Medicine and Hepatology, Fondazione Policlinico Universitario Campus Bio-Medico and Università Campus Bio-Medico di Roma, Rome, Italy
| | - Naim Alkhouri
- Department of Hepatology, Arizona Liver Health, Chandler, AZ, USA
| | - Jenny E. Blau
- Early Clinical Development, Early CVRM, AstraZeneca, Gaithersburg, USA
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Chen VL, Kuppa A, Oliveri A, Chen Y, Ponnandy P, Patel PB, Palmer ND, Speliotes EK. Human genetics of metabolic dysfunction-associated steatotic liver disease: from variants to cause to precision treatment. J Clin Invest 2025; 135:e186424. [PMID: 40166930 PMCID: PMC11957700 DOI: 10.1172/jci186424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/02/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by increased hepatic steatosis with cardiometabolic disease and is a leading cause of advanced liver disease. We review here the genetic basis of MASLD. The genetic variants most consistently associated with hepatic steatosis implicate genes involved in lipoprotein input or output, glucose metabolism, adiposity/fat distribution, insulin resistance, or mitochondrial/ER biology. The distinct mechanisms by which these variants promote hepatic steatosis result in distinct effects on cardiometabolic disease that may be best suited to precision medicine. Recent work on gene-environment interactions has shown that genetic risk is not fixed and may be exacerbated or attenuated by modifiable (diet, exercise, alcohol intake) and nonmodifiable environmental risk factors. Some steatosis-associated variants, notably those in patatin-like phospholipase domain-containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2), are associated with risk of developing adverse liver-related outcomes and provide information beyond clinical risk stratification tools, especially in individuals at intermediate to high risk for disease. Future work to better characterize disease heterogeneity by combining genetics with clinical risk factors to holistically predict risk and develop therapies based on genetic risk is required.
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Affiliation(s)
- Vincent L. Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Annapurna Kuppa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Antonino Oliveri
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Yanhua Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Prabhu Ponnandy
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Puja B. Patel
- Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Nicholette D. Palmer
- Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Elizabeth K. Speliotes
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA
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Azizi N, Naghibi H, Shakiba M, Morsali M, Zarei D, Abbastabar H, Ghanaati H. Evaluation of MRI proton density fat fraction in hepatic steatosis: a systematic review and meta-analysis. Eur Radiol 2025; 35:1794-1807. [PMID: 39254718 DOI: 10.1007/s00330-024-11001-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Revised: 06/24/2024] [Accepted: 07/15/2024] [Indexed: 09/11/2024]
Abstract
BACKGROUND Amidst the global rise of metabolic dysfunction-associated steatotic liver disease (MASLD), driven by increasing obesity rates, there is a pressing need for precise, non-invasive diagnostic tools. Our research aims to validate MRI Proton Density Fat Fraction (MRI-PDFF) utility, compared to liver biopsy, in grading hepatic steatosis in MASLD. METHODS A systematic search was conducted across Embase, PubMed/Medline, Scopus, and Web of Science until January 13, 2024, selecting studies that compare MRI-PDFF with liver biopsy for hepatic steatosis grading, defined as grades 0 (< 5% steatosis), 1 (5-33% steatosis), 2 (34-66% steatosis), and 3 (> 66% steatosis). RESULTS Twenty-two studies with 2844 patients were included. The analysis showed high accuracy of MRI-PDFF with AUCs of 0.97 (95% CI = 0.96-0.98) for grade 0 vs ≥ 1, 0.91 (95% CI = 0.88-0.93) for ≤ 1 vs ≥ 2, and 0.91 (95% CI = 0.88-0.93) for ≤ 2 vs 3, diagnostic odds ratio (DOR) from 98.74 (95% CI = 58.61-166.33) to 23.36 (95% CI = 13.76-39.68), sensitivity and specificity from 0.93 (95% CI = 0.88-0.96) to 0.76 (95% CI = 0.63-0.85) and 0.93 (95% CI = 0.88-0.96) to 0.89 (95% CI = 0.84-0.93), respectively. Likelihood ratio (LR) + ranged from 13.3 (95% CI = 7.4-24.0) to 7.2 (95% CI = 4.9-10.5), and LR - from 0.08 (95% CI = 0.05-0.13) to 0.27 (95% CI = 0.17-0.42). The proposed MRI-PDFF threshold of 5.7% for liver fat content emerges as a potential cut-off for the discrimination between grade 0 vs ≥ 1 (p = 0.075). CONCLUSION MRI-PDFF is a precise non-invasive technique for diagnosing and grading hepatic steatosis, warranting further studies to establish its diagnostic thresholds. CLINICAL RELEVANCE STATEMENT This study underscores the high diagnostic accuracy of MRI-PDFF for distinguishing between various grades of hepatic steatosis for early detection and management of MASLD, though further research is necessary for broader application. KEY POINTS MRI-PDFF offers precision in diagnosing and monitoring hepatic steatosis. The diagnostic accuracy of MRI-PDFF decreases as the grade of hepatic steatosis advances. A 5.7% MRI-PDFF threshold differentiates steatotic from non-steatotic livers.
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Affiliation(s)
- Narges Azizi
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science, Tehran, Iran
| | - Hamed Naghibi
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science, Tehran, Iran
| | - Madjid Shakiba
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science, Tehran, Iran
| | - Mina Morsali
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science, Tehran, Iran
| | - Diana Zarei
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science, Tehran, Iran
| | - Hedayat Abbastabar
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science, Tehran, Iran
| | - Hossein Ghanaati
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Science, Tehran, Iran.
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Razpotnik M, Bota S, Wimmer P, Hofer P, Hackl M, Fürstner M, Alber H, Mohr R, Wree A, Walia N, Engelmann C, Demir M, Tacke F, Peck-Radosavljevic M. Development of Liver-Heart Score for Early Detection of Myocardial Contractile Dysfunction in Cirrhosis by Strain Imaging. Liver Int 2025; 45:e70062. [PMID: 40105366 DOI: 10.1111/liv.70062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 01/12/2025] [Accepted: 03/01/2025] [Indexed: 03/20/2025]
Abstract
AIM Cirrhotic cardiomyopathy is characterised by myocardial dysfunction in patients with cirrhosis in the absence of other cardiac conditions. We aimed to develop and validate a scoring system to identify patients at high risk for reduced global longitudinal strain, a newly proposed marker of myocardial dysfunction in the updated diagnostic criteria for cirrhotic cardiomyopathy. METHODS Prospectively recruited patients with cirrhosis in the training and validation groups underwent identical hepatological and cardiological evaluations, including strain echocardiography. Risk factors for myocardial dysfunction were identified using logistic regression. RESULTS In a cohort of 452 consecutive patients, 278 were excluded due to non-cirrhotic cardiomyopathy or conditions potentially affecting strain measurements. The prevalence of reduced global longitudinal strain was 9.8% (13/133) in the training group and 19.5% (8/41) in the validation group. Multivariate logistic regression revealed BMI ≥ 28 kg/m2 (OR 7.02), CAP > 260 dB/m (OR 8.53), and age > 57 years (OR 4.68) as independent predictors of reduced myocardial contractility. These variables were combined and weighted based on their beta coefficients to develop the Liver-heart score (CAP > 260 dB/m [2 pts], BMI ≥ 28 kg/m2 [2 pts], age > 57 years [1 pt]). The AUC-ROC was 0.84 in the training and 0.83 in the validation cohort. A Liver-heart score of 5 points was associated with increased mortality, observed at 2 years (44.4% vs. 17.3%) and the end of the follow-up period (66.7% vs. 37.7%, HR 1.3, p < 0.01). CONCLUSION The Liver-heart score can accurately rule out reduced myocardial contractility and may be useful for risk stratification in cirrhotic patients.
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Affiliation(s)
- Marcel Razpotnik
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Charité-Universitätsmedizin Berlin, Berlin, Germany
- Internal Medicine and Gastroenterology (IMuG) and Emergency Medicine (ZAE), Klinikum Klagenfurt Am Wörthersee, Klagenfurt, Austria
| | - Simona Bota
- Internal Medicine and Gastroenterology (IMuG) and Emergency Medicine (ZAE), Klinikum Klagenfurt Am Wörthersee, Klagenfurt, Austria
| | - Philipp Wimmer
- Internal Medicine and Cardiology (IMuK), Klinikum Klagenfurt Am Wörthersee, Klagenfurt, Austria
| | - Peter Hofer
- Internal Medicine and Cardiology (IMuK), Klinikum Klagenfurt Am Wörthersee, Klagenfurt, Austria
| | - Michael Hackl
- Internal Medicine and Cardiology (IMuK), Klinikum Klagenfurt Am Wörthersee, Klagenfurt, Austria
| | - Matthias Fürstner
- Institute for Diagnostic and Interventional Radiology, Klinikum Klagenfurt Am Wörthersee, Klagenfurt, Austria
| | - Hannes Alber
- Internal Medicine and Cardiology (IMuK), Klinikum Klagenfurt Am Wörthersee, Klagenfurt, Austria
| | - Raphael Mohr
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Alexander Wree
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Nirbaanjot Walia
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Charité-Universitätsmedizin Berlin, Berlin, Germany
- Biostatistics Unit, Melbourne School of Population and Health, The University of Melbourne, Melbourne, Australia
| | - Cornelius Engelmann
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Münevver Demir
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Markus Peck-Radosavljevic
- Internal Medicine and Gastroenterology (IMuG) and Emergency Medicine (ZAE), Klinikum Klagenfurt Am Wörthersee, Klagenfurt, Austria
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9
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Gratacós-Ginès J, Alvarado-Tapias E, Martí-Aguado D, López-Pelayo H, Bataller R, Pose E. Diagnosis and Management of Early Stages of ALD. Semin Liver Dis 2025. [PMID: 39965759 DOI: 10.1055/a-2541-2892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/20/2025]
Abstract
Early forms of alcohol-associated liver disease (ALD) include different stages in the progression of compensated liver disease ranging from steatosis to steatohepatitis and fibrosis. ALD has been classically diagnosed at advanced stages more frequently than other liver diseases. This fact probably contributed to the scarcity of studies on early forms of ALD. Recent studies have investigated the prevalence of early ALD in the general population and have described the natural history of alcohol-induced steatosis and fibrosis, which have been linked to worse prognosis compared with early stages of other chronic liver diseases. In addition, studies on screening and early diagnosis of ALD in at-risk populations have shown that these strategies allow early detection and intervention. Of note, up to 28% of the United States population has concurrent alcohol use and metabolic syndrome, and estimated prevalence of advanced fibrosis among heavy drinkers with metabolic syndrome has increased from 3% in the 1990s to more than 10% in the 2010s. Therefore, new challenges and treatment opportunities will emerge for patients with ALD. In this review, we provide an overview of the state of the art in early ALD, focusing on natural history, diagnosis, and management, and provide insights into future perspectives.
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Affiliation(s)
- Jordi Gratacós-Ginès
- Liver Unit, Hospital Clínic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Edilmar Alvarado-Tapias
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Department of Gastroenterology and Hepatology, Hospital of Santa Creu and Sant Pau, Autonomous University of Barcelona, Barcelona, Spain
| | - David Martí-Aguado
- Digestive Disease Department, Clínic University Hospital, Biomedical Research Institute INCLIVA, Valencia, Spain
| | - Hugo López-Pelayo
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Addictions Unit, Psychiatry and Psychology Service, ICN, Hospital Clínic de Barcelona, Barcelona, Spain
| | - Ramón Bataller
- Liver Unit, Hospital Clínic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Elisa Pose
- Liver Unit, Hospital Clínic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
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10
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Chen G, Tang C, Wang L, Hou Y, Tian K, Yi L, Yang Y. Ultrasonography for Rare Lumbar Hernia Diagnosis: Multimodal Imaging Insights. JOURNAL OF CLINICAL ULTRASOUND : JCU 2025. [PMID: 40091482 DOI: 10.1002/jcu.23966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 01/16/2025] [Accepted: 01/23/2025] [Indexed: 03/19/2025]
Abstract
This case report highlights the role of ultrasonography in diagnosing a rare right lumbar hernia in a 57-year-old male presenting with a painless lumbar mass. Ultrasound revealed a hypoechoic mass with disrupted fascial continuity. CT imaging was used for confirmation, showing herniated omental fat. The patient underwent successful surgical repair with mesh implantation and experienced an uneventful recovery. This case underscores the diagnostic value of ultrasonography as a non-invasive, real-time imaging modality in identifying lumbar hernias and differentiating them from other soft tissue masses, complemented by CT for comprehensive evaluation. Early diagnosis ensured effective management and favorable outcomes for the patient.
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Affiliation(s)
- Guo Chen
- Department of Ultrasound, Luzhou People's Hospital, Luzhou, Sichuan, China
| | - Caili Tang
- Department of Ultrasound, Luzhou People's Hospital, Luzhou, Sichuan, China
| | - Li Wang
- Department of Ultrasound, Luzhou People's Hospital, Luzhou, Sichuan, China
| | - Yiwei Hou
- The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, China
- Department of Endocrinology, Yichang Central People's Hospital, Yichang, Hubei, China
| | - Kecan Tian
- Medical Technology College of Qiqihar Medical College, Qiqihar, Heilongjiang, China
| | - Li Yi
- Medical Technology College of Qiqihar Medical College, Qiqihar, Heilongjiang, China
| | - Yu Yang
- The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, China
- Department of Hepatobiliary Surgery, Yichang Central People's Hospital, Yichang, Hubei, China
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11
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Li X, Min M, Duan F, Ruan X, Xu L. Biochemical, sex hormonal, and anthropometric predictors of non-alcoholic fatty liver disease in polycystic ovary syndrome. BMC Womens Health 2025; 25:118. [PMID: 40087649 PMCID: PMC11908060 DOI: 10.1186/s12905-025-03648-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 03/03/2025] [Indexed: 03/17/2025] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is linked to non-alcoholic fatty liver disease (NAFLD). Biochemical, sex hormonal, and anthropometric indicators have been explored for screening NAFLD in PCOS patients. However, the accuracy of NAFLD screening using these indicators in PCOS patients remains uncertain. This study aimed to identify biochemical, sex hormonal, and anthropometric indicators associated with NAFLD in overweight and obese PCOS patients and assess the diagnostic efficacy of combined indicators. METHODS This cross-sectional study (Clinical trial number ChiCTR1900020986; Registration date January 24th, 2019) involved 87 overweight or obese women with PCOS (mean age 29 ± 4 years). Measurements included anthropometric indices, biochemistry, sex hormone levels, and liver proton density fat fraction (PDFF). Correlation analysis, intergroup comparisons, and logistic regression analysis were used to identify risk factors for NAFLD (PDFF > 5.1%). The receiver operating characteristic curve, area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value were used to determine cut-off values and evaluate diagnostic accuracy. RESULTS Liver PDFF was 7.69% (3.93%, 14.80%) in overweight and obese PCOS patients, with 67.8% diagnosed with NAFLD. NAFLD was associated with increased body mass index (BMI), abdominal circumference (AC), and triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), glucose, insulin, and free testosterone (FT) levels, and with decreased high-density lipoprotein-cholesterol (HDL-C) and sex hormone-binding globulin (SHBG) levels (P < 0.05). Risk factors for NAFLD in PCOS included BMI > 26.8 kg/m2, AC > 88.3 cm, triglyceride > 1.57 mmol/L, TC > 4.67 mmol/L, LDL-C > 3.31 mmol/L, glucose > 4.83 mmol/L, insulin > 111.35 pmol/L, FT > 7.6 pg/mL and SHBG < 25 nmol/L (β = 1.411-2.667, P < 0.005). A multi-indicator model including triglycerides, LDL-C, glucose, insulin, and SHBG showed higher diagnostic accuracy (AUC = 0.899, P < 0.001) for screening NAFLD in PCOS patients than single indicators (AUC = 0.667-0.761, P < 0.05). CONCLUSIONS Overweight and obese PCOS patients have higher incidences of liver PDFF and NAFLD. A multi-indicator model including triglycerides > 1.57 mmol/L, LDL-C > 3.31 mmol/L, glucose > 4.83 mmol/L, insulin > 111.35 pmol/L, and SHBG < 25 nmol/L is highly accurate for screening NAFLD in overweight and obese PCOS patients.
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Affiliation(s)
- Xintong Li
- Department of Radiology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, PR China
| | - Min Min
- Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, PR China
- Department of Gynecology, Aviation General Hospital, Beijing, China
| | - Fangfang Duan
- Clinical Epidemiology Research Center, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Xiangyan Ruan
- Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, PR China.
| | - Li Xu
- Department of Radiology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, PR China.
