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Quagliariello V, Berretta M, Bisceglia I, Giacobbe I, Iovine M, Barbato M, Maurea C, Canale ML, Paccone A, Inno A, Scherillo M, Oliva S, Cadeddu Dessalvi C, Mauriello A, Fonderico C, Maratea AC, Gabrielli D, Maurea N. In the Era of Cardiovascular-Kidney-Metabolic Syndrome in Cardio-Oncology: From Pathogenesis to Prevention and Therapy. Cancers (Basel) 2025; 17:1169. [PMID: 40227756 DOI: 10.3390/cancers17071169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 03/21/2025] [Accepted: 03/27/2025] [Indexed: 04/15/2025] Open
Abstract
Cardiovascular-kidney-metabolic (CKM) syndrome represents a complex interplay between cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders, significantly impacting cancer patients. The presence of CKM syndrome in cancer patients not only worsens their prognosis but also increases the risk of major adverse cardiovascular events (MACE), reduces quality of life (QoL), and affects overall survival (OS). Furthermore, several anticancer therapies, including anthracyclines, tyrosine kinase inhibitors, immune checkpoint inhibitors, and hormonal treatments, can exacerbate CKM syndrome by inducing cardiotoxicity, nephrotoxicity, and metabolic dysregulation. This review explores the pathophysiology of CKM syndrome in cancer patients and highlights emerging therapeutic strategies to mitigate its impact. We discuss the role of novel pharmacological interventions, including sodium-glucose cotransporter-2 inhibitors (SGLT2i), proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), and soluble guanylate cyclase (sGC) activators, as well as dietary and lifestyle interventions. Optimizing the management of CKM syndrome in cancer patients is crucial to improving OS, enhancing QoL, and reducing MACE. By integrating cardiometabolic therapies into oncologic care, we can create a more comprehensive treatment approach that reduces the burden of cardiovascular and renal complications in this vulnerable population. Further research is needed to establish personalized strategies for CKM syndrome prevention and treatment in cancer patients.
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Affiliation(s)
- Vincenzo Quagliariello
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Massimiliano Berretta
- Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
| | - Irma Bisceglia
- Servizi Cardiologici Integrati, Dipartimento Cardio-Toraco-Vascolare, Azienda Ospedaliera San Camillo Forlanini, 00148 Rome, Italy
| | - Ilaria Giacobbe
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Martina Iovine
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Matteo Barbato
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Carlo Maurea
- ASL NA1, UOC Neurology and Stroke Unit, Ospedale del Mare, 23807 Naples, Italy
| | | | - Andrea Paccone
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Alessandro Inno
- Medical Oncology, IRCCS Ospedale Sacro Cuore Don Calabria, 37024 Negrar di Valpolicella, Italy
| | - Marino Scherillo
- Cardiologia Interventistica e UTIC, A.O. San Pio, Presidio Ospedaliero Gaetano Rummo, 82100 Benevento, Italy
| | - Stefano Oliva
- Cardio-Oncology Unit, IRCCS Istituto Tumori, "Giovanni Paolo II", 70124 Bari, Italy
| | | | - Alfredo Mauriello
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Celeste Fonderico
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Anna Chiara Maratea
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Domenico Gabrielli
- U.O.C. Cardiologia, Dipartimento Cardio-Toraco-Vascolare, Azienda Ospedaliera San Camillo Forlanini, 00152 Rome, Italy
| | - Nicola Maurea
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
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Lloyd AJ, Martinez-Martin MJP, Warren-Walker A, Hitchings MD, Moron-Garcia OM, Watson A, Villarreal-Ramos B, Lyons L, Wilson T, Allison G, Beckmann M. Green Tea with Rhubarb Root Reduces Plasma Lipids While Preserving Gut Microbial Stability in a Healthy Human Cohort. Metabolites 2025; 15:139. [PMID: 39997764 PMCID: PMC11857281 DOI: 10.3390/metabo15020139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 02/18/2025] [Indexed: 02/26/2025] Open
Abstract
Background/Objectives: Cardiovascular diseases remain a leading cause of mortality and morbidity, and dyslipidaemia is one of the major risk factors. The widespread use of herbs and medicinal plants in traditional medicine has garnered increasing recognition as a valuable resource for increasing wellness and reducing the onset of disease. Several epidemiologic and clinical studies have shown that altering blood lipid profiles and maintaining gut homeostasis may protect against cardiovascular diseases. Methods: A randomised, active-controlled parallel human clinical trial (n = 52) with three herbal tea infusions (green (Camellia sinensis) tea with rhubarb root, green tea with senna, and active control green tea) daily for 21 days in a free-living healthy adult cohort was conducted to assess the potential for health benefits in terms of plasma lipids and gut health. Paired plasma samples were analysed using Afinion lipid panels (total cholesterol, LDL (low-density lipoprotein) cholesterol, HDL (high-density lipoprotein) cholesterol, triglycerides, and non-HDL cholesterol) and paired stool samples were analysed using 16S rRNA amplicon sequencing to determine bacterial diversity within the gut microbiome. Results: Among participants providing fasting blood samples before and after the intervention (n = 47), consumption of herbal rhubarb root tea and green tea significantly lowered total cholesterol, LDL-cholesterol, and non-HDL cholesterol (p < 0.05) in plasma after 21 days of daily consumption when compared with concentrations before the intervention. No significant change was observed in the senna tea group. In participants providing stool samples (n = 48), no significant differences in overall microbial composition were observed between pre- and post-intervention, even at the genus level. While no significant changes in overall microbial composition were observed, specific bacterial genera, such as Dorea spp., showed correlations with LDL cholesterol concentrations, suggesting potential microbiota-mediated effects of tea consumption. Diet and BMI was maintained in each of the three groups before and after the trial. Conclusions: It was found that drinking a cup of rhubarb root herbal or green tea infusion for 21 days produced beneficial effects on lipid profiles and maintained gut eubiosis without observable adverse effects in a healthy human cohort. More studies are needed to fully understand the effects of rhubarb root and green tea in fatty acid metabolism and gut microbial composition.
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Affiliation(s)
- Amanda J. Lloyd
- Department of Life Sciences, Aberystwyth University, Aberystwyth SY23 3DA, Wales, UK; (M.P.M.-M.); (A.W.-W.); (A.W.); (B.V.-R.); (L.L.); (T.W.); (M.B.)
| | - MJ Pilar Martinez-Martin
- Department of Life Sciences, Aberystwyth University, Aberystwyth SY23 3DA, Wales, UK; (M.P.M.-M.); (A.W.-W.); (A.W.); (B.V.-R.); (L.L.); (T.W.); (M.B.)
| | - Alina Warren-Walker
- Department of Life Sciences, Aberystwyth University, Aberystwyth SY23 3DA, Wales, UK; (M.P.M.-M.); (A.W.-W.); (A.W.); (B.V.-R.); (L.L.); (T.W.); (M.B.)
| | - Matthew D. Hitchings
- Faculty of Medicine Health & Life Science, Swansea University, Swansea SA2 8QA, Wales, UK;
| | - Odin M. Moron-Garcia
- Department of Life Sciences, Aberystwyth University, Aberystwyth SY23 3DA, Wales, UK; (M.P.M.-M.); (A.W.-W.); (A.W.); (B.V.-R.); (L.L.); (T.W.); (M.B.)
| | - Alison Watson
- Department of Life Sciences, Aberystwyth University, Aberystwyth SY23 3DA, Wales, UK; (M.P.M.-M.); (A.W.-W.); (A.W.); (B.V.-R.); (L.L.); (T.W.); (M.B.)
| | - Bernardo Villarreal-Ramos
- Department of Life Sciences, Aberystwyth University, Aberystwyth SY23 3DA, Wales, UK; (M.P.M.-M.); (A.W.-W.); (A.W.); (B.V.-R.); (L.L.); (T.W.); (M.B.)
| | - Laura Lyons
- Department of Life Sciences, Aberystwyth University, Aberystwyth SY23 3DA, Wales, UK; (M.P.M.-M.); (A.W.-W.); (A.W.); (B.V.-R.); (L.L.); (T.W.); (M.B.)
| | - Thomas Wilson
- Department of Life Sciences, Aberystwyth University, Aberystwyth SY23 3DA, Wales, UK; (M.P.M.-M.); (A.W.-W.); (A.W.); (B.V.-R.); (L.L.); (T.W.); (M.B.)
| | - Gordon Allison
- Institute of Biology, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3EB, Wales, UK;
| | - Manfred Beckmann
- Department of Life Sciences, Aberystwyth University, Aberystwyth SY23 3DA, Wales, UK; (M.P.M.-M.); (A.W.-W.); (A.W.); (B.V.-R.); (L.L.); (T.W.); (M.B.)
