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Rroji M, Spahia N, Figurek A, Spasovski G. Targeting Diabetic Atherosclerosis: The Role of GLP-1 Receptor Agonists, SGLT2 Inhibitors, and Nonsteroidal Mineralocorticoid Receptor Antagonists in Vascular Protection and Disease Modulation. Biomedicines 2025; 13:728. [PMID: 40149704 PMCID: PMC11940462 DOI: 10.3390/biomedicines13030728] [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: 02/09/2025] [Revised: 03/03/2025] [Accepted: 03/12/2025] [Indexed: 03/29/2025] Open
Abstract
Atherosclerosis is a closely related complication of diabetes mellitus (DM), driven by endothelial dysfunction, inflammation, and oxidative stress. The progression of atherosclerosis is accelerated by hyperglycemia, insulin resistance, and hyperlipidemia. Novel antidiabetic agents, SGLT2 inhibitors, and GLP-1 agonists improve glycemic control and offer cardiovascular protection, reducing the risk of major adverse cardiovascular events (MACEs) and heart failure hospitalization. These agents, along with nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), promise to mitigate metabolic disorders and their impact on endothelial function, oxidative stress, and inflammation. This review explores the potential molecular mechanisms through which these drugs may prevent the development of atherosclerosis and cardiovascular disease (CVD), supported by a summary of preclinical and clinical evidence.
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Affiliation(s)
- Merita Rroji
- Department of Nephrology, University of Medicine Tirana, 1001 Tirana, Albania
- Department of Nephrology, University Hospital Center Mother Tereza, 1001 Tirana, Albania;
| | - Nereida Spahia
- Department of Nephrology, University Hospital Center Mother Tereza, 1001 Tirana, Albania;
| | - Andreja Figurek
- Institute of Anatomy, University of Zurich, 8057 Zurich, Switzerland;
| | - Goce Spasovski
- Department of Nephrology, University Sts. Cyril and Methodius, 1000 Skopje, North Macedonia;
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Luthra R, Sheth A. Understanding MASH: An Examination of Progression and Clinical Outcomes by Disease Severity in the TARGET-NASH Database. Adv Ther 2025; 42:1165-1195. [PMID: 39739194 PMCID: PMC11787050 DOI: 10.1007/s12325-024-03085-4] [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: 10/18/2024] [Accepted: 12/04/2024] [Indexed: 01/02/2025]
Abstract
INTRODUCTION Metabolic dysfunction-associated steatohepatitis (MASH), the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), is linked to cardiometabolic risk factors such as obesity and type 2 diabetes (T2D). The rising prevalence of MASH and risk of hepatic and extra-hepatic complications emphasize the need for a better understanding of disease progression and associated outcomes. This study aimed to evaluate the incidence of, and demographic and clinical characteristics associated with, progression to MASH-related complications by disease severity in patients with non-cirrhotic MASH or MASH cirrhosis. Alignment between noninvasive tests (NITs) and biopsy-determined fibrosis stage was also assessed. METHODS This analysis used data from the TARGET-NASH cohort that includes adults with MASH across academic and community sites in the United States. Patients with non-cirrhotic MASH or MASH cirrhosis were stratified by disease severity based on fibrosis stage or cirrhosis. Progression to MASH-related outcomes, including all-cause mortality, cirrhosis, and liver transplantation, was assessed. RESULTS Among the 2378 patients included in this analysis, 48% had MASH cirrhosis. Incidence of all-cause mortality increased with disease severity from 0.14/100 person-months (100PM) at fibrosis stage 0-1 (F0-F1) to 2.02/100PM with compensated cirrhosis and 4.62/100PM with decompensated cirrhosis. Compared with patients with F0-F1, risk of progression to cirrhosis was higher in patients with F3 [hazard ratio (HR), 95% confidence interval (CI); 18.66, 10.97-31.73] and F2 (HR, 95% CI; 3.74, 2.00-6.98). Among those who progressed to MASH-related outcomes, 67.9% had T2D and 73.9% had hypertension. Vibration-controlled transient elastography showed better alignment with biopsy-determined fibrosis stage than Fibrosis-4 Index (FIB-4). CONCLUSIONS Progression to all-cause mortality in patients with MASH was significantly associated with the presence of higher fibrosis stage and cirrhosis. Cardiometabolic comorbidities such as T2D and hypertension were prevalent in patients with MASH progression. Early identification and management of MASH may mitigate disease progression and liver-related complications.
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Affiliation(s)
- Rakesh Luthra
- Novo Nordisk Inc., 800 Scudders Mill Rd, Plainsboro, NJ, 08536, USA
| | - Aarth Sheth
- Novo Nordisk Inc., 800 Scudders Mill Rd, Plainsboro, NJ, 08536, USA.
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Bhardwaj M, Mazumder PM. An insight on the additive impact of type 2 diabetes mellitus and nonalcoholic fatty liver disease on cardiovascular consequences. Mol Biol Rep 2025; 52:169. [PMID: 39873861 DOI: 10.1007/s11033-025-10249-0] [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: 04/29/2024] [Accepted: 01/10/2025] [Indexed: 01/30/2025]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are associated with a multifactorial complicated aetiology that is often coexisting and has a strong and distinct connection with cardiovascular diseases (CVDs). In order to accomplish effective and appropriate therapeutic strategies, a deeper understanding of the bidirectional interaction between NAFLD patients, NAFLD patients with T2DM, and NAFLD patients with CVDs is required to control the concomitant rise in prevalence of these conditions worldwide. This article also aims to shed light on the epidemiology and mechanisms behind the relationship between T2DM, NAFLD and the related cardiovascular consequences. METHOD Literature was collected from PubMed, Medline, Embase, Web of Science and Google scholar from inception to June, 2024. For surveying literature different combinations and formats of terms including NAFLD, NASH, T2DM and CVDs were used. RESULTS In the recent decade, clinical and epidemiological studies have been conducted and provide strong evidence that NAFLD is closely linked with CVD progression along with associated morbidity and mortality in both patients with and without T2DM. Several mechanistic approaches contribute to cardiovascular consequences and abnormalities in cardiac biomarkers in T2DM and NAFLD patients, including adipose tissue malfunction, mitochondrial dysfunction, the microbiota, genetic and epigenetic alterations contributing to insulin resistance, glucotoxicity and lipotoxicity. CONCLUSION The study reveals a complex interplay between diabetes, hepatic and cardiovascular complications, leading to significant morbidity and mortality in diabetic and NAFLD patients. This pandemic necessitates further research to identify mitigating variables and develop effective treatment approaches.
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Affiliation(s)
- Monika Bhardwaj
- Department of Pharmaceutical Sciences & Technology, BIT Mesra, Ranchi, 835215, India
| | - Papiya Mitra Mazumder
- Department of Pharmaceutical Sciences & Technology, BIT Mesra, Ranchi, 835215, India.
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Sedighi M, Saber A, Bagheri A, Hazratian S, Pasdar Y, Najafi F, Moradinazar M, Soleimani D. The associations between diet-induced inflammation and the improvement or worsening of hepatic steatosis and fibrosis: a longitudinal analysis of RaNCD cohort study. Nutr Metab (Lond) 2025; 22:5. [PMID: 39833863 PMCID: PMC11749311 DOI: 10.1186/s12986-025-00897-1] [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: 10/18/2024] [Accepted: 01/08/2025] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Persistent inflammation plays a crucial role in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to scrutinize the associations of diet-induced inflammation with the improvement or worsening of hepatic steatosis and fibrosis in MASLD. METHODS This longitudinal study involved 2,537 participants from the Ravanser Non-Communicable Disease (RaNCD) cohort (2015-2023). Dietary intake was assessed using the 118-item food frequency questionnaire (FFQ), and diet-induced inflammation was determined using the dietary inflammatory index (DII). The AST to platelet ratio index (APRI) and Fibrosis-4 (FIB-4) were used as confirmed predictive indicators for hepatic fibrosis and the hepatic steatosis index (HSI) was used for hepatic steatosis. RESULTS Adherence to an inflammatory diet independently increases the risk of worsening hepatic steatosis (RR:1.39; 95%CI: 1.02-1.93; P-value: 0.04) and reduces the risk of improving hepatic steatosis (RR: 66; 95% CI: 0.48-0.98; P-value: 0.01) compared to an anti-inflammatory diet. The DII scores did not show any connection to hepatic fibrosis, as determined by FIB-4 (β: - 1.08; 95%CI: - 2.43 to 0.27; P-value: 0.12) and APRI (β: 0.22; 95%CI: - 1.51 to 1.95; P-value: 0.80). CONCLUSIONS These results underscore the importance of dietary composition in managing hepatic steatosis and highlight the need for further research to explore the mechanisms underlying these associations.
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Affiliation(s)
- Mohammad Sedighi
- Nutritional Sciences Department, School of Nutrition Sciences and Food Technology, Kermanshah University of Medical Sciences, Dolat-Abad Street, Isar Square, Kermanshah, Iran
| | - Amir Saber
- Nutritional Sciences Department, School of Nutrition Sciences and Food Technology, Kermanshah University of Medical Sciences, Dolat-Abad Street, Isar Square, Kermanshah, Iran
| | - Amir Bagheri
- Nutritional Sciences Department, School of Nutrition Sciences and Food Technology, Kermanshah University of Medical Sciences, Dolat-Abad Street, Isar Square, Kermanshah, Iran
| | - Saba Hazratian
- Nutritional Sciences Department, School of Nutrition Sciences and Food Technology, Kermanshah University of Medical Sciences, Dolat-Abad Street, Isar Square, Kermanshah, Iran
| | - Yahya Pasdar
- Research Center for Environmental Determinants of Health, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Farid Najafi
- Research Center for Environmental Determinants of Health, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mehdi Moradinazar
- Research Center for Environmental Determinants of Health, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Davood Soleimani
- Nutritional Sciences Department, School of Nutrition Sciences and Food Technology, Kermanshah University of Medical Sciences, Dolat-Abad Street, Isar Square, Kermanshah, Iran.
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Marginean CM, Pirscoveanu D, Cazacu SM, Popescu MS, Marginean IC, Iacob GA, Popescu M. Non-Alcoholic Fatty Liver Disease, Awareness of a Diagnostic Challenge—A Clinician’s Perspective. GASTROENTEROLOGY INSIGHTS 2024; 15:1028-1053. [DOI: 10.3390/gastroent15040071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease globally. NAFLD is a complex pathology, considered to be the hepatic expression of metabolic syndrome (MetS). It is supposed to become the main indication for liver transplantation in the coming years and is estimated to affect 57.5–74.0% of obese people, 22.5% of children and 52.8% of obese children, with 50% of individuals with type 2 diabetes being diagnosed with NAFLD. Recent research has proved that an increase in adipose tissue insulin resistance index is an important marker of liver injury in patients with NAFLD. Despite being the main underlying cause of incidental liver damage and a growing worldwide health problem, NAFLD is mostly under-appreciated. Currently, NAFLD is considered a multifactorial disease, with various factors contributing to its pathogenesis, associated with insulin resistance and diabetes mellitus, but also with cardiovascular, kidney and endocrine disorders (polycystic ovary syndrome, hypothyroidism, growth hormone deficiency). Hepatitis B and hepatitis C, sleep apnea, inflammatory bowel diseases, cystic fibrosis, viral infections, autoimmune liver diseases and malnutrition are some other conditions in which NAFLD can be found. The aim of this review is to emphasize that, from the clinician’s perspective, NAFLD is an actual and valuable key diagnosis factor for multiple conditions; thus, efforts need to be made in order to increase recognition of the disease and its consequences. Although there is no global consensus, physicians should consider screening people who are at risk of NAFLD. A large dissemination of current concepts on NAFLD and an extensive collaboration between physicians, such as gastroenterologists, internists, cardiologists, diabetologists, nutritionists and endocrinologists, is equally needed to ensure we have the knowledge and resources to address this public health challenge.
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Affiliation(s)
- Cristina Maria Marginean
- Internal Medicine Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Denisa Pirscoveanu
- Neurology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Sergiu Marian Cazacu
- Research Center of Gastroenterology and Hepatology, Gastroenterology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Marian Sorin Popescu
- Internal Medicine Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | | | - George Alexandru Iacob
- Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Mihaela Popescu
- Endocrinology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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Bhardwaj M, Mazumder PM. The gut-liver axis: emerging mechanisms and therapeutic approaches for nonalcoholic fatty liver disease and type 2 diabetes mellitus. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:8421-8443. [PMID: 38861011 DOI: 10.1007/s00210-024-03204-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 05/30/2024] [Indexed: 06/12/2024]
Abstract
Nonalcoholic fatty liver disease (NAFLD), more appropriately known as metabolic (dysfunction) associated fatty liver disease (MAFLD), a prevalent condition in type 2 diabetes mellitus (T2DM) patients, is a complex condition involving hepatic lipid accumulation, inflammation, and liver fibrosis. The gut-liver axis is closely linked to metabolic dysfunction, insulin resistance, inflammation, and oxidative stress that are leading to the cooccurrence of MAFLD and T2DM cardiovascular diseases (CVDs). The purpose of this review is to raise awareness about the role of the gut-liver axis in the progression of MAFLD, T2DM and CVDs with a critical analysis of available treatment options for T2DM and MAFLD and their impact on cardiovascular health. This study analysed over 100 articles on this topic, using online searches and predefined keywords, to understand and summarise published research. Numerous studies have shown a strong correlation between gut dysfunction, particularly the gut microbiota and its metabolites, and the occurrence and progression of MAFLD and type 2 diabetes mellitus (T2DM). Herein, this article also examines the impact of the gut-liver axis on MAFLD, T2DM, and related complications, focusing on the role of gut microbiota dysbiosis in insulin resistance, T2DM and obesity-related cardiovascular complications. The study suggests potential treatment targets for MAFLD linked to T2DM, focusing on cardiovascular outcomes and the molecular mechanism of the gut-liver axis, as gut microbiota dysbiosis contributes to obesity-related metabolic abnormalities.
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Affiliation(s)
- Monika Bhardwaj
- Department of Pharmaceutical Sciences & Technology, BIT Mesra, Ranchi, 835215, India
| | - Papiya Mitra Mazumder
- Department of Pharmaceutical Sciences & Technology, BIT Mesra, Ranchi, 835215, India.