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12
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Larson EL, Ellias SD, Blezek DJ, Klug J, Hartman RP, Ziller NF, Bamlet H, Mao SA, Perry DK, Nimma IR, Badurdeen D, Yang L, Leise MD, Watt KD, Diwan TS, Taner T, Rosen CD, Elli EF, Madura JA, Jadlowiec CC, Lizaola-Mayo B, Kellogg TA, Heimbach JK. Simultaneous liver transplant and sleeve gastrectomy provides durable weight loss, improves metabolic syndrome and reduces allograft steatosis. J Hepatol 2025:S0168-8278(25)00139-4. [PMID: 40089069 DOI: 10.1016/j.jhep.2025.02.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 02/06/2025] [Accepted: 02/18/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND AND AIMS The prevalence of obesity and metabolic syndrome (MetS) is rising among liver transplant (LT) candidates, many of whom have Metabolic-Associated Steatotic Liver Disease (MASLD). Following LT, untreated obesity often causes recurrent MASLD. We treated patients with obesity with LT and concurrent sleeve gastrectomy (LTSG), aiming to determine long-term impact on obesity, MetS and recurrent MASLD after transplantation. METHODS A multicenter retrospective cohort study analyzed patients undergoing LTSG using a single clinical protocol (n=72), and patients with BMI >30 who underwent LT alone for MASLD (n=185). Follow-up duration was 4-153 (median 41) months for LTSG and 12-161 (median 75) months for LT. Outcomes included mortality, graft loss, BMI, MetS components, allograft steatosis and fibrosis. RESULTS Mortality and graft loss were not significantly different between LT and LTSG patients. Post-LTSG patients had significantly lower prevalence of diabetes for >8 years (p<0.05); hypertension decreased from 61.1% to 35.8% (p<0.01). LTSG patients, with average starting BMI of 45.5, had significant weight loss compared to baseline for >9 years (p<0.001). LT-alone patients, average starting BMI 34.0, experienced no significant change in BMI or diabetes. Development of allograft steatosis was significantly lower in LTSG vs LT patients (p=0.004). Fibrosis prevalence was reduced in LTSG vs LT patients 3-10 years postoperatively; although not statically significant, relative risk ratio was 0.46 (p=0.09). One LTSG patient had a gastric sleeve leak; one required hiatal hernia repair. Severe GERD occurred in 11.1% of LTSG patients; risk factors included pre-existing diabetes and GERD. CONCLUSIONS LTSG results in sustained weight loss, resolution of diabetes and hypertension, and reduced recurrence of steatosis and possibly fibrosis compared to LT alone. It confers no increase in mortality or graft loss.
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Affiliation(s)
- Ellen L Larson
- William Von Liebig Center for Transplantation Mayo Clinic College of Medicine Rochester MN USA
| | - Samia D Ellias
- William Von Liebig Center for Transplantation Mayo Clinic College of Medicine Rochester MN USA
| | - Daniel J Blezek
- William Von Liebig Center for Transplantation Mayo Clinic College of Medicine Rochester MN USA
| | - Jason Klug
- William Von Liebig Center for Transplantation Mayo Clinic College of Medicine Rochester MN USA
| | - Robert P Hartman
- Department of Radiology, Mayo Clinic College of Medicine Rochester MN USA
| | - Nickie Francisco Ziller
- William Von Liebig Center for Transplantation Mayo Clinic College of Medicine Rochester MN USA
| | - Heather Bamlet
- William Von Liebig Center for Transplantation Mayo Clinic College of Medicine Rochester MN USA
| | - Shennen A Mao
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Dana K Perry
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Induja R Nimma
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Dilhana Badurdeen
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Liu Yang
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Michael D Leise
- William Von Liebig Center for Transplantation Mayo Clinic College of Medicine Rochester MN USA
| | - Kymberly D Watt
- William Von Liebig Center for Transplantation Mayo Clinic College of Medicine Rochester MN USA
| | - Tayyab S Diwan
- William Von Liebig Center for Transplantation Mayo Clinic College of Medicine Rochester MN USA
| | - Timucin Taner
- William Von Liebig Center for Transplantation Mayo Clinic College of Medicine Rochester MN USA
| | - Charles D Rosen
- William Von Liebig Center for Transplantation Mayo Clinic College of Medicine Rochester MN USA
| | - Enrique F Elli
- Department of Surgery, Division of General Surgery, Mayo Clinic Arizona
| | - James A Madura
- Department of Surgery, Division of General Surgery, Mayo Clinic Arizona
| | | | - Blanca Lizaola-Mayo
- Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic Arizona
| | - Todd A Kellogg
- William Von Liebig Center for Transplantation Mayo Clinic College of Medicine Rochester MN USA
| | - Julie K Heimbach
- William Von Liebig Center for Transplantation Mayo Clinic College of Medicine Rochester MN USA.
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13
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Huang DQ, Wong VWS, Rinella ME, Boursier J, Lazarus JV, Yki-Järvinen H, Loomba R. Metabolic dysfunction-associated steatotic liver disease in adults. Nat Rev Dis Primers 2025; 11:14. [PMID: 40050362 DOI: 10.1038/s41572-025-00599-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/07/2025] [Indexed: 03/09/2025]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the umbrella term that comprises metabolic dysfunction-associated steatotic liver, or isolated hepatic steatosis, through to metabolic dysfunction-associated steatohepatitis, the progressive necroinflammatory disease form that can progress to fibrosis, cirrhosis and hepatocellular carcinoma. MASLD is estimated to affect more than one-third of adults worldwide. MASLD is closely associated with insulin resistance, obesity, gut microbial dysbiosis and genetic risk factors. The obesity epidemic and the growing prevalence of type 2 diabetes mellitus greatly contribute to the increasing burden of MASLD. The treatment and prevention of major metabolic comorbidities such as type 2 diabetes mellitus and obesity will probably slow the growth of MASLD. In 2023, the field decided on a new nomenclature and agreed on a set of research and action priorities, and in 2024, the US FDA approved the first drug, resmetirom, for the treatment of non-cirrhotic metabolic dysfunction-associated steatohepatitis with moderate to advanced fibrosis. Reliable, validated biomarkers that can replace histology for patient selection and primary end points in MASH trials will greatly accelerate the drug development process. Additionally, noninvasive tests that can reliably determine treatment response or predict response to therapy are warranted. Sustained efforts are required to combat the burden of MASLD by tackling metabolic risk factors, improving risk stratification and linkage to care, and increasing access to therapeutic agents and non-pharmaceutical interventions.
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Affiliation(s)
- Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Vincent W S Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Mary E Rinella
- University of Chicago Pritzker School of Medicine, Chicago, IL, USA
| | - Jerome Boursier
- Service d'Hépato-Gastroentérologie et Oncologie Digestive, Centre Hospitalier Universitaire d'Angers, Angers, France
- Laboratoire HIFIH, SFR ICAT 4208, Université d'Angers, Angers, France
| | - Jeffrey V Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
- City University of New York Graduate School of Public Health and Health Policy, New York, NY, USA
| | - Hannele Yki-Järvinen
- Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Minerva Foundation Institute for Medical Research, Helsinki, Finland
| | - Rohit Loomba
- MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, San Diego, CA, USA.
- Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, San Diego, CA, USA.
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Ali B, Kamani L, Salim A, Alam A, Zuberi BF, Farooqi JI, Naqvi AB, Ali Z, Majid S, Hashmi ZY, Choudhry AA, Salih M, Khan AA, Azam SMZ, Abbas Z, Siddique M, Nawaz AA. HEPNET Position Statement-I, Case Definition, Classification, Screening & Diagnosis of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Pakistan: A Resource for Primary and Secondary Care Physicians. Pak J Med Sci 2025; 41:929-938. [PMID: 40103882 PMCID: PMC11911726 DOI: 10.12669/pjms.41.3.10081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 09/18/2024] [Accepted: 02/15/2025] [Indexed: 03/20/2025] Open
Abstract
The Hep-Net position paper comes at a significant time in the history of Metabolically Associated Fatty Liver Disease (MAFLD) due to the rapid rise in this disease entity in the past decade. Metabolically Associated Fatty Liver Disease, by its very name, encompasses several common metabolic disease entities, top among those being diabetes and obesity. For Pakistan, the situation is serious as it is among the top 10 countries globally regarding the prevalence of obesity and number one in terms of diabetes, with over a quarter of adults affected. There remains slight ambiguity as regards the nomenclature of MAFLD, with western societies preferring to remove the word "fatty" and substitute with `'steatotic" i.e. MASLD. Regardless of names/titles the metabolic nature of the disease and its management remains the same and fortunately, that is something where universal consensus is present. Under the umbrella of Hep-Net, eminent hepatologists from all over Pakistan have pooled their efforts to formulate guidelines that are specifically tailored to the Pakistani population, its specific lifestyle and relevant interventions that are needed to treat fatty/steatotic liver disease. By virtue of its multi-systemic consequences, metabolic fatty liver disease represents the most significant and expensive disease entity, globally. Prevention, through public education and timely intervention in diagnosed cases will serve to avert a healthcare storm that will far outweigh viral hepatitis.
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Affiliation(s)
- Bushra Ali
- Bushra Ali, Fatima Memorial Hospital College of Medicine and Dentistry, Lahore, Pakistan
| | - Lubna Kamani
- Lubna Kamani, Liaquat National Hospital, National Medical Center, Karachi, Pakistan
| | - Adnan Salim
- Adnan Salim, Shaikh Zayed Medical Complex Lahore, Pakistan
| | - Altaf Alam
- Altaf Alam, Consultant Gastroenterologist, Evercare Hospital Lahore, Lahore, Pakistan
| | | | | | | | - Zeeshan Ali
- Zeeshan Ali, Jinnah Sindh Medical University & Jinnah Postgraduate Medical Center Karachi, Pakistan
| | - Shahid Majid
- Shahid Majid, The Indus Hospital and Health Network, Karachi, Pakistan
| | | | - Asad A Choudhry
- Asad A Choudhry, Consultant Gastroenterologist, Chaudhry Hospital, Gujranwala
| | - Muhammad Salih
- Muhammad Salih, Shifa International Hospital, Islamabad, Pakistan
| | - Anwar Ahmed Khan
- Anwaar Ahmed Khan, Doctors Hospital and Medical Center, Lahore, Pakistan
| | - Syed M. Zahid Azam
- Syed M. Zahid Azam, National Institute of Liver & GI Diseases, Dow University, Karachi, Pakistan
| | - Zaigham Abbas
- Zaigham Abbas, Ziauddin University Hospital Clifton Karachi, Pakistan
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15
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Pietri O, Chicaud M, Andreani T, Chrétien Y, Limousin W, Lemoinne S, Chazouilleres O, Wendum D. Unexplained Chronically Elevated Aminotransferases: Liver Biopsy Gives Major Information with Therapeutic Implication in One Patient Out of Seven. Dig Dis Sci 2025; 70:1178-1189. [PMID: 39681748 DOI: 10.1007/s10620-024-08730-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Accepted: 11/03/2024] [Indexed: 12/18/2024]
Abstract
BACKGROUND & AIMS Liver biopsy contribution in patients with unexplained elevation of transaminases is not clearly established. The aim was to study liver biopsy contribution in patients with unexplained elevated transaminases strictly defined according to the current guidelines, reflecting the present clinical practice. METHODS In a retrospective study, we identified all the liver biopsies performed in patients with elevated transaminases for at least six months. Patients with a particular context, or with an identified cause of liver disease were excluded. The biopsies were classified according to the 4 following injury patterns: hepatitic, biliary, steatotic, vascular. RESULTS 87 patients were included. Liver biopsy showed minimal changes or a normal histology in 48%, a steatotic pattern in 21%, a hepatitic pattern in 13%, a vascular pattern in 8%, a biliary pattern in 1%, and a mixed pattern in 8%. A cause could be determined in 21% of patients with normal histology, 85% with steatosis, 56% with hepatitis, 75% with biliary, but in none with isolated vascular pattern. Liver biopsy had important clinical and therapeutic implications in 15% of patients, with a diagnosis of autoimmune hepatitis, primary biliary cholangitis or metabolic dysfunction-associated steatohepatitis. Elevation of transaminases > 10 upper normal limit was present in all the patients with confirmed autoimmune hepatitis, but in only 7% of others. CONCLUSION Liver biopsy had important clinical and therapeutic implications in 15% of patients. However, the majority of patients had minimal changes without a cause, or minor vascular lesions of uncertain significance.
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Affiliation(s)
- Olivia Pietri
- AP-HP, Saint-Antoine Hospital, Department of Hepatology, Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (CRMR MIVB-H), ERN RARE-LIVER, Sorbonne Université, Paris, France
| | - Matthieu Chicaud
- AP-HP, Hôpital Saint Antoine, Department of Pathology, Paris, France
| | - Tony Andreani
- AP-HP, Saint-Antoine Hospital, Department of Hepatology, Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (CRMR MIVB-H), ERN RARE-LIVER, Sorbonne Université, Paris, France
| | - Yves Chrétien
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, Paris, France
| | - Wendy Limousin
- AP-HP, Saint-Antoine Hospital, Department of Hepatology, Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (CRMR MIVB-H), ERN RARE-LIVER, Sorbonne Université, Paris, France
| | - Sara Lemoinne
- AP-HP, Saint-Antoine Hospital, Department of Hepatology, Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (CRMR MIVB-H), ERN RARE-LIVER, Sorbonne Université, Paris, France
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, Paris, France
| | - Olivier Chazouilleres
- AP-HP, Saint-Antoine Hospital, Department of Hepatology, Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (CRMR MIVB-H), ERN RARE-LIVER, Sorbonne Université, Paris, France
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, Paris, France
| | - Dominique Wendum
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, Paris, France.
- AP-HP, Hôpital Saint Antoine, Department of Pathology, Paris, France.
- AP-HP, Hôpital Saint Antoine, Service d'Anatomie et Cytologie Pathologiques, 184 rue du faubourg Saint-Antoine, F-75012, Paris, France.
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Du T, Huang Y, Lv Y, Yuan G. Liver fibrotic burden across the spectrum of hypothyroidism. J Gastroenterol 2025; 60:315-327. [PMID: 39601802 PMCID: PMC11880098 DOI: 10.1007/s00535-024-02184-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 11/12/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND Data regarding the prevalence of hepatic fibrotic burden across the spectrum of hypothyroidism are scarce. Hence, we aimed to evaluate the prevalence of liver fibrotic burden across the spectrum of hypothyroidism. METHODS 30,091 individuals who attended a Health Management Centre between 2019 and 2021 were cross-sectionally analyzed. Participants were categorized as having strict-normal thyroid function, low-normal thyroid function, subclinical hypothyroidism, and overt hypothyroidism. Hepatic fibrosis was assessed by vibration-controlled transient elastography (VCTE). Significant and advanced fibrosis were defined as liver stiffness measurement in VCTE of 8.1-9.6 and 9.7-13.5 kPa, respectively. RESULTS Among both men and women, low-normal thyroid function group, subclinical hypothyroidism group, and overt hypothyroidism group all have more liver fibrosis present, including mild fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis, than the strict-normal thyroid function group. The low-normal thyroid function group have the similar liver fibrotic burden to the subclinical hypothyroidism group. The highest liver fibrotic burden was noted in the overt hypothyroidism group. Both significant and advanced liver fibrosis were significantly associated with low-normal thyroid function, subclinical hypothyroidism, and overt hypothyroidism in both men and women. CONCLUSIONS Liver fibrotic burden are highly prevalent in subjects with overt hypothyroidism. Moreover, fibrotic burden increased across the spectrum of hypothyroidism even within the low normal thyroid function. These results suggested that screening for liver fibrosis in patients with hypothyroidism is necessary.
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Affiliation(s)
- Tingting Du
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China
| | - Yuchai Huang
- Department of Health Management Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yongman Lv
- Department of Health Management Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
| | - Gang Yuan
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, China.
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Mitsinikos T, Aw MM, Bandsma R, Godoy M, Ibrahim SH, Mann JP, Memon I, Mohan N, Mouane N, Porta G, Verduci E, Xanthakos S. FISPGHAN statement on the global public health impact of metabolic dysfunction-associated steatotic liver disease. J Pediatr Gastroenterol Nutr 2025; 80:397-407. [PMID: 39727048 DOI: 10.1002/jpn3.12399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 09/26/2024] [Accepted: 10/03/2024] [Indexed: 12/28/2024]
Abstract
As rates of obesity rise worldwide, incidence of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease, is increasing, worsening the burden of healthcare systems. The council of the Federation of International Societies for Pediatric Gastroenterology, Hepatology, and Nutrition (FISPGHAN) identified the topic of MASLD epidemiology, treatment, and prevention as a global priority issue to be addressed by an expert team, with the goal to describe feasible and evidence-based actions that may contribute to reducing MASLD risk. The FISPGHAN member societies nominated experts in the field. The FISPGHAN council selected and appointed members of the expert team and a chair. The subtopics included in this manuscript were chosen through a consensus of the experts involved. We review the epidemiology, natural history, and screening and management. We further expand to relevant public health measures aimed at MASLD prevention, including identifying interventions that could reduce risk factors (environmental and iatrogenic), optimize maternal and newborn health, and support healthier lifestyles for older children and adolescents on a local, national, and international scale. While recognizing that various aspects of population health and public policy can shape MASLD risk, we also review what we can do on an individual level to support our patients to reduce the significant burden of this ever rising disease in pediatrics.