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Wang J, Wang Z, Yu Y, Cheng S, Wu J. Advances in research on metabolic dysfunction-associated steatotic liver disease. Life Sci 2025; 362:123362. [PMID: 39761743 DOI: 10.1016/j.lfs.2024.123362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Revised: 12/13/2024] [Accepted: 12/31/2024] [Indexed: 01/12/2025]
Abstract
The global increase in obesity-related metabolic disorders has led to metabolic dysfunction-associated steatotic liver disease (MASLD) emerging as one of the most prevalent chronic liver disease worldwide. Despite growing concerns, the exact pathogenesis of MASLD remains unclear and no definitive treatments have been made available. Consequently, the need for comprehensive research on MASLD is more critical than ever. Gaining insight into the mechanisms of the disease can lay the groundwork for identifying new therapeutic targets and can facilitate the development of diagnostic tools that enable the early detection and intervention of MASLD. Research has discovered a multifactorial etiology for MASLD, suggesting that potential therapeutic strategies should be considered from a variety of perspectives. This review delves into the pathogenesis of MASLD, current diagnostic approaches, potential therapeutic targets, the status of clinical trials for emerging drugs, and the most promising treatment methods available today. With a focus on therapeutic targets, the aim is to offer fresh insights and guide for future research in the treatment of MASLD.
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Affiliation(s)
- Jiawang Wang
- Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, China
| | - Zhongyu Wang
- School of Basic Medical Sciences, Guangxi Medical University, Nanning 530021, China
| | - Yao Yu
- Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, China
| | - Si Cheng
- Beijing Tiantan Hospital, Capital Medical University, Beijing 10070, China; China National Clinical Research Center for Neurological Diseases, Beijing 10070, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 10070, China.
| | - Jianping Wu
- Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070, China; Department of Pharmacology, Hubei University of Medicine, Shiyan 440070, China; Beijing Tiantan Hospital, Capital Medical University, Beijing 10070, China; China National Clinical Research Center for Neurological Diseases, Beijing 10070, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 10070, China.
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Vo J, Truyen TT, Uy-Evanado A, Sargsyan A, Chugh H, Young C, Hurst S, Miyake CY, Reinier K, Chugh SS. Sudden cardiac death associated with fatty liver disease. IJC HEART & VASCULATURE 2025; 56:101602. [PMID: 39867850 PMCID: PMC11759637 DOI: 10.1016/j.ijcha.2025.101602] [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: 12/10/2024] [Revised: 12/30/2024] [Accepted: 01/03/2025] [Indexed: 01/28/2025]
Abstract
Background Fatty liver disease or steatotic liver disease (SLD) affects 25% of the global population and has been associated with heart disease. However, there is a lack of postmortem studies in the context of sudden cardiac death (SCD). Objectives To investigate the relationship between SLD and SCD. Methods A post-mortem case-case study was conducted in victims of SCD from an ongoing community-based study in Southern California (Ventura, CA, 2015-2023). Diagnosis of SLD was determined from post-mortem liver histopathology reports. For each patient, demographic variables, laboratory values, and presence of co-morbidities were ascertained from medical records and were compared between patients with and without SLD. Results Of 162 individuals with SCD, there were 101 SLD cases and 61 without SLD. Individuals with SLD were found to have higher BMI (31.6 ± 7.6 vs. 26.7 ± 5.7, p < 0.001), higher prevalence of heavy drinking (28 % vs. 12 %, p = 0.008), heavier liver weights (2433.6 g ± 940.6 vs 1934.7 g ± 505.3, p < 0.001), and were more often Hispanic (37 vs. 18 %, p = 0.01). Patients with SLD had lower prevalence of coronary artery disease (CAD) (49 % vs. 70 %). Multivariable logistic regression analysis showed that CAD was a negative predictor of SCD with SLD (OR = 0.35, 95 % CI 0.14 - 0.83). Conclusion Among adults with SCD, SLD was associated with higher prevalence of Hispanic ethnicity and lower prevalence of CAD. Given the major rise in SLD burden, these ethnicity-based differences as well as the specific nature of non-ischemic SCD etiologies warrant urgent further investigation.
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Affiliation(s)
- Jonathan Vo
- Center for Cardiac Arrest Prevention, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Health System, Los Angeles, CA, USA
| | - Thien T.T.T. Truyen
- Center for Cardiac Arrest Prevention, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Health System, Los Angeles, CA, USA
| | - Audrey Uy-Evanado
- Center for Cardiac Arrest Prevention, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Health System, Los Angeles, CA, USA
| | - Arayik Sargsyan
- Center for Cardiac Arrest Prevention, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Health System, Los Angeles, CA, USA
| | - Harpriya Chugh
- Center for Cardiac Arrest Prevention, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Health System, Los Angeles, CA, USA
| | | | - Sean Hurst
- Oregon State Medical Examiner’s Office, USA
| | - Christina Y. Miyake
- Department of Pediatrics, Texas Children’s Hospital, USA
- Department of Molecular Physiology and Biophysics, Baylor College of Medicine, USA
| | - Kyndaron Reinier
- Center for Cardiac Arrest Prevention, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Health System, Los Angeles, CA, USA
| | - Sumeet S. Chugh
- Center for Cardiac Arrest Prevention, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Health System, Los Angeles, CA, USA
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Zhou L, Sun D, Bai H. Efficacy of fish oil supplementation on metabolic dysfunction-associated steatotic liver disease: a meta-analysis. Front Nutr 2025; 12:1524830. [PMID: 39927279 PMCID: PMC11804523 DOI: 10.3389/fnut.2025.1524830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 01/08/2025] [Indexed: 02/11/2025] Open
Abstract
Objective Globally, the occurrence of Metabolic dysfunction-associated steatotic liver disease (MASLD) is on a steady rise. Fish oil has anti-inflammatory effects and can improve lipid metabolism. The article aims to assess the impact of fish oil supplementation on MASLD. Methods We conducted a systematic search of Cochrane, Embase, PubMed, and Web of Science up to September 31, 2024, for randomized control trials (RCTs). The risk of bias of the included RCTs was evaluated using the Cochrane Collaboration's tool. Outcomes measured were aspects of liver injury, lipid profile, insulin resistance, anthropometric measurements, and more. Results Seven randomized controlled trials (RCTs) involving 439 participants were incorporated into the analysis. In general, the risk of bias in these RCTs was either low or not clearly defined. Pooled analysis showed that triglycerides [TG, pooled standard mean difference (SMD): -0.40 (95% CI: -0.58 to -0.21)], aspartate transaminase [AST, SMD: -0.29 (95% CI: -0.48 to -0.10)], HOMA-IR [SMD: -2.06 (95% CI: -3.36 to -0.49)] and waist circumference [Waist-C, SMD: -0.31 (95% CI: -0.54 to -0.08)] were significantly improved. But showed no significant benefits on alanine transaminase [ALT, SMD: -0.15 (95% CI: -0.45 to 0.15)], gamma-glutamyl transpeptidase [GGT, SMD: -0.07 (95% CI: -0.26 to 0.12)], body mass index [BMI, SMD: 0.16 (95% CI: -0.34 to 0.02)], high-density lipoprotein cholesterol [HDL, SMD: 0.02 (95% CI: -0.18 to 0.22)], low-density lipoprotein cholesterol [LDL, SMD: -0.01 (95% CI: -0.20 to 0.18)], Total Cholesterol [TC, SMD: -0.34 (95% CI: -0.70 to 0.01)] and so on. Conclusion The current evidence supports the fish oil supplementation in improving MASLD. Fish oil supplementation may also regulate blood lipids and improve glucose metabolism disorders. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier CRD42024513246.