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Chao TH, Lin TH, Cheng CI, Wu YW, Ueng KC, Wu YJ, Lin WW, Leu HB, Cheng HM, Huang CC, Wu CC, Lin CF, Chang WT, Pan WH, Chen PR, Ting KH, Su CH, Chu CS, Chien KL, Yen HW, Wang YC, Su TC, Liu PY, Chang HY, Chen PW, Juang JMJ, Lu YW, Lin PL, Wang CP, Ko YS, Chiang CE, Hou CJY, Wang TD, Lin YH, Huang PH, Chen WJ. 2024 Guidelines of the Taiwan Society of Cardiology on the Primary Prevention of Atherosclerotic Cardiovascular Disease --- Part II. ACTA CARDIOLOGICA SINICA 2024; 40:669-715. [PMID: 39582845 PMCID: PMC11579689 DOI: 10.6515/acs.202411_40(6).20240724b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 07/24/2024] [Indexed: 11/26/2024]
Abstract
For the primary prevention of atherosclerotic cardiovascular disease (ASCVD), the recommended treatment target for each modifiable risk factor is as follows: reducing body weight by 5-10%; blood pressure < 130/80 mmHg (systolic pressure < 120 mmHg in high-risk individuals); low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL in high-risk individuals, LDL-C < 115 mg/dL in moderate-risk individuals, LDL-C < 130 mg/dL in low-risk individuals, and LDL-C < 160 mg/dL in those with a minimal; complete and persistent abstinence from cigarette smoking; hemoglobin A1C < 7.0%; fulfilling recommended amounts of the six food groups according to the Taiwan food guide; and moderate-intensity physical activity 150 min/wk or vigorous physical activity 75 min/wk. For the primary prevention of ASCVD by pharmacological treatment in individuals with modifiable risk factors/clinical conditions, statins are the first-line therapy for reducing LDL-C levels; some specific anti-diabetic drugs proven to be effective in randomized controlled trials for the primary prevention of ASCVD are recommended in patients with type 2 diabetes mellitus; pharmacological treatment is recommended to assist in weight management for obese patients with a body mass index ≥ 30 kg/m2 (or 27 kg/m2 who also have at least one ASCVD risk factor or obesity-related comorbidity); an angiotensin-converting enzyme inhibitor, a glucagon-like peptide-1 receptor agonist, a sodium-dependent glucose cotransporter-2 inhibitor, and finerenone can be used in diabetic patients with chronic kidney disease for the primary prevention of ASCVD. Of note, healthcare providers are at full discretion in clinical practice, owing to the diversity of individuals and practice, and the availability of resources and facilities.
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Affiliation(s)
- Ting-Hsing Chao
- Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
- Division of Cardiology, Department of Internal Medicine, Chung-Shan Medical University Hospital; School of Medicine, Chung Shan Medical University, Taichung
| | - Tsung-Hsien Lin
- Division of Cardiology, Department of Internal Medicine Kaohsiung Medical University Hospital
- Faculty of Medicine and Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University
| | - Cheng-I Cheng
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung; School of Medicine, College of Medicine, Chang Gung University, Taoyuan
| | - Yen-Wen Wu
- Division of Cardiology, Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
- Graduate Institute of Medicine, Yuan Ze University, Taoyuan
| | - Kwo-Chang Ueng
- Division of Cardiology, Department of Internal Medicine, Chung-Shan Medical University Hospital; School of Medicine, Chung Shan Medical University, Taichung
| | - Yih-Jer Wu
- Department of Medicine and Institute of Biomedical Sciences, MacKay Medical College, New Taipei City
- Cardiovascular Center, Department of Internal Medicine, MacKay Memorial Hospital, Taipei
| | - Wei-Wen Lin
- Cardiovascular center, Taichung Veterans General Hospital, Taichung
| | - Hsing-Ban Leu
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
- Cardiovascular Research Center, National Yang Ming Chiao Tung University
- Healthcare and Management Center
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital
| | - Hao-Min Cheng
- Ph.D. Program of Interdisciplinary Medicine (PIM), National Yang Ming Chiao Tung University College of Medicine; Division of Faculty Development; Center for Evidence-based Medicine, Taipei Veterans General Hospital; Institute of Public Health; Institute of Health and Welfare Policy, National Yang Ming Chiao Tung University College of Medicine
| | - Chin-Chou Huang
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital
- Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei
| | - Chih-Cheng Wu
- Center of Quality Management, National Taiwan University Hospital Hsinchu Branch, Hsinchu; College of Medicine, National Taiwan University, Taipei; Institute of Biomedical Engineering, National Tsing-Hua University, Hsinchu; Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan
| | - Chao-Feng Lin
- Department of Medicine, MacKay Medical College, New Taipei City; Department of Cardiology, MacKay Memorial Hospital, Taipei
| | - Wei-Ting Chang
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung; Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center, Tainan
| | - Wen-Han Pan
- Institute of Biomedical Sciences, Academia Sinica, Taipei; Institute of Population Health Sciences, National Health Research Institutes, Miaoli; Institute of Biochemistry and Biotechnology, National Taiwan University
| | - Pey-Rong Chen
- Department of Dietetics, National Taiwan University Hospital, Taipei
| | - Ke-Hsin Ting
- Division of Cardiology, Department of Internal Medicine, Yunlin Christian Hospital, Yunlin
| | - Chun-Hung Su
- Division of Cardiology, Department of Internal Medicine, Chung-Shan Medical University Hospital; School of Medicine, Chung Shan Medical University, Taichung
| | - Chih-Sheng Chu
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung
| | - Kuo-Liong Chien
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University; Department of Internal Medicine, National Taiwan University Hospital and College of Medicine; Population Health Research Center, National Taiwan University, Taipei
| | - Hsueh-Wei Yen
- Division of Cardiology, Department of Internal Medicine Kaohsiung Medical University Hospital
| | - Yu-Chen Wang
- Division of Cardiology, Asia University Hospital; Department of Medical Laboratory Science and Biotechnology, Asia University; Division of Cardiology, China Medical University College of Medicine and Hospital, Taichung
| | - Ta-Chen Su
- Cardiovascular Center, Department of Internal Medicine, National Taiwan University Hospital
- Department of Environmental and Occupational Medicine, National Taiwan University College of Medicine
| | - Pang-Yen Liu
- Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center
| | - Hsien-Yuan Chang
- Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Po-Wei Chen
- Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Jyh-Ming Jimmy Juang
- Heart Failure Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine, and National Taiwan University Hospital
| | - Ya-Wen Lu
- Cardiovascular center, Taichung Veterans General Hospital, Taichung
- Cardiovascular Research Center, National Yang Ming Chiao Tung University
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei
| | - Po-Lin Lin
- Division of Cardiology, Department of Internal Medicine, Hsinchu MacKay Memorial Hospital, Hsinchu
| | - Chao-Ping Wang
- Division of Cardiology, E-Da Hospital; School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung
| | - Yu-Shien Ko
- Cardiovascular Division, Chang Gung Memorial Hospital; College of Medicine, Chang Gung University, Taoyuan
| | - Chern-En Chiang
- General Clinical Research Center and Division of Cardiology, Taipei Veterans General Hospital and National Yang Ming Chiao Tung University
| | - Charles Jia-Yin Hou
- Cardiovascular Center, Department of Internal Medicine, MacKay Memorial Hospital, Taipei
| | - Tzung-Dau Wang
- Cardiovascular Center and Divisions of Hospital Medicine and Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine
| | - Yen-Hung Lin
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei
| | - Po-Hsun Huang
- Cardiovascular Research Center, National Yang Ming Chiao Tung University
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital
| | - Wen-Jone Chen
- Department of Internal Medicine, Min-Sheng General Hospital, Taoyuan; Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
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Boccatonda A, D’Ardes D, Moronti V, Santilli J, Cipollone A, Lessiani G, Di Gregorio N, Serra C, Piscaglia F, Ferri C, Cipollone F. From MASLD to PAD: Looking for Cardiovascular Disease Starting from Metabolic Status. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1781. [PMID: 39596967 PMCID: PMC11596241 DOI: 10.3390/medicina60111781] [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: 09/08/2024] [Revised: 10/19/2024] [Accepted: 10/21/2024] [Indexed: 11/29/2024]
Abstract
Background: Peripheral artery disease (PAD) is still the least studied and evaluated form in clinical practice among atherosclerotic pathologies, despite the increased mortality and comorbidities related to it. The relationship between steatotic liver disease and an increased risk of cardiovascular disease has been extensively documented. Methods: The purpose of this work is to perform a review of the evidence linking NAFLD or MASLD to PAD, and examine possible clinical scenarios that arise from this new terminology. Results: The new definition of metabolic dysfunction-associated steatotic liver disease (MASLD) includes the presence of cardiometabolic risk factors and hepatic steatosis without any other underlying causes of hepatic steatosis; this terminology, coined in the hepatological field, could generate confusion, especially in the initial stages of its diffusion and among different medical specialists. Conclusions: Some recent data in the literature have strengthened the evidence of a pathological link between hepatic metabolic alteration (NAFLD or MAFLD) and PAD.
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Affiliation(s)
- Andrea Boccatonda
- Diagnostic and Therapeutic Interventional Ultrasound Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.B.); (C.S.)
| | - Damiano D’Ardes
- Department of Medicine and Aging Science, Institute of “Clinica Medica”, “G. D’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy; (A.C.); (F.C.)
| | - Veronica Moronti
- Department of Life, Health & Environmental Sciences and Internal Medicine, ASL Avezzano-Sulmona-L’Aquila, San Salvatore Hospital, University of L’Aquila, 67100 L’Aquila, Italy (J.S.); (N.D.G.); (C.F.)
| | - Jessica Santilli
- Department of Life, Health & Environmental Sciences and Internal Medicine, ASL Avezzano-Sulmona-L’Aquila, San Salvatore Hospital, University of L’Aquila, 67100 L’Aquila, Italy (J.S.); (N.D.G.); (C.F.)
| | - Alessia Cipollone
- Department of Medicine and Aging Science, Institute of “Clinica Medica”, “G. D’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy; (A.C.); (F.C.)
| | | | - Nicoletta Di Gregorio
- Department of Life, Health & Environmental Sciences and Internal Medicine, ASL Avezzano-Sulmona-L’Aquila, San Salvatore Hospital, University of L’Aquila, 67100 L’Aquila, Italy (J.S.); (N.D.G.); (C.F.)
| | - Carla Serra
- Diagnostic and Therapeutic Interventional Ultrasound Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.B.); (C.S.)
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Claudio Ferri
- Department of Life, Health & Environmental Sciences and Internal Medicine, ASL Avezzano-Sulmona-L’Aquila, San Salvatore Hospital, University of L’Aquila, 67100 L’Aquila, Italy (J.S.); (N.D.G.); (C.F.)
| | - Francesco Cipollone
- Department of Medicine and Aging Science, Institute of “Clinica Medica”, “G. D’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy; (A.C.); (F.C.)
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Zheng H, Sechi LA, Navarese EP, Casu G, Vidili G. Metabolic dysfunction-associated steatotic liver disease and cardiovascular risk: a comprehensive review. Cardiovasc Diabetol 2024; 23:346. [PMID: 39342178 PMCID: PMC11439309 DOI: 10.1186/s12933-024-02434-5] [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: 06/12/2024] [Accepted: 09/09/2024] [Indexed: 10/01/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), poses a significant global health challenge due to its increasing prevalence and strong association with cardiovascular disease (CVD). This comprehensive review summarizes the current knowledge on the MASLD-CVD relationship, compares analysis of how different terminologies for fatty liver disease affect cardiovascular (CV) risk assessment using different diagnostic criteria, explores the pathophysiological mechanisms connecting MASLD to CVD, the influence of MASLD on traditional CV risk factors, the role of noninvasive imaging techniques and biomarkers in the assessment of CV risk in patients with MASLD, and the implications for clinical management and prevention strategies. By incorporating current research and clinical guidelines, this review provides a comprehensive overview of the complex interplay between MASLD and cardiovascular health.
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Affiliation(s)
- Haixiang Zheng
- Department of Biomedical Sciences, University of Sassari, 07100, Sassari, Italy
- Department of Cardiology, The Second Affiliated Hospital of Shantou University Medical College, 515041, Shantou, China
| | - Leonardo Antonio Sechi
- Department of Biomedical Sciences, University of Sassari, 07100, Sassari, Italy
- Complex Structure of Microbiology and Virology, AOU Sassari, 07100, Sassari, Italy
| | - Eliano Pio Navarese
- Clinical and Experimental Cardiology, Clinical and Interventional Cardiology, University of Sassari, Sassari, Italy
| | - Gavino Casu
- Clinical and Experimental Cardiology, Clinical and Interventional Cardiology, University of Sassari, Sassari, Italy
| | - Gianpaolo Vidili
- Department of Medicine, Surgery, and Pharmacy, University of Sassari, Azienda Ospedaliero, 07100, Sassari, Italy.
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10
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Zhang Y, Bu Y, Zhao R, Han C. Metabolic-associated fatty liver disease and pregnancy complications: new challenges and clinical perspectives. Ther Adv Endocrinol Metab 2024; 15:20420188241274350. [PMID: 39350947 PMCID: PMC11440543 DOI: 10.1177/20420188241274350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 07/22/2024] [Indexed: 10/04/2024] Open
Abstract
The term metabolic-associated fatty liver disease (MAFLD), with a global prevalence estimated at 38.77%, has gradually replaced the traditional concept of non-alcoholic fatty liver disease (NAFLD). Compared to the general population, the incidence of MAFLD is notably higher among pregnant women, posing potential risks to both maternal and neonatal health. This review summarizes the latest research on MAFLD, focusing on its association with pregnancy complications. Additionally, it provides a comparative analysis with previous studies on NAFLD, presenting a comprehensive perspective for clinical management. Findings suggest that pregnant women with MAFLD face a higher risk of gestational hypertension and cesarean delivery compared to those with NAFLD, while the risk for gestational diabetes mellitus remains similar between the two conditions. Additionally, MAFLD is associated with an increased likelihood of delivering large-for-gestational-age infants and heightened risks of preterm birth and low birth weight. Current treatment strategies for MAFLD focus on lifestyle modifications, such as dietary adjustments and increased physical activity. However, there is an urgent need for the development of safe and effective pharmacological treatments, particularly tailored toward pregnant women. Future research should delve deeper into the causal relationships between MAFLD and pregnancy complications and explore optimal therapeutic approaches to improve outcomes for mothers and their infants.
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Affiliation(s)
- Yang Zhang
- Department of Clinical Nutrition, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Yifan Bu
- Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
| | - Rui Zhao
- Department of General Surgery, Unit 1, The Sixth People’s Hospital of Shenyang, 85 Heping S Ave, Shenyang 110001, China
| | - Cheng Han
- Department of Clinical Nutrition, Affiliated Zhongshan Hospital of Dalian University, #6 Jiefang Road, Dalian 116001, China
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11
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Dayanand Y, Pather R, Xulu N, Booysen I, Sibiya N, Khathi A, Ngubane P. Exploring the Biological Effects of Anti-Diabetic Vanadium Compounds in the Liver, Heart and Brain. Diabetes Metab Syndr Obes 2024; 17:3267-3278. [PMID: 39247428 PMCID: PMC11380877 DOI: 10.2147/dmso.s417700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Accepted: 08/21/2023] [Indexed: 09/10/2024] Open
Abstract
The prevalence of diabetes mellitus and diabetes-related complications is rapidly increasing worldwide, placing a substantial financial burden on healthcare systems. Approximately 537 million adults are currently diagnosed with type 1 or type 2 diabetes globally. However, interestingly, the increasing morbidity rate is primarily influenced by the effects of long-term hyperglycemia on vital organs such as the brain, the liver and the heart rather than the ability of the body to use glucose effectively. This can be attributed to the summation of the detrimental effects of excessive glucose on major vascular systems and the harmful side effects attributed to the current treatment associated with managing the disease. These drugs have been implicated in the onset and progression of cardiovascular disease, hepatocyte injury and cognitive dysfunction, thereby warranting extensive research into alternative treatment strategies. Literature has shown significant progress in utilizing metal-based compounds, specifically those containing transition metals such as zinc, magnesium and vanadium, in managing hyperglycaemia. Amongst these metals, research carried out on vanadium reflected the most promising anti-diabetic efficacy in cell culture and animal studies. This was attributed to the ability to improve glucose management in the bloodstream by enhancing its uptake and metabolism in the kidney, brain, skeletal muscle, heart and liver. Despite this, organic vanadium was considered toxic due to its accumulative characteristics. To alleviate vanadium's toxic nature while subsequently manipulating its therapeutic properties, vanadium complexes were synthesized using either vanadate or vanadyl as a base compound. This review attempts to evaluate organic vanadium salts' therapeutic and toxic effects, highlight vanadium complexes' research and provide insight into the novel dioxidovanadium complex synthesized in our laboratory to alleviate hyperglycaemia-associated macrovascular complications in the brain, heart and liver.