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Affiliation(s)
- Tania Mitsinikos
- Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital Los Angeles, Los Angeles, California, USA
- Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, California, USA
| | - Marion M Aw
- Division of Paediatric Gastroenterology, Nutrition, Hepatology and Liver Transplantation, National University of Singapore, Singapore
- Department of Paediatrics, National University Health System, Singapore
| | - Robert Bandsma
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Marcela Godoy
- Division of Pediatric Gastroenterology, Hospital Clinico San Borja Arriaran, Santiago, Chile
- Department of Pediatrics, University of Chile, Santiago, Chile
| | - Samar H Ibrahim
- Department of Pediatric and Adolescent Medicine, Division of Pediatric Gastroenterology, Mayo Clinic, Rochester, Minnesota, USA
| | - Jake P Mann
- Department of Immunology and immunotherapy, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK
| | - Iqbal Memon
- Division of Gastroenterology, Hepatology, and Nutrition, Sir Syed College of Medical Sciences for Girls, Karachi, Pakistan
| | - Neelam Mohan
- Department of Pediatric Gastroenterology, Hepatology & Liver Transplantation, Medanta The Medicity, Gurugram, Haryana, India
| | - Nezha Mouane
- Department of Pediatric Hepatology, Gastroenterology and Nutrition, Academic Children's Hospital, Mohammed V University, Rabat, Morocco
| | - Gilda Porta
- Pediatric Hepatology, Transplant Unit, Hospital Sírio-Libanês, Hospital Municipal Infantil Menino Jesus, São Paulo, Brazil
| | - Elvira Verduci
- Department of Pediatrics, Ospedale dei Bambini Vittore Buzzi, University of Milan, Milan, Italy
- Department of Health Sciences, University of Milan, Milan, Italy
| | - Stavra Xanthakos
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
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Amirkalali B, Hassanzadeh P, Sheikholmolooki F, Gholizadeh E, Doustmohammadian A, Safarnezhad Tameshkel F, Motamed N, Maadi M, Sohrabi M, Sobhrakhshankhah E, Zamani F, Ajdarkosh H. The crucial role of hypertension in determining latent classes of metabolic syndrome in northern Iran and predictive power of these classes in non-alcoholic fatty liver: a gender-based insight. Front Endocrinol (Lausanne) 2025; 16:1405833. [PMID: 40093747 PMCID: PMC11906334 DOI: 10.3389/fendo.2025.1405833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Accepted: 01/22/2025] [Indexed: 03/19/2025] Open
Abstract
Introduction This study investigates the subclasses of metabolic syndrome (Mets) and their relationship with non-alcoholic fatty liver (NAFLD) and the probable predictive role of serum vitamin D and CRP levels. Methods This community-based, cross-sectional study was performed on adults in the framework of the Amol cohort prospective study (AmolCPS). Mets was defined as Adult Treatment Panel III criteria (ATP III) and ultrasound was used to diagnose NAFLD. Anthropometric and blood pressure measurements were conducted, and biochemical measurements were assessed after fasting. Data analysis included Latent class analysis, two-tailed χ2 statistics, one-way analysis of variance, and logistic regression using Mplus (version 7.4) and spss (version 26) softwares. Results The study involved 2308 participants, with a mean age of 43.17 ± 12.30 years. Mets prevalence was 25.64%, with three identified classes: Mets with Hypertension (HTN), Mets without HTN (Non-HTN), and Low Risk. Mets with HTN had a high probability of at least four components, particularly high SBP. Non-HTN had at least three high probable components, especially high TG and low HDL but not high SBP and DBP. The low-risk class had a low probability of all components except low HDL in women. Serum vitamin D and CRP levels did not significantly predict Mets classes in men, while CRP level significantly predicted the HTN class in women (OR:1.03, CI:1.004-1.067). Both HTN, and Non-HTN Mets classes significantly increased the odds of NAFLD compared to the low risk class, especially in women (HTN class OR: 4.20 vs 2.94; non-HTN class OR: 5.60 vs 3.12 in women and men respectively). Conclusion The latent class analysis in northern Iran identified three Mets classes: HTN, Non-HTN, and low-risk, with hypertension playing a crucial role in determining these classes. These classes were stronger predictors of NAFLD in women. Serum CRP and vitamin D levels did not emerge as significant predictors of the classes, except for serum CRP in the HTN class among women.
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Affiliation(s)
- Bahareh Amirkalali
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Parvin Hassanzadeh
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Sheikholmolooki
- Department of Nutrition, Health and Statistics Surveillance Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Esmaeel Gholizadeh
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Azam Doustmohammadian
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | | | - Nima Motamed
- Department of Social Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mansooreh Maadi
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Masoudreza Sohrabi
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Elham Sobhrakhshankhah
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Farhad Zamani
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Ajdarkosh
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
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Real Martinez Y, Fernandez-Garcia CE, Fuertes-Yebra E, Calvo Soto M, Berlana A, Barrios V, Caldas M, Gonzalez Moreno L, Garcia-Buey L, Molina Baena B, Sampedro-Nuñez M, Beceiro MJ, García-Monzón C, González-Rodríguez Á. Assessment of skeletal muscle alterations and circulating myokines in metabolic dysfunction-associated steatotic liver disease: A cross-sectional study. World J Gastroenterol 2025; 31:100039. [PMID: 39991673 PMCID: PMC11755261 DOI: 10.3748/wjg.v31.i7.100039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 12/04/2024] [Accepted: 12/25/2024] [Indexed: 01/20/2025] Open
Abstract
BACKGROUND Skeletal muscle alterations (SMAs) are being increasingly recognized in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and appear to be associated with deleterious outcomes in these patients. However, their actual prevalence and pathophysiology remain to be elucidated. AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD. METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria, recruited from the outpatient clinics of a tertiary level hospital. The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography. Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort. Statistical analysis was performed comparing results according to liver fibrosis and steatosis. RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis. Interestingly, serum levels of fibroblast growth factor-21 (FGF21) were significantly higher in patients with MASLD with advanced hepatic fibrosis (F3-F4) than in those with lower fibrosis stages (F0-F2) (197.49 ± 198.27 pg/mL vs 95.62 ± 83.67 pg/mL; P = 0.049). In addition, patients with MASLD with severe hepatosteatosis (S3) exhibited significantly higher serum levels of irisin (1116.87 ± 1161.86 pg/mL) than those with lower grades (S1-S2) (385.21 ± 375.98 pg/mL; P = 0.001). CONCLUSION SMAs were uncommon in the patients with MASLD studied. Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis, respectively, with potential implications as biomarkers.
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Affiliation(s)
- Yolanda Real Martinez
- Servicio Aparato Digestivo, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - Carlos Ernesto Fernandez-Garcia
- Unidad de Investigación, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria La Princesa, Madrid 28009, Spain
| | - Esther Fuertes-Yebra
- Unidad de Investigación, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria La Princesa, Madrid 28009, Spain
| | - Mario Calvo Soto
- Servicio Aparato Digestivo, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - Angela Berlana
- Unidad de Investigación, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria La Princesa, Madrid 28009, Spain
| | - Vicente Barrios
- Department of Endocrinology, Department of Pediatrics, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid 28009, Spain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Maria Caldas
- Servicio Aparato Digestivo, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - Leticia Gonzalez Moreno
- Servicio Aparato Digestivo, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - Luisa Garcia-Buey
- Servicio Aparato Digestivo, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - Begoña Molina Baena
- Servicio de Endocrinología y Nutrición, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - Miguel Sampedro-Nuñez
- Servicio de Endocrinología y Nutrición, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - Maria J Beceiro
- Servicio Aparato Digestivo, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - C García-Monzón
- Unidad de Investigación, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria La Princesa, Madrid 28009, Spain
| | - Águeda González-Rodríguez
- Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM), CSIC-UAM, Madrid 28029, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Madrid 28029, Spain
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Xu J, Deng M, Weng Y, Feng H, He X. Cross-sectional study on the association between serum uric acid levels and non-alcoholic fatty liver disease in an elderly population. Sci Rep 2025; 15:5678. [PMID: 39956839 PMCID: PMC11830768 DOI: 10.1038/s41598-025-90590-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Accepted: 02/13/2025] [Indexed: 02/18/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disorder strongly associated with metabolic dysfunction, particularly in elderly populations where it presents with higher prevalence and severity. This study aimed to investigate the association between serum uric acid (SUA) levels and NAFLD in older adults, focusing on the independent effect of hyperuricemia on NAFLD risk. We enrolled 469 individuals aged ≥ 65 years who underwent community health checkups. The exposure variable was baseline SUA levels, while the outcome variable was the occurrence of NAFLD. Covariates included age, sex, BMI, blood pressure, diabetes status, lipids (TC, TG, LDL, HDL), glycemic indices (FPG, HBA1C), and physical activity. Multivariable logistic regression was applied to estimate the independent effect of SUA levels and hyperuricemia on NAFLD. Hyperuricemia was significantly associated with increased NAFLD risk (adjusted OR 2.16, 95% CI 1.28-3.67). Stratified analysis revealed a stronger association in individuals with elevated triglycerides (TG ≥ 2.26 mmol/L, OR 7.07, 95% CI 1.72-29.18). However, the association between SUA as a continuous variable and NAFLD risk was attenuated after adjusting for metabolic factors. Hyperuricemia independently increases NAFLD risk in older adults, particularly in those with elevated triglycerides, suggesting a potential synergistic effect. These findings highlight the importance of incorporating SUA assessments into routine metabolic evaluations and developing targeted interventions to mitigate NAFLD risk.
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Affiliation(s)
- Jianqing Xu
- Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Ming Deng
- Department of Cardiology, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen, China.
| | - Yinghui Weng
- Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Hui Feng
- Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Xuelian He
- Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, China
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21
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Wang Y, Wang P. Development and validation of a new diagnostic prediction model for NAFLD based on machine learning algorithms in NHANES 2017-2020.3. Hormones (Athens) 2025:10.1007/s42000-025-00634-6. [PMID: 39939537 DOI: 10.1007/s42000-025-00634-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 02/03/2025] [Indexed: 02/14/2025]
Abstract
AIMS Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that can trigger the metabolic syndrome. Early prevention and treatment of NAFLD is still a huge challenge for patients and clinicians. The aim of this study was to develop and validate machine learning (ML)-based predictive models. The model with optimal performance would be developed as a set of simple arithmetic tools for predicting the risk of NAFLD individually. METHODS Statistical analyses were performed in 2428 individuals extracted from the National Health and Nutrition Examination Survey (NHANES, cycle 2017-2020.3) database. Feature variables were selected by the least absolute shrinkage and selection operator (LASSO) regression. Seven ML algorithms, including logistic regression (LR), decision tree (DT), random forest (RF), extreme gradient boosting (XGB), K-nearest neighbor (KNN), light gradient boosting machine (LightGBM), and multilayer perceptron (MLP), were used to construct models based on the feature variables and evaluate their performance. The model with the best performance was transformed into a diagnostic predictive nomogram (DPN). The DPN was developed into an online calculator and an Excel algorithm tool. Receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and subgroup analyses were used to compare and assess the predictive abilities of the DPN and six existing NAFLD predictive models, including the ZJU index, the hepatic steatosis index (HSI), the triglyceride-glucose index (TyG), the Framingham steatosis index (FSI), the fatty liver index (FLI), and the visceral adiposity index (VAI). RESULTS Among the 2428 participants, the prevalence of NAFLD was 47.45%. LASSO regression identified eight variables from 39 variables, including body mass index (BMI), waist circumference (WC), alanine aminotransferase (ALT), triglyceride (TG), diabetes, hypertension, uric acid (UA), and race. Among the models constructed by the seven algorithms mentioned above, the LR-based model performed the best, demonstrating outstanding performance in terms of area under the curve (AUC, 0.823), accuracy (0.754), precision (0.768), specificity (0.804), and positive predictive value (0.768). It was then transformed into the DPN, which was successfully developed as an online calculator and an Excel algorithm tool. The diagnostic accuracy (AUC 0.856, 95% confidence interval (CI) 0.839-0.874, and AUC 0.823, 95% CI 0.793-0.854, respectively) and net clinical benefit of DPN in the training and validation sets were superior to those of the ZJU, HSI, TyG, FSI, FLI, and VAI. The results were maintained in subgroup analyses. CONCLUSIONS The LR model based on ML was developed, exhibiting good performance. DPN can be used as an individualized tool for rapid detection of NAFLD.
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Affiliation(s)
- Yazhi Wang
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu, 730000, China
| | - Peng Wang
- The Department of Pharmacy, The 987th Hospital of Joint Logistics Support Force of People's Liberation Army, Baoji, Shaanxi, 721004, China.
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22
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Parlar MA, Mutlu H, Doğantekin B, Musaoğlu İS, Albayrakoğlu ND, Yavuz ML, Özbolat ZB, Kaplan M. The Association of Statin Therapy with Liver and Pancreatic Fat Fraction in Type 2 Diabetes Mellitus. Diagnostics (Basel) 2025; 15:426. [PMID: 40002577 PMCID: PMC11854770 DOI: 10.3390/diagnostics15040426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 02/02/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives: It has been shown that the use of statins in patients with type 2 diabetes mellitus (T2DM) worsens hyperglycemia and hemoglobin A1c levels but may help in the preservation of pancreatic β-cell function. The potential role of a high pancreatic fat fraction (PFF) in this process has not yet been clarified. This study aimed to investigate whether the liver fat fraction (LFF) and PFF in T2DM patients is affected by statin therapy. Methods: This cross-sectional study involved a total of 140 T2DM patients, including both those who were receiving (n = 70) and those who were not receiving (n = 70) statin therapy. The mapping of the LFF and PFF utilizing the IDEAL-IQ sequence was conducted in magnetic resonance imaging. Results: In T2DM patients who used statins, the median PFF was higher compared to those who did not use statins (8.4 vs. 6.2%, p = 0.021), while the median LFF was found to be similar (8.4 vs. 8.9, p = 0.572). Variations in PFF were associated with the use of various statins (non-statin group: 6.2 vs. atovastatin: 8.7 vs. rosuvastatin: 3.2 vs. pitavastatin: 9.2, p = 0.004). The multivariable regression analysis indicated that insulin usage decreased log(LFF) by a factor of 0.16-fold (ꞵ ± SE = -0.16 ± 0.05, p = 0.010), and rosuvastatin usage reduced log(PFF) by 0.16-fold (ꞵ ± SE = -0.16 ± 0.07, p = 0.025), irrespective of other risk factors. Furthermore, the use of atorvastatin (ꞵ ± SE = 0.17 ± 0.06, p = 0.011) and pitavastatin (ꞵ ± SE = 0.19 ± 0.07, p = 0.008) were independently associated with an increase in log(PFF). Conclusions: In patients with T2DM, statin use did not show a significant effect on the liver fat fraction, but it caused differences in the pancreatic fat fraction. The observation of a lower pancreatic fat fraction in patients taking a rosuvastatin and atorvastatin dose of 40 mg/day suggests that different types and doses of statins may have varying effects on pancreatic fat accumulation.
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Affiliation(s)
- Mehmet Akif Parlar
- Department of Internal Medicine, Sultan 2. Abdülhamid Han Training and Research Hospital, University of Health Sciences, Selimiye Neighborhood, Tıbbiye Street, 34668 Istanbul, Turkey; (H.M.); (B.D.); (İ.S.M.); (N.D.A.); (M.K.)
| | - Hakan Mutlu
- Department of Internal Medicine, Sultan 2. Abdülhamid Han Training and Research Hospital, University of Health Sciences, Selimiye Neighborhood, Tıbbiye Street, 34668 Istanbul, Turkey; (H.M.); (B.D.); (İ.S.M.); (N.D.A.); (M.K.)
| | - Betül Doğantekin
- Department of Internal Medicine, Sultan 2. Abdülhamid Han Training and Research Hospital, University of Health Sciences, Selimiye Neighborhood, Tıbbiye Street, 34668 Istanbul, Turkey; (H.M.); (B.D.); (İ.S.M.); (N.D.A.); (M.K.)
| | - İsmail Serhat Musaoğlu
- Department of Internal Medicine, Sultan 2. Abdülhamid Han Training and Research Hospital, University of Health Sciences, Selimiye Neighborhood, Tıbbiye Street, 34668 Istanbul, Turkey; (H.M.); (B.D.); (İ.S.M.); (N.D.A.); (M.K.)
| | - Nisa Demirboşnak Albayrakoğlu
- Department of Internal Medicine, Sultan 2. Abdülhamid Han Training and Research Hospital, University of Health Sciences, Selimiye Neighborhood, Tıbbiye Street, 34668 Istanbul, Turkey; (H.M.); (B.D.); (İ.S.M.); (N.D.A.); (M.K.)
| | - Mustafa Lütfi Yavuz
- Department of Cardiology, Istanbul University Faculty of Medicine, 34093 Istanbul, Turkey;
| | - Zehra Buşra Özbolat
- Deparment of Chest Diseases, Çerkezköy State Hospital, Tekirdağ Provincial Health Directorate, 59100 Tekirdağ, Turkey;
| | - Mustafa Kaplan
- Department of Internal Medicine, Sultan 2. Abdülhamid Han Training and Research Hospital, University of Health Sciences, Selimiye Neighborhood, Tıbbiye Street, 34668 Istanbul, Turkey; (H.M.); (B.D.); (İ.S.M.); (N.D.A.); (M.K.)