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Affiliation(s)
- Like Zhou
- Department of Gastroenterology, Weihai Maternal and Child Health Hospital, Weihai, China
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Mladenova IL, Tan EF, Ng JY, Sharma P. Non-alcoholic fatty liver disease (NAFLD) and its association to cardiovascular disease: A comprehensive meta-analysis. JRSM Cardiovasc Dis 2025; 14:20480040251325929. [PMID: 40123646 PMCID: PMC11930486 DOI: 10.1177/20480040251325929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 11/13/2024] [Accepted: 11/18/2024] [Indexed: 03/25/2025] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) affects up to nearly a third of the Western population and has been inconsistently associated with cardiovascular diseases (CVDs). Therefore, we conducted a comprehensive meta-analysis to quantify the correlation of NAFLD with all major vascular diseases, acute coronary syndrome (ACS), subclinical atherosclerosis and endothelial dysfunction. Methods We searched PubMed and Embase for studies looking at the relationship between NAFLD and cardiovascular diseases published through September 2023. The parameters we used to assess cardiovascular diseases include acute coronary syndrome, brachial flow-mediated dilatation (FMD), serum asymmetric dimethylarginine (ADMA), carotid intima-media thickness (CIMT), and carotid stenosis (>50%). Data from these studies were then collected and meta-analysis was performed using the random effects model. RevMan v5.4 was used for statistical analysis. Results We interrogated a total of 114 publications which met our inclusion criteria. NAFLD patients showed statistically significant reduction in FMD% [MD: -4.83 (95% CI: -5.84 to 3.81, p < .00001)] and increased serum ADMA [MD: 0.08 (95% CI: 0.05-0.11, p < .00001)]. Mean CIMT was also increased in NAFLD patients [MD 0.13 (95% CI: 0.12-0.14, p < .00001)]. NAFLD showed a higher prevalence of pathological CIMT [MD: 0.11 (95% CI: 0.10-0.12, p < .00001)] and increased carotid plaques [OR: 2.08 (95% CI: 1.52-2.86, p < .00001)]. Furthermore, we demonstrated statistically significant increase in cardiovascular diseases among NAFLD patients compared to controls [OR: 1.92 (95% CI: 1.53-2.41, p < .00001)]. Conclusion NAFLD is a strong predictor for endothelial dysfunction, subclinical atherosclerosis and cardiovascular disease. Further studies are required to determine whether incidental findings of fatty liver on abdominal ultrasonography should prompt the need for detailed assessment of other CVD risk factors.
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Affiliation(s)
| | - Eu Fon Tan
- Queen Mary University of London, London, UK
| | | | - Pankaj Sharma
- Institute of Cardiovascular Research, Royal Holloway University, Egham, Greater London, UK
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Kim A, Kang D, Choi SC, Sinn DH, Gwak GY. Cardiometabolic risk factors and coronary atherosclerosis progression in patients with metabolic dysfunction-associated steatotic liver disease: the influential role of quantity over type. J Gastroenterol Hepatol 2025; 40:258-264. [PMID: 39568183 DOI: 10.1111/jgh.16787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 09/11/2024] [Accepted: 10/13/2024] [Indexed: 11/22/2024]
Abstract
BACKGROUND AND AIM Individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) who are at an increased risk of cardiovascular disease (CVD) are critical to identify and manage. We aimed to assess whether the risk of CVD in patients with MASLD differed according to the type or number of cardiometabolic risk factors. METHODS This longitudinal cohort study involved 5674 adults who underwent at least two health checkups between 2004 and 2021. Steatotic liver disease (SLD) was assessed using ultrasonography and participants with SLD were classified as having either non-MASLD or MASLD. CVD risk was evaluated using coronary artery calcium (CAC) progression as measured using multidetector computed tomography scans. RESULTS Over an average 5.8-year follow-up period, patients with MASLD exhibited faster CAC progression than those with non-MASLD (18% vs 11%, P < 0.01). MASLD with any cardiometabolic risk factor exacerbated CAC progression; however, the degree of CAC progression was similar among the different risk components. The adjusted ratios (95% CI) of CAC progression rates comparing non-MASLD with MASLD with one, two, three, four, and five cardiometabolic risk factors were 1.02 (0.99, 1.06), 1.04 (1.01, 1.08), 1.07 (1.03, 1.10), 1.08 (1.05, 1.11), and 1.11 (1.07, 1.15), respectively. CONCLUSIONS In individuals with MASLD, all cardiometabolic risk factors contributed to the deterioration of coronary atherosclerosis, with no specific factor exerting a dominant influence. Coronary atherosclerosis progression is directly associated with the cumulative number of cardiometabolic risk factors. Therefore, identifying and managing an increasing number of these factors is imperative in clinical practice, even when MASLD is diagnosed based on only one risk factor.
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Affiliation(s)
- Aryoung Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, South Korea
| | - Danbee Kang
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
- Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - Sung Chul Choi
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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Chen Z, Yang Y, Tian Y, Yang J, Xiong H. Diagnosis of Nonalcoholic Fatty Liver Disease via a H 2S-Responsive Bioluminescent Probe Combined with Firefly Luciferase mRNA Delivery. Anal Chem 2024; 96:9236-9243. [PMID: 38767294 DOI: 10.1021/acs.analchem.4c01462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/22/2024]
Abstract
The early detection of nonalcoholic fatty liver disease (NAFLD) through bioluminescent probes is of great significance. However, there remains a challenge to apply them in nontransgenic natural animals due to the lack of exogenous luciferase. To address this issue, we herein report a new strategy for in situ monitoring of endogenous hydrogen sulfide (H2S) in the liver of NAFLD mice by leveraging a H2S-responsive bioluminescent probe (H-Luc) combined with firefly luciferase (fLuc) mRNA delivery. The probe H-Luc was created by installing a H2S recognition moiety, 2,4-dinitrophenol, onto the luciferase substrate (d-luciferin), which is allowed to release cage-free d-luciferin in the presence of H2S via a nucleophilic aromatic substitution reaction. In the meantime, the intracellular luciferase was introduced by lipid nanoparticle (LNP)-mediated fLuc mRNA delivery, rendering it suitable for bioluminescence (BL) imaging in vitro and in vivo. Based on this luciferase-luciferin system, the endogenous H2S could be sensitively and selectively detected in living cells, showing a low limit of detection (LOD) value of 0.72 μM. More importantly, after systematic administration of fLuc mRNA-loaded LNPs in vivo, H-Luc was able to successfully monitor the endogenous H2S levels in the NAFLD mouse model for the first time, displaying a 28-fold higher bioluminescence intensity than that in the liver of normal mice. We believe that this strategy may shed new light on the diagnosis of inflammatory liver disease, further elucidating the roles of H2S.
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Affiliation(s)
- Zhaoming Chen
- Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Yuexia Yang
- Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Yang Tian
- Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Jieyu Yang
- Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Hu Xiong
- Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
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Toke N, Rathod A, Phalak P, Patel V. Endothelial dysfunction and cardiovascular risk in non-alcoholic fatty liver disease – a systematic review and meta-analysis. EGYPTIAN LIVER JOURNAL 2024; 14:40. [DOI: 10.1186/s43066-024-00348-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 05/26/2024] [Indexed: 01/03/2025] Open
Abstract
Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder that has been associated with an increased risk of cardiovascular diseases. Endothelial dysfunction, characterized by impaired flow-mediated dilation (FMD) of the brachial artery, is a known predictor of cardiovascular risk. However, the relationship between NAFLD and endothelial dysfunction, as well as the impact of NAFLD on clinical cardiovascular events, remains unclear.