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Affiliation(s)
- Yalka Dayanand
- School of Laboratory Medicine and Medical Science, University of Kwazulu-Natal, Durban, South Africa
| | - Reveshni Pather
- School of Laboratory Medicine and Medical Science, University of Kwazulu-Natal, Durban, South Africa
| | - Nombuso Xulu
- School of Laboratory Medicine and Medical Science, University of Kwazulu-Natal, Durban, South Africa
| | - Irvin Booysen
- School of Chemistry and Physics, University of Kwazulu-Natal, Pietermaritzburg, South Africa
| | - Ntethelelo Sibiya
- Pharmacology Division, Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa
| | - Andile Khathi
- School of Laboratory Medicine and Medical Science, University of Kwazulu-Natal, Durban, South Africa
| | - Phikelelani Ngubane
- School of Laboratory Medicine and Medical Science, University of Kwazulu-Natal, Durban, South Africa
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12
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Batta A, Hatwal J. Excess cardiovascular mortality in men with non-alcoholic fatty liver disease: A cause for concern! World J Cardiol 2024; 16:380-384. [PMID: 39086893 PMCID: PMC11287457 DOI: 10.4330/wjc.v16.i7.380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 05/25/2024] [Accepted: 06/17/2024] [Indexed: 07/23/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has emerged as the commonest cause of chronic liver disease worldwide in recent years. With time, our understanding of NAFLD has evolved from an isolated liver condition to a systemic disease with significant manifestations beyond the liver. Amongst them, cardiovascular diseases (CVDs) are the most important and clinically relevant. Recent research supports a strong independent link between NALFD and CVD beyond the shared risk factors and pathophysiology. Female sex hormones are well known to not only protect against CVD in pre-menopausal females, but also contribute to improved adipose tissue function and preventing its systemic deposition. Recent research highlights the increased risk of major adverse cardiovascular-cerebral events (MACCE) amongst male with NAFLD compared to females. Further, racial variation was observed in MACCE outcomes in NAFLD, with excess mortality in the Native Americans and Asian Pacific Islanders compared to the other races.
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Affiliation(s)
- Akash Batta
- Department of Cardiology, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India.
| | - Juniali Hatwal
- Department of Internal Medicine, Post Graduate Institute of Medical Education & Research, Chandigarh 160012, India
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13
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Zannad F, Sanyal AJ, Butler J, Ferreira JP, Girerd N, Miller V, Pandey A, Parikh CR, Ratziu V, Younossi ZM, Harrison SA. MASLD and MASH at the crossroads of hepatology trials and cardiorenal metabolic trials. J Intern Med 2024; 296:24-38. [PMID: 38738988 DOI: 10.1111/joim.13793] [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: 05/14/2024]
Abstract
Steatotic liver disease (SLD) is a worldwide public health problem, causing considerable morbidity and mortality. Patients with SLD are at increased risk for major adverse cardiovascular (CV) events, type 2 diabetes mellitus and chronic kidney disease. Conversely, patients with cardiometabolic conditions have a high prevalence of SLD. In addition to epidemiological evidence linking many of these conditions, there is evidence of shared pathophysiological processes. In December 2022, a unique multi-stakeholder, multi-specialty meeting, called MOSAIC (Metabolic multi Organ Science Accelerating Innovation in Clinical Trials) was convened to foster collaboration across metabolic, hepatology, nephrology and CV disorders. One of the goals of the meeting was to consider approaches to drug development that would speed regulatory approval of treatments for multiple disorders by combining liver and cardiorenal endpoints within a single study. Non-invasive tests, including biomarkers and imaging, are needed in hepatic and cardiorenal trials. They can be used as trial endpoints, to enrich trial populations, to diagnose and risk stratify patients and to assess treatment efficacy and safety. Although they are used in proof of concept and phase 2 trials, they are often not acceptable for regulatory approval of therapies. The challenge is defining the optimal combination of biomarkers, imaging and morbidity/mortality outcomes and ensuring that they are included in future trials while minimizing the burden on patients, trialists and trial sponsors. This paper provides an overview of some of the wide array of CV, liver and kidney measurements that were discussed at the MOSAIC meeting.
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Affiliation(s)
- Faiez Zannad
- Université de Lorraine, Inserm Clinical Investigation Center at Institut Lorrain du Coeur et des Vaisseaux, University Hospital of Nancy, Nancy, France
| | - Arun J Sanyal
- Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Javed Butler
- Baylor Scott and White Research Institute, Dallas, Texas, USA
- University of Mississippi, Jackson, Mississippi, USA
| | - João Pedro Ferreira
- UnIC@RISE, Cardiovascular Research and Development Center, Department Surgery Physiology, University of Porto, Porto, Portugal
- Centre d'Investigations Cliniques Plurithématique 1433, INSERM, Université de Lorraine, Nancy, France
- F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), INSERM U1116, Centre Hospitalier Régional Universitaire de Nancy, Nancy, France
| | - Nicolas Girerd
- Université de Lorraine, Centre d'Investigation Clinique-Plurithématique, CHRU Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France
| | - Veronica Miller
- Forum for Collaborative Research, Washington, District of Columbia, USA
- University of California Berkeley School of Public Health, Berkeley, California, USA
| | | | - Chirag R Parikh
- Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Vlad Ratziu
- Sorbonne Université, Hôpital Pitié-Salpêtrière, Institute for Cardiometabolism and Nutrition, INSERM UMRS, Paris, France
| | | | - Stephen A Harrison
- Visiting Professor of Hepatology Radcliffe Department of Medicine, University of Oxford, Oxford, UK
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Castillo-Núñez Y, Almeda-Valdes P, González-Gálvez G, Arechavaleta-Granell MDR. Metabolic dysfunction-associated steatotic liver disease and atherosclerosis. Curr Diab Rep 2024; 24:158-166. [PMID: 38700793 DOI: 10.1007/s11892-024-01542-6] [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] [Accepted: 04/22/2024] [Indexed: 06/22/2024]
Abstract
PURPOSE OF REVIEW To update information about the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and atherosclerosis. This review emphasizes the potential mechanisms linking MASLD with atherosclerosis and the possible causal relationships between these conditions. RECENT FINDINGS An increased risk of cardiovascular disease is related to MASLD. Several molecular, cellular, and metabolic mechanisms have been described to explain the development of atherothrombosis in MASLD patients. These include atherogenic dyslipidemia, low-grade vascular inflammation, endothelial dysfunction, foam cell formation, proliferation of vascular smooth muscle cells, insulin resistance, gut microbiota dysbiosis, activation of renin-angiotensin and sympathetic nervous systems, hypercoagulability, and decreased fibrinolysis. Also, there is recent evidence suggesting an association between genetically driven liver fat and coronary heart disease mediated by the causal effect of apoB-containing lipoproteins. Several meta-analyses and systematic reviews have reported a strong association between MASLD and cardiovascular outcomes. MASLD is an important and independent risk factor for atherosclerosis development. Multiple mechanisms may be involved in this association. Further research is required to establish a causal association between MASLD and atherosclerosis.
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Affiliation(s)
- Yulino Castillo-Núñez
- Department of Endocrinology, Hospital Dr. Salvador B. Gautier, Santo Domingo, Dominican Republic.
| | - Paloma Almeda-Valdes
- Endocrinology and Metabolism Department, Metabolic Diseases Research Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
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Ziółkiewicz A, Niziński P, Soja J, Oniszczuk T, Combrzyński M, Kondracka A, Oniszczuk A. Potential of Chlorogenic Acid in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Animal Studies and Clinical Trials-A Narrative Review. Metabolites 2024; 14:346. [PMID: 38921480 PMCID: PMC11205996 DOI: 10.3390/metabo14060346] [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: 05/27/2024] [Revised: 06/17/2024] [Accepted: 06/19/2024] [Indexed: 06/27/2024] Open
Abstract
Chlorogenic acid (CGA) is a natural polyphenol found in coffee, tea, vegetables, and fruits. It exhibits strong antioxidant activity and possesses several other biological properties, including anti-inflammatory effects, antimicrobial activity, and insulin-sensitizing properties. Moreover, it may improve lipid and glucose metabolism. This review summarizes the available information on the therapeutic effect of CGA in metabolic dysfunction-associated steatotic liver disease (MASLD). As the literature search engine, the browsers in the PubMed, Scopus, Web of Science databases, and ClinicalTrials.gov register were used. Animal trials and clinical studies suggest that CGA has promising therapeutic potential in treating MASLD and hepatic steatosis. Its mechanisms of action include antioxidant, anti-inflammatory, and anti-apoptotic effects via the activation of the Nrf2 signaling pathway and the inhibition of the TLR4/NF-κB signaling cascade. Furthermore, the alleviation of liver disease by CGA also involves other important molecules such as AMPK and important physiological processes such as the intestinal barrier and gut microbiota. Nevertheless, the specific target cell and key molecule to which CGA is directed remain unidentified and require further study.
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Affiliation(s)
- Agnieszka Ziółkiewicz
- Department of Inorganic Chemistry, Medical University of Lublin, Dr Witolda Chodźki 4a, 20-093 Lublin, Poland; (A.Z.); (A.O.)
| | - Przemysław Niziński
- Department of Pharmacology, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
| | - Jakub Soja
- Department of Thermal Technology and Food Process Engineering, University of Life Sciences in Lublin, Głęboka 31, 20-612 Lublin, Poland; (J.S.); (T.O.); (M.C.)
| | - Tomasz Oniszczuk
- Department of Thermal Technology and Food Process Engineering, University of Life Sciences in Lublin, Głęboka 31, 20-612 Lublin, Poland; (J.S.); (T.O.); (M.C.)
| | - Maciej Combrzyński
- Department of Thermal Technology and Food Process Engineering, University of Life Sciences in Lublin, Głęboka 31, 20-612 Lublin, Poland; (J.S.); (T.O.); (M.C.)
| | - Adrianna Kondracka
- Department of Obstetrics and Pathology of Pregnancy, Medical University of Lublin, 20-081 Lublin, Poland;
| | - Anna Oniszczuk
- Department of Inorganic Chemistry, Medical University of Lublin, Dr Witolda Chodźki 4a, 20-093 Lublin, Poland; (A.Z.); (A.O.)
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16
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Meddeb M, Koleini N, Jun S, Keykhaei M, Farshidfar F, Zhao L, Kwon S, Lin B, Keceli G, Paolocci N, Hahn V, Sharma K, Pearce EL, Kass DA. ATP Citrate Lyase Supports Cardiac Function and NAD+/NADH Balance And Is Depressed in Human Heart Failure. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.06.09.598152. [PMID: 38915649 PMCID: PMC11195057 DOI: 10.1101/2024.06.09.598152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/26/2024]
Abstract
BACKGROUND ATP-citrate lyase (ACLY) converts citrate into acetyl-CoA and oxaloacetate in the cytosol. It plays a prominent role in lipogenesis and fat accumulation coupled to excess glucose, and its inhibition is approved for treating hyperlipidemia. In RNAseq analysis of human failing myocardium, we found ACLY gene expression is reduced; however the impact this might have on cardiac function and/or metabolism has not been previously studied. As new ACLY inhibitors are in development for cancer and other disorders, such understanding has added importance. METHODS Cardiomyocytes, ex-vivo beating hearts, and in vivo hearts with ACLY inhibited by selective pharmacologic (BMS303141, ACLYi) or genetic suppression, were studied. Regulation of ACLY gene/protein expression, and effects of ACLYi on function, cytotoxicity, tricarboxylic acid (TCA)-cycle metabolism, and redox and NAD+/NADH balance were assessed. Mice with cardiac ACLY knockdown induced by AAV9-acly-shRNA or cardiomyocyte tamoxifen-inducible Acly knockdown were studied. RESULTS Acly gene expression was reduced more in obese patients with heart failure and preserved EF (HFpEF) than HF with reduced EF. In vivo pressure-overload and in vitro hormonal stress increased ACLY protein expression, whereas it declined upon fatty-acid exposure. Acute ACLYi (1-hr) dose-dependently induced cytotoxicity in adult and neonatal cardiomyocytes, and caused substantial reduction of systolic and diastolic function in myocytes and ex-vivo beating hearts. In the latter, ATP/ADP ratio also fell and lactate increased. U13C-glucose tracing revealed an ACLYdependent TCA-bypass circuit in myocytes, where citrate generated in mitochondria is transported to the cytosol, metabolized by ACLY and then converted to malate to re-enter mitochondria,bypassing several NADH-generating steps. ACLYi lowered NAD+/NADH ratio and restoring this balance ameliorated cardiomyocyte toxicity. Oxidative stress was undetected with ACLYi. Adult hearts following 8-weeks of reduced cardiac and/or cardiomyocyte ACLY downregulation exhibited ventricular dilation and reduced function that was prevented by NAD augmentation. Cardiac dysfunction from ACLY knockdown was worse in hearts subjected to sustained pressureoverload, supporting a role in stress responses. CONCLUSIONS ACLY supports normal cardiac function through maintenance of the NAD+/NADH balance and is upregulated by hemodynamic and hormonal stress, but depressed by lipid excess. ACLY levels are most reduced in human HFpEF with obesity potentially worsening cardio-metabolic reserve.
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Linero PL, Castilla-Guerra L. Management of Cardiovascular Risk in the Non-alcoholic Fatty Liver Disease Setting. Eur Cardiol 2024; 19:e02. [PMID: 38807854 PMCID: PMC11131151 DOI: 10.15420/ecr.2023.19] [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: 04/12/2023] [Accepted: 10/02/2023] [Indexed: 05/30/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an overlooked and undetected pathology, which affects more than 32% of adults worldwide. NAFLD is becoming more common in Western industrialised countries, particularly in patients with central obesity, type 2 diabetes, dyslipidaemia and metabolic syndrome. Although NAFLD has traditionally been interpreted as a liver disease with a high risk of liver-related complications, NAFLD is an underappreciated and independent risk factor for atherosclerotic cardiovascular disease, which is the principal cause of death in patients with NAFLD. Treatment options to counteract both the progression and development of cardiovascular disease and NAFLD include lifestyle interventions, such as weight loss, increased physical activity and dietary modification, and optimal medical therapy of comorbid conditions; nevertheless, further studies are needed to define optimal treatment strategies for the prevention of both hepatic and cardiovascular complications of NAFLD.