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Kim JY, Kwan BS, Cho JH, Kim HI, Ko NG, Jin M, Lee OJ. Persistently Active Helicobacter pylori Infection Is Associated with the Development of Metabolic Dysfunction-Associated Steatotic Liver Disease. J Clin Med 2025; 14:1073. [PMID: 40004603 PMCID: PMC11856028 DOI: 10.3390/jcm14041073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 01/31/2025] [Accepted: 02/06/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives: Previous studies suggested a link between Helicobacter pylori (H. pylori) infection and steatotic liver disease, now termed metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to identify the association of active H. pylori infection and the new concept of MASLD in a longitudinal cohort. Methods: We reviewed 1497 health examinees who had two endoscopic biopsies for H. pylori activity without hepatic steatosis at the baseline abdominal ultrasonography. Subjects were classified into four groups based on H. pylori activity. Multivariable Cox models assessed the link between active H. pylori infection status and incident MASLD. Results: Over a median follow-up of 31.1 months, 247 subjects (16.5%) developed MASLD. The groups were: H. pylori naïve (n = 57, 15.6%), de novo (n = 31, 15.3%), eradicated (n = 32, 16.1%), and persistent (n = 127, 17.4%). The H. pylori persistent group had a higher risk of MASLD compared to naïve group (hazard ratio: 1.41; 95% confidence interval: 1.01-1.96; p-value = 0.045). The association between H. pylori infection and incident MASLD was significant only with ongoing infection. Conclusions: Persistent H. pylori infection increases the risk of MASLD, indicating that active infection may contribute to MASLD development. Eradicating active H. pylori infection might help lower the incidence of MASLD.
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Affiliation(s)
- Jun Young Kim
- Department of Medicine, Gyeongsang National University Graduate School, Jinju 52727, Republic of Korea;
- Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 51353, Republic of Korea
| | - Byung Soo Kwan
- Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 51353, Republic of Korea
| | - Jung Hwan Cho
- Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 51353, Republic of Korea
| | - Hye In Kim
- Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 51353, Republic of Korea
| | - Nak Gyeong Ko
- Department of Research & Support, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 51353, Republic of Korea
| | - Mihyeon Jin
- Department of Research & Support, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 51353, Republic of Korea
| | - Ok Jae Lee
- Department of Internal Medicine, Gyeongsang National University College of Medicine and Gyeongsang National University Hospital, Jinju 52727, Republic of Korea
- Institute of Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea
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24
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Wang J, Wang Z, Yu Y, Cheng S, Wu J. Advances in research on metabolic dysfunction-associated steatotic liver disease. Life Sci 2025; 362:123362. [PMID: 39761743 DOI: 10.1016/j.lfs.2024.123362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Revised: 12/13/2024] [Accepted: 12/31/2024] [Indexed: 01/12/2025]
Abstract
The global increase in obesity-related metabolic disorders has led to metabolic dysfunction-associated steatotic liver disease (MASLD) emerging as one of the most prevalent chronic liver disease worldwide. Despite growing concerns, the exact pathogenesis of MASLD remains unclear and no definitive treatments have been made available. Consequently, the need for comprehensive research on MASLD is more critical than ever. Gaining insight into the mechanisms of the disease can lay the groundwork for identifying new therapeutic targets and can facilitate the development of diagnostic tools that enable the early detection and intervention of MASLD. Research has discovered a multifactorial etiology for MASLD, suggesting that potential therapeutic strategies should be considered from a variety of perspectives. This review delves into the pathogenesis of MASLD, current diagnostic approaches, potential therapeutic targets, the status of clinical trials for emerging drugs, and the most promising treatment methods available today. With a focus on therapeutic targets, the aim is to offer fresh insights and guide for future research in the treatment of MASLD.
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Affiliation(s)
- Jiawang Wang
- Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, China
| | - Zhongyu Wang
- School of Basic Medical Sciences, Guangxi Medical University, Nanning 530021, China
| | - Yao Yu
- Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, China
| | - Si Cheng
- Beijing Tiantan Hospital, Capital Medical University, Beijing 10070, China; China National Clinical Research Center for Neurological Diseases, Beijing 10070, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 10070, China.
| | - Jianping Wu
- Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, China; Department of Pharmacology, Hubei University of Medicine, Shiyan 440070, China; Beijing Tiantan Hospital, Capital Medical University, Beijing 10070, China; China National Clinical Research Center for Neurological Diseases, Beijing 10070, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 10070, China.
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25
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Koh J, Mohamed A, Kong G, Wong E, Chen Y, Anand VV, Chong B, Chin YH, Wang JW, Khoo CM, Chan SP, Muthiah M, Dimitriadis GK, Chan MYY, Loh PH, Chew NWS. Long-term all-cause mortality of metabolic-dysfunction associated steatotic liver disease based on body weight phenotypes following acute myocardial infarction: A retrospective cohort study. Diabetes Obes Metab 2025; 27:683-696. [PMID: 39529446 DOI: 10.1111/dom.16062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 10/17/2024] [Accepted: 10/25/2024] [Indexed: 11/16/2024]
Abstract
OBJECTIVE Metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity increases risk of cardiovascular disease. This cohort study examines the prognostic value of MASLD, across body weight categories, in a secondary preventative acute myocardial infarction (AMI) cohort. METHODS Patients with AMI were stratified into four phenotypes-obesity MASLD, non-obesity MASLD, obesity non-MASLD, non-obesity non-MASLD. The primary outcome was all-cause mortality. Cox regression analysis was performed to investigate determinants of long-term all-cause mortality. RESULTS Of 5702 patients, majority were in the non-obesity non-MASLD group (66.7%), followed by obesity MASLD (16.1%), non-obesity MASLD (11.2%) and non-obesity MASLD (6.0%). Across the four phenotypes, obesity MASLD had the highest cardiometabolic burden, followed by non-obesity MASLD. Non-obesity MASLD had the highest risk of heart failure (p = 0.034), cardiogenic shock (p < 0.001), and all-cause long-term mortality (p = 0.019). The non-obesity MASLD (HR 1.400, 95%CI 1.077-1.820, p = 0.012) and obesity MASLD phenotypes (HR 1.222, 95%CI 1.005-1.485, p = 0.044) were independently associated with long-term all-cause mortality. CONCLUSIONS Obesity and non-obesity MASLD phenotypes were predictors of all-cause mortality following AMI, with an even larger magnitude of mortality risk in the non-obesity MASLD group. The recognition of MASLD and its body weight phenotypes will be beneficial in the prognostication following AMI.
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Affiliation(s)
- Jaycie Koh
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Ayman Mohamed
- King Fahd Military Medical Complex, Dhahran, Saudi Arabia
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
- Cardiology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Gwyneth Kong
- Department of Medicine, National University Hospital, Singapore, Singapore
| | - Esther Wong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Yiming Chen
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Vickram Vijay Anand
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Bryan Chong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Yip Han Chin
- Department of Medicine, National University Hospital, Singapore, Singapore
| | - Jiong-Wei Wang
- Cardiovascular Research Institute, National University Heart Centre, National University Health System, Singapore, Singapore
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Chin Meng Khoo
- Division of Endocrinology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Siew Pang Chan
- Department of Medicine, National University Hospital, Singapore, Singapore
- Cardiovascular Research Institute, National University Heart Centre, National University Health System, Singapore, Singapore
| | - Mark Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Georgios K Dimitriadis
- Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, London, UK
- Obesity, Type 2 Diabetes and Immunometabolism Research Group, Department of Diabetes, Faculty of Cardiovascular Medicine & Sciences, School of Life Course Sciences, King's College London, London, UK
| | - Mark Yan-Yee Chan
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Poay-Huan Loh
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Cardiology, Department of Medicine, Ng Teng Fong General Hospital, Singapore, Singapore
| | - Nicholas W S Chew
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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26
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Maffeis C, Morandi A, Zusi C, Olivieri F, Fornari E, Cavarzere P, Piona C, Corradi M, Emiliani F, Da Ros A, Berni Canani R, Mantovani A, Targher G. Hepatic lipogenesis marked by GCKR-modulated triglycerides increases serum FGF21 in children/teens with obesity. Diabetes Obes Metab 2025; 27:825-834. [PMID: 39611214 DOI: 10.1111/dom.16081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 10/31/2024] [Accepted: 11/08/2024] [Indexed: 11/30/2024]
Abstract
AIMS Fibroblast growth factor 21 (FGF21) decreases hepatic lipogenesis in animal models, and FGF21 analogues decrease serum triglycerides (TG) in adults in phase-2 trials. On the other hand, serum FGF21 is associated with higher TG in observational studies of people with obesity, raising a sort of paradox. We tested the hypothesis that FGF21 is induced by TG in youth with obesity, as a compensatory mechanism. MATERIALS AND METHODS We recruited 159 children/adolescents with obesity (80 males, 12.7 ± 2.1 years). Besides serum FGF21 and lipid dosages, we genotyped the Pro446Leu variant at glucokinase regulator (GCKR) as a known marker of genetically increased hepatic de novo lipogenesis, and we used it as an instrumental variable to establish a cause-and-effect relationship between FGF21 and TG, according to a Mendelian randomization analysis. RESULTS The Pro446Leu variant increased circulating TG (β = +0.35, p < 0.001), which was positively associated with circulating FGF21 (β = +0.42, p < 0.001). The Pro446Leu variant increased FGF-21 (β = +0.14, p = 0.031) with the expected slope (β-coefficient) in case of association entirely mediated by TG: 0.35 (slope between Pro446Ala and TG) × 0.42 (slope between TG and FGF21) = 0.14. CONCLUSIONS Hepatic lipogenesis, marked by GCKR-modulated triglycerides, is significantly associated with increased serum FGF-21 in children/adolescents with obesity.
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Affiliation(s)
- Claudio Maffeis
- Department of Surgery, Dentistry, Gynecology and Pediatrics, Section of Pediatric Diabetes and Metabolism, University of Verona, Verona, Italy
- Department of Mother and Child, Pediatric Unit B, University Hospital of Verona, Verona, Italy
| | - Anita Morandi
- Department of Surgery, Dentistry, Gynecology and Pediatrics, Section of Pediatric Diabetes and Metabolism, University of Verona, Verona, Italy
- Department of Mother and Child, Pediatric Unit B, University Hospital of Verona, Verona, Italy
| | - Chiara Zusi
- Department of Surgery, Dentistry, Gynecology and Pediatrics, Section of Pediatric Diabetes and Metabolism, University of Verona, Verona, Italy
| | - Francesca Olivieri
- Department of Mother and Child, Pediatric Unit B, University Hospital of Verona, Verona, Italy
| | - Elena Fornari
- Department of Mother and Child, Pediatric Unit B, University Hospital of Verona, Verona, Italy
| | - Paolo Cavarzere
- Department of Mother and Child, Pediatric Unit B, University Hospital of Verona, Verona, Italy
| | - Claudia Piona
- Department of Surgery, Dentistry, Gynecology and Pediatrics, Section of Pediatric Diabetes and Metabolism, University of Verona, Verona, Italy
- Department of Mother and Child, Pediatric Unit B, University Hospital of Verona, Verona, Italy
| | - Massimiliano Corradi
- Department of Surgery, Dentistry, Gynecology and Pediatrics, Section of Pediatric Diabetes and Metabolism, University of Verona, Verona, Italy
| | - Federica Emiliani
- Department of Surgery, Dentistry, Gynecology and Pediatrics, Section of Pediatric Diabetes and Metabolism, University of Verona, Verona, Italy
| | - Alessandro Da Ros
- Postgraduate School of Pediatrics, University of Verona, Verona, Italy
| | - Roberto Berni Canani
- Department of Translational Medical Science, University of Naples Federico II, Naples, Italy
| | | | - Giovanni Targher
- Department of Medicine, University of Verona, Verona, Italy
- Metabolic Diseases Research Unit, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar di Valpolicella, Italy
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27
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Wu Y, Xu W. Clarifications and enhancements for cardiovascular risk study in metabolic dysfunction-associated steatotic liver disease. Eur J Intern Med 2025; 132:158-159. [PMID: 39632135 DOI: 10.1016/j.ejim.2024.11.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 11/26/2024] [Indexed: 12/07/2024]
Affiliation(s)
- Yinfang Wu
- Department of Gastrointestinal and Minimally Invasive Surgery, Shaoxing Second Hospital, Shaoxing, Zhejiang, China.
| | - Weixing Xu
- Department of Gastrointestinal and Minimally Invasive Surgery, Shaoxing Second Hospital, Shaoxing, Zhejiang, China; Department of Clinical Medicine, Shaoxing University School of Medicine, Zhejiang, China
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28
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Arteaga I, Chacón C, Martínez-Escudé A, Rojano IR, Diez-Fadrique G, Carmona-Cervelló M, Torán-Monserrat P. Evaluating Pediatric NAFLD with Controlled Attenuation Parameter: A Comprehensive Narrative Review. Diagnostics (Basel) 2025; 15:299. [PMID: 39941229 PMCID: PMC11816681 DOI: 10.3390/diagnostics15030299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/09/2025] [Accepted: 01/24/2025] [Indexed: 02/16/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) in the pediatric population has emerged as a significant health concern due to its alarming rise in prevalence. In children, the characteristics of the disease differ from those seen in adults. NAFLD may progress to more severe liver disease in children compared to adults with similar profiles. Liver biopsy remains the gold standard for diagnosis; its invasive nature and high cost limit its use as a first-line tool. Alternatively, magnetic resonance imaging (MRI) techniques, such as magnetic resonance imaging-estimated liver proton density fat fraction (MRI-PDFF), have shown a good correlation with the degree of histological steatosis, although their use is limited by high costs and limited accessibility. Controlled attenuation parameter (CAP), integrated with vibration-controlled transient elastography (VCTE) (FibroScan®), is a novel non-invasive, accessible, and effective method for diagnosing hepatic steatosis. In this article, we reviewed the existing literature on the diagnostic accuracy of CAP in pediatric NAFLD. The PubMed and EMBASE databases were searched. Seven relevant studies were identified, conducted in pediatric hospital populations with specific demographic characteristics. Two of these studies compared CAP with liver biopsy, one compared CAP with liver biopsy and MRI-PDFF, and the remaining four compared CAP with MRI. Overall, CAP proved to be accurate in detecting the presence or absence of fatty infiltration, positioning it as a promising tool to simplify the diagnosis of NAFLD in children. However, further studies in larger populations are needed to confirm these findings and facilitate its implementation in routine clinical practice.
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Affiliation(s)
- Ingrid Arteaga
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
- Grup de Recerca en Malalties Hepàtiques a l’Atenció Primària (GRemHAp), IDIAP Jordi Gol, USR Metro-Nord, 08303 Mataró, Spain
- Primary Healthcare Center Vall del Tenes, Gerència d’Àmbit d’Atenció Primària Metropolitana Nord, Institut Català de la Salut, 08186 Llicà d’Amunt, Spain
| | - Carla Chacón
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
- Grup de Recerca en Malalties Hepàtiques a l’Atenció Primària (GRemHAp), IDIAP Jordi Gol, USR Metro-Nord, 08303 Mataró, Spain
- Ph.D. Programme in Medicine and Translational Research, Faculty of Medicine, University of Barcelona, 08193 Barcelona, Spain
| | - Alba Martínez-Escudé
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
- Grup de Recerca en Malalties Hepàtiques a l’Atenció Primària (GRemHAp), IDIAP Jordi Gol, USR Metro-Nord, 08303 Mataró, Spain
- Primary Healthcare Center La Llagosta, Gerència d’Àmbit d’Atenció Primària Metropolitana Nord, Institut Català de la Salut, 08120 La Llagosta, Spain
- Department of Medicine, Faculty of Medicine, Autonomous University of Barcelona, 08193 Bellaterra, Spain
| | - Irene Ruiz Rojano
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
- Grup de Recerca en Malalties Hepàtiques a l’Atenció Primària (GRemHAp), IDIAP Jordi Gol, USR Metro-Nord, 08303 Mataró, Spain
- Primary Healthcare Center Dr. Barraquer, Gerència d’Àmbit d’Atenció Primària Metropolitana Nord, Institut Català de la Salut, 08930 Sant Adrià del Besos, Spain
| | - Galadriel Diez-Fadrique
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
| | - Meritxell Carmona-Cervelló
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
| | - Pere Torán-Monserrat
- Unitat de Suport a la Recerca (USR) Metropolitana Nord, Fundació Institut Universitari d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAP Jordi Gol), 08303 Mataró, Spain; (I.A.); (C.C.); (A.M.-E.); (I.R.R.); (G.D.-F.); (M.C.-C.)