Objective
The aim of this systematic literature review was to determine the association between endothelial dysfunction, as measured by FMD of the brachial artery, and NAFLD. Additionally, we aimed to investigate the relationship between NAFLD and clinical cardiovascular events (CVE).
Methods
A systematic search was conducted in PubMed, Scopus, ScienceDirect, and Google Scholar for articles published between 2000 and July 2023. The reference lists of the included studies were also searched to retrieve possible additional studies. Original studies published in English focusing on adults with NAFLD and endothelial dysfunction are included. Editorials, commentaries, letters and studies focusing on pediatric populations and non-NAFLD liver diseases were excluded. The quality of included studies was appraised using the Newcastle–Ottawa scale. Meta-analyses were performed using Review Manager 5.4 software.
Results
The initial search yielded a total of 1792 articles and ultimately only 20 studies met the criteria. A total 6396 NAFLD patients were studied. Meta-analysis showed that individuals diagnosed with NAFLD had significantly lower brachial FMD values compared to their respective control groups (standardized mean difference: -4.63, 95% confidence interval: -5.68 to -3.58, p < 0.0001). Furthermore, NAFLD patients exhibited a significantly higher risk of clinical cardiovascular events compared to controls (odds ratio: 2.61; 95% CI: 1.41–4.83, p < 0.002). Subgroup analysis of studies focusing on non-alcoholic steatohepatitis (NASH) versus pure steatosis demonstrated that individuals with NASH had even lower FMD values than those with pure steatosis (standardized mean difference: -3.84, 95% confidence interval: -7.56 to -0.13, p = 0.03, I2 = 66%).
Limitations, bias and heterogeneity
The review included studies published in English language, over last 23 years and specified database resulted in language bias and might have missed older pertinent studies from another important database. The overall heterogeneity is attributed to variations in study populations, outcome measurements, differences in methodological approaches among included studies, and diverse diagnostic criteria for NAFLD.
Conclusion
Individuals with NAFLD exhibited impaired brachial FMD, indicating compromised endothelial function. Furthermore, NAFLD patients had an elevated risk of clinical cardiovascular events.
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Chew NWS, Pan XH, Chong B, Chandramouli C, Muthiah M, Lam CSP. Type 2 diabetes mellitus and cardiometabolic outcomes in metabolic dysfunction-associated steatotic liver disease population. Diabetes Res Clin Pract 2024; 211:111652. [PMID: 38574897 DOI: 10.1016/j.diabres.2024.111652] [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: 11/08/2023] [Accepted: 04/01/2024] [Indexed: 04/06/2024]
Abstract
The metabolic syndrome, characterized by type 2 diabetes mellitus (T2DM), hypertension, hyperlipidemia, and obesity, collectively increases the risk of cardiovascular diseases. Nonalcoholic fatty liver disease (NAFLD) is a prominent manifestation, affecting over a third of the global population with a concerning annual increase in prevalence. Nearly 70 % of overweight individuals have NAFLD, and NAFLD-related deaths are predicted to rise, especially among young adults. The association of T2DM and NAFLD has led to the proposal of "metabolic dysfunction-associated steatotic liver disease" (MASLD) terminology, encompassing individuals with T2DM, overweight/obesity, hypertension, hypertriglyceridemia, or low HDL-cholesterol. Patients with MASLD will likely have double the risk of developing T2DM, and the combination of insulin resistance, overweight/obesity, and MASLD significantly elevates the risk of T2DM. Cardiovascular diseases remain the leading cause of mortality in the MASLD and T2DM population, with MASLD directly associated with coronary artery disease, compounded by coexisting insulin resistance and T2DM. Urgency lies in early detection of subclinical cardiovascular diseases among patients with T2DM and MASLD. Novel strategies targeting multiple pathways offer hope for effectively improving cardiometabolic health. Understanding and addressing the intertwined factors contributing to these disorders can pave the way towards better management and prevention of cardiometabolic complications.
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Affiliation(s)
- Nicholas W S Chew
- Yong Loo Lin School of Medicine, National University Singapore, Singapore; Department of Cardiology, National University Heart Centre, National University Health System, Singapore
| | - Xin Hui Pan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Bryan Chong
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Chanchal Chandramouli
- National Heart Centre Singapore, Singapore; Duke-National University of Singapore Medical School, Singapore, Singapore
| | - Mark Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Carolyn S P Lam
- National Heart Centre Singapore, Singapore; Duke-National University of Singapore Medical School, Singapore, Singapore; George Institute for Global Health, Sydney, Australia; Department of Cardiology, University of Groningen, Groningen, the Netherlands.
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11
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Kim A, Kang D, Choi SC, Cho J, Sinn DH, Gwak GY. Steatotic liver disease and its newly proposed sub-classifications correlate with progression of the coronary artery calcium score. PLoS One 2024; 19:e0301126. [PMID: 38530817 DOI: 10.1371/journal.pone.0301126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 03/08/2024] [Indexed: 03/28/2024] Open
Abstract
BACKGROUND & AIMS A new nomenclature, Steatotic Liver Disease (SLD), has been proposed by consensus with sub-classifications and requires evidence-based validation. We assessed whether the presence and severity of SLD, as well as its sub-classifications, are associated with the progression of coronary atherosclerosis. METHODS This longitudinal cohort study included 13,811 adults who participated in repeated regular health screening examinations between January 1, 2004 and December 31, 2021 that included assessments of their coronary artery calcium (CAC) scores. SLD was defined using abdominal ultrasonography and classified as metabolic dysfunction associated steatotic liver disease (MASLD), MASLD with increased alcohol intake (MetALD), and cryptogenic SLD. SLD severity was assessed using fibrosis-4 (FIB-4) scores. The progression of CAC scores was measured using multidetector CT scans. RESULTS The average duration of follow-up was 5.8 years. During follow-up, the annual rate of CAC progression in participants with and without SLD was 18% (95% CI 17%-19%) and 14% (95% CI 13%-14%) (p < 0.01), respectively. The multivariable ratios of progression rates when we compared participants with cryptogenic SLD, MASLD, or MetALD with those without SLD were 0.98 (95% CI 0.95-1.01), 1.03 (95% CI 1.03-1.04), and 1.07 (95% CI 1.04-1.09), respectively. The multivariable ratios of progression rates when we compared participants with SLD with FIB-4 score <1.3 and SLD with FIB-4 score ≥1.3 with those without SLD were 1.03 (95% CI 1.02-1.04), and 1.05 (95% CI 1.04-1.06), respectively. CONCLUSIONS SLD was associated with a higher risk of coronary atherosclerosis, and the risk differed by sub-classifications and severity. These findings suggest that the newly proposed definition has clinical relevance in terms of stratifying cardiovascular disease risk.