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Affiliation(s)
- Paula Luque Linero
- Vascular Risk Unit, Department of Internal Medicine, Hospital Virgen MacarenaSeville, Spain
| | - Luis Castilla-Guerra
- Vascular Risk Unit, Department of Internal Medicine, Hospital Virgen MacarenaSeville, Spain
- Department of Medicine, University of SevilleSeville, Spain
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18
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Badmus OO, da Silva AA, Li X, Taylor LC, Greer JR, Wasson AR, McGowan KE, Patel PR, Stec DE. Cardiac lipotoxicity and fibrosis underlie impaired contractility in a mouse model of metabolic dysfunction-associated steatotic liver disease. FASEB Bioadv 2024; 6:131-142. [PMID: 38706754 PMCID: PMC11069051 DOI: 10.1096/fba.2023-00139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 02/20/2024] [Accepted: 02/23/2024] [Indexed: 05/07/2024] Open
Abstract
The leading cause of death among patients with metabolic dysfunction-associated steatotic liver disease (MASLD) is cardiovascular disease. A significant percentage of MASLD patients develop heart failure driven by functional and structural alterations in the heart. Previously, we observed cardiac dysfunction in hepatocyte-specific peroxisome proliferator-activated receptor alpha knockout (Ppara HepKO), a mouse model that exhibits hepatic steatosis independent of obesity and insulin resistance. The goal of the present study was to determine mechanisms that underlie hepatic steatosis-induced cardiac dysfunction in Ppara HepKO mice. Experiments were performed in 30-week-old Ppara HepKO and littermate control mice fed regular chow. We observed decreased cardiomyocyte contractility (0.17 ± 0.02 vs. 0.24 ± 0.02 μm, p < 0.05), increased cardiac triglyceride content (0.96 ± 0.13 vs. 0.68 ± 0.06 mM, p < 0.05), collagen type 1 (4.65 ± 0.25 vs. 0.31 ± 0.01 AU, p < 0.001), and collagen type 3 deposition (1.32 ± 0.46 vs. 0.05 ± 0.03 AU, p < 0.05). These changes were associated with increased apoptosis as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining (30.9 ± 4.7 vs. 13.1 ± 0.8%, p < 0.006) and western blots showing increased cleaved caspase-3 (0.27 ± 0.006 vs. 0.08 ± 0.01 AU, p < 0.003) and pro-caspase-3 (5.4 ± 1.5 vs. 0.5 ± 0.3 AU, p < 0.02), B-cell lymphoma protein 2-associated X (0.68 ± 0.07 vs. 0.04 ± 0.04 AU, p < 0.001), and reduced B-cell lymphoma protein 2 (0.29 ± 0.01 vs. 1.47 ± 0.54 AU, p < 0.05). We further observed elevated circulating natriuretic peptides and exercise intolerance in Ppara HepKO mice when compared to controls. Our data demonstrated that lipotoxicity, and fibrosis underlie cardiac dysfunction in MASLD.
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Affiliation(s)
- Olufunto O. Badmus
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Alexandre A. da Silva
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Xuan Li
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Lucy C. Taylor
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Jennifer R. Greer
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Andrew R. Wasson
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Karis E. McGowan
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - Parth R. Patel
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
| | - David E. Stec
- Department of Physiology & Biophysics, Cardiorenal, and Metabolic Diseases Research Center, Cardiovascular‐Renal Research CenterUniversity of Mississippi Medical CenterJacksonMississippiUSA
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19
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Li Y, Liu Y. Adherence to an antioxidant diet and lifestyle is associated with reduced risk of cardiovascular disease and mortality among adults with nonalcoholic fatty liver disease: evidence from NHANES 1999-2018. Front Nutr 2024; 11:1361567. [PMID: 38650637 PMCID: PMC11033446 DOI: 10.3389/fnut.2024.1361567] [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: 12/26/2023] [Accepted: 03/27/2024] [Indexed: 04/25/2024] Open
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) stands a prevalent chronic liver condition significantly influenced by oxidative stress. We investigated the unclear relationship between antioxidant-rich diet and lifestyle and cardiovascular disease (CVD) prevalence rate and mortality in adult patients with NAFLD. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHAENS) spanning from 1999 to 2018 to investigate the association between adherence to an antioxidant-rich diet and lifestyle and the cardiovascular disease (CVD) prevalence rate and mortality in adult patients with NAFLD. The study employed the Oxidative Balance Score (OBS) to define antioxidant diet and lifestyle. Results Including 8,670 adult patients with NAFLD, the study revealed an inverse association between OBS and the prevalence of most CVD conditions. Fully adjusted models demonstrated that each unit increase in diet OBS, lifestyle OBS, and overall OBS corresponded to a 2, 7, and 2% reduction in all-cause mortality, respectively. In models 2, findings revealed that lifestyle Q2 and Q3 were linked to reduced cancer mortality, whereas diet and overall OBS did not exhibit an association. Additionally, Stratified analysis revealed that age (<45 years) and education level (> high school) significantly influenced the association between the OBS and the prevalence of CVD. Conclusion These results underscore the protective link between adherence to an antioxidant diet and lifestyle and a diminished prevalence of CVD and mortality in adults with NAFLD, particularly among younger and higher-educated populations.
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Affiliation(s)
| | - Yipin Liu
- Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China
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20
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Lee ECZ, Anand VV, Razavi AC, Alebna PL, Muthiah MD, Siddiqui MS, Chew NWS, Mehta A. The Global Epidemic of Metabolic Fatty Liver Disease. Curr Cardiol Rep 2024; 26:199-210. [PMID: 38376745 DOI: 10.1007/s11886-024-02025-6] [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] [Accepted: 01/22/2024] [Indexed: 02/21/2024]
Abstract
PURPOSE OF REVIEW The objective of this manuscript is to examine the current literature on the epidemiology of metabolic dysfunction-associated steatotic liver disease (MASLD), its correlation with cardiovascular disease (CVD) outcomes, as well as to evaluate the update in nomenclature from non-alcoholic liver disease (NAFLD). RECENT FINDINGS The update of diagnostic criteria from NAFLD to MASLD reduces the stigma associated with alcohol consumption and poor health choices. It also shines a light on the crucial role of cardiometabolic risk factors in disease pathophysiology. The incidence and prevalence of MASLD are projected to increase significantly in the future as the population burden of cardiometabolic risk factors rises. MASLD is also a potent risk factor for developing CVD that should be tackled by using a multi-disciplinary team with a holistic approach. As the new nomenclature for metabolic liver disease is adopted on a global scale, more research is needed to investigate the applicability of findings from previous trials focusing on NAFLD. It is anticipated that the epidemic of MASLD will continue to increase globally, hence the urgent need for therapeutic approaches to reverse this trend.
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Affiliation(s)
- Ethan C Z Lee
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Vickram V Anand
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Alex C Razavi
- Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
| | - Pamela L Alebna
- VCU Health Pauley Heart Center, Virginia Commonwealth University School of Medicine, 1200 East Broad Street, PO Box 980036, Richmond, VA, 23298, USA
| | - Mark D Muthiah
- Division of Gastroenterology & Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Mohammad S Siddiqui
- Stravitz-Sanyal Institute of Liver Disease and Metabolic Health, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Nicholas W S Chew
- Department of Cardiology, National University Heart Centre, National University Health System, Singapore, Singapore
| | - Anurag Mehta
- VCU Health Pauley Heart Center, Virginia Commonwealth University School of Medicine, 1200 East Broad Street, PO Box 980036, Richmond, VA, 23298, USA.
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21
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Desai R, Alvi AT, Vasavada A, Pulakurthi YS, Patel B, Mohammed AS, Doshi S, Ogbu I. Sex and racial disparities in non-alcoholic fatty liver disease-related cardiovascular events: National inpatient sample analysis (2019). World J Cardiol 2024; 16:137-148. [PMID: 38576521 PMCID: PMC10989223 DOI: 10.4330/wjc.v16.i3.137] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Revised: 01/15/2024] [Accepted: 02/18/2024] [Indexed: 03/21/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) increases cardiovascular disease (CVD) risk irrespective of other risk factors. However, large-scale cardiovascular sex and race differences are poorly understood. AIM To investigate the relationship between NAFLD and major cardiovascular and cerebrovascular events (MACCE) in subgroups using a nationally representative United States inpatient sample. METHODS We examined National Inpatient Sample (2019) to identify adult hospitalizations with NAFLD by age, sex, and race using ICD-10-CM codes. Clinical and demographic characteristics, comorbidities, and MACCE-related mortality, acute myocardial infarction (AMI), cardiac arrest, and stroke were compared in NAFLD cohorts by sex and race. Multivariable regression analyses were adjusted for sociodemographic characteristics, hospitalization features, and comorbidities. RESULTS We examined 409130 hospitalizations [median 55 (IQR 43-66) years] with NFALD. NAFLD was more common in females (1.2%), Hispanics (2%), and Native Americans (1.9%) than whites. Females often reported non-elective admissions, Medicare enrolment, the median age of 55 (IQR 42-67), and poor income. Females had higher obesity and uncomplicated diabetes but lower hypertension, hyperlipidemia, and complicated diabetes than males. Hispanics had a median age of 48 (IQR 37-60), were Medicaid enrollees, and had non-elective admissions. Hispanics had greater diabetes and obesity rates than whites but lower hypertension and hyperlipidemia. MACCE, all-cause mortality, AMI, cardiac arrest, and stroke were all greater in elderly individuals (P < 0.001). MACCE, AMI, and cardiac arrest were more common in men (P < 0.001). Native Americans (aOR 1.64) and Asian Pacific Islanders (aOR 1.18) had higher all-cause death risks than whites. CONCLUSION Increasing age and male sex link NAFLD with adverse MACCE outcomes; Native Americans and Asian Pacific Islanders face higher mortality, highlighting a need for tailored interventions and care.
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Affiliation(s)
- Rupak Desai
- Independent Researcher, Atlanta, GA 30079, United States
| | - Ali Tariq Alvi
- Department of Internal Medicine, HCA Florida Westside Hospital, Plantation, FL 33324, United States
| | - Advait Vasavada
- Department of Internal Medicine, M.P. Shah Medical Coll, Jamnagar 361008, India
| | | | - Bhavin Patel
- Department of Internal Medicine, Trinity Health Oakland Hospital, Pontiac, MI 48341, United States
| | - Adil Sarvar Mohammed
- Department of Internal Medicine, Central Michigan University College of Medicine, Saginaw, MI 48602, United States
| | - Shreyans Doshi
- Department of Internal Medicine, UCF College of Medicine HCA GME Consortium, Gainesville, FL 32605, United States
| | - Ikechukwu Ogbu
- Department of Internal Medicine, Mountainview Hospital, Las Vegas, NV 89108, United States.
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22
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Al Hashmi K, Giglio RV, Pantea Stoian A, Patti AM, Al Waili K, Al Rasadi K, Ciaccio M, Rizzo M. Metabolic dysfunction-associated fatty liver disease: current therapeutic strategies. Front Nutr 2024; 11:1355732. [PMID: 38567250 PMCID: PMC10985255 DOI: 10.3389/fnut.2024.1355732] [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: 12/14/2023] [Accepted: 03/11/2024] [Indexed: 04/04/2024] Open
Abstract
The definition of "Metabolic Associated Fatty Liver Disease - MAFLD" has replaced the previous definition of Nonalcoholic Fatty Liver Disease (NAFLD), because cardiometabolic criteria have been added for the prevention of cardiological risk in these patients. This definition leads to an in-depth study of the bidirectional relationships between hepatic steatosis, Type 2 Diabetes Mellitus (T2DM), Cardiovascular Disease (CVD) and/or their complications. Lifestyle modification, which includes correct nutrition combined with regular physical activity, represents the therapeutic cornerstone of MAFLD. When therapy is required, there is not clear accord on how to proceed in an optimal way with nutraceutical or pharmacological therapy. Numerous studies have attempted to identify nutraceuticals with a significant benefit on metabolic alterations and which contribute to the improvement of hepatic steatosis. Several evidences are supporting the use of silymarin, berberine, curcumin, Nigella sativa, Ascophyllum nodosum, and Fucus vesiculosus, vitamin E, coenzyme Q10 and Omega-3. However, more evidence regarding the long-term efficacy and safety of these compounds are required. There is numerous evidence that highlights the use of therapies such as incretins or the use of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors or other similar therapies which, by assisting existing therapies for pathologies such as diabetes, hypertension, insulin resistance, have given a breakthrough in prevention and the reduction of cardiometabolic risk. This review gave an overview of the current therapeutic strategies that are expected to aid in the treatment and prevention of MAFLD.
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Affiliation(s)
- Khamis Al Hashmi
- Department of Physiology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
| | - Rosaria Vincenza Giglio
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy
- Department of Laboratory Medicine, University Hospital, Palermo, Italy
| | - Anca Pantea Stoian
- Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Angelo Maria Patti
- Internal Medicine Unit, “Vittorio Emanuele II” Hospital, Castelvetrano, Italy
| | - Khalid Al Waili
- Department of Biochemistry, Sultan Qaboos University Hospital, Muscat, Oman
| | - Khalid Al Rasadi
- Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
- Medical Research Center, Sultan Qaboos University, Muscat, Oman
| | - Marcello Ciaccio
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy
- Department of Laboratory Medicine, University Hospital, Palermo, Italy
| | - Manfredi Rizzo
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
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Rafaqat S, Gluscevic S, Mercantepe F, Rafaqat S, Klisic A. Interleukins: Pathogenesis in Non-Alcoholic Fatty Liver Disease. Metabolites 2024; 14:153. [PMID: 38535313 PMCID: PMC10972081 DOI: 10.3390/metabo14030153] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 02/23/2024] [Accepted: 03/01/2024] [Indexed: 07/26/2024] Open
Abstract
Inflammatory cytokines have been implicated as crucial contributors to the onset and progression of non-alcoholic fatty liver disease (NAFLD). The exact mechanisms by which interleukins (ILs) contribute to NAFLD may vary, and ongoing research is aimed at understanding the specific roles of different ILs in the pathogenesis of this condition. In addition, variations in environmental factors and genetics in each individual can influence the onset and/or progression of NAFLD. The lack of clinical studies related to the potential therapeutic properties of IL-1 inhibitors currently does not allow us to conclude their validity as a therapeutic option, although preclinical studies show promising results. Further studies are needed to elucidate their beneficial properties in NAFLD treatment.
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Affiliation(s)
- Saira Rafaqat
- Department of Zoology, Lahore College for Women University, Lahore 54600, Pakistan
| | - Sanja Gluscevic
- Clinical Center of Montenegro, Department for Neurology, 81000 Podgorica, Montenegro
| | - Filiz Mercantepe
- Department of Endocrinology and Metabolism, Faculty of Medicine, Recep Tayyip Erdogan University, 53010 Rize, Turkey
| | - Sana Rafaqat
- Department of Biotechnology (Human Genetics), Lahore College for Women University, Lahore 54600, Pakistan
| | - Aleksandra Klisic
- Faculty of Medicine, University of Montenegro, 81000 Podgorica, Montenegro
- Center for Laboratory Diagnostics, Primary Health Care Center, 81000 Podgorica, Montenegro
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24
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Tarantino G, Citro V. Could Adverse Effects of Antibiotics Due to Their Use/Misuse Be Linked to Some Mechanisms Related to Nonalcoholic Fatty Liver Disease? Int J Mol Sci 2024; 25:1993. [PMID: 38396671 PMCID: PMC10888279 DOI: 10.3390/ijms25041993] [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: 01/12/2024] [Revised: 01/31/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
Nonalcoholic fatty liver disease, recently re-named metabolic dysfunction-associated steatotic fatty liver disease, is considered the most prevalent liver disease worldwide. Its molecular initiation events are multiple and not always well-defined, comprising insulin resistance, chronic low-grade inflammation, gut dysbiosis, and mitochondrial dysfunction, all of them acting on genetic and epigenetic grounds. Nowadays, there is a growing public health threat, which is antibiotic excessive use and misuse. This widespread use of antibiotics not only in humans, but also in animals has led to the presence of residues in derived foods, such as milk and dairy products. Furthermore, antibiotics have been used for many decades to control certain bacterial diseases in high-value fruit and vegetables. Recently, it has been emphasised that antibiotic-induced changes in microbial composition reduce microbial diversity and alter the functional attributes of the microbiota. These antibiotic residues impact human gut flora, setting in motion a chain of events that leads straight to various metabolic alterations that can ultimately contribute to the onset and progression of NAFLD.