- Grup de Recerca en Malalties Hepàtiques a l’Atenció Primària (GRemHAp), IDIAP Jordi Gol, USR Metro-Nord, 08303 Mataró, Spain
- Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain
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29
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Chew NWS, Mehta A, Goh RSJ, Zhang A, Chen Y, Chong B, Chew HSJ, Shabbir A, Brown A, Dimitriadis GK, Huang DQ, Foo R, le Roux CW, Figtree GA, Fudim M, Pandey A, Mamas MA, Hausenloy DJ, Richards AM, Nicholls SJ, Chan MY, Muthiah MD, Sanyal A, Sperling LS. Cardiovascular-Liver-Metabolic Health: Recommendations in Screening, Diagnosis, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Cardiovascular Disease via Modified Delphi Approach. Circulation 2025; 151:98-119. [PMID: 39723980 DOI: 10.1161/circulationaha.124.070535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2024]
Abstract
There is a new awareness of the widespread nature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular-liver-metabolic health. Metabolic dysfunction and associated insulin resistance, together with the predilection for ectopic fat deposition in the liver and surrounding tissues, are associated with elevated risk of endothelial dysfunction, systemic inflammatory response, and ectopic fat deposition in the epicardium. This complex pathophysiology can accelerate atherogenic dyslipidemia, atherogenesis, diastolic dysfunction, valvular calcification, and cardiac arrhythmias. Despite the mounting evidence of mechanistic pathways underpinning MASLD and CVD, current recommendations have not clearly focused upon MASLD as a risk factor or target for intervention in CVD. We have brought together a diverse range of international experts committed to promoting cardiovascular-liver-metabolic health and related outcomes across the globe. The overarching goal of this document is to offer a construct for clinicians in the cardiovascular field with regards to (1) diagnosis and screening of MASLD through the use of noninvasive serum and imaging tests; (2) screening for CVD in all individuals with MASLD regardless of established atherosclerotic risk factors; and (3) the approach to management of MASLD with respect to prevention of CVD through lifestyle, as well as pharmacologic and surgical strategies. To achieve this, the modified Delphi method was applied and a series of evidence-based quality standard recommendations have been identified.
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Affiliation(s)
- Nicholas W S Chew
- Department of Cardiology, National University Heart Centre (N.W.S.C., A.Z., R.F., M.Y.C.), National University Health System, Singapore
- Yong Loo Lin School of Medicine (N.S.W.C., R.G., Y.C., B.C., D.Q.H., R.F., M.Y.C., M.M., D.J.H.), National University of Singapore, Singapore
| | - Anurag Mehta
- Virginia Commonwealth University Health Pauley Heart Center, Division of Cardiology (A.M.), Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond
| | - Rachel Sze Jen Goh
- Yong Loo Lin School of Medicine (N.S.W.C., R.G., Y.C., B.C., D.Q.H., R.F., M.Y.C., M.M., D.J.H.), National University of Singapore, Singapore
| | - Audrey Zhang
- Department of Cardiology, National University Heart Centre (N.W.S.C., A.Z., R.F., M.Y.C.), National University Health System, Singapore
| | - Yiming Chen
- Yong Loo Lin School of Medicine (N.S.W.C., R.G., Y.C., B.C., D.Q.H., R.F., M.Y.C., M.M., D.J.H.), National University of Singapore, Singapore
| | - Bryan Chong
- Yong Loo Lin School of Medicine (N.S.W.C., R.G., Y.C., B.C., D.Q.H., R.F., M.Y.C., M.M., D.J.H.), National University of Singapore, Singapore
| | - Han Shi Jocelyn Chew
- Alice Lee Centre for Nursing Studies (J.C.), National University of Singapore, Singapore
| | - Asim Shabbir
- National University of Singapore, Department of Surgery (A.Shabbir), National University Hospital, Singapore
| | - Adrian Brown
- University College London Centre for Obesity Research; Bariatric Centre for Weight Management and Metabolic Surgery, University College London Hospital NHS Trust; and National Institute of Health Research, UCLH Biomedical Research Centre, London, UK (A.B.)
| | - Georgios K Dimitriadis
- Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust; and Faculty of Cardiovascular Medicine and Sciences, Department of Diabetes, Obesity, Type 2 Diabetes and Immunometabolism Research Group, School of Life Course Sciences, King's College, London, UK (G.K.D.)
| | - Daniel Q Huang
- National University Centre for Organ Transplantation (D.Q.H., M.M.), National University Health System, Singapore
- Yong Loo Lin School of Medicine (N.S.W.C., R.G., Y.C., B.C., D.Q.H., R.F., M.Y.C., M.M., D.J.H.), National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine (D.Q.H., M.M.), National University Hospital, Singapore
| | - Roger Foo
- Department of Cardiology, National University Heart Centre (N.W.S.C., A.Z., R.F., M.Y.C.), National University Health System, Singapore
- Yong Loo Lin School of Medicine (N.S.W.C., R.G., Y.C., B.C., D.Q.H., R.F., M.Y.C., M.M., D.J.H.), National University of Singapore, Singapore
| | - Carel W le Roux
- Diabetes Complications Research Centre, University College Dublin, Ireland (C.R.l.R.)
| | - Gemma A Figtree
- Department of Cardiology, Royal North Shore Hospital, Australia (G.A.F.)
| | - Marat Fudim
- Duke University Medical Center; and Duke Clinical Research Institute, Durham, NC (M.F.)
| | - Ambarish Pandey
- Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas (A.P.)
| | - Mamas A Mamas
- Keele Cardiovascular Research Group, School of Medicine, Keele University, UK (M.A.M.)
| | - Derek J Hausenloy
- Yong Loo Lin School of Medicine (N.S.W.C., R.G., Y.C., B.C., D.Q.H., R.F., M.Y.C., M.M., D.J.H.), National University of Singapore, Singapore
- Duke-NUS Medical School, Cardiovascular and Metabolic Disorders Programme; and National Heart Centre Singapore, National Heart Research Institute, Singapore (D.J.H.)
- University College London, The Hatter Cardiovascular Institute, UK (D.J.H.)
| | - A Mark Richards
- Christchurch Heart Institute, University of Otago, New Zealand (A.M.R.)
- Cardiovascular Research Institute, National University Heart Centre Singapore, Singapore (A.M.R.)
| | | | - Mark Y Chan
- Department of Cardiology, National University Heart Centre (N.W.S.C., A.Z., R.F., M.Y.C.), National University Health System, Singapore
- Yong Loo Lin School of Medicine (N.S.W.C., R.G., Y.C., B.C., D.Q.H., R.F., M.Y.C., M.M., D.J.H.), National University of Singapore, Singapore
| | - Mark D Muthiah
- National University Centre for Organ Transplantation (D.Q.H., M.M.), National University Health System, Singapore
- Yong Loo Lin School of Medicine (N.S.W.C., R.G., Y.C., B.C., D.Q.H., R.F., M.Y.C., M.M., D.J.H.), National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine (D.Q.H., M.M.), National University Hospital, Singapore
| | - Arun Sanyal
- Division of Gastroenterology, Hepatology and Nutrition (A.Sanyal), Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond
| | - Laurence S Sperling
- Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute; and Emory University School of Medicine, Atlanta, GA (L.S.S.)
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30
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Alpízar Salazar M, Olguín Reyes SE, Medina Estévez A, Saturno Lobos JA, De Aldecoa Castillo JM, Carrera Aguas JC, Alaniz Monreal S, Navarro Rodríguez JA, Alpízar Sánchez DMF. Natural History of Metabolic Dysfunction-Associated Steatotic Liver Disease: From Metabolic Syndrome to Hepatocellular Carcinoma. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:88. [PMID: 39859069 PMCID: PMC11766802 DOI: 10.3390/medicina61010088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 12/30/2024] [Accepted: 01/04/2025] [Indexed: 01/27/2025]
Abstract
Introduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) stems from disrupted lipid metabolism in the liver, often linked to obesity, type 2 diabetes, and dyslipidemia. In Mexico, where obesity affects 36.9% of adults, MASLD prevalence has risen, especially with metabolic syndrome affecting 56.31% by 2018. MASLD can progress to Metabolic Dysfunction-Associated Steatohepatitis (MASH), affecting 5.27% globally, leading to severe complications like cirrhosis and hepatocellular carcinoma. Background: Visceral fat distribution varies by gender, impacting MASLD development due to hormonal influences. Insulin resistance plays a central role in MASLD pathogenesis, exacerbated by high-fat diets and specific fatty acids, leading to hepatic steatosis. Lipotoxicity from saturated fatty acids further damages hepatocytes, triggering inflammation and fibrosis progression in MASH. Diagnosing MASLD traditionally involves invasive liver biopsy, but non-invasive methods like ultrasound and transient elastography are preferred due to their safety and availability. These methods detect liver steatosis and fibrosis with reasonable accuracy, offering alternatives to biopsy despite varying sensitivity and specificity. Conclusions: MASLD as a metabolic disorder underscores its impact on public health, necessitating improved awareness and early management strategies to mitigate its progression to severe liver diseases.
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Affiliation(s)
- Melchor Alpízar Salazar
- Endocrinology, Specialized Center for Diabetes, Obesity and Prevention of Cardiovascular Diseases (CEDOPEC), Mexico City 11650, Mexico
| | - Samantha Estefanía Olguín Reyes
- Clinical Research, Specialized Center for Diabetes, Obesity and Prevention of Cardiovascular Diseases (CEDOPEC), Mexico City 11650, Mexico; (S.E.O.R.); (A.M.E.); (J.A.S.L.); (S.A.M.); (J.A.N.R.); (D.M.F.A.S.)
| | - Andrea Medina Estévez
- Clinical Research, Specialized Center for Diabetes, Obesity and Prevention of Cardiovascular Diseases (CEDOPEC), Mexico City 11650, Mexico; (S.E.O.R.); (A.M.E.); (J.A.S.L.); (S.A.M.); (J.A.N.R.); (D.M.F.A.S.)
| | - Julieta Alejandra Saturno Lobos
- Clinical Research, Specialized Center for Diabetes, Obesity and Prevention of Cardiovascular Diseases (CEDOPEC), Mexico City 11650, Mexico; (S.E.O.R.); (A.M.E.); (J.A.S.L.); (S.A.M.); (J.A.N.R.); (D.M.F.A.S.)
| | - Jesús Manuel De Aldecoa Castillo
- Clinical Nutrition, Specialized Center for Diabetes, Obesity and Prevention of Cardiovascular Diseases (CEDOPEC), Mexico City 11650, Mexico;
| | - Juan Carlos Carrera Aguas
- Clinical Nutrition, Specialized Center for Diabetes, Obesity and Prevention of Cardiovascular Diseases (CEDOPEC), Mexico City 11650, Mexico;
| | - Samary Alaniz Monreal
- Clinical Research, Specialized Center for Diabetes, Obesity and Prevention of Cardiovascular Diseases (CEDOPEC), Mexico City 11650, Mexico; (S.E.O.R.); (A.M.E.); (J.A.S.L.); (S.A.M.); (J.A.N.R.); (D.M.F.A.S.)
| | - José Antonio Navarro Rodríguez
- Clinical Research, Specialized Center for Diabetes, Obesity and Prevention of Cardiovascular Diseases (CEDOPEC), Mexico City 11650, Mexico; (S.E.O.R.); (A.M.E.); (J.A.S.L.); (S.A.M.); (J.A.N.R.); (D.M.F.A.S.)
| | - Dulce María Fernanda Alpízar Sánchez
- Clinical Research, Specialized Center for Diabetes, Obesity and Prevention of Cardiovascular Diseases (CEDOPEC), Mexico City 11650, Mexico; (S.E.O.R.); (A.M.E.); (J.A.S.L.); (S.A.M.); (J.A.N.R.); (D.M.F.A.S.)
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Liang Z, Huang R, Zhang L. Correlation between hepatic steatosis severity diagnosed by ultrasound and metabolic indexes in elderly patients with MAFLD. Front Med (Lausanne) 2025; 11:1467773. [PMID: 39839645 PMCID: PMC11747716 DOI: 10.3389/fmed.2024.1467773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Accepted: 12/23/2024] [Indexed: 01/23/2025] Open
Abstract
Objective To explore the connection between metabolic parameters and the severity of hepatic steatosis determined through ultrasound in elderly individuals with metabolic dysfunction-associated fatty liver disease (MAFLD). Methods 4,663 senior individuals who were 65 years of age or older were included in this research. They were examined physically at the Ninghai Street Community Health Service Center in Yantai City between June 7, 2021, and October 15, 2021. There were two categories of individuals identified: the MAFLD group (n = 2,985) and the non-MAFLD group (n = 1,678). Based on liver ultrasonography results, individuals in the MAFLD group were further separated into three groups: mild (n = 2,104), moderate (n = 766), and severe (n = 115). To identify indicators of risk for the severity of hepatic steatosis, metabolic data was contrasted between the groups employing logistic regression. Results In comparison to the non-MAFLD group, the MAFLD group showed significantly elevated levels of body mass index (BMI), blood pressure, gender, age, lipid profile, alanine transaminase (ALT), and fasting blood glucose (FBG; p < 0.05). Among individuals with MAFLD, there was a positive correlation between BMI, FBG, ALT, and aspartate transaminase (AST) levels and the severity of hepatic steatosis (p < 0.05). Logistic regression analysis indicated that BMI, female gender, FBG, ALT, triglycerides (TG), and serum uric acid (SUA) constituted risk factors for increased severity of hepatic steatosis in MAFLD. Conclusion The severity of hepatic steatosis in elderly MAFLD patients is significantly correlated with female gender, BMI, ALT, FBG, TG, and SUA.
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Affiliation(s)
| | | | - Lingyun Zhang
- General Practice Department, Binzhou Medical University, Yantai, Shandong, China
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El-Sayed SM, El-Sayed GA, Mansour M A, Haridy Ahmed E, Kamar SA. A comparative study on the effect of melatonin and orlistat combination versus orlistat alone on high fat diet-induced hepatic changes in the adult male albino rats (a histological and morphometric study). Ultrastruct Pathol 2025; 49:20-38. [PMID: 39679624 DOI: 10.1080/01913123.2024.2438380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 11/10/2024] [Accepted: 12/02/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the extremely usual reason of chronic liver disease, extending from simple hepatic steatosis (HS), nonalcoholic steatohepatitis (NASH) to advanced hepatic fibrosis and cirrhosis. Though orlistat is a Food and Drug Administration (FDA) approved drug for long-duration management of obesity, few cases of severe hepatic insult were declared. Melatonin is an efficient antioxidant; it also regulates metabolic processes that lead to fat accumulation and obesity. AIM OF THE WORK The current research aimed to compare the impact of orlistat, melatonin, and their combination on the structural changes of the hepatic tissue of adult male albino rats supplied with high fat diet (HFD). MATERIAL AND METHODS Thirty adult male albino rats divided into five groups. Liver specimens were divided into two parts. One-half was processed to obtain paraffin blocks, and the other half was processed to obtain semithin sections. Morphometric study and statistical analysis were done. RESULTS Hepatic tissue from the HFD group showed steatosis, ballooning, and inflammation and all these parameters were moderately improved - except for inflammation which worsened with therapy. Combined orlistat and melatonin-treated groups showed marked improvement of all parameters as well as marked improvement in the hepatic fibrosis.Orlistat/Melatonin combination therapy is both safe and effective in comparison to orlistat and melatonin monotherapy.
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Affiliation(s)
- Sayed M El-Sayed
- Anatomy and Embryology Department, Ain Shams University, Cairo, Egypt
| | - Gehan A El-Sayed
- Anatomy and Embryology Department, Ain Shams University, Cairo, Egypt
| | - Mansour M A
- Anatomy and Embryology Department, Ain Shams University, Cairo, Egypt
| | - Enas Haridy Ahmed
- Anatomy and Embryology Department, Ain Shams University, Cairo, Egypt
- Faculty of Medicine, Hail University, Hail, Kingdom of Saudi Arabia
| | - Sherif A Kamar
- Anatomy and Embryology Department, Ain Shams University, Cairo, Egypt
- Faculty of Dentistry, Al-Ahliyya Amman University, Amman, Jordan
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Yang X, Rao H, Yuan Y, Hu N, Zhang X, Zeng Y, Xia G. Correlation analysis of the triglyceride-glucose index and related parameters in metabolic dysfunction-associated fatty liver disease. Sci Rep 2025; 15:23. [PMID: 39748005 PMCID: PMC11695697 DOI: 10.1038/s41598-024-84809-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 12/27/2024] [Indexed: 01/04/2025] Open
Abstract
This study aimed to investigate the correlation and predictive value of TyG and related parameters with metabolic dysfunction-associated fatty liver disease (MAFLD) MAFLD. This study retrospectively included individuals who underwent health examinations and abdominal ultrasound from July 2021 to June 2024 at the Affiliated Hospital of Southwest Medical University, Sichuan Province, China. A total of 71,299 subjects' clinical and laboratory data were extracted, the correlation between TyG and related parameters and MAFLD was analyzed via univariate and multivariate logistic regression methods, and the nonlinear relationship between the TyG index and the risk of MAFLD was explored via restricted cubic spline (RCS) analysis. The predictive value of TyG and related parameters for MAFLD was assessed using the receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC). TyG and related parameters were positively correlated with MAFLD, and the results remained unchanged after adjustment for the corresponding parameters. RCS analysis revealed a significant dose‒response relationship between TyG and related parameters and MAFLD. ROC curve analysis revealed AUC values of 0.83 (0.82-0.83), 0.92 (0.91-0.92), 0.90 (0.90-0.91), and 0.87 (0.87-0.88) for TyG, TyG-BMI, TyG-WC, and TyG-WHR, respectively. Subgroup analyses revealed that the TyG index and related parameters had greater predictive value in the female, younger, and BMI < 23.7 populations.