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Affiliation(s)
- Aryoung Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, South Korea
| | - Danbee Kang
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
- Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - Sung Chul Choi
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - Juhee Cho
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
- Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
- Departments of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, United States of America
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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12
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Dong W, Gong Y, Zhao J, Wang Y, Li B, Yang Y. A combined analysis of TyG index, SII index, and SIRI index: positive association with CHD risk and coronary atherosclerosis severity in patients with NAFLD. Front Endocrinol (Lausanne) 2024; 14:1281839. [PMID: 38260163 PMCID: PMC10802119 DOI: 10.3389/fendo.2023.1281839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 12/08/2023] [Indexed: 01/24/2024] Open
Abstract
Background Insulin resistance(IR) and inflammation have been regarded as common potential mechanisms in coronary heart disease (CHD) and non-alcoholic fatty liver disease (NAFLD). Triglyceride-glucose (TyG) index is a novel biomarker of insulin resistance, System immune-inflammation index(SII) and Systemic inflammation response index(SIRI) are novel biomarkers of inflammation, these biomarkers have not been studied in CHD with NAFLD patients. This study investigated the correlation between the TyG index, SII index, and SIRI index and CHD risk among NAFLD patients. Methods This cross-sectional study included 407 patients with NAFLD in the Department of Cardiology, The Second Hospital of Shanxi Medical University. Of these, 250 patients with CHD were enrolled in the NAFLD+CHD group and 157 patients without CHD were enrolled as NAFLD control. To balance covariates between groups, 144 patients were selected from each group in a 1:1 ratio based on propensity score matching (PSM). Potential influences were screened using Lasso regression analysis. Univariate and multivariate logistic regression analyses and the Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to assess independent risk and protective factors for CHD. Construction of nomogram using independent risk factors screened by machine learning. The receiver operating characteristic(ROC) curve was used to assess the ability of these independent risk factors to predict coronary heart disease. The relationship between the Gensini score and independent risk factors was reflected using the Sankey diagram. Results The LASSO logistic regression analysis and Logistic regression analyses suggest that TyG index (OR, 2.193; 95% CI, 1.242-3.873; P = 0.007), SII index (OR, 1.002; 95% CI, 1.001-29 1.003; P <0.001), and SIRI index (OR,1.483;95%CI,1.058-2.079,P=0.022) are independent risk factors for CHD. At the same time, Neutrophils, TG, and LDL-C were also found to be independent risk factors in patients, HDL-C was a protective factor for CHD in patients with NAFLD. Further analysis using three machine learning algorithms found these independent risk factors to have good predictive value for disease diagnosis, SII index shows the highest predictive value. ROC curve analysis demonstrated that combining the SII index, SIRI index, and TyG index can improve the diagnostic ability of non-alcoholic liver cirrhosis patients with CHD.ROC curve analysis showed that the combined analysis of these independent risk factors improved the predictive value of CHD(AUC: 0.751; 95% CI: 0.704-0.798; P <0.001). Conclusion TyG index, SII index, and SIRI index are all independent risk factors for CHD in patients with NAFLD and are strongly associated with prediction and the severity of CHD.
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Affiliation(s)
- Wenyuan Dong
- Vasculocardiology Department, The Third People’s Hospital of Datong, Datong, Shanxi, China
- Key Laboratory of Cardiovascular Diseases, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yuxin Gong
- Key Laboratory of Cardiovascular Diseases, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Pathology, Tongji Hospital Affiliated to Tongji Medical College Hust, Wuhan, Hubei, China
| | - Jianqi Zhao
- Vasculocardiology Department, The First People’s Hospital of Jinzhong, Jinzhong, Shanxi, China
| | - Yanan Wang
- Vasculocardiology Department, The Third People’s Hospital of Datong, Datong, Shanxi, China
| | - Bao Li
- Key Laboratory of Cardiovascular Diseases, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
| | - Youdong Yang
- Vasculocardiology Department, The Third People’s Hospital of Datong, Datong, Shanxi, China
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13
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Kleb C, Sims OT, Fares M, Ruthmann N, Ansari K, Esfeh JM. Screening Modalities for Coronary Artery Disease in Liver Transplant Candidates: A Review of the Literature. J Cardiothorac Vasc Anesth 2023; 37:2611-2620. [PMID: 37690949 DOI: 10.1053/j.jvca.2023.08.126] [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: 05/21/2023] [Revised: 07/16/2023] [Accepted: 08/09/2023] [Indexed: 09/12/2023]
Abstract
Patients with cirrhosis undergoing liver transplant (LT) are at high risk of postoperative cardiopulmonary complications. It is known that patients with coronary artery disease (CAD) have greater rates of post-LT morbidity and mortality than patients without CAD. Thus, identifying significant CAD in LT candidates is of the utmost importance to optimize survival posttransplant. Consensus is lacking on the ideal screening test for CAD in LT candidates. Traditional exercise and many pharmacologic stress tests are impractical and inaccurate in patients with cirrhosis due to their unique physiology. The purpose of this review is to describe different screening modalities for CAD among LT candidates. The background, diagnostic accuracy, and limitations of each screening modality are described to achieve this goal.
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Affiliation(s)
- Cerise Kleb
- Department of Gastroenterology, University of Maryland Medical Center, Baltimore, MD.
| | - Omar T Sims
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH; Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH
| | - Maan Fares
- Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH
| | - Nicholas Ruthmann
- Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH
| | - Kianoush Ansari
- Department of Diagnostic Radiology, University Hospital Cleveland Medical Center, Cleveland, OH
| | - Jamak Modaresi Esfeh
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH
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14
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McCall KD, Walter D, Patton A, Thuma JR, Courreges MC, Palczewski G, Goetz DJ, Bergmeier S, Schwartz FL. Anti-Inflammatory and Therapeutic Effects of a Novel Small-Molecule Inhibitor of Inflammation in a Male C57BL/6J Mouse Model of Obesity-Induced NAFLD/MAFLD. J Inflamm Res 2023; 16:5339-5366. [PMID: 38026235 PMCID: PMC10658948 DOI: 10.2147/jir.s413565] [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: 04/08/2023] [Accepted: 10/31/2023] [Indexed: 12/01/2023] Open
Abstract
Purpose Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic (dysfunction) associated fatty liver disease (MAFLD), is the most common chronic liver disease in the United States. Presently, there is an intense and ongoing effort to identify and develop novel therapeutics for this disease. In this study, we explored the anti-inflammatory activity of a new compound, termed IOI-214, and its therapeutic potential to ameliorate NAFLD/MAFLD in male C57BL/6J mice fed a high fat (HF) diet. Methods Murine macrophages and hepatocytes in culture were treated with lipopolysaccharide (LPS) ± IOI-214 or DMSO (vehicle), and RT-qPCR analyses of inflammatory cytokine gene expression were used to assess IOI-214's anti-inflammatory properties in vitro. Male C57BL/6J mice were also placed on a HF diet and treated once daily with IOI-214 or DMSO for 16 weeks. Tissues were collected and analyzed to determine the effects of IOI-214 on HF diet-induced NAFL D/MAFLD. Measurements such as weight, blood glucose, serum cholesterol, liver/serum triglyceride, insulin, and glucose tolerance tests, ELISAs, metabolomics, Western blots, histology, gut microbiome, and serum LPS binding protein analyses were conducted. Results IOI-214 inhibited LPS-induced inflammation in macrophages and hepatocytes in culture and abrogated HF diet-induced mesenteric fat accumulation, hepatic inflammation and steatosis/hepatocellular ballooning, as well as fasting hyperglycemia without affecting insulin resistance or fasting insulin, cholesterol or TG levels despite overall obesity in vivo in male C57BL/6J mice. IOI-214 also decreased systemic inflammation in vivo and improved gut microbiota dysbiosis and leaky gut. Conclusion Combined, these data indicate that IOI-214 works at multiple levels in parallel to inhibit the inflammation that drives HF diet-induced NAFLD/MAFLD, suggesting that it may have therapeutic potential for NAFLD/MAFLD.