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Affiliation(s)
- Giovanni Tarantino
- Department of Clinical Medicine and Surgery, Medical School of Naples, Federico II University, 80131 Naples, Italy
| | - Vincenzo Citro
- Department of General Medicine, Umberto I Hospital, Nocera Inferiore (SA), 84014 Nocera Inferiore, Italy;
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25
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Maurotti S, Pujia R, Ferro Y, Mare R, Russo R, Coppola A, Gazzaruso C, Montalcini T, Pujia A, Paone S, Mollace V, Mazza E. A nutraceutical with Citrus bergamia and Cynara cardunculus improves endothelial function in adults with non-alcoholic fatty liver disease. Nutrition 2024; 118:112294. [PMID: 38042043 DOI: 10.1016/j.nut.2023.112294] [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: 07/03/2023] [Revised: 10/27/2023] [Accepted: 10/30/2023] [Indexed: 12/04/2023]
Abstract
OBJECTIVE Polyphenol intake may prevent hepatic steatosis and cardiovascular disease by potentially improving endothelial function. The purposes of this study are to investigate the association between fatty liver disease and endothelial dysfunction and to test the effects of a nutraceutical containing extracts made from Citrus bergamia and Cynara cardunculus on peripheral vascular endothelial function in adults with liver steatosis. METHODS We analyzed data from 32 individuals with hepatic steatosis and endothelial dysfunction (reactive hyperemia index ≤ 1.67). Sixteen subjects took 1 capsule/d (300 mg/d) containing Cynara cardunculus extract and bergamot polyphenol fraction, while the other 16 subjects matched for age, sex, and body mass index took 1 capsule/d of placebo (maltodextrin) for 12 wk. All anthropometric parameters were assessed at baseline and after 12 wk as were lipids, glucose, and reactive hyperemia index using an EndoPAT 2000. RESULTS The mean age was 52 ± 9 y. The mean reactive hyperemia index was 1.15 ± 0.4. After 12 wk, we found a greater increase in reactive hyperemia index in the participants taking the nutraceutical rather than placebo (0.58 ± 0.5 versus 0.13 ± 0.5; P = 0.02, respectively). The stepwise multivariable analysis confirmed a positive association between reactive hyperemia index change and the nutraceutical treatment (B = 0.38; P = 0.025) and negative association with reactive hyperemia index values at baseline (B = -0.81; P < 0.001). No association was found between the reduction in the amount of intrahepatic fat and the improvement of endothelial function (B = 0.002; P = 0.56). CONCLUSIONS A nutraceutical containing bergamot and artichoke extracts improves peripheral vascular endothelial function in adults with hepatic steatosis and early phase of atherosclerosis.
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Affiliation(s)
- Samantha Maurotti
- Department of Clinical and Experimental Medicine, Magna Græcia University of Catanzaro, Catanzaro, Italy
| | - Roberta Pujia
- Department of Medical and Surgical Sciences, Magna Græcia University of Catanzaro, Catanzaro, Italy
| | - Yvelise Ferro
- Department of Medical and Surgical Sciences, Magna Græcia University of Catanzaro, Catanzaro, Italy.
| | - Rosario Mare
- Department of Medical and Surgical Sciences, Magna Græcia University of Catanzaro, Catanzaro, Italy
| | - Raffaella Russo
- Department of Medical and Surgical Sciences, Magna Græcia University of Catanzaro, Catanzaro, Italy
| | - Adriana Coppola
- Diabetes and Endocrine-Metabolic Diseases Unit, Istituto Clinico Beato Matteo, Gruppo Ospedaliero San Donato, Vigevano, Italy
| | - Carmine Gazzaruso
- Diabetes and Endocrine-Metabolic Diseases Unit, Istituto Clinico Beato Matteo, Gruppo Ospedaliero San Donato, Vigevano, Italy; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | - Tiziana Montalcini
- Department of Clinical and Experimental Medicine, Magna Græcia University of Catanzaro, Catanzaro, Italy; Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), Magna Græcia University of Catanzaro, Catanzaro, Italy
| | - Arturo Pujia
- Department of Medical and Surgical Sciences, Magna Græcia University of Catanzaro, Catanzaro, Italy; Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), Magna Græcia University of Catanzaro, Catanzaro, Italy
| | - Sara Paone
- Institute of Research for Food Safety & Health, Department of Health Sciences, Magna Græcia University of Catanzaro, Catanzaro, Italy
| | - Vincenzo Mollace
- Institute of Research for Food Safety & Health, Department of Health Sciences, Magna Græcia University of Catanzaro, Catanzaro, Italy
| | - Elisa Mazza
- Department of Medical and Surgical Sciences, Magna Græcia University of Catanzaro, Catanzaro, Italy
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26
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Barazesh M, Jalili S, Akhzari M, Faraji F, Khorramdin E. Recent Progresses on Pathophysiology, Diagnosis, Therapeutic Modalities,
and Management of Non-alcoholic Fatty Liver Disorder. CURRENT DRUG THERAPY 2024; 19:20-48. [DOI: 10.2174/1574885518666230417111247] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 01/30/2023] [Accepted: 02/06/2023] [Indexed: 01/03/2025]
Abstract
Abstract:
Non-alcoholic fatty liver disease (NAFLD) is currently the utmost common chronic liver
disorder that happens through all age groups and is identified to occur in 14%-30% of the general
population, demonstrating a critical and grossing clinical issue because of the growing incidence of
obesity and overweight. From the histological aspect, it looks like alcoholic liver damage, but it happens in patients who avoid remarkable alcohol usage. NAFLD comprises a broad spectrum, ranging
from benign hepatocellular steatosis to inflammatory nonalcoholic steatohepatitis (NASH), different
levels of fibrosis, and cirrhosis. Patients with NASH are more susceptible to more rapid progression to
cirrhosis and hepatocellular carcinoma. There is no single factor that drives proceeding from simple
steatosis to NASH. However, a combination of multi parameters such as genetic background, gut microflora, intake of high fat/ fructose dietary contents or methionine/choline-deficient diet, and consequently accumulated hepatocellular lipids mainly including triglycerides and also other bio-analytes,
such as free fatty acids, cholesterol, and phospholipids display a crucial role in disease promotion.
NAFLD is related to overweight and insulin resistance (IR) and is regarded as the hepatic presentation
of the metabolic syndrome, an amalgamation of medical statuses such as hyperlipidemia, hypertension, type 2 diabetes, and visceral obesity. Despite the increasing prevalence of this disease, which
imposes a remarkable clinical burden, most affected patients remain undiagnosed in a timely manner,
largely related to the asymptomatic entity of NAFLD patients and the unavailability of accurate and
efficient noninvasive diagnostic tests. However, liver biopsy is considered a gold standard for NAFLD
diagnosis, but due to being expensive and invasiveness is inappropriate for periodic disease screening.
Some noninvasive monitoring approaches have been established recently for NAFLD assessment. In
addition to the problem of correct disease course prediction, no effective therapeutic modalities are
approved for disease treatment. Imaging techniques can commonly validate the screening and discrimination of NAFLD; nevertheless, staging the disease needs a liver biopsy. The present therapeutic approaches depend on weight loss, sports activities, and dietary modifications, although different insulin-sensitizing drugs, antioxidants, and therapeutic agents seem hopeful. This review aims to focus on
the current knowledge concerning epidemiology, pathogenesis, and different biochemical experiments
and imaging modalities applied to diagnose the different grades of NAFLD and its management, as
well as new data about pharmacological therapies for this disorder.
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Affiliation(s)
- Mahdi Barazesh
- School of Paramedical, Gerash University of Medical Sciences, Gerash, Iran
| | - Sajad Jalili
- Department of Orthopedics, School of
Medicine, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran
| | - Morteza Akhzari
- School of Nursing, Larestan University of
Medical Sciences, Larestan, Iran
| | - Fouzieyeh Faraji
- School of Paramedical, Gerash University of Medical Sciences, Gerash, Iran
| | - Ebrahim Khorramdin
- Department of Orthopedics, School of
Medicine, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran
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Pezzino S, Luca T, Castorina M, Puleo S, Latteri S, Castorina S. Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines. Life (Basel) 2024; 14:93. [PMID: 38255708 PMCID: PMC10820028 DOI: 10.3390/life14010093] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 01/04/2024] [Accepted: 01/05/2024] [Indexed: 01/24/2024] Open
Abstract
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, making it one of the most prevalent chronic liver disorders. MASLD encompasses a range of liver pathologies, from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) with inflammation, hepatocyte damage, and fibrosis. Interestingly, the liver exhibits close intercommunication with fatty tissue. In fact, adipose tissue could contribute to the etiology and advancement of MASLD, acting as an endocrine organ that releases several hormones and cytokines, with the adipokines assuming a pivotal role. The levels of adipokines in the blood are altered in people with MASLD, and recent research has shed light on the crucial role played by adipokines in regulating energy expenditure, inflammation, and fibrosis in MASLD. However, MASLD disease is a multifaceted condition that affects various aspects of health beyond liver function, including its impact on hemostasis. The alterations in coagulation mechanisms and endothelial and platelet functions may play a role in the increased vulnerability and severity of MASLD. Therefore, more attention is being given to imbalanced adipokines as causative agents in causing disturbances in hemostasis in MASLD. Metabolic inflammation and hepatic injury are fundamental components of MASLD, and the interrelation between these biological components and the hemostasis pathway is delineated by reciprocal influences, as well as the induction of alterations. Adipokines have the potential to serve as the shared elements within this complex interrelationship. The objective of this review is to thoroughly examine the existing scientific knowledge on the impairment of hemostasis in MASLD and its connection with adipokines, with the aim of enhancing our comprehension of the disease.
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Affiliation(s)
- Salvatore Pezzino
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
| | - Tonia Luca
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
- Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy;
| | | | - Stefano Puleo
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
| | - Saverio Latteri
- Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy;
| | - Sergio Castorina
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
- Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy;
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Charlton M, Tonnu-Mihara I, Teng CC, Zhou Z, Asefaha F, Luthra R, Hoovler A, Uzoigwe C. The clinical and economic burdens of metabolic dysfunction-associated steatohepatitis. J Med Econ 2024; 27:919-930. [PMID: 38953706 DOI: 10.1080/13696998.2024.2374642] [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: 05/03/2024] [Accepted: 06/27/2024] [Indexed: 07/04/2024]
Abstract
AIMS This study aimed to assess and compare the health care resource utilization (HCRU) and medical cost of metabolic dysfunction-associated steatohepatitis (MASH) by disease severity based on Fibrosis-4 Index (FIB-4) score among US adults in a real-world setting. MATERIALS AND METHODS This observational cohort study used claims data from the Healthcare Integrated Research Database (HIRD) to compare all-cause, cardiovascular (CV)-related, and liver-related HCRU, including hospitalization, and medical costs stratified by FIB-4 score among patients with MASH (identified by International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] code K75.81). Hospitalization and medical costs were compared by FIB-4 score using generalized linear regression with negative binomial and gamma distribution models, respectively, while controlling for confounders. RESULTS The cohort included a total of 5,104 patients with MASH and comprised 3,162, 1,343, and 599 patients with low, indeterminate, and high FIB-4 scores, respectively. All-cause hospitalization was significantly higher in the high FIB-4 cohort when compared with the low FIB-4 reference after covariate adjustment (rate ratio, 1.63; 95% CI, 1.32-2.02; p < .0001). CV-related hospitalization was similar across all cohorts; however, CV-related costs were 1.26 times higher (95% CI, 1.11-1.45; p < .001) in the indeterminate cohort and 2.15 times higher (95% CI, 1.77-2.62; p < .0001) in the high FIB-4 cohort when compared with the low FIB-4 cohort. Patients with indeterminate and high FIB-4 scores had 2.97 (95% CI, 1.78-4.95) and 12.08 (95% CI, 7.35-19.88) times the rate of liver-related hospitalization and were 3.68 (95% CI, 3.11-4.34) and 33.73 (95% CI, 27.39-41.55) times more likely to incur liver-related costs, respectively (p < .0001 for all). LIMITATIONS This claims-based analysis relied on diagnostic coding accuracy, which may not capture the presence of all diseases or all care received. CONCLUSIONS High and indeterminate FIB-4 scores were associated with significantly higher liver-related clinical and economic burdens than low FIB-4 scores among patients with MASH.
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Affiliation(s)
| | | | - Chia-Chen Teng
- Department of Research, Carelon Research, Wilmington, DE, USA
| | - Ziqi Zhou
- Department of Research, Carelon Research, Wilmington, DE, USA
| | | | - Rakesh Luthra
- Health Economics and Outcomes Research, Novo Nordisk Inc, Plainsboro, NJ, USA
| | | | - Chioma Uzoigwe
- Real World Evidence, Novo Nordisk Inc, Plainsboro, NJ, USA
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Lei P, Lü J, Yao T, Zhang P, Chai X, Wang Y, Jiang M. Verbascoside exerts an anti-atherosclerotic effect by regulating liver glycerophospholipid metabolism. FOOD SCIENCE AND HUMAN WELLNESS 2023. [DOI: 10.1016/j.fshw.2023.03.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
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30
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Huang S, Shi K, Li Y, Wang J, Jiang L, Gao Y, Yan WF, Shen LT, Yang ZG. Effect of Metabolic Dysfunction-Associated Fatty Liver Disease on Left Ventricular Deformation and Atrioventricular Coupling in Patients With Metabolic Syndrome Assessed by MRI. J Magn Reson Imaging 2023; 58:1098-1107. [PMID: 36591962 DOI: 10.1002/jmri.28588] [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: 11/05/2022] [Revised: 12/22/2022] [Accepted: 12/23/2022] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) was recently recognized as an important risk factor for cardiovascular diseases. PURPOSE To examine the effect of MAFLD on cardiac function in metabolic syndrome by MRI. STUDY TYPE Retrospective. POPULATION One hundred seventy-nine patients with metabolic syndrome (MetS), 101 with MAFLD (MAFLD [+]) and 78 without (MAFLD [-]). Eighty-one adults without any of the components of MetS or cardiac abnormalities were included as control group. FIELD STRENGTH/SEQUENCE 3.0 T; balanced steady-state free precession sequence. ASSESSMENT Left atrial (LA) strain was assessed during three phases: reservoir strain (LA-RS), conduit strain (LA-CS), and booster strain (LA-BS). Left ventricular (LV) global longitudinal (LV-GLS) strain was also derived. The left atrioventricular coupling index (LACI) was calculated as the ratio of LA end-diastolic volume (LA-EDV) and LV-EDV. STATISTICAL TESTS Student's t test or Mann-Whitney U test; One-way analysis of variance. A P value <0.05 was considered statistically significant. RESULTS Among MetS patients, individuals with MAFLD had significantly lower magnitude LV-GLS (-11.6% ± 3.3% vs. -13.8% ± 2.7%) than those without MAFLD. For LA strains, LA-RS (36.9% ± 13.7% vs. 42.9% ± 13.5%) and LA-CS (20.0% ± 10.6% vs. 24.1% ± 9.2%) were also significantly reduced in MAFLD (+) compared to MAFLD (-). The LACIs (17.2% [12.9-21.2] % vs. 15.8% [12.2-19.7] %) were significantly higher in patients with MAFLD compared to those without MAFLD. After adjustment for other clinical factors, MAFLD was found to be independently correlated with LV-GLS (β = -0.270) and LACI (β = 0.260). DATA CONCLUSION MAFLD had an unfavorable effect on LV myocardial strain in MetS. Moreover, LA strain and atrioventricular coupling were further impaired in patients with concomitant MAFLD compared to those without MAFLD. Last, MAFLD was independently associated with subclinical LV dysfunction and atrioventricular coupling after adjustment for other clinical factors. EVIDENCE LEVEL 3 TECHNICAL EFFICACY: 3.