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Affiliation(s)
- Xin Yang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Street Taiping No.25, Region Jiangyang, Luzhou, 646099, Sichuan, China
| | - Huiting Rao
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Street Taiping No.25, Region Jiangyang, Luzhou, 646099, Sichuan, China
| | - Yi Yuan
- Department of Presbyatrics, Luzhou People's Hospital, Luzhou, China
| | - Nan Hu
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Street Taiping No.25, Region Jiangyang, Luzhou, 646099, Sichuan, China
| | - Xinmei Zhang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Street Taiping No.25, Region Jiangyang, Luzhou, 646099, Sichuan, China
| | - Yingxin Zeng
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Street Taiping No.25, Region Jiangyang, Luzhou, 646099, Sichuan, China
| | - Guodong Xia
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Street Taiping No.25, Region Jiangyang, Luzhou, 646099, Sichuan, China.
- Department of Health Management Center, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
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He W, Chen J, Wu Y, Xu Y, Gao J, Wu J, Li X, Liu X, Zhang M, Sun Q. Quantitative contrast-enhanced ultrasonography in the diagnosis and grading of hepatic steatosis in brain-dead donors. Quant Imaging Med Surg 2025; 15:326-338. [PMID: 39839054 PMCID: PMC11744146 DOI: 10.21037/qims-24-1004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Accepted: 11/19/2024] [Indexed: 01/23/2025]
Abstract
Background The presence of hepatic steatosis (HS) is a crucial histological parameter for evaluating the suitability of liver transplantation. However, to date, no studies have used contrast-enhanced ultrasonography (CEUS) to diagnose and grade HS in brain-dead donors. This study aimed to detect and quantify hepatic microcirculatory perfusion in brain-dead donors using CEUS and to assess the utility of CEUS in the diagnosis and grading of HS. Methods This prospective study enrolled 88 livers from brain-dead donors (44 with HS and 44 without HS) aged ≥18 years between June 2020 and January 2024. The donors had a mean age of 45.42±9.59 years, and 70 were male (79.5%). CEUS was conducted on the livers of the brain-dead donors 24 h before organ procurement, and time-intensity curves were generated. The main measures included the arrival time, time-to-peak, peak intensity of the hepatic artery (PIHA), peak intensity of the portal vein (PIPV), and peak intensity of the liver parenchyma (PILP), and hepatorenal index (HRI). Logistic regression analyses were used to identify the significant factors associated with HS, and the areas under the curve (AUC) of the receiver operating characteristic curves were used to evaluate diagnostic performance. Results The PIHA (P<0.001), PIPV (P<0.001), and PILP (P=0.001) were significantly shorter in the steatosis group than the non-steatosis group. The one-way analysis of variance revealed significant decreases in the PIHA (P<0.001), PIPV (P<0.001), and PILP (P<0.001) as HS grades increased. The multivariate regression analysis indicated that the PIHA was an independent factor for both HS [odds ratio (OR) =0.97, 95% confidence interval (CI): 0.94-0.99, P=0.01] and moderate-to-severe HS (OR =0.96, 95% CI: 0.93-0.99, P=0.009). The AUC values of the PIHA and HRI for diagnosing moderate-to-severe HS were 0.88 and 0.69, respectively. The optimal cut-off value of the PIHA for diagnosing moderate-to-severe HS was 173.04, with a sensitivity of 92.9% (13 of 14 livers), specificity of 68.9% (51 of 74 livers), and positive and negative predictive values of 36.1% and 98.1%, respectively. Conclusions CEUS showed promising results in the diagnosis and grading of HS in brain-dead donors. The PIHA, a CEUS-derived parameter, could serve as a diagnostic tool for moderate-to-severe HS.
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Affiliation(s)
- Weiming He
- Organ Transplant Center, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City People’s Hospital, Zhongshan, China
| | - Jiazhen Chen
- Organ Transplant Center, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City People’s Hospital, Zhongshan, China
| | - Yuqiang Wu
- Organ Transplant Center, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City People’s Hospital, Zhongshan, China
| | - Yuguang Xu
- Ultrasound Imaging Department, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City People’s Hospital, Zhongshan, China
| | - Junying Gao
- Organ Transplant Center, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City People’s Hospital, Zhongshan, China
| | - Jianlong Wu
- Organ Transplant Center, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City People’s Hospital, Zhongshan, China
| | - Xingwen Li
- Ultrasound Imaging Department, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City People’s Hospital, Zhongshan, China
| | - Xiaozhen Liu
- Ultrasound Imaging Department, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City People’s Hospital, Zhongshan, China
| | - Mingman Zhang
- Department of Hepatobiliary Surgery, Children’s Hospital of Chongqing Medical University, Chongqing, China
| | - Qiang Sun
- Organ Transplant Center, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City People’s Hospital, Zhongshan, China
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Torres-Macho J, Schutzer CM. Point-of-Care Ultrasound in Clinical Care: Abdomen. Med Clin North Am 2025; 109:31-45. [PMID: 39567100 DOI: 10.1016/j.mcna.2024.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2024]
Abstract
Abdominal point-of-care ultrasound is an essential diagnostic tool for internal medicine physicians. It can identify intraperitoneal free fluid, evaluate the liver for size, presence of steatosis, and assessment for possible cirrhosis. Diagnosing cholelithiasis or cholecystitis can expedite care. Physical examination for mild splenomegaly may be insensitive. In such cases, sonographic measurements may provide a more definitive diagnosis. With the proper training, these organs can be evaluated at the bedside and guide clinical decision making.
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Affiliation(s)
- Juan Torres-Macho
- Clinical Ultrasound Unit, Infanta Leonor-Virgen de la Torre University Hospital, Av Gran vía del Este 80, Madrid 28031, Spain.
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Mladenova IL, Tan EF, Ng JY, Sharma P. Non-alcoholic fatty liver disease (NAFLD) and its association to cardiovascular disease: A comprehensive meta-analysis. JRSM Cardiovasc Dis 2025; 14:20480040251325929. [PMID: 40123646 PMCID: PMC11930486 DOI: 10.1177/20480040251325929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 11/13/2024] [Accepted: 11/18/2024] [Indexed: 03/25/2025] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) affects up to nearly a third of the Western population and has been inconsistently associated with cardiovascular diseases (CVDs). Therefore, we conducted a comprehensive meta-analysis to quantify the correlation of NAFLD with all major vascular diseases, acute coronary syndrome (ACS), subclinical atherosclerosis and endothelial dysfunction. Methods We searched PubMed and Embase for studies looking at the relationship between NAFLD and cardiovascular diseases published through September 2023. The parameters we used to assess cardiovascular diseases include acute coronary syndrome, brachial flow-mediated dilatation (FMD), serum asymmetric dimethylarginine (ADMA), carotid intima-media thickness (CIMT), and carotid stenosis (>50%). Data from these studies were then collected and meta-analysis was performed using the random effects model. RevMan v5.4 was used for statistical analysis. Results We interrogated a total of 114 publications which met our inclusion criteria. NAFLD patients showed statistically significant reduction in FMD% [MD: -4.83 (95% CI: -5.84 to 3.81, p < .00001)] and increased serum ADMA [MD: 0.08 (95% CI: 0.05-0.11, p < .00001)]. Mean CIMT was also increased in NAFLD patients [MD 0.13 (95% CI: 0.12-0.14, p < .00001)]. NAFLD showed a higher prevalence of pathological CIMT [MD: 0.11 (95% CI: 0.10-0.12, p < .00001)] and increased carotid plaques [OR: 2.08 (95% CI: 1.52-2.86, p < .00001)]. Furthermore, we demonstrated statistically significant increase in cardiovascular diseases among NAFLD patients compared to controls [OR: 1.92 (95% CI: 1.53-2.41, p < .00001)]. Conclusion NAFLD is a strong predictor for endothelial dysfunction, subclinical atherosclerosis and cardiovascular disease. Further studies are required to determine whether incidental findings of fatty liver on abdominal ultrasonography should prompt the need for detailed assessment of other CVD risk factors.
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Affiliation(s)
| | - Eu Fon Tan
- Queen Mary University of London, London, UK
| | | | - Pankaj Sharma
- Institute of Cardiovascular Research, Royal Holloway University, Egham, Greater London, UK
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Kim A, Kang D, Choi SC, Sinn DH, Gwak GY. Cardiometabolic risk factors and coronary atherosclerosis progression in patients with metabolic dysfunction-associated steatotic liver disease: the influential role of quantity over type. J Gastroenterol Hepatol 2025; 40:258-264. [PMID: 39568183 DOI: 10.1111/jgh.16787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 09/11/2024] [Accepted: 10/13/2024] [Indexed: 11/22/2024]
Abstract
BACKGROUND AND AIM Individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) who are at an increased risk of cardiovascular disease (CVD) are critical to identify and manage. We aimed to assess whether the risk of CVD in patients with MASLD differed according to the type or number of cardiometabolic risk factors. METHODS This longitudinal cohort study involved 5674 adults who underwent at least two health checkups between 2004 and 2021. Steatotic liver disease (SLD) was assessed using ultrasonography and participants with SLD were classified as having either non-MASLD or MASLD. CVD risk was evaluated using coronary artery calcium (CAC) progression as measured using multidetector computed tomography scans. RESULTS Over an average 5.8-year follow-up period, patients with MASLD exhibited faster CAC progression than those with non-MASLD (18% vs 11%, P < 0.01). MASLD with any cardiometabolic risk factor exacerbated CAC progression; however, the degree of CAC progression was similar among the different risk components. The adjusted ratios (95% CI) of CAC progression rates comparing non-MASLD with MASLD with one, two, three, four, and five cardiometabolic risk factors were 1.02 (0.99, 1.06), 1.04 (1.01, 1.08), 1.07 (1.03, 1.10), 1.08 (1.05, 1.11), and 1.11 (1.07, 1.15), respectively. CONCLUSIONS In individuals with MASLD, all cardiometabolic risk factors contributed to the deterioration of coronary atherosclerosis, with no specific factor exerting a dominant influence. Coronary atherosclerosis progression is directly associated with the cumulative number of cardiometabolic risk factors. Therefore, identifying and managing an increasing number of these factors is imperative in clinical practice, even when MASLD is diagnosed based on only one risk factor.
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Affiliation(s)
- Aryoung Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, South Korea
| | - Danbee Kang
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
- Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - Sung Chul Choi
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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Drazinos P, Gatos I, Katsakiori PF, Tsantis S, Syrmas E, Spiliopoulos S, Karnabatidis D, Theotokas I, Zoumpoulis P, Hazle JD, Kagadis GC. Comparison of deep learning schemes in grading non-alcoholic fatty liver disease using B-mode ultrasound hepatorenal window images with liver biopsy as the gold standard. Phys Med 2025; 129:104862. [PMID: 39626614 DOI: 10.1016/j.ejmp.2024.104862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 10/11/2024] [Accepted: 11/27/2024] [Indexed: 01/07/2025] Open
Abstract
BACKGROUND/INTRODUCTION To evaluate the performance of pre-trained deep learning schemes (DLS) in hepatic steatosis (HS) grading of Non-Alcoholic Fatty Liver Disease (NAFLD) patients, using as input B-mode US images containing right kidney (RK) cortex and liver parenchyma (LP) areas indicated by an expert radiologist. METHODS A total of 112 consecutively enrolled, biopsy-validated NAFLD patients underwent a regular abdominal B-mode US examination. For each patient, a radiologist obtained a B-mode US image containing RK cortex and LP and marked a point between the RK and LP, around which a window was automatically cropped. The cropped image dataset was augmented using up-sampling, and the augmented and non-augmented datasets were sorted by HS grade. Each dataset was split into training (70%) and testing (30%), and fed separately as input to InceptionV3, MobileNetV2, ResNet50, DenseNet201, and NASNetMobile pre-trained DLS. A receiver operating characteristic (ROC) analysis of hepatorenal index (HRI) measurements by the radiologist from the same cropped images was used for comparison with the performance of the DLS. RESULTS With the test data, the DLS reached 89.15 %-93.75 % accuracy when comparing HS grades S0-S1 vs. S2-S3 and 79.69 %-91.21 % accuracy for S0 vs. S1 vs. S2 vs. S3 with augmentation, and 80.45-82.73 % accuracy when comparing S0-S1 vs. S2-S3 and 59.54 %-63.64 % accuracy for S0 vs. S1 vs. S2 vs. S3 without augmentation. The performance of radiologists' HRI measurement after ROC analysis was 82 %, 91.56 %, and 96.19 % for thresholds of S ≥ S1, S ≥ S2, and S = S3, respectively. CONCLUSION All networks achieved high performance in HS assessment. DenseNet201 with the use of augmented data seems to be the most efficient supplementary tool for NAFLD diagnosis and grading.
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Affiliation(s)
- Petros Drazinos
- 3DMI Research Group, Department of Medical Physics, School of Medicine, University of Patras, Rion, GR 26504, Greece; Diagnostic Echotomography SA, Kifissia, GR 14561, Greece
| | - Ilias Gatos
- 3DMI Research Group, Department of Medical Physics, School of Medicine, University of Patras, Rion, GR 26504, Greece
| | - Paraskevi F Katsakiori
- 3DMI Research Group, Department of Medical Physics, School of Medicine, University of Patras, Rion, GR 26504, Greece
| | - Stavros Tsantis
- 3DMI Research Group, Department of Medical Physics, School of Medicine, University of Patras, Rion, GR 26504, Greece
| | - Efstratios Syrmas
- 3DMI Research Group, Department of Medical Physics, School of Medicine, University of Patras, Rion, GR 26504, Greece
| | - Stavros Spiliopoulos
- Second Department of Radiology, School of Medicine, University of Athens, Athens, GR 12461, Greece
| | - Dimitris Karnabatidis
- Department of Radiology, School of Medicine, University of Patras, Patras, GR 26504, Greece
| | | | | | - John D Hazle
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - George C Kagadis
- 3DMI Research Group, Department of Medical Physics, School of Medicine, University of Patras, Rion, GR 26504, Greece; Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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De Matteis C, Crudele L, Di Buduo E, Cantatore S, Gadaleta RM, Cariello M, Suppressa P, Antonica G, Berardi E, Graziano G, Moschetta A. Hyperhomocysteinemia is linked to MASLD. Eur J Intern Med 2025; 131:49-57. [PMID: 39482164 DOI: 10.1016/j.ejim.2024.10.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 09/14/2024] [Accepted: 10/10/2024] [Indexed: 11/03/2024]
Abstract
BACKGROUND AND AIMS Homocysteine (Hcy) levels are elevated in different conditions, including cardiovascular diseases (CVD), diabetes, and metabolic-associated steatotic liver disease (MASLD). In this observational retrospective study, we analyzed Hcy levels in a population of 901 outpatients, considering its putative etiological role in MASLD. METHODS A total of 901 outpatients underwent physical and biochemical evaluations. Abdominal and carotid ultrasound were performed to assess liver steatosis, carotid intima-media thickness (IMT) and presence of atherosclerotic plaque. RESULTS Hyperhomocysteinemia (HHcy) was identified in 140 subjects (16 %). Patients with HHcy showed glucose metabolism impairment (p < 0.001), altered lipid profile (p < 0.001), low Vitamin D levels (p < 0.0001), increased cardiovascular risk (p < 0.001). We then investigated the relationship between Hcy and MASLD (OR=3.6, p < 0.0001), finding that the relationship remained significant also when accounting for confounding variables (age, sex) (OR=3.2, p < 0.0001). Hcy values were significantly higher (p < 0.0001) in patients with MASLD (n = 78, 29.4 ± 10.1μmol/l) compared to those without MASLD (20.4 ± 4.8 1μmol/l). Furthermore, in MASLD patients we found a direct correlation between Hcy level and waist circumference (r = 0.3, p < 0.001) and an inverse correlation with both HDL-c (r=-0.4, p < 0.001) and Vitamin D levels (r=-0.24, p < 0.05). CONCLUSIONS Our data suggest an intriguing scenario whereby HHcy is present in patients with MASLD and is associated to lower vitamin D and altered glucose and lipid profile. Thus, considering Hcy levels may help clinicians with the management of patients with increased MASLD risk.