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Affiliation(s)
- Kelly D McCall
- Molecular and Cellular Biology Program, Ohio University College of Arts & Sciences, Athens, OH, USA
- Department of Biological Sciences, Ohio University College of Arts & Sciences, Athens, OH, USA
- Department of Specialty Medicine, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
- Department of Biomedical Sciences, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
- Diabetes Institute, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
- Biomedical Engineering Program, Ohio University Russ College of Engineering and Technology, Athens, OH, USA
| | - Debra Walter
- Molecular and Cellular Biology Program, Ohio University College of Arts & Sciences, Athens, OH, USA
- Department of Biological Sciences, Ohio University College of Arts & Sciences, Athens, OH, USA
| | - Ashley Patton
- Molecular and Cellular Biology Program, Ohio University College of Arts & Sciences, Athens, OH, USA
- Department of Biological Sciences, Ohio University College of Arts & Sciences, Athens, OH, USA
| | - Jean R Thuma
- Department of Specialty Medicine, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
| | - Maria C Courreges
- Department of Specialty Medicine, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
| | | | - Douglas J Goetz
- Molecular and Cellular Biology Program, Ohio University College of Arts & Sciences, Athens, OH, USA
- Biomedical Engineering Program, Ohio University Russ College of Engineering and Technology, Athens, OH, USA
- Department of Chemical & Biomolecular Engineering, Ohio University Russ College of Engineering and Technology, Athens, OH, USA
| | - Stephen Bergmeier
- Molecular and Cellular Biology Program, Ohio University College of Arts & Sciences, Athens, OH, USA
- Biomedical Engineering Program, Ohio University Russ College of Engineering and Technology, Athens, OH, USA
- Department of Chemistry & Biochemistry, Ohio University College of Arts & Sciences, Athens, OH, USA
| | - Frank L Schwartz
- Department of Specialty Medicine, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
- Diabetes Institute, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA
- Biomedical Engineering Program, Ohio University Russ College of Engineering and Technology, Athens, OH, USA
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15
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Meyer G, Gruendl M, Chifu I, Hahner S, Werner J, Weiß J, Kienitz T, Quinkler M, Badenhoop K, Herrmann E, Friedrich-Rust M, Bojunga J. Glucocorticoid Replacement for Adrenal Insufficiency and the Development of Non-Alcoholic Fatty Liver Disease. J Clin Med 2023; 12:6392. [PMID: 37835036 PMCID: PMC10573835 DOI: 10.3390/jcm12196392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 09/18/2023] [Accepted: 10/05/2023] [Indexed: 10/15/2023] Open
Abstract
Glucocorticoid excess is a known risk factor for non-alcoholic fatty liver disease (NAFLD). Our objective was to analyse the impact of glucocorticoid replacement therapy on the development of NAFLD and NAFLD-related fibrosis and, therefore, on cardiovascular as well as hepatic morbidity in patients with adrenal insufficiency. Two hundred and fifteen individuals with primary (n = 111) or secondary (n = 104) adrenal insufficiency were investigated for hepatic steatosis and fibrosis using the fatty liver index (FLI), NAFLD fibrosis score (NAFLD-FS), Fibrosis-4 Index (FiB-4) plus sonographic transient elastography. Results were correlated with glucocorticoid doses and cardiometabolic risk parameters. The median dose of hydrocortisone equivalent was 20 mg daily, with a median therapy duration of 15 years. The presence and grade of hepatic steatosis and fibrosis were significantly correlated with cardiometabolic risk factors. We could not find any significant correlations between single, daily or cumulative doses of glucocorticoids and the grade of liver steatosis, nor with fibrosis measured via validated sonographic techniques. In patients with adrenal insufficiency, glucocorticoid replacement within a physiological range of 15-25 mg hydrocortisone equivalent per day does not appear to pose an additional risk for the development of NAFLD, subsequent liver fibrosis, or the cardiovascular morbidity associated with these conditions.
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Affiliation(s)
- Gesine Meyer
- Division of Endocrinology, Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany (J.B.)
| | - Madeleine Gruendl
- Division of Endocrinology, Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany (J.B.)
| | - Irina Chifu
- Endocrinology and Diabetes Unit, Department of Medicine I, University Hospital Wuerzburg, 97080 Wuerzburg, Germany
| | - Stefanie Hahner
- Endocrinology and Diabetes Unit, Department of Medicine I, University Hospital Wuerzburg, 97080 Wuerzburg, Germany
| | - Johanna Werner
- Endocrinology and Diabetes Unit, Department of Medicine I, University Hospital Wuerzburg, 97080 Wuerzburg, Germany
| | - Johannes Weiß
- Division of Hepatology, Department of Medicine II, University Hospital Wuerzburg, 97080 Wuerzburg, Germany
| | - Tina Kienitz
- Endocrinology in Charlottenburg, 10627 Berlin, Germany
| | | | - Klaus Badenhoop
- Division of Endocrinology, Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany (J.B.)
| | - Eva Herrmann
- Institut for Biostatistics and Mathematic Modelling, Goethe University Frankfurt, 60590 Frankfurt, Germany
| | - Mireen Friedrich-Rust
- Division of Hepatology, Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany
| | - Joerg Bojunga
- Division of Endocrinology, Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany (J.B.)
- Division of Hepatology, Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany
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Attaran F, Emami S, Sohrabi M, Malek M, Ajdarkosh H, Khoonsari M, Ismail-Beigi F, Khamseh ME. Effect of Empagliflozin and Pioglitazone on left ventricular function in patients with type two diabetes and nonalcoholic fatty liver disease without established cardiovascular disease: a randomized single-blind clinical trial. BMC Gastroenterol 2023; 23:327. [PMID: 37742004 PMCID: PMC10517489 DOI: 10.1186/s12876-023-02948-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 09/06/2023] [Indexed: 09/25/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic disorder that increases the risk for cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Global longitudinal strain (GLS) is an indicator of left ventricular (LV) mechanics and can detect subclinical myocardial dysfunction. We compared the effects of pioglitazone and empagliflozin on GLS in patients with T2DM and NAFLD without established atherosclerotic cardiovascular disease. METHODS This study was a 24-week randomized, single-blind, and parallel-group (1: 1 ratio) clinical trial. Seventy-three participants with T2DM (being treated with metformin) and NAFLD but without established atherosclerotic cardiovascular disease (ASCVD) were randomized to empagliflozin or pioglitazone. Liver steatosis and fibrosis were measured using transient elastography, and GLS was measured by echocardiography. The primary endpoint was the change in GLS from baseline to week 24. Secondary end points include changes in controlled attenuation parameter (CAP) and Liver stiffness measure (LSM). RESULTS In this study, GLS improved by 1.56 ± 2.34% (P < 0.01) in the pioglitazone group and 1.06 ± 1.83% (P < 0.01) in the empagliflozin group without a significant difference between the two groups (P = 0.31). At baseline, GLS was inversely associated with the severity of liver fibrosis: r = - 0.311, P = 0.007. LSM in the pioglitazone and empagliflozin group [(-0.73 ± 1.59) and (-1.11 ± 1.33)] kpa (P < 0.01) decreased significantly. It was without substantial difference between the two groups (P = 0.26). Empagliflozin and pioglitazone both improved controlled attenuation parameter. The improvement was more critical in the empagliflozin group: -48.22 + 35.02 dB/m vs. -25.67 + 41.50 dB/m, P = 0.01. CONCLUSION Subclinical cardiac dysfunction is highly important in patients with T2DM and with NAFLD. Empagliflozin and Pioglitazone improve LV mechanics and fibrosis in patients without established ASCVD. This has a prognostic importance on cardiovascular outcomes in high-risk patients with T2DM. Moreover, empagliflozin ameliorates liver steatosis more effectively them pioglitazone. This study can serve as a start point hypothesis for the future. Further studies are needed to explore the concept in larger populations. TRIAL REGISTRATION This trial was registered in the Iranian Registry of Clinical Trials (IRCT): "A Comparison between the Effect of Empagliflozin and Pioglitazone on Echocardiographic Indices in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease" IRCT20190122042450N5, 29 November 2020. https://www.irct.ir/search/result?query=IRCT20190122042450N5 .
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Affiliation(s)
- Fereshte Attaran
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Iran University of Medical Science, No. 10, Firoozeh St., Vali-asr Ave., Vali-asr Sq, Tehran, Iran
| | - Sepideh Emami
- Department of Cardiology, Firoozgar Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Masoudreza Sohrabi
- Gastrointestinal and liver diseases research center, Iran University of Medical Sciences, Tehran, Iran
| | - Mojtaba Malek
- Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Ajdarkosh
- Gastrointestinal and liver diseases research center, Iran University of Medical Sciences, Tehran, Iran
| | - Mahmoodreza Khoonsari
- Gastrointestinal and liver diseases research center, Iran University of Medical Sciences, Tehran, Iran
| | | | - Mohammad E Khamseh
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Science, Tehran, Iran.