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Affiliation(s)
- Shan Huang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ke Shi
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yuan Li
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jin Wang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Li Jiang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yue Gao
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Wei-Feng Yan
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Li-Ting Shen
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zhi-Gang Yang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Yang K, Song M. New Insights into the Pathogenesis of Metabolic-Associated Fatty Liver Disease (MAFLD): Gut-Liver-Heart Crosstalk. Nutrients 2023; 15:3970. [PMID: 37764755 PMCID: PMC10534946 DOI: 10.3390/nu15183970] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 09/11/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
Metabolism-associated fatty liver disease (MAFLD) is a multifaceted disease that involves complex interactions between various organs, including the gut and heart. It is defined by hepatic lipid accumulation and is related to metabolic dysfunction, obesity, and diabetes. Understanding the intricate interplay of the gut-liver-heart crosstalk is crucial for unraveling the complexities of MAFLD and developing effective treatment and prevention strategies. The gut-liver crosstalk participates in the regulation of the metabolic and inflammatory processes through host-microbiome interactions. Gut microbiota have been associated with the development and progression of MAFLD, and its dysbiosis contributes to insulin resistance, inflammation, and oxidative stress. Metabolites derived from the gut microbiota enter the systemic circulation and influence both the liver and heart, resulting in the gut-liver-heart axis playing an important role in MAFLD. Furthermore, growing evidence suggests that insulin resistance, endothelial dysfunction, and systemic inflammation in MAFLD may contribute to an increased risk of cardiovascular disease (CVD). Additionally, the dysregulation of lipid metabolism in MAFLD may also lead to cardiac dysfunction and heart failure. Overall, the crosstalk between the liver and heart involves a complex interplay of molecular pathways that contribute to the development of CVD in patients with MAFLD. This review emphasizes the current understanding of the gut-liver-heart crosstalk as a foundation for optimizing patient outcomes with MAFLD.
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Affiliation(s)
| | - Myeongjun Song
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
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Yao Y, Shen Y. Cross-talk between gut microbiota and liver steatosis: Complications and therapeutic target. Open Life Sci 2023; 18:20220699. [PMID: 37671098 PMCID: PMC10476486 DOI: 10.1515/biol-2022-0699] [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: 03/22/2023] [Revised: 07/11/2023] [Accepted: 07/30/2023] [Indexed: 09/07/2023] Open
Abstract
Liver steatosis is the most widespread chronic liver condition. Its global incidence is rising swiftly and is currently estimated to be 24%. Liver steatosis is strongly related with numerous metabolic syndrome characteristics, like obesity, insulin resistance, hyperlipidemia, and hypertension. The gastrointestinal tract contains about 100 trillion commensal organisms and more than 7,000 distinct bacterial strains. Fat deposition in the liver without secondary causes is known as liver steatosis. Dysregulation of the gut flora is one of the factors connected to the onset of fatty liver disease. Dietary choices may alter constitution of the microbiome and cause gut microbiome dysbiosis, particularly due to the intake of food high in fructose sugars, animal products, and saturated fats. Various gut bacteria cause nutrient metabolism in multiple ways, setting off different inflammatory cascades that encourage liver disease and pathways that help fat build up in the liver. Due to their relatively stable nature, genetic factors may not be responsible for the constant increase in liver steatosis incidence. Genetic factors set the stage for liver steatosis pathogenesis. This review will offer an overview of our present knowledge of the roles played by gut microbiota in regulating the development of liver steatosis, potential side effects, and potential treatment targets.
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Affiliation(s)
- Yuan Yao
- Department of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- The Queen Mary School, Nanchang University, Nanchang, Jiangxi 330031, China
| | - Yunfeng Shen
- Department of Endocrinology and Metabolism, Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, The Second Affiliated Hospital of Nanchang University, 330006, Nanchang, China
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Bourcigaux N, Dubost E, Buzzi JC, Donadille B, Corpechot C, Poujol-Robert A, Christin-Maitre S. Focus on Liver Function Abnormalities in Patients With Turner Syndrome: Risk Factors and Evaluation of Fibrosis Risk. J Clin Endocrinol Metab 2023; 108:2255-2261. [PMID: 36896592 DOI: 10.1210/clinem/dgad108] [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: 09/26/2022] [Revised: 02/07/2023] [Accepted: 02/22/2023] [Indexed: 03/11/2023]
Abstract
CONTEXT Liver function abnormalities (LFAs) have been described in patients with Turner syndrome (TS). Although a high risk of cirrhosis has been reported, there is a need to assess the severity of liver damage in a large cohort of adult patients with TS. OBJECTIVE Evaluate the types of LFAs and their respective prevalence, search for their risk factors, and evaluate the severity of liver impairment by using a noninvasive fibrosis marker. METHODS This was a monocentric retrospective cross-sectional study. Data were collected during a day hospital visit. The main outcome measures were liver enzymes (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase), FIB-4 score, liver ultrasound imaging, elastography, and liver biopsies, when available. RESULTS 264 patients with TS were evaluated at a mean age of 31.15 ± 11.48 years. The overall prevalence of LFAs was 42.8%. The risk factors were age, body mass index, insulin resistance, and an X isochromosome (Xq). The mean FIB-4 sore of the entire cohort was 0.67 ± 0.41. Less than 10% of patients were at risk of developing fibrosis. Cirrhosis was observed in 2/19 liver biopsies. There was no significant difference in the prevalence of LFAs between premenopausal patients with natural cycles and those receiving hormone replacement therapy (P = .063). A multivariate analysis adjusted for age showed no statistically significant correlation between hormone replacement therapy and abnormal gamma-glutamyl transferase levels (P = .12). CONCLUSION Patients with TS have a high prevalence of LFA. However, 10% are at high risk of developing fibrosis. The FIB-4 score is useful and should be part of the routine screening strategy. Longitudinal studies and better interactions with hepatologists should improve our knowledge of liver disease in patients with TS.
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Affiliation(s)
- Nathalie Bourcigaux
- Endocrine and Reproductive Medicine Unit, Center of Rare Endocrine Diseases of Growth and Development (CMERCD), FIRENDO, Endo ERN Hôpital Saint-Antoine, Sorbonne University, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France
| | - Emma Dubost
- Endocrine and Reproductive Medicine Unit, Center of Rare Endocrine Diseases of Growth and Development (CMERCD), FIRENDO, Endo ERN Hôpital Saint-Antoine, Sorbonne University, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France
| | - Jean-Claude Buzzi
- Medical Information Department, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France
| | - Bruno Donadille
- Endocrine and Reproductive Medicine Unit, Center of Rare Endocrine Diseases of Growth and Development (CMERCD), FIRENDO, Endo ERN Hôpital Saint-Antoine, Sorbonne University, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France
| | - Christophe Corpechot
- Department of Hepatology, Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (MIVB-H), French Network for Rare Liver Diseases in Children and Adults FILFOIE, European Reference Network (ERN) RARE-LIVER, Saint-Antoine Hospital & Research Center, Assistance Publique-Hôpitaux de Paris (APHP), Inserm & Sorbonne University, 75011 Paris, France
- Inserm Unité mixte de Recherche (UMR)933, 75011 Paris, France
| | - Armelle Poujol-Robert
- Department of Hepatology, Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (MIVB-H), French Network for Rare Liver Diseases in Children and Adults FILFOIE, European Reference Network (ERN) RARE-LIVER, Saint-Antoine Hospital & Research Center, Assistance Publique-Hôpitaux de Paris (APHP), Inserm & Sorbonne University, 75011 Paris, France
| | - Sophie Christin-Maitre
- Endocrine and Reproductive Medicine Unit, Center of Rare Endocrine Diseases of Growth and Development (CMERCD), FIRENDO, Endo ERN Hôpital Saint-Antoine, Sorbonne University, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France
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Zhou XD, Targher G, Byrne CD, Somers V, Kim SU, Chahal CAA, Wong VWS, Cai J, Shapiro MD, Eslam M, Steg PG, Sung KC, Misra A, Li JJ, Brotons C, Huang Y, Papatheodoridis GV, Sun A, Yilmaz Y, Chan WK, Huang H, Méndez-Sánchez N, Alqahtani SA, Cortez-Pinto H, Lip GYH, de Knegt RJ, Ocama P, Romero-Gomez M, Fudim M, Sebastiani G, Son JW, Ryan JD, Ikonomidis I, Treeprasertsuk S, Pastori D, Lupsor-Platon M, Tilg H, Ghazinyan H, Boursier J, Hamaguchi M, Nguyen MH, Fan JG, Goh GBB, Al Mahtab M, Hamid S, Perera N, George J, Zheng MH. An international multidisciplinary consensus statement on MAFLD and the risk of CVD. Hepatol Int 2023; 17:773-791. [PMID: 37204656 PMCID: PMC10198034 DOI: 10.1007/s12072-023-10543-8] [Citation(s) in RCA: 58] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Accepted: 04/18/2023] [Indexed: 05/20/2023]
Abstract
BACKGROUND Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25-30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists. METHODS AND RESULTS A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management. CONCULSIONS The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research.
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Affiliation(s)
- Xiao-Dong Zhou
- Department of Cardiovascular Medicine, The Heart Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Giovanni Targher
- Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, University of Verona, Verona, Italy
| | - Christopher D Byrne
- Southampton National Institute for Health and Care Research Biomedical Research Centre, University Hospital Southampton, and University of Southampton, Southampton General Hospital, Southampton, UK
| | - Virend Somers
- Department of Cardiovascular Medicine, Mayo Clinic College of Medicine, Rochester, USA
| | - Seung Up Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - C Anwar A Chahal
- Department of Cardiovascular Medicine, Mayo Clinic College of Medicine, Rochester, USA
- Center for Inherited Cardiovascular Diseases, WellSpan Health, Lancaster, PA, USA
- Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS Trust, London, EC1A 7BE, West Smithfield, UK
| | - Vincent Wai-Sun Wong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Jingjing Cai
- Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Michael D Shapiro
- Center for Prevention of Cardiovascular Disease, Section on Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, University of Sydney, Sydney, NSW, 2145, Australia
| | - Philippe Gabriel Steg
- Université Paris -Cité, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, FACT (French Alliance for Cardiovascular Trials), INSERM U1148, Paris, France
| | - Ki-Chul Sung
- Department of Internal Medicine, Division of Cardiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Anoop Misra
- Fortis C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, Chirag Enclave, National Diabetes Obesity and Cholesterol Foundation and Diabetes Foundation (India), New Delhi, India
| | - Jian-Jun Li
- State Key Laboratory of Cardiovascular Diseases, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Carlos Brotons
- Biomedical Research Institute Sant Pau (IIB Sant Pau), Sardenya Primary Health Care Center, Barcelona, Spain
| | - Yuli Huang
- Department of Cardiology, Shunde Hospital, Southern Medical University, Jiazi Road, Lunjiao Town, Shunde District, Foshan, China
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Aijun Sun
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yusuf Yilmaz
- Institute of Gastroenterology, Marmara University, Istanbul, Turkey
- Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey
| | - Wah Kheong Chan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Hui Huang
- Department of Cardiology, The Eighth Affiliated Hospital of Sun Yat-Sen University, 3025 Shennan Middle Road, Shenzhen, China
| | - Nahum Méndez-Sánchez
- Liver Research Unit, Medica Sur Clinic and Foundation and Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | - Saleh A Alqahtani
- Liver Transplantation Unit, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD, USA
| | - Helena Cortez-Pinto
- Laboratório de Nutrição e Metabolismo, Faculdade de Medicina, Clínica Universitária de Gastrenterologia, Universidade de Lisboa, Lisbon, Portugal
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, UK
- Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Gravendijkwal 230, Room Ha 206, Rotterdam, The Netherlands
| | - Ponsiano Ocama
- Department of Internal Medicine, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - Manuel Romero-Gomez
- Department of Digestive and Liver Diseases, Institute of Biomedicine of Seville, University Hospital Virgen del Rocio, University of Seville, Seville, Spain
| | - Marat Fudim
- Department of Cardiology, Duke University School of Medicine, Durham, NC, USA
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
| | - Giada Sebastiani
- Division of Gastroenterology and Hepatology, Chronic Viral Illness Service, McGill University Health Centre, Royal Victoria Hospital, 1001 Blvd. Décarie, Montreal, Canada
| | - Jang Won Son
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - John D Ryan
- Department of Hepatology, RCSI School of Medicine and Medical Sciences, Dublin/Beaumont Hospital, Dublin, Ireland
| | - Ignatios Ikonomidis
- Preventive Cardiology Laboratory and Cardiometabolic Clinic, Second Cardiology Department, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Daniele Pastori
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Monica Lupsor-Platon
- Department of Medical Imaging, "Prof. Dr. Octavian Fodor" Regional Institute of Gastroenterology and Hepathology, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University Innsbruck, Innsbruck, Austria
| | - Hasmik Ghazinyan
- Department of Hepatology, Nork Clinical Hospital of Infectious Disease, Yerevan, Armenia
| | - Jerome Boursier
- Hepato-Gastroenterology Department, University Hospital, 4 Larrey Street, 49933, Angers Cedex 09, France
- HIFIH Laboratory, UPRES 3859, SFR 4208, LUNAM University, Angers, France
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-Cho, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, Japan
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, USA
| | - Jian-Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - George Boon-Bee Goh
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore, Singapore
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Saeed Hamid
- Department of Medicine, Aga Khan University, Stadium Road, Karachi, 74800, Pakistan
| | - Nilanka Perera
- Department of Medicine, University of Sri Jayewardenepura, Nugegoda, Sri Lanka
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, University of Sydney, Sydney, NSW, 2145, Australia.
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, China.
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China.
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Masenga SK, Muchaili L, Hamooya BM. Cardiovascular Outcomes Among Persons with HIV and Nonalcoholic Fatty Liver Disease. AIDS 2023; 37:1329-1331. [PMID: 37822712 PMCID: PMC10564394 DOI: 10.1097/qad.0000000000003562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/13/2023]
Affiliation(s)
- Sepiso K. Masenga
- HAND Research group, School of Medicine and Health Sciences, Mulungushi University, Livingstone, Zambia
- School of Public Health, University of Zambia, Lusaka, Zambia
- Vanderbilt Institute for Global Health, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Lweendo Muchaili
- HAND Research group, School of Medicine and Health Sciences, Mulungushi University, Livingstone, Zambia
| | - Benson M. Hamooya
- HAND Research group, School of Medicine and Health Sciences, Mulungushi University, Livingstone, Zambia
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Rossell J, Rojo-López MI, Julve J, Mauricio D. The Bittersweet Beat: Diabetes Complications. J Clin Med 2023; 12:4018. [PMID: 37373711 DOI: 10.3390/jcm12124018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 06/09/2023] [Indexed: 06/29/2023] Open
Abstract
In this Editorial, we are focusing on a selection of articles recently published in the Journal of Clinical Medicine dealing with relevant aspects of cardiometabolic complications of diabetes mellitus [...].