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Affiliation(s)
- Carlo De Matteis
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70124 Bari, Italy
| | - Lucilla Crudele
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70124 Bari, Italy
| | - Ersilia Di Buduo
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70124 Bari, Italy
| | - Salvatore Cantatore
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70124 Bari, Italy
| | | | - Marica Cariello
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70124 Bari, Italy
| | - Patrizia Suppressa
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70124 Bari, Italy
| | - Gianfranco Antonica
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70124 Bari, Italy
| | - Elsa Berardi
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70124 Bari, Italy
| | - Giusi Graziano
- Center for Outcomes Research and Clinical Epidemiology (CORESEARCH), 65124 Pescara, Italy
| | - Antonio Moschetta
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70124 Bari, Italy; INBB National Institute for Biostructure and Biosystems, Viale delle Medaglie d'Oro 305, 00136 Roma, Italy.
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40
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Marín Baselga R, Teigell-Muñoz FJ, Porcel JM, Ramos Lázaro J, García Rubio S. Ultrasound for body composition assessment: a narrative review. Intern Emerg Med 2025; 20:23-34. [PMID: 39240412 DOI: 10.1007/s11739-024-03756-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 08/21/2024] [Indexed: 09/07/2024]
Abstract
Ultrasound has become an increasingly valuable tool for the assessment of body composition, offering several applications and indications in clinical practice. Ultrasound allows bedside evaluation of muscle mass, fat compartments, and extravascular water, providing a cost-effective, portable, and accessible alternative to traditional methods, such as Dual-energy X-ray Absorptiometry (DEXA), Bioelectrical Impedance Analysis (BIA), Computed Tomography (CT), and Magnetic Resonance Imaging (MRI). It is particularly useful in evaluating conditions, such as malnutrition, sarcopenia, and sarcopenic obesity, which require poor muscle mass to establish a diagnosis. The potential uses of ultrasound in body composition assessment include measurement of muscle thickness, cross-sectional area, pennation angle, and echo-intensity, which are indicative of muscle health. Additionally, ultrasound can be used to evaluate various fat compartments, including visceral, subcutaneous, and ectopic fat, which are important for understanding metabolic health and cardiovascular risk. However, the widespread adoption of ultrasound is challenged by the lack of standardized measurements and the absence of ultrasound measures in the validated diagnostic criteria. This article reviews the current applications of ultrasound in body composition assessment, highlighting the recent advancements and the correlation between ultrasound parameters and clinical outcomes. It discusses the advantages of ultrasound while also addressing its limitations, such as the need for standardized protocols and cut-off points. By providing a comprehensive update based on recent publications, this article aims to enhance the clinical utility of ultrasound in assessing and monitoring body composition and pave the way for future research in this field.
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Affiliation(s)
| | | | - José M Porcel
- Internal Medicine Department, Hospital Universitario Arnau Vilanova, IRBLleida, Lleida, Spain
| | - Javier Ramos Lázaro
- Internal Medicine Department, Hospital Universitario de La Santa Creu I Sant Pau, Barcelona, Spain
| | - Samuel García Rubio
- Internal Medicine Department, Hospital Santa Marina, ISS BioBizkaia, Bilbao, Spain.
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Hobeika C, Ronot M, Guiu B, Ferraioli G, Iijima H, Tada T, Lee DH, Kuroda H, Lee YH, Lee JM, Kim SY, Cassinotto C, Maiocchi L, Raimondi A, Nishimura T, Kumada T, Kwon EY, Jang JK, Correas JM, Valla D, Vilgrain V, Dioguardi Burgio M. Ultrasound-based steatosis grading system using 2D-attenuation imaging: An individual patient data meta-analysis with external validation. Hepatology 2025; 81:212-227. [PMID: 38652643 DOI: 10.1097/hep.0000000000000895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 03/07/2024] [Indexed: 04/25/2024]
Abstract
BACKGROUND AND AIMS Noninvasive tools assessing steatosis, such as ultrasonography-based 2D-attenuation imaging (ATI), are needed to tackle the worldwide burden of steatotic liver disease. This one-stage individual patient data (IPD) meta-analysis aimed to create an ATI-based steatosis grading system. APPROACH AND RESULTS A systematic review (EMBASE + MEDLINE, 2018-2022) identified studies, including patients with histologically or magnetic resonance imaging proton-density fat fraction (MRI-PDFF)-verified ATI for grading steatosis (S0 to S3). One-stage IPD meta-analyses were conducted using generalized mixed models with a random study-specific intercept. Created ATI-based steatosis grading system (aS0 to aS3) was externally validated on a prospective cohort of patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (n=174, histologically and MRI-PDFF-verified steatosis). Eleven enrolled studies included 1374 patients, classified into S0, S1, S2, and S3 in 45.4%, 35.0%, 9.3%, and 10.3% of the cases. ATI was correlated with histological steatosis ( r = 0.60; 95% CI: 0.52, 0.67; p < 0.001) and MRI-PDFF ( r = 0.70; 95% CI: 0.66, 0.73; p < 0.001) but not with liver stiffness ( r = 0.03; 95% CI: -0.04, 0.11, p = 0.343). Steatosis grade was an independent factor associated with ATI (coefficient: 0.24; 95% CI: [0.22, 0.26]; p < 0.001). ATI marginal means within S0, S1, S2, and S3 subpopulations were 0.59 (95% CI: [0.58, 0.61]), 0.69 (95% CI [0.67, 0.71]), 0.78 (95% CI: [0.76, 0.81]), and 0.85 (95% CI: [0.83, 0.88]) dB/cm/MHz; all contrasts between grades were significant ( p < 0.0001). Three ATI thresholds were calibrated to create a new ATI-based steatosis grading system (aS0 to aS3, cutoffs: 0.66, 0.73, and 0.81 dB/cm/MHz). Its external validation showed Obuchowski measures of 0.84 ± 0.02 and 0.82 ± 0.02 with histologically based and MRI-PDFF-based references. CONCLUSIONS ATI is a reliable, noninvasive marker of steatosis. This validated ATI-based steatosis grading system could be valuable in assessing patients with metabolic dysfunction-associated steatotic liver disease.
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Affiliation(s)
- Christian Hobeika
- Department of HPB Surgery and Liver Transplantation, AP-HP, Hôpital Beaujon, Clichy, France
- Université Paris Cité, Inserm, CArcinose Péritoine Paris-Technologies, Paris, France
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Maxime Ronot
- Department of Radiology, Hôpital Beaujon, AP-HP.Nord, Clichy, France
- Université Paris Cité, Inserm, Centre de recherche sur l'inflammation, Paris, France
| | - Boris Guiu
- Department of Radiology, St-Eloi University Hospital, Montpellier, France
| | - Giovanna Ferraioli
- Dipartimento di Scienze Clinico-Chirurgiche, Diagnostiche e Pediatriche, University of Pavia, Pavia, Italy
| | - Hiroko Iijima
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo Medical University, Hyogo, Japan
| | - Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital, Hyogo, Japan
| | - Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hidekatsu Kuroda
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Iwate Medical University, Iwate, Japan
| | - Young Hwan Lee
- Department of Radiology, Wonkwang University School of Medicine and Hospital, Iksan, Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | | | - Laura Maiocchi
- Ultrasound Unit, Dipartimento Servizi Diagnostici e per Immagini Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Ambra Raimondi
- Dipartimento di Scienze Clinico-Chirurgiche, Diagnostiche e Pediatriche, University of Pavia, Pavia, Italy
- Ultrasound Unit, Dipartimento Servizi Diagnostici e per Immagini Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Takashi Nishimura
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo Medical University, Hyogo, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Gifu, Japan
| | - Eun Young Kwon
- Department of Radiology, Wonkwang University School of Medicine and Hospital, Iksan, Korea
| | - Jong Keon Jang
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jean-Michel Correas
- AP-HP, Hôpital Necker Enfants Malades, Service d'Imagerie Adulte, Paris, France
- Sorbonne Université, CNRS, INSERM Laboratoire d'Imagerie Biomédicale, Paris, France
| | - Dominique Valla
- Université Paris Cité, Inserm, Centre de recherche sur l'inflammation, Paris, France
- Service d'hépatologie, Hôpital Beaujon, Clichy, France
| | - Valérie Vilgrain
- Department of Radiology, Hôpital Beaujon, AP-HP.Nord, Clichy, France
- Université Paris Cité, Inserm, Centre de recherche sur l'inflammation, Paris, France
| | - Marco Dioguardi Burgio
- Department of Radiology, Hôpital Beaujon, AP-HP.Nord, Clichy, France
- Université Paris Cité, Inserm, Centre de recherche sur l'inflammation, Paris, France
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Park SJ, Kim YN, Oh BK, Kang J. Risk factors for metabolic syndrome in the premetabolic state assessed using hierarchical clustering study in a health screening group. Sci Rep 2024; 14:31169. [PMID: 39732771 DOI: 10.1038/s41598-024-82513-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 12/05/2024] [Indexed: 12/30/2024] Open
Abstract
Early detection of a premetabolic status that is at risk for metabolic syndrome (MetS) but not meeting the criteria is crucial. This study examined 27,623 participants aged 20-50 (mean: 40.7) years who underwent initial health screening at Kangbuk Samsung Hospital (2011-2019), focusing on individuals with one or two MetS components. Hierarchical agglomerative clustering was used to form MetS risk clusters based on initial and follow-up data, including age, resting heart rate (rHR), serum uric acid (UA), C-reactive protein (CRP), gamma-glutamyl transpeptidase, and ferritin levels, and nonalcoholic fatty liver disease (NAFLD), periodontal disease, and Helicobacter pylori infection duration. Kaplan-Meier and generalized additive models were used to present the restricted mean survival time (RMST) and identify onset contributors. Clusters with NAFLD and elevated UA levels had the highest MetS risk, whereas those with uniformly low biomarker levels revealed the lowest risk. During follow-up, a cluster initially comprising 60.2% moderate-risk patients exhibited high biomarker levels and had the worst MetS prognosis (RMST: 211 days). UA, CRP levels, and rHR contributed to the incidence of MetS in the fitted model. Machine learning can predict the premetabolic state at MetS risk in a population-based cohort.
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Affiliation(s)
- Se-Jun Park
- Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
| | - Yu Na Kim
- Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
| | - Byeong Kil Oh
- Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jeonggyu Kang
- Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
- Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, 06355, Republic of Korea.
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Rodionov RN, Jarzebska N, Koay YC, Li M, Kuhn M, Bornstein SR, Martens-Lobenhoffer J, Eslam M, Chen FW, Rubets E, Markov AG, Weiss N, Birkenfeld A, Schwarz P, Bode-Böger SM, Perakakis N, O’Sullivan JF, George J. Symmetric dimethylguanidino valeric acid, a novel single biomarker of hepatic steatosis. iScience 2024; 27:111366. [PMID: 39660051 PMCID: PMC11629207 DOI: 10.1016/j.isci.2024.111366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 02/26/2024] [Accepted: 11/08/2024] [Indexed: 12/12/2024] Open
Abstract
There is an unmet need for a biomarker of liver fat. We identified dimethylguanidino valeric acid (DMGV) as a circulating biomarker of liver fat. Here, we assess its two isoforms-symmetric (SDGV) and asymmetric (ADGV)-as biomarkers of steatosis. We determined plasma ADGV, SDGV, related metabolites, alanine aminotransferase (ALT), and the fatty liver index (FLI) in two cohorts and compared their diagnostic performance for liver fat detection. SDGV was the strongest predictor of moderate to severe steatosis. Changes in SDGV correlated with changes in liver fat % in a prospective cohort. In a murine model of fatty liver disease, protein levels and activity of alanine:glyoxylate aminotransferase 2 (AGXT2), which produces SDGV, were increased and coincided with elevation of SDGV concentrations. SDGV is a biomarker of liver fat and its increase in hepatic steatosis results from the upregulation of AGXT2 activity.
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Affiliation(s)
- Roman N. Rodionov
- Department of Internal Medicine III, University Center for Vascular Medicine, Technische Universität Dresden, 01307 Dresden, Germany
- College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Adelaide, SA 5042 Australia
| | - Natalia Jarzebska
- Department of Internal Medicine III, University Center for Vascular Medicine, Technische Universität Dresden, 01307 Dresden, Germany
- Department of Anaesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
| | - Yen Chin Koay
- Cardiometabolic Medicine, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
- Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia
| | - Mengbo Li
- Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia
| | - Matthias Kuhn
- Institute for Medical Informatics and Biometry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Stefan R. Bornstein
- Department of Internal Medicine III, University Center for Vascular Medicine, Technische Universität Dresden, 01307 Dresden, Germany
- German Center for Diabetes Research (DZD e.V.), Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany
- Department of Diabetes, School of Life Course Science and Medicine, King’s College London, London, UK
| | - Jens Martens-Lobenhoffer
- Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
| | - Mohammad Eslam
- Institute of Clinical Pharmacology, Otto-von-Guericke University, Magdeburg, Germany
| | - Fei Wen Chen
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Elena Rubets
- Department of General Physiology, St. Petersburg State University, St. Petersburg, Russia
| | - Alexander G. Markov
- Department of General Physiology, St. Petersburg State University, St. Petersburg, Russia
| | - Norbert Weiss
- Department of Internal Medicine III, University Center for Vascular Medicine, Technische Universität Dresden, 01307 Dresden, Germany
| | - Andreas Birkenfeld
- German Center for Diabetes Research (DZD e.V.), Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany
- Department of Internal Medicine IV, Department of Endocrinology, Diabetology and Nephrology, University Hospital of Eberhard-Karls-University Tübingen, Tübingen, Germany
- Germany and Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls University of Tübingen, 72074 Tübingen, Germany
| | - Peter Schwarz
- Department of Internal Medicine III, University Center for Vascular Medicine, Technische Universität Dresden, 01307 Dresden, Germany
- German Center for Diabetes Research (DZD e.V.), Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany
- Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
| | | | - Nikolaos Perakakis
- Department of Internal Medicine III, University Center for Vascular Medicine, Technische Universität Dresden, 01307 Dresden, Germany
- German Center for Diabetes Research (DZD e.V.), Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany
- Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
| | - John F. O’Sullivan
- Department of Internal Medicine III, University Center for Vascular Medicine, Technische Universität Dresden, 01307 Dresden, Germany
- Cardiometabolic Medicine, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
- Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia
- Department of Cardiology, Royal Price Alfred Hospital, Sydney, NSW, Australia
| | - Jacob George
- Institute of Clinical Pharmacology, Otto-von-Guericke University, Magdeburg, Germany
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Vamja R, M Y, Vala V, Ramachandran A, Nagda J. Diagnostic accuracy of Fatty Liver Index (FLI) for detecting Metabolic Associated Fatty Liver Disease (MAFLD) in adults attending a tertiary care hospital, a cross-sectional study. Clin Diabetes Endocrinol 2024; 10:46. [PMID: 39668382 PMCID: PMC11639111 DOI: 10.1186/s40842-024-00197-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 07/17/2024] [Indexed: 12/14/2024] Open
Abstract
BACKGROUND Metabolic-associated fatty liver disease (MAFLD) is a major public health problem worldwide. This study aimed to determine the prevalence of MAFLD and evaluate the diagnostic accuracy of the Fatty Liver Index (FLI) compared to ultrasonography for detecting fatty liver in adults attending a tertiary care hospital in Gujarat, India. METHODS This cross-sectional study included 500 adults visiting the outpatient department between January 2023 and December 2023. MAFLD was diagnosed on ultrasound. FLI was calculated using body mass index, waist circumference, triglycerides, and gamma-glutamyl transpeptidase levels. FLI ≥ 60 indicated fatty liver. Logistic regression analysis identified factors associated with fatty liver. RESULTS MAFLD prevalence was 32.2% on ultrasound. High FLI (≥ 60) was present in 26.2%. Male sex, higher BMI, waist circumference, night shift work, diabetes, and triglycerides were independent predictors of fatty liver. FLI showed excellent diagnostic accuracy with a sensitivity of 96%, specificity of 92.5%, and AUC of 0.92 for detecting fatty liver on ultrasound. CONCLUSION MAFLD prevalence among adults was high in this hospital-based sample. FLI can serve as an accurate non-invasive tool for identifying individuals with a high probability of MAFLD. These findings emphasize the need for larger population-based studies and the implementation of regular MAFLD screening programs in high-risk groups.