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17
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Khoshbaten M, Maleki SH, Hadad S, Baral A, Rocha AV, Poudel L, Abdshah A. Association of nonalcoholic fatty liver disease and carotid media-intima thickness: A systematic review and a meta-analysis. Health Sci Rep 2023; 6:e1554. [PMID: 37701352 PMCID: PMC10493365 DOI: 10.1002/hsr2.1554] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 07/04/2023] [Accepted: 08/29/2023] [Indexed: 09/14/2023] Open
Abstract
Introduction The relationship between cardiovascular disorders and nonalcoholic fatty liver disease (NAFLD) has been extensively studied. To better pool this data and make a more definite conclusion, we performed a meta-analysis to evaluate the association between NAFLD and the thickness of media and intima of carotid artery (CIMT) and cardiovascular disorders. Methods We searched PubMed, Ovid, Scopus, ProQuest, Web of Science, and the Cochrane Library, and analyzed the pooled data using R studio and the "metafor" package. Results The final analysis included a total of 59 studies with 16,179 cases and 26,120 control individuals. NAFLD was shown to be associated with an increase of 0.1231 mm (20.6%) in carotid artery intima-media thickness (CIMT) (p = 0.002, 95% confidence interval [CI]: 0.0462-0.2000) in individuals with NAFLD. The prevalence of atherosclerotic plaques in the carotid arteries and the occurrence of NAFLD are significantly correlated, according to a meta-analysis based on 17 distinct studies (p = 0.001, 1.28-1.43, 95% CI, odds ratio = 1.356). Conclusion Patients with increased CIMT are considerably more likely to have NAFLD. Large prospective investigations are required to corroborate these findings and their prognostic significance, along with the effectiveness of the available interventions.
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Affiliation(s)
- Manouchehr Khoshbaten
- Liver and Gastrointestinal Diseases Research CenterTabriz University of Medical SciencesTabrizIran
| | - Sepideh H. Maleki
- Department of PathologyImam Reza Hospital, Tabriz University of Medical SciencesTabrizIran
| | - Sara Hadad
- Liver and Gastrointestinal Diseases Research CenterTabriz University of Medical SciencesTabrizIran
| | - Amrit Baral
- Department of Public Health SciencesMiller School of Medicine, University of MiamiMiamiFloridaUSA
| | - Ana V. Rocha
- Department of Public Health SciencesMiller School of Medicine, University of MiamiMiamiFloridaUSA
| | | | - Alireza Abdshah
- Department of Public Health SciencesMiller School of Medicine, University of MiamiMiamiFloridaUSA
- School of MedicineTehran University of Medical SciencesTehranIran
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Guan H, Liu K, Fan X, Yu H, Qin Y, Yang J, Zhu Z, Shen C, Pan E, Lu Y, Zhou J, Su J, Wu M. Association of gamma-glutamyl transferase concentrations with all-cause and cause-specific mortality in Chinese adults with type 2 diabetes. J Diabetes 2023; 15:674-684. [PMID: 37161588 PMCID: PMC10415869 DOI: 10.1111/1753-0407.13399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 03/06/2023] [Accepted: 04/15/2023] [Indexed: 05/11/2023] Open
Abstract
BACKGROUND Evidence links gamma-glutamyl transferase (GGT) to mortality in the general population. However, the relationship of GGT with all-cause and cause-specific mortality risk has been little explored in type 2 diabetes mellitus (T2DM) patients. METHODS We recruited 20 340 community-dwelling T2DM patients between 2013 and 2014 in Jiangsu, China. Cox regression models were used to assess associations of GGT with all-cause and specific-cause mortality. Restricted cubic splines were used to analyze dose-response relationships between GGT and mortality. Stratified analysis was conducted to examine potential interaction effects by age, sex, smoking status, body mass index (BMI), diabetes duration, and dyslipidemia. RESULTS During a median follow-up period of 7.04 years (interquartile range: 6.98-7.08), 2728 deaths occurred, including 902 (33.09%) due to cardiovascular disease (CVD), and 754 (27.58%) due to cancer. GGT concentrations were positively associated with all-cause, CVD, and cancer mortality. Multivariable hazard ratios (HRs) for the highest (Q5) vs. the lowest quintile (Q1) were 1.63 (95% confidence intervals [CI]: 1.44-1.84) for all-cause mortality, 1.87 (95% CI: 1.49-2.35) for CVD mortality, and 1.43 (95% CI: 1.13-1.81) for cancer mortality. Effect modification by BMI and dyslipidemia was observed for all-cause mortality (both p for interaction <.05), and HRs were stronger in the BMI <25 kg/m2 group and those without dyslipidemia. CONCLUSIONS Our findings suggest that, in Chinese T2DM patients, elevated serum GGT concentrations were associated with mortality for all-cause, CVD, and cancer, and further research is needed to elucidate the role of obesity, nonalcoholic fatty liver disease, and lipids in this association.
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Affiliation(s)
- Haoyu Guan
- Department of Epidemiology, School of Public HealthNanjing Medical UniversityNanjingChina
| | - Ke Liu
- Department of Epidemiology and Health Statistics, School of Public HealthSoutheast UniversityNanjingChina
| | - Xikang Fan
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
| | - Hao Yu
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
| | - Yu Qin
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
| | - Jie Yang
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
| | - Zheng Zhu
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
| | - Chong Shen
- Department of Epidemiology, School of Public HealthNanjing Medical UniversityNanjingChina
| | - Enchun Pan
- Department of Chronic Disease Prevention and ControlHuai'an City Center for Disease Control and PreventionHuai'anChina
| | - Yan Lu
- Department of Chronic Disease Prevention and ControlSuzhou City Center for Disease Control and PreventionSuzhouChina
| | - Jinyi Zhou
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
| | - Jian Su
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
| | - Ming Wu
- Department of Epidemiology, School of Public HealthNanjing Medical UniversityNanjingChina
- Department of Non‐communicable Chronic Disease ControlProvincial Center for Disease Control and PreventionNanjingChina
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Basheer M, Saad E, Jeries H, Assy N. Liver Fat Storage Is a Better Predictor of Coronary Artery Disease than Visceral Fat. Metabolites 2023; 13:896. [PMID: 37623840 PMCID: PMC10456344 DOI: 10.3390/metabo13080896] [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: 06/16/2023] [Revised: 07/26/2023] [Accepted: 07/27/2023] [Indexed: 08/26/2023] Open
Abstract
Fatty liver is one aspect of metabolic syndrome. The roles and contributions of fatty liver and visceral fat storage to coronary artery disease (CAD) are not clear. This study measured associations among visceral fat storage, fatty liver, insulin resistance, atherosclerosis, and CAD. Patients were divided into three groups: excess visceral fat (visceral fat area >330 ± 99 cm2), non-alcoholic fatty liver disease (NAFLD), and a control group. The definition of fatty liver is liver minus spleen density greater than or equal to -10. We defined early atherosclerosis as intima-media thickness of the common carotid artery >7 mm in men and >0.65 mm in women, measured with Doppler ultrasound. Visceral fat area was defined using CT (>330 ± 99 cm2). Insulin-resistance biomarkers (HOMA), CRP, and oxidant-antioxidant status (MDA-Paraoxonase) were also measured. Patients with high liver or visceral fat showed higher coronary plaque prevalence (50% (p < 0.001), 38% (p < 0.01), respectively vs. 25% in the control group), higher prevalence of coronary stenosis (30% (p < 0.001), 22% (p < 0.01) vs. 11% in the control group), higher intimal thickening (0.98 ± 0.3 (p< 0.01), 0.86 ± 0.1 (p < 0.01) vs. 0.83 ± 0.1 in the control group), higher HOMA (4.0 ± 3.0 (p < 0.005), 3.0 ± 1.0 (p < 0.001) vs. 1.5 ± 1.2 in the control group), and higher triglyceride levels (196.8 ± 103 (p < 0.005), 182.6 ± 90.87 (p < 0.005) vs. 145 ± 60 in the control group). Multiple logistic regression analysis showed that fatty liver predicted CAD (OR 2.7, 95% CI 2.3-4.9, p < 0.001) independently of visceral fat storage (OR 2.01, 95% CI 1.2-2.8, p < 0.001). Liver fat storage is a strong independent risk factor for CAD and carotid atherosclerosis and contributes more than visceral fat storage.