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Affiliation(s)
- Joana Rossell
- Institut d'Investigació Biomèdica de l'Hospital de la Santa Creu i Sant Pau (IIB-Sant Pau), 08041 Barcelona, Spain
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08041 Barcelona, Spain
- Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
| | - Marina Idalia Rojo-López
- Institut d'Investigació Biomèdica de l'Hospital de la Santa Creu i Sant Pau (IIB-Sant Pau), 08041 Barcelona, Spain
- Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
| | - Josep Julve
- Institut d'Investigació Biomèdica de l'Hospital de la Santa Creu i Sant Pau (IIB-Sant Pau), 08041 Barcelona, Spain
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08041 Barcelona, Spain
- Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
| | - Didac Mauricio
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08041 Barcelona, Spain
- Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
- Faculty of Medicine, University of Vic/Central University of Catalonia (UVIC/UCC), 08500 Vic, Spain
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Gheorghe L, Nemteanu R, Clim A, Botnariu GE, Costache II, Plesa A. Risk Scores for Prediction of Major Cardiovascular Events in Non-Alcoholic Fatty Liver Disease: A No Man's Land? Life (Basel) 2023; 13:life13040857. [PMID: 37109386 PMCID: PMC10146692 DOI: 10.3390/life13040857] [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: 02/16/2023] [Revised: 03/18/2023] [Accepted: 03/21/2023] [Indexed: 04/29/2023] Open
Abstract
Over the past 100 years, cardiovascular disease (CVD) has become a leading cause of mortality and morbidity in developed countries, and similar trends have occurred for chronic liver disease. Subsequent research also indicated that people with non-alcoholic fatty liver disease (NAFLD) had a twofold increased risk of CV events and that this risk was doubled in those with liver fibrosis. However, no validated CVD risk score specific for NAFLD patients has yet been validated, as traditional risk scores tend to underestimate the CV risk in NAFLD patients. From a practical perspective, identifying NAFLD patients and assessing severity of liver fibrosis when concurrent atherosclerotic risk factors are already established may serve as an important criterion in new CV risk scores. The current review aims to assess current risk scores and their utility for the prediction of CV events among patients with NAFLD.
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Affiliation(s)
- Liliana Gheorghe
- Department of Radiology, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
- Radiology Clinic, "St. Spiridon" County Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Roxana Nemteanu
- Medical I Department, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, Saint Spiridon Hospital, 700111 Iasi, Romania
| | - Andreea Clim
- Medical I Department, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Gina Eosefina Botnariu
- Diabetes, Nutrition and Metabolic Diseases Department, University of Medicine and Pharmacy "Gr. T. Popa", 700115 Iasi, Romania
| | - Irina Iuliana Costache
- Medical I Department, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
- Cardiology Clinic, "St. Spiridon" County Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Alina Plesa
- Medical I Department, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, Saint Spiridon Hospital, 700111 Iasi, Romania
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From NAFLD to MAFLD: Definition, Pathophysiological Basis and Cardiovascular Implications. Biomedicines 2023; 11:biomedicines11030883. [PMID: 36979861 PMCID: PMC10046146 DOI: 10.3390/biomedicines11030883] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 02/13/2023] [Accepted: 02/28/2023] [Indexed: 03/15/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is defined as a chronic liver disease characterized by excessive fat accumulation in the liver without another obvious cause (no excessive alcohol consumption, hepatotoxic medications, toxins, viral infections, genetic hepatic diseases), therefore it is an exclusion diagnosis. The term NAFLD literally refers to non-alcohol related hepatopathy and does not adequately correlate with metabolic dysfunction and related cardiovascular risks. Therefore, researchers and scientific societies have moved towards changing the terminology. The novel nomenclature for a metabolic-associated fatty liver disease (MAFLD) has been proposed in 2020 by a group of experts to overcome the issues related to the old terminology. The diagnosis of MAFLD is based on the presence of hepatic steatosis and at least one between these three conditions: type 2 diabetes mellitus (T2DM), obesity or metabolic dysregulation. MAFLD has been shown to be an independent risk factor for cardiovascular diseases and atherosclerosis. It is better related to the main risk factors for atherosclerosis and cardiovascular diseases than NAFLD, such as dyslipidemia, T2DM and hypertension. The aim of this review is to highlight the reasons why the term NAFLD is moving to the term MAFLD, what are the conceptual basis of this choice and its clinical implications, particularly in the cardiovascular field.
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Chua D, Low ZS, Cheam GX, Ng AS, Tan NS. Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm. Int J Mol Sci 2022; 23:14762. [PMID: 36499091 PMCID: PMC9737809 DOI: 10.3390/ijms232314762] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 11/15/2022] [Accepted: 11/23/2022] [Indexed: 11/29/2022] Open
Abstract
Fatty liver disease is an emerging contributor to disease burden worldwide. The past decades of work established the heterogeneous nature of non-alcoholic fatty liver disease (NAFLD) etiology and systemic contributions to the pathogenesis of the disease. This called for the proposal of a redefinition in 2020 to that of metabolic dysfunction-associated fatty liver disease (MAFLD) to better reflect the current understanding of the disease. To date, several clinical cohort studies comparing NAFLD and MAFLD hint at the relevancy of the new nomenclature in enriching for patients with more severe hepatic injury and extrahepatic comorbidities. However, the underlying systemic pathogenesis is still not fully understood. Preclinical animal models have been imperative in elucidating key biological mechanisms in various contexts, including intrahepatic disease progression, interorgan crosstalk and systemic dysregulation. Furthermore, they are integral in developing novel therapeutics against MAFLD. However, substantial contextual variabilities exist across different models due to the lack of standardization in several aspects. As such, it is crucial to understand the strengths and weaknesses of existing models to better align them to the human condition. In this review, we consolidate the implications arising from the change in nomenclature and summarize MAFLD pathogenesis. Subsequently, we provide an updated evaluation of existing MAFLD preclinical models in alignment with the new definitions and perspectives to improve their translational relevance.
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Affiliation(s)
- Damien Chua
- Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 11 Mandalay Road, Singapore 308232, Singapore
| | - Zun Siong Low
- Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 11 Mandalay Road, Singapore 308232, Singapore
| | - Guo Xiang Cheam
- School of Biological Sciences, Nanyang Technological University Singapore, 60 Nanyang Drive, Singapore 637551, Singapore
| | - Aik Seng Ng
- Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK
| | - Nguan Soon Tan
- Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 11 Mandalay Road, Singapore 308232, Singapore
- School of Biological Sciences, Nanyang Technological University Singapore, 60 Nanyang Drive, Singapore 637551, Singapore
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Abebe G, Ayanaw D, Ayelgn Mengstie T, Dessie G, Malik T. Assessment of fatty liver and its correlation with glycemic control in patients with type 2 diabetes mellitus attending Dessie Comprehensive Specialized Hospital, Northeast Ethiopia. SAGE Open Med 2022; 10:20503121221124762. [PMID: 36161212 PMCID: PMC9490463 DOI: 10.1177/20503121221124762] [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: 04/02/2022] [Accepted: 08/16/2022] [Indexed: 11/16/2022] Open
Abstract
Objectives: The purpose of conducting this study was to assess fatty liver disease and its correlation with glycemic control in type 2 diabetes mellitus patients. In addition, evaluation of associated factors and correlation analysis between the fatty liver index and hemoglobin A1C level in patients with type 2 diabetes mellitus was another aim of this study. Methods: A hospital-based cross-sectional study was conducted among type 2 diabetes mellitus patients attending at diabetes clinic of Dessie Comprehensive Specialized Hospital located in south Wollo, Ethiopia. It was conducted from July to August 2021. The fatty liver index was calculated to assess fatty liver disease. Simple descriptive statistics, multivariate analysis, and an independent sample t-test were utilized for statistical analysis. Multiple logistic regression analysis was used to determine the associated factors of fatty liver. The p value < 0.05 was considered as statistically significant. Results: In this study, the mean ± standard deviation values of body mass index among type 2 diabetes mellitus patients were 25.82 ± 3.64, 28.04 ± 2.43, and 22.70 ± 2.62 in both fatty and non-fatty liver cases, respectively. In this study, the prevalence of fatty liver among type 2 diabetes mellitus patients was 58.4%. There was a significant positive correlation between the level of Hemoglobin A1C or glycated hemoglobin and fatty liver index (p value = 0.008, r = 0.35). The development of fatty liver was 4.6 times more likely among patients with type 2 diabetes mellitus who had insufficient physical exercise than sufficient exercise. Patients with insulin and oral hypoglycemic drugs were 0.8 folds less likely to have a fatty liver as compared to oral hypoglycemic drug treatment. Conclusion: The results of this study showed that the prevalence of non-alcoholic fatty liver disease was elevated among patients with type 2 diabetes mellitus who had higher levels of body mass index, waist circumference, triglycerides, glycated hemoglobin, and gamma-glutamyltransferase. Therefore, glycemic control, sufficient physical exercise, and insulin treatment may reduce the risk of fatty liver disease in patients with type 2 diabetes mellitus.
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Affiliation(s)
- Gashaw Abebe
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
| | - Daniel Ayanaw
- Department of Internal Medicine, School of Medicine, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
| | - Tiget Ayelgn Mengstie
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Gashaw Dessie
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Tabarak Malik
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
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Nasiri-Ansari N, Androutsakos T, Flessa CM, Kyrou I, Siasos G, Randeva HS, Kassi E, Papavassiliou AG. Endothelial Cell Dysfunction and Nonalcoholic Fatty Liver Disease (NAFLD): A Concise Review. Cells 2022; 11:2511. [PMID: 36010588 PMCID: PMC9407007 DOI: 10.3390/cells11162511] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 08/07/2022] [Accepted: 08/10/2022] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. It is strongly associated with obesity, type 2 diabetes (T2DM), and other metabolic syndrome features. Reflecting the underlying pathogenesis and the cardiometabolic disorders associated with NAFLD, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has recently been proposed. Indeed, over the past few years, growing evidence supports a strong correlation between NAFLD and increased cardiovascular disease (CVD) risk, independent of the presence of diabetes, hypertension, and obesity. This implies that NAFLD may also be directly involved in the pathogenesis of CVD. Notably, liver sinusoidal endothelial cell (LSEC) dysfunction appears to be implicated in the progression of NAFLD via numerous mechanisms, including the regulation of the inflammatory process, hepatic stellate activation, augmented vascular resistance, and the distortion of microcirculation, resulting in the progression of NAFLD. Vice versa, the liver secretes inflammatory molecules that are considered pro-atherogenic and may contribute to vascular endothelial dysfunction, resulting in atherosclerosis and CVD. In this review, we provide current evidence supporting the role of endothelial cell dysfunction in the pathogenesis of NAFLD and NAFLD-associated atherosclerosis. Endothelial cells could thus represent a "golden target" for the development of new treatment strategies for NAFLD and its comorbid CVD.
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Affiliation(s)
- Narjes Nasiri-Ansari
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Theodoros Androutsakos
- Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Christina-Maria Flessa
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
| | - Ioannis Kyrou
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Laboratory of Dietetics and Quality of Life, Department of Food Science and Human Nutrition, School of Food and Nutritional Sciences, Agricultural University of Athens, 11855 Athens, Greece
| | - Gerasimos Siasos
- Third Department of Cardiology, ‘Sotiria’ Thoracic Diseases General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Harpal S. Randeva
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
| | - Eva Kassi
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
- Endocrine Unit, 1st Department of Propaedeutic Internal Medicine, ‘Laiko’ General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Athanasios G. Papavassiliou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
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Chen Y, Ma L, Ge Z, Pan Y, Xie L. Key Genes Associated With Non-Alcoholic Fatty Liver Disease and Polycystic Ovary Syndrome. Front Mol Biosci 2022; 9:888194. [PMID: 35693550 PMCID: PMC9174783 DOI: 10.3389/fmolb.2022.888194] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 04/25/2022] [Indexed: 11/13/2022] Open
Abstract
Background: Polycystic ovary syndrome (PCOS) is the most common metabolic and endocrinopathies disorder in women of reproductive age and non-alcoholic fatty liver (NAFLD) is one of the most common liver diseases worldwide. Previous research has indicated potential associations between PCOS and NAFLD, but the underlying pathophysiology is still not clear. The present study aims to identify the differentially expressed genes (DEGs) between PCOS and NAFLD through the bioinformatics method, and explore the associated molecular mechanisms. Methods: The microarray datasets GSE34526 and GSE63067 were downloaded from Gene Expression Omnibus (GEO) database and analyzed to obtain the DEGs between PCOS and NAFLD with the GEO2R online tool. Next, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the DEGs were performed. Then, the protein-protein interaction (PPI) network was constructed and the hub genes were identified using the STRING database and Cytoscape software. Finally, NetworkAnalyst was used to construct the network between the targeted microRNAs (miRNAs) and the hub genes. Results: A total of 52 genes were identified as DEGs in the above two datasets. GO and KEGG enrichment analysis indicated that DEGs are mostly enriched in immunity and inflammation related pathways. In addition, nine hub genes, including TREM1, S100A9, FPR1, NCF2, FCER1G, CCR1, S100A12, MMP9, and IL1RN were selected from the PPI network by using the cytoHubba and MCODE plug-in. Then, four miRNAs, including miR-20a-5p, miR-129-2-3p, miR-124-3p, and miR-101-3p, were predicted as possibly the key miRNAs through the miRNA-gene network construction. Conclusion: In summary, we firstly constructed a miRNA-gene regulatory network depicting interactions between the predicted miRNA and the hub genes in NAFLD and PCOS, which provides novel insights into the identification of potential biomarkers and valuable therapeutic leads for PCOS and NAFLD.
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Affiliation(s)
- Yong Chen
- Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Leikai Ma
- Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zhouling Ge
- Department of Respiratory Medicine, The Third Affiliated Hospital of Shanghai University (Wenzhou People’s Hospital), Wenzhou, China
| | - Yizhao Pan
- Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Lubin Xie
- Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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Tao ZY, Zeng J. Role of non-alcoholic fatty liver disease in development of cardiovascular disease. Shijie Huaren Xiaohua Zazhi 2022; 30:136-139. [DOI: 10.11569/wcjd.v30.i3.136] [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] [Indexed: 02/06/2023] Open
Abstract
With the improvement of the economic level and changes in dietary structure and lifestyle, the incidence of non-alcoholic fatty liver disease (NAFLD) has been increasing. It has gradually become the main cause of chronic liver diseases in the world. Cardiovascular disease (CVD) is the main cause of death in NAFLD patients, and more and more studies have found that there is a correlation between the two conditions. NAFLD patients are at greater risk of developing CVD than normal patients. Associated mechanisms may be related to dysfunction of blood vessels and endothelial cells, bile acid metabolism, oxidative stress, systemic inflammation, and activation of the renin-angiotensin system. Among them, metabolic syndrome plays an important role. Therefore, early identification of cardiovascular disease-related risk factors in NAFLD patients and thereby reducing cardiovascular-related complications are essential to improve the prognosis of those patients.