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Affiliation(s)
- Roshni Vamja
- Department of Community Medicine, M P Shah Medical College, New PG Hostel, MP Shah Medical College Campus, GG Hospital, Patel Colony Post, Jamnagar, Gujarat, 361008, India
| | - Yogesh M
- Department of Community Medicine, M P Shah Medical College, New PG Hostel, MP Shah Medical College Campus, GG Hospital, Patel Colony Post, Jamnagar, Gujarat, 361008, India.
| | - Vijay Vala
- Department of General Medicine, Shantabaa Medical College and General Hospital, Amreli, India
| | - Arya Ramachandran
- Department of Community Medicine, M P Shah Medical College, New PG Hostel, MP Shah Medical College Campus, GG Hospital, Patel Colony Post, Jamnagar, Gujarat, 361008, India
| | - Jay Nagda
- Department of Community Medicine, M P Shah Medical College, New PG Hostel, MP Shah Medical College Campus, GG Hospital, Patel Colony Post, Jamnagar, Gujarat, 361008, India
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López-Mendez I, Romero-Flores JL, Castro-Narro G, Uribe M, Juárez-Hernández E. Factors associated with obtaining lower IQR-CAP values in the detection of hepatic steatosis by transient elastography. Ann Hepatol 2024; 30:101762. [PMID: 39638039 DOI: 10.1016/j.aohep.2024.101762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 10/14/2024] [Accepted: 11/11/2024] [Indexed: 12/07/2024]
Abstract
INTRODUCTION AND OBJECTIVES Controlled attenuation parameter (CAP) has been developed as a non-invasive method for detecting liver steatosis. The aim of the study was to determine factors associated with non-obtaining lower IQR-CAP values. MATERIALS AND METHODS Retrospective revision of medical records of CAP studies for steatosis screening. Anthropometrical, biochemical, and quality variables were collected. A logistic regression analysis was performed to determine independent associations with non-obtaining IQR-CAP <30, <20, and <10 in all patients and then adjusted for obesity/overweight and severity of steatosis. RESULTS 5061 studies were analyzed. Median IQR-CAP was 26 [IQR 20-33] dB/m. Steatosis prevalence was 39.4 % (n = 1996). In overweight patients, significant alcohol consumption was an independent factor for non-obtaining IQR-CAP <30; meanwhile, in obese patients glucose impairment, AST, skPa>8 and steatosis severity were independent factors for non-obtaining lower IQR-CAP values. According to steatosis severity, the presence of anthropometric characteristics of obesity and significant alcohol consumption were independent factors for non-obtaining lower IQR-CAP values. CONCLUSIONS In steatosis detection by CAP, obesity, significant alcohol consumption, glucose impairments, and minimal liver function test alterations were independent factors associated with non-obtaining lower values of IQR-CAP.
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Affiliation(s)
- Iván López-Mendez
- Transplant and Hepatology Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico.
| | | | | | - Misael Uribe
- Gastroenterology and Obesity Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico
| | - Eva Juárez-Hernández
- Translational Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico.
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Lin Y, Wang C, Huang Y, Shen H, Wu W, Yeh H, Huang C, Su C, Yang Y, Wu M, Lin H, Hou M. Models incorporating physical, laboratory and gut metabolite markers can be used to predict severe hepatic steatosis in MAFLD patients. Kaohsiung J Med Sci 2024; 40:1095-1105. [PMID: 39494987 PMCID: PMC11618486 DOI: 10.1002/kjm2.12904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 10/17/2024] [Accepted: 10/17/2024] [Indexed: 11/05/2024] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD) induced-severe hepatic steatosis poses significant health risks. Early prediction of this condition is crucial for prompt intervention. Short-chain fatty acids (SCFAs) and tryptophan are gut metabolites correlated with MAFLD pathogenesis in the gut-liver axis. This study aims to construct prediction models for severe hepatic steatosis by including SCFAs and tryptophan metabolites. This study enrolled 83 participants from the outpatient department in 2023. Physical measurements, serum metabolic and inflammatory markers, metabolites of serum SCFAs and tryptophan were collected. Severe hepatic steatosis was diagnosed using vibration-controlled transient elastography and abdominal sonography. All 40 (48.2%) participants diagnosed with severe hepatic steatosis had MAFLD, while approximately three-quarters of those without severe hepatic steatosis had MAFLD. In comparison to the non-severe hepatic steatosis group, individuals with severe hepatic steatosis exhibited higher levels of waist and arm circumference, serum triglyceride (TG), and lower levels of serum high-density lipoprotein cholesterol (HDL-C) and AST/ALT ratio. They also had higher serum levels of lipopolysaccharide-binding protein, isovaleric acid, and propionic acid, and lower levels of 3-methylvaleric acid, indole-3-propionic acid, and indoxyl sulfate. Models incorporating these markers predicted severe hepatic steatosis. One model additionally included waist circumference and triglyceride-glucose index, while the other incorporated arm circumference and TG/HDL-C ratio. The area under the curve reached 0.958 and 0.938, respectively (p < 0.001). SCFAs and tryptophan metabolites are valuable in predicting severe hepatic steatosis. Further research is needed to investigate the roles of these metabolites in MAFLD.
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Grants
- NSTC 112-2314-B-A049-043-MY3 Ministry of Science and Technology, Taiwan
- MOST111-2314-B-001-009 Ministry of Science and Technology, Taiwan
- V113D71-001-MY2-1 Taipei Veterans General Hospital, Taipei, Taiwan
- V113D71-003-MY2-1 Taipei Veterans General Hospital, Taipei, Taiwan
- V113C-024 Taipei Veterans General Hospital, Taipei, Taiwan
- VTA113-A-4-2 Taipei Veterans General Hospital, Taipei, Taiwan
- V113EA-005 Taipei Veterans General Hospital, Taipei, Taiwan
- V113EA-019 Taipei Veterans General Hospital, Taipei, Taiwan
- Ministry of Science and Technology, Taiwan
- Taipei Veterans General Hospital, Taipei, Taiwan
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Affiliation(s)
- Yi‐Hsuan Lin
- Department of Medical EducationTaipei Veterans General HospitalTaipeiTaiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Department of Family MedicineTaipei Veterans General HospitalTaipeiTaiwan
| | - Ching‐Hsiang Wang
- Department of Medical EducationTaipei Veterans General HospitalTaipeiTaiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Yen‐Hsun Huang
- Department of Medical EducationTaipei Veterans General HospitalTaipeiTaiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Hsiao‐Chin Shen
- Department of Medical EducationTaipei Veterans General HospitalTaipeiTaiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Wei‐Kai Wu
- Bachelor Program of Biotechnology and Food NutritionNational Taiwan UniversityTaipeiTaiwan
- Department of Medical ResearchNational Taiwan University HospitalTaipeiTaiwan
| | - Hsiao‐Yun Yeh
- Department of Medical EducationTaipei Veterans General HospitalTaipeiTaiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Department of Family MedicineTaipei Veterans General HospitalTaipeiTaiwan
| | - Chia‐Chang Huang
- Department of Medical EducationTaipei Veterans General HospitalTaipeiTaiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Chien‐Wei Su
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Division of General Medicine, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanTaipeiTaiwan
| | - Ying‐Ying Yang
- Department of Medical EducationTaipei Veterans General HospitalTaipeiTaiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Division of Gastroenterology and Hepatology, Department of Internal MedicineTaipei Veterans General HospitalTaipeiTaiwan
| | - Ming‐Shiang Wu
- Department of Internal MedicineNational Taiwan University HospitalTaipeiTaiwan
| | - Han‐Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Internal MedicineTaipei Veterans General HospitalTaipeiTaiwan
| | - Ming‐Chih Hou
- Division of Gastroenterology and Hepatology, Department of Internal MedicineTaipei Veterans General HospitalTaipeiTaiwan
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47
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Román Garrido M, Salcedo Joven I, Montero-Peña C, Madrigal Laguía P. [Use of clinical ultrasound in primary care: Cardiovascular risk]. Semergen 2024; 50:102387. [PMID: 39615269 DOI: 10.1016/j.semerg.2024.102387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 10/01/2024] [Accepted: 10/08/2024] [Indexed: 12/17/2024]
Abstract
From primary care we work on the prevention and treatment of cardiovascular risk in our patients. The physical examination, the electrocardiogram and the analysis are the classic parameters and continue being the most efficient way to estimate the presence and control of cardiovascular factors and target organ damage, to optimize the cardiovascular risk stratification. The use of ultrasound by the primary care doctor to complete the clinical information is a reality that helps to strengthen the diagnostic suspicion, monitorize the clinical evolution and even decide the best therapeutic plan. This work proposes to establish the bases for the use of ultrasound for the diagnosis of carotid/femoral atheromatosis, the use of echocardioscopy, screening for abdominal aortic aneurysm, the assessment of hepatic steatosis and the study of the kidney in patients with chronic kidney disease.
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Affiliation(s)
- M Román Garrido
- Urgencias Hospitalarias, Complejo Asistencial Universitario de Salamanca, Salamanca, España; Grupo Ecografia Semergen, España.
| | - I Salcedo Joven
- Grupo Ecografia Semergen, España; Centro de Salud Estrecho de Corea, Madrid, España
| | - C Montero-Peña
- Grupo Ecografia Semergen, España; Urgencias Atención Primaria, Centro de salud La Milagrosa, Jerez de la Frontera, Cádiz, España
| | - P Madrigal Laguía
- Grupo Ecografia Semergen, España; Centro de salud Casas-Ibáñez, Casas-Ibáñez, Albacete, España
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48
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Maffeis C, Piona C, Morandi A, Marigliano M, Morotti E, Mancioppi V, Caiazza E, Zusi C, Emiliani F, Mantovani A, Colecchia A, Targher G. Glycaemic control metrics and metabolic dysfunction-associated steatotic liver disease in children and adolescents with type 1 diabetes. Diabetes Obes Metab 2024; 26:5896-5905. [PMID: 39344839 DOI: 10.1111/dom.15961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 08/22/2024] [Accepted: 09/02/2024] [Indexed: 10/01/2024]
Abstract
AIM The aim was to examine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), a risk factor for atherosclerotic cardiovascular disease, and its association with glycaemic control metrics in children and adolescents with type 1 diabetes (T1D). MATERIALS AND METHODS We enrolled 244 children and adolescents with T1D (115 girls, mean age: 16.2 ± 3.2 years). The diagnosis of MASLD was defined by the presence of hepatic steatosis on ultrasonography in combination with at least one of five common cardiometabolic risk factors. Metrics of short-term and long-term glycaemic control, blood pressure, lipids, anthropometric characteristics and three genetic variants strongly related to MASLD susceptibility (rs738409 [patatin-like phospholipase domain-containing 3], rs58542926 [transmembrane 6 superfamily member 2] and rs1260326 [glucokinase regulator]) were assessed. Characteristics of these subjects with and without MASLD were compared using the unpaired Student t test, Mann-Whitney test or χ2 test as appropriate. Logistic regression analyses were performed to determine the main independent predictors of MASLD. RESULTS The prevalence of MASLD was 27.5% in children and adolescents with T1D. Blood pressure, total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein cholesterol, HbA1c and time above range (TAR) were significantly higher in subjects with MASLD than in those without MASLD. Mean HbA1c values from diabetes onset (adjusted odds ratio [OR]: 1.703, 95% confidence interval [CI]: 1.040-2.787, p = 0.034), TAR (adjusted OR: 1.028, 95% CI: 1.009-1.047, p = 0.006) and plasma LDL cholesterol (adjusted OR: 1.045, 95% CI: 1.013-1.078, p = 0.004) were independently associated with the presence of MASLD. CONCLUSIONS MASLD is a common condition in children and adolescents with T1D. The mean HbA1c values from diabetes onset, TAR and LDL cholesterol levels were the independent predictors of MASLD.
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Affiliation(s)
- Claudio Maffeis
- Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics and Gynecology, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Claudia Piona
- Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics and Gynecology, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Anita Morandi
- Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics and Gynecology, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Marco Marigliano
- Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics and Gynecology, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Elisa Morotti
- Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics and Gynecology, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Valentina Mancioppi
- Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics and Gynecology, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Erika Caiazza
- Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics and Gynecology, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Chiara Zusi
- Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics and Gynecology, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Federica Emiliani
- Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics and Gynecology, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Antonio Colecchia
- Gastroenterology Unit, Department of Specialistic Medicines, University Hospital of Modena and Reggio Emilia, Modena, Italy
| | - Giovanni Targher
- Department of Medicine, University of Verona, Verona, Italy
- Metabolic Diseases Research Unit, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar di Valpolicella, Italy
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49
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Lv Q, Zhao H. The association of metabolic dysfunction-associated steatotic liver disease (MASLD) with the risk of myocardial infarction: a systematic review and meta-analysis. Ann Med 2024; 56:2306192. [PMID: 38253023 PMCID: PMC10810647 DOI: 10.1080/07853890.2024.2306192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 01/11/2024] [Indexed: 01/24/2024] Open
Abstract
Objective While studies have documented how metabolic dysfunction-associated steatotic liver disease (MASLD) can contribute to cardiovascular disease (CVD), whether MASLD is associated with myocardial infarction (MI) remains debateable. Herein, we systematically reviewed published articles and performed a meta-analysis to determine the relationship between MASLD and MI risk.Methods PubMed, MEDLINE, Embase, Web of Science, CNKI, CBM, VIP, and WanFang databases were searched, and the DerSimonian Laird method was used to obtain hazard ratios (HRs) for binary variables to assess the correlation between MASLD and MI risk. Subgroup analyses for the study region, MASLD diagnosis, quality score, study design, and follow-up time were conducted simultaneously for the selected studies retrieved from the time of database establishment to March 2022. All study procedures were independently conducted by two investigators.Results The final analysis included seven articles, including eight prospective and two retrospective cohort studies. The MI risk was higher among MASLD patients than among non-MASLD patients (HR = 1.26; 95% CI: 1.08-1.47, p = 0.003). The results of the subgroup analysis of the study region revealed an association of MASLD with MI risk among Americans and Asians, but not in Europeans. Subgroup analyses of MASLD diagnosis showed that ultrasonography and other (fatty liver index[FLI] and computed tomography [CT)]) diagnostic methods, but not international classification of disease (ICD), increased the risk of MI. Subgroup analysis of the study design demonstrated a stronger relationship between MASLD and MI in retrospective studies but not in prospective studies. Subgroup analysis based on the follow-up duration revealed the association of MASLD with MI risk in cases with < 3 years of follow-up but not with ≥3 years of follow-up.Conclusion MASLD increases the risk of MI, independent of traditional risk factors.
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Affiliation(s)
- Qiong Lv
- Department of Electrocardiogram, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Huashan Zhao
- Department of General Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
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50
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Zhang R, Ren S, Mi H, Wang M, He T, Zhang R, Jiang W, Su C. Fatty liver index as an independent predictor of all-cause and disease-specific mortality. Eur J Gastroenterol Hepatol 2024; 36:1453-1463. [PMID: 39400538 PMCID: PMC11527378 DOI: 10.1097/meg.0000000000002865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 09/13/2024] [Indexed: 10/15/2024]
Abstract
PURPOSE This study aims to assess the prognostic value of the fatty liver index (FLI), a noninvasive tool for hepatic steatosis assessment, in predicting all-cause and disease-specific mortality. METHODS We linked data from the National Health and Nutrition Examination Survey III (1988-1994) with Public-Use Mortality Files, forming a cohort of 11 297 participants with a median follow-up period of 26.25 years. Cox proportional hazards models were used to evaluate the association between FLI and all-cause mortality, while Fine and Gray's models assessed the relationship between FLI and disease-specific mortality. RESULTS The FLI ≥ 60 was independently associated with an increased risk of all-cause mortality (hazard ratio = 1.24, P < 0.001), as well as mortality from malignant neoplasms (hazard ratio = 1.18, P = 0.048), diabetes (hazard ratio = 2.62, P = 0.001), and cardiovascular diseases (CVDs) (hazard ratio = 1.18, P = 0.018), compared to FLI < 30. No significant associations were found with Alzheimer's disease, influenza and pneumonia, chronic lower respiratory diseases, or renal disorders. Subgroup analyses indicated that individuals who were females aged 40-60 (hazard ratio = 1.67, P = 0.003), non-overweight (hazard ratio = 1.75, P = 0.007), or without abdominal obesity (hazard ratio = 1.75, P = 0.007) exhibited a stronger association between FLI ≥ 60 and all-cause mortality. CONCLUSION These findings support the prognostic value of the FLI for predicting mortality from all causes, malignant neoplasms, diabetes, and CVDs. Targeted attention is needed in postmenopausal women, non-overweight, and non-abdominally obese populations.
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Affiliation(s)
| | - Shuhao Ren
- School of Public Health, Xiamen University
| | - Hongfei Mi
- Department of Public Health, Zhongshan Hospital, Fudan University (Xiamen Branch)
- Department of Public Health, Xiamen Clinical Research Center for Cancer Therapy
| | | | - Tingjuan He
- Department of Public Health, Zhongshan Hospital, Fudan University (Xiamen Branch)
- Department of Public Health, Xiamen Clinical Research Center for Cancer Therapy
| | | | - Wei Jiang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University (Xiamen Branch), Xiamen, Fujian, China
| | - Chenghao Su
- Department of Public Health, Zhongshan Hospital, Fudan University (Xiamen Branch)
- Department of Public Health, Xiamen Clinical Research Center for Cancer Therapy
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