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Affiliation(s)
- Zheng-Yu Tao
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Jing Zeng
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
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Garbuzenko DV. Pathophysiological mechanisms of cardiovascular disorders in non-alcoholic fatty liver disease. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2022; 15:194-203. [PMID: 36311966 PMCID: PMC9589137 DOI: 10.22037/ghfbb.v15i3.2549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 07/12/2022] [Indexed: 12/02/2022]
Abstract
Non-alcoholic fatty liver disease is one of the main liver diseases worldwide. The most common cause of death in patients with non-alcoholic fatty liver disease is cardiovascular disease. The relationship between these two conditions has been well established. Indeed, identical reasons may contribute to the development of cardiovascular disease and non-alcoholic fatty liver disease with lifestyle factors such as smoking, sedentariness, poor nutritional habits, and physical inactivity being major aspects. This review focuses on potential pathophysiological mechanisms of cardiovascular disorders in non-alcoholic fatty liver. PubMed, EMBASE, Orphanet, MIDLINE, Google Scholar, and Cochrane Library were searched for articles published between 2006 and 2022. Relevant articles were selected using the following terms: "Non-alcoholic fatty liver disease," "Сardiovascular diseases," "Pathophysiological mechanisms." The reference lists of all identified articles were searched for other relevant publications as well. The pathophysiological mechanisms of cardiovascular disorders in non-alcoholic fatty liver remain largely speculative and may include systemic low-grade inflammation, atherogenic dyslipidemia, abnormal glucose metabolism and hepatic insulin resistance, endothelial dysfunction, gut dysbiosis, as well as the associated cardiac remodeling, which are influenced by interindividual genetic and epigenetic variations. It is clear that the identification of pathophysiological mechanisms underlying cardiovascular disorders in non-alcoholic fatty liver disease will make the selection of therapeutic measures more optimal and effective.
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Schattenberg JM, Anstee QM, Caussy C, Bugianesi E, Popovic B. Differences between current clinical guidelines for screening, diagnosis and management of nonalcoholic fatty liver disease and real-world practice: a targeted literature review. Expert Rev Gastroenterol Hepatol 2021; 15:1253-1266. [PMID: 34493137 DOI: 10.1080/17474124.2021.1974295] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and is associated with obesity and metabolic comorbidities. Liver steatosis can progress to nonalcoholic steatohepatitis (NASH) exhibiting a relevant risk of fibrosis and ultimately liver failure. To date, no approved treatment for NASH to reduce its clinical and humanistic burden has been developed. AREAS COVERED We undertook a literature review to identify English language, national and international clinical guidelines for NAFLD regarding diagnosis, assessment and management, and determined their points of agreement and difference. Additionally, we investigated published literature relating to real-world management of NAFLD and NASH. EXPERT OPINION National (China, England/Wales, Italy, the USA) and international society (Asia-Pacific, Europe, World Gastroenterology Organization) guidelines were identified and analyzed. All guidelines addressed identifying and diagnosing subjects with likely NAFLD, as well as assessment and management of individuals with risk factors for advanced disease, including fibrosis. Real-world practice reveals widespread suboptimal awareness and implementation of guidelines. In the absence of proven therapeutics, such gaps risk failure to recognize patients in need of specialist care and monitoring, highlighting the need for clear, easy-to-apply care pathways to aid in reducing the clinical and humanistic burden of NAFLD and NASH.
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Affiliation(s)
- Jörn M Schattenberg
- Director of Metabolic Liver Research Program, Department of Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Quentin M Anstee
- Faculty of Medical Sciences, Chair of Experimental Hepatology, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.,Liver Disease Deputy Theme Lead, Newcastle Nihr Biomedical Research Centre, Newcastle upon Tyne Hospitals Nhs Trust, Newcastle upon Tyne, UK
| | - Cyrielle Caussy
- Associate Professor, Département Endocrinologie, Diabète Et Nutrition, Hospices Civils De Lyon, Hôpital Lyon Sud, Lyon, France
| | - Elisabetta Bugianesi
- Department of Medical Sciences, Division of Gastroenterology, Deputy Director and Scientific Director, University of Torino, Torino, Italy
| | - Branko Popovic
- Global Medical Lead Digestive Health, Consumer Healthcare, Medical Affairs, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany
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Gutiérrez-Cuevas J, Santos A, Armendariz-Borunda J. Pathophysiological Molecular Mechanisms of Obesity: A Link between MAFLD and NASH with Cardiovascular Diseases. Int J Mol Sci 2021; 22:ijms222111629. [PMID: 34769060 PMCID: PMC8583943 DOI: 10.3390/ijms222111629] [Citation(s) in RCA: 127] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Obesity is now a worldwide epidemic ensuing an increase in comorbidities’ prevalence, such as insulin resistance, type 2 diabetes (T2D), metabolic dysfunction-associated fatty liver disease (MAFLD), nonalcoholic steatohepatitis (NASH), hypertension, cardiovascular disease (CVD), autoimmune diseases, and some cancers, CVD being one of the main causes of death in the world. Several studies provide evidence for an association between MAFLD and atherosclerosis and cardio-metabolic disorders, including CVDs such as coronary heart disease and stroke. Therefore, the combination of MAFLD/NASH is associated with vascular risk and CVD progression, but the underlying mechanisms linking MAFLD/NASH and CVD are still under investigation. Several underlying mechanisms may probably be involved, including hepatic/systemic insulin resistance, atherogenic dyslipidemia, hypertension, as well as pro-atherogenic, pro-coagulant, and pro-inflammatory mediators released from the steatotic/inflamed liver. MAFLD is strongly associated with insulin resistance, which is involved in its pathogenesis and progression to NASH. Insulin resistance is a major cardiovascular risk factor in subjects without diabetes. However, T2D has been considered the most common link between MAFLD/NASH and CVD. This review summarizes the evidence linking obesity with MAFLD, NASH, and CVD, considering the pathophysiological molecular mechanisms involved in these diseases. We also discuss the association of MAFLD and NASH with the development and progression of CVD, including structural and functional cardiac alterations, and pharmacological strategies to treat MAFLD/NASH and cardiovascular prevention.
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Affiliation(s)
- Jorge Gutiérrez-Cuevas
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Guadalajara 44340, Jalisco, Mexico
- Correspondence: (J.G.-C.); (J.A.-B.); Tel.: +52-331-062-2083 (J.G.-C.); +52-333-677-8741 (J.A.-B.)
| | - Arturo Santos
- Tecnologico de Monterrey, School of Medicine and Health Sciences, Campus Guadalajara, Zapopan 45201, Jalisco, Mexico;
| | - Juan Armendariz-Borunda
- Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Guadalajara 44340, Jalisco, Mexico
- Tecnologico de Monterrey, School of Medicine and Health Sciences, Campus Guadalajara, Zapopan 45201, Jalisco, Mexico;
- Correspondence: (J.G.-C.); (J.A.-B.); Tel.: +52-331-062-2083 (J.G.-C.); +52-333-677-8741 (J.A.-B.)
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Park J, Kim G, Kim H, Lee J, Lee YB, Jin SM, Hur KY, Kim JH. The association of hepatic steatosis and fibrosis with heart failure and mortality. Cardiovasc Diabetol 2021; 20:197. [PMID: 34583706 PMCID: PMC8479901 DOI: 10.1186/s12933-021-01374-8] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 08/28/2021] [Indexed: 12/20/2022] Open
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic disease and independently affects the development of cardiovascular (CV) disease. We investigated whether hepatic steatosis and/or fibrosis are associated with the development of incident heart failure (iHF), hospitalized HF (hHF), mortality, and CV death in both the general population and HF patients. Methods We analyzed 778,739 individuals without HF and 7445 patients with pre-existing HF aged 40 to 80 years who underwent a national health check-up from January 2009 to December 2012. The presence of hepatic steatosis and advanced hepatic fibrosis was determined using cutoff values for fatty liver index (FLI) and BARD score. We evaluated the association of FLI or BARD score with the development of iHF, hHF, mortality and CV death using multivariable-adjusted Cox regression models. Results A total of 28,524 (3.7%) individuals in the general population and 1422 (19.1%) pre-existing HF patients developed iHF and hHF respectively. In the multivariable-adjusted model, participants with an FLI ≥ 60 were at increased risk for iHF (hazard ratio [HR], 95% confidence interval [CI], 1.30, 1.24–1.36), hHF (HR 1.54, 95% CI 1.44–1.66), all-cause mortality (HR 1.62, 95% CI 1.54–1.70), and CV mortality (HR 1.41 95% CI 1.22–1.63) in the general population and hHF (HR 1.26, 95% CI 1.21–1.54) and all-cause mortality (HR 1.54 95% CI 1.24–1.92) in the HF patient group compared with an FLI < 20. Among participants with NAFLD, advanced liver fibrosis was associated with increased risk for iHF, hHF, and all-cause mortality in the general population and all-cause mortality and CV mortality in the HF patient group (all p < 0.05). Conclusion Hepatic steatosis and/or advanced fibrosis as assessed by FLI and BARD score was significantly associated with the risk of HF and mortality. Supplementary Information The online version contains supplementary material available at 10.1186/s12933-021-01374-8.
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Affiliation(s)
- Jiyun Park
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Gyuri Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Hasung Kim
- Data Science Team, Hanmi Pharm. Co., Ltd., Seoul, Korea
| | - Jungkuk Lee
- Data Science Team, Hanmi Pharm. Co., Ltd., Seoul, Korea
| | - You-Bin Lee
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Sang-Man Jin
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Kyu Yeon Hur
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Jae Hyeon Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea. .,Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology, Seoul, Republic of Korea.
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Semmler G, Wernly S, Bachmayer S, Leitner I, Wernly B, Egger M, Schwenoha L, Datz L, Balcar L, Semmler M, Stickel F, Niederseer D, Aigner E, Datz C. Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)-Rather a Bystander Than a Driver of Mortality. J Clin Endocrinol Metab 2021; 106:2670-2677. [PMID: 33982065 DOI: 10.1210/clinem/dgab339] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Indexed: 12/12/2022]
Abstract
CONTEXT Recently, the novel metabolic dysfunction-associated fatty liver disease (MAFLD) definition has been introduced. OBJECTIVE To assess the relevance of MAFLD for mortality. METHODS Single-center cohort-study using colorectal cancer screening program involving 4718 subjects aged 45 to 80 who were grouped according to their body mass index (BMI) and the presence or absence of MAFLD. Mortality was compared among these groups by performing a systematic read-out of the national health insurance system, fatty liver (FL) was diagnosed using ultrasound. RESULTS Overall prevalence of FL was 47.9%: 1200 (25.4%) patients were lean (BMI < 25 kg/m2) and did not have MAFLD, 73 (1.5%) patients were lean and had nonalcoholic fatty liver disease but did not fulfill criteria for MAFLD, and 221 (4.7%) patients were lean and fulfilled criteria for MAFLD. Additionally, 1043 (22.1%) and 925 (19.6%) subjects had MAFLD with overweight (BMI 25-30 kg/m2) and obesity (BMI ≥ 30 kg/m2), respectively, while 1041 (22.1%) and 215 (4.6%) had overweight and obesity, respectively, without FL. During a median follow-up of 7.5 (interquartile range: 4.0-9.6) years, 278 deaths (5.9%) occurred. Of these, 98 (2.1%) were cancer-related, 65 (1.4%) were cardiovascular, and 17 (0.4%) were liver-related. Overall survival was similar between patient strata (after 5 years: 93.9%-98.2%) with lean MAFLD having the numerically worst survival. Although lean and overweight patients with MAFLD had a numerically worse outcome compared to their non-MAFLD counterparts, this association was driven by age and metabolic comorbidities (predominantly diabetes) rather than the presence of MAFLD. CONCLUSION Presence of MAFLD does not increase mortality in a cohort of individuals aged 45 to 80 years.
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Affiliation(s)
- Georg Semmler
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Salzburg, Austria
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Sarah Wernly
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Salzburg, Austria
| | - Sebastian Bachmayer
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Salzburg, Austria
| | - Isabella Leitner
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Salzburg, Austria
| | - Bernhard Wernly
- Second Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria
| | - Matthias Egger
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Salzburg, Austria
| | - Lena Schwenoha
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Salzburg, Austria
| | - Leonora Datz
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Salzburg, Austria
| | - Lorenz Balcar
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Salzburg, Austria
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Marie Semmler
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Salzburg, Austria
| | - Felix Stickel
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - David Niederseer
- Department of Cardiology, University Heart Center Zurich, University Hospital Zurich, Zurich, Switzerland
| | - Elmar Aigner
- First Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria
| | - Christian Datz
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Salzburg, Austria
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Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases. Int J Mol Sci 2021; 22:ijms22136949. [PMID: 34203309 PMCID: PMC8268967 DOI: 10.3390/ijms22136949] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 06/19/2021] [Accepted: 06/25/2021] [Indexed: 12/16/2022] Open
Abstract
The prevalence of NAFLD (non-alcoholic fatty liver disease) is a rapidly increasing problem, affecting a huge population around the globe. However, CVDs (cardiovascular diseases) are the most common cause of mortality in NAFLD patients. Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense LDL (low-density lipoprotein) particles, and decreased HDL-C (high-density lipoprotein cholesterol) levels, is often observed in NAFLD patients. In this review, we summarize recent genetic evidence, proving the diverse nature of metabolic pathways involved in NAFLD pathogenesis. Analysis of available genetic data suggests that the altered operation of fatty-acid β-oxidation in liver mitochondria is the key process, connecting NAFLD-mediated dyslipidemia and elevated CVD risk. In addition, we discuss several NAFLD-associated genes with documented anti-atherosclerotic or cardioprotective effects, and current pharmaceutical strategies focused on both NAFLD treatment and reduction of CVD risk.
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50
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Taniguchi K, Ikeda Y, Nagase N, Tsuji A, Kitagishi Y, Matsuda S. Implications of Gut-Brain axis in the pathogenesis of Psychiatric disorders. AIMS BIOENGINEERING 2021. [DOI: 10.3934/bioeng.2021021] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
<abstract>
<p>Psychiatric disorders may extremely impair the quality of life with patients and are important reasons of social disability. Several data have shown that psychiatric disorders are associated with an altered composition of gut microbiota. Dietary intake could determine the microbiota, which contribute to produce various metabolites of fermentation such as short chain fatty acids. Some of the metabolites could result in epigenetic alterations leading to the disease susceptibility. Epigenetic dysfunction is in fact implicated in various psychiatric and neurologic disorders. For example, it has been shown that neuroepigenetic dysregulation occurs in psychiatric disorders including schizophrenia. Several studies have demonstrated that the intestinal microbiome may influence the function of central nervous system. Furthermore, it has been proved that the alterations in the gut microbiota-composition might affect in the bidirectional communication between gut and brain. Similarly, evidences demonstrating the association between psychiatric disorders and the gut microbiota have come from preclinical studies. It is clear that an intricate symbiotic relationship might exist between host and microbe, although the practical significance of the gut microbiota has not yet to be determined. In this review, we have summarized the function of gut microbiota in main psychiatric disorders with respect to the mental health. In addition, we would like to discuss the potential mechanisms of the disorders for the practical diagnosis and future treatment by using bioengineering of microbiota and their metabolites.</p>
</abstract>
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