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Affiliation(s)
- Maamoun Basheer
- Internal Medicine Department, Galilee Medical Center, Nahariya 221001, Israel; (M.B.); (E.S.); (H.J.)
| | - Elias Saad
- Internal Medicine Department, Galilee Medical Center, Nahariya 221001, Israel; (M.B.); (E.S.); (H.J.)
- Azrieli Faculty of Medicine, Bar-Ilan University, Safad 1311502, Israel
| | - Helena Jeries
- Internal Medicine Department, Galilee Medical Center, Nahariya 221001, Israel; (M.B.); (E.S.); (H.J.)
| | - Nimer Assy
- Internal Medicine Department, Galilee Medical Center, Nahariya 221001, Israel; (M.B.); (E.S.); (H.J.)
- Azrieli Faculty of Medicine, Bar-Ilan University, Safad 1311502, Israel
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20
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Deravi N, Dehghani Firouzabadi F, Moosaie F, Asadigandomani H, Arab Bafrani M, Yoosefi N, Poopak A, Dehghani Firouzabadi M, Poudineh M, Rabizadeh S, Kamel I, Nakhjavani M, Esteghamati A. Non-alcoholic fatty liver disease and incidence of microvascular complications of diabetes in patients with type 2 diabetes: a prospective cohort study. Front Endocrinol (Lausanne) 2023; 14:1147458. [PMID: 37342261 PMCID: PMC10277724 DOI: 10.3389/fendo.2023.1147458] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 05/17/2023] [Indexed: 06/22/2023] Open
Abstract
Objective To investigate the association between non-alcoholic fatty liver disease (NAFLD) and liver enzymes with the incidence of microvascular complications (neuropathy, retinopathy, and nephropathy) in a cohort of Iranian patients with type 2 diabetes. Methods For a total population of 3123 patients with type 2 diabetes, a prospective study was designed for 1215 patients with NAFLD and 1908 gender and age-matched control patients without NAFLD. The two groups were followed for a median duration of 5 years for the incidence of microvascular complications. The association between having NAFLD, the level of liver enzymes, aspartate aminotransferase to platelet ratio index (APRI), Fibrosis-4 (FIB-4) value, and the incidence risk of diabetic retinopathy, neuropathy, and nephropathy were assessed through logistic regression analysis. Results NAFLD was found to be associated with incidence of diabetic neuropathy and nephropathy (Odds ratio: 1.338 (95% confidence interval: 1.091-1.640) and 1.333 (1.007-1.764), respectively). Alkaline-phosphatase enzyme was found to be associated with higher risks of diabetic neuropathy and nephropathy ((Risk estimate: 1.002 (95% CI: 1.001-1.003) and 1.002 (1.001-1.004), respectively)). Moreover, gamma-glutamyl transferase was associated with a higher risk of diabetic nephropathy (1.006 (1.002-1.009). Aspartate aminotransferase and alanine aminotransferase were inversely associated with the risk of diabetic retinopathy (0.989 (0.979-0.998) and 0.990 (0.983-0.996), respectively). Furthermore, ARPI_T (1), ARPI_T (2), and ARPI_T (3) were shown to be associated with NAFLD (1.440 (1.061-1.954), 1.589 (1.163-2.171), and 2.673 (1.925, 3.710), respectively). However, FIB-4 score was not significantly associated with risk of microvascular complications. Conclusion Despite the benign nature of NAFLD, patients with type 2 diabetes should be always assessed for NAFLD to ensure early diagnosis and entry into proper medical care. Regular screenings of microvascular complications of diabetes is also suggested for these patients.
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Affiliation(s)
- Niloofar Deravi
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Student Research committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Fatemeh Moosaie
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hassan Asadigandomani
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Melika Arab Bafrani
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Niyoosha Yoosefi
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Poopak
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Dehghani Firouzabadi
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohadeseh Poudineh
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Soghra Rabizadeh
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ibrahim Kamel
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Manouchehr Nakhjavani
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Esteghamati
- Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Béland-Bonenfant S, Petit JM, Vergès B. NAFLD et NASH au cours du diabète : données épidémiologiques, cliniques et pronostiques. MÉDECINE DES MALADIES MÉTABOLIQUES 2023; 17:248-252. [DOI: 10.1016/j.mmm.2023.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Possible, probable, and certain hypercortisolism: A continuum in the risk of comorbidity. ANNALES D'ENDOCRINOLOGIE 2023; 84:272-284. [PMID: 36736771 DOI: 10.1016/j.ando.2023.01.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 01/17/2023] [Indexed: 02/04/2023]
Abstract
Hypercortisolism may be considered as a continuum in terms of both hormonal and cardiometabolic abnormalities. It ranges from cases with "normal" hormonal profile and low to intermediate risk of comorbidity to florid cases with clear clinical and hormonal evidence of glucocorticoid excess and clearly increased cardiometabolic risk. Even in patients with nonfunctioning adrenal incidentaloma (NFAI), defined as adrenal incidentaloma with normal results on the currently available hormonal test for evaluation of hypercortisolism, cardiometabolic and mortality risk is higher than in the general population without adrenal lesions. Mild hypercortisolism or autonomous cortisol secretion (ACS) is a term used for patients with adrenal incidentaloma and pathological dexamethasone suppression test (DST) results, but without specific clinical signs of hypercortisolism. It is widely known that this condition is linked to higher prevalence of several cardiometabolic comorbidities, including diabetes, hypertension, osteoporosis and metabolic syndrome, than in patients with NFAI or without adrenal tumor. In case of overt Cushing's syndrome, cardiovascular risk is extremely high, and standard mortality ratio is high, cardiovascular disease being the leading cause of death. The present review summarizes the current evidence for a detrimental cardiometabolic profile in patients with possible (NFAI), probable (ACS) and certain hypercortisolism (overt Cushing's syndrome).
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Oxidative Stress Modulation by ncRNAs and Their Emerging Role as Therapeutic Targets in Atherosclerosis and Non-Alcoholic Fatty Liver Disease. Antioxidants (Basel) 2023; 12:antiox12020262. [PMID: 36829822 PMCID: PMC9952114 DOI: 10.3390/antiox12020262] [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: 12/21/2022] [Revised: 01/18/2023] [Accepted: 01/20/2023] [Indexed: 01/27/2023] Open
Abstract
Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are pathologies related to ectopic fat accumulation, both of which are continuously increasing in prevalence. These threats are prompting researchers to develop effective therapies for their clinical management. One of the common pathophysiological alterations that underlies both diseases is oxidative stress (OxS), which appears as a result of lipid deposition in affected tissues. However, the molecular mechanisms that lead to OxS generation are different in each disease. Non-coding RNAs (ncRNAs) are RNA transcripts that do not encode proteins and function by regulating gene expression. In recent years, the involvement of ncRNAs in OxS modulation has become more recognized. This review summarizes the most recent advances regarding ncRNA-mediated regulation of OxS in atherosclerosis and NAFLD. In both diseases, ncRNAs can exert pro-oxidant or antioxidant functions by regulating gene targets and even other ncRNAs, positioning them as potential therapeutic targets. Interestingly, both diseases have common altered ncRNAs, suggesting that the same molecule can be targeted simultaneously when both diseases coexist. Finally, since some ncRNAs have already been used as therapeutic agents, their roles as potential drugs for the clinical management of atherosclerosis and NAFLD are analyzed.
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24
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Bortz JH. Metabolic-Associated Fatty Liver Disease: Opportunistic Screening at CT Colonography. CT COLONOGRAPHY FOR RADIOGRAPHERS 2023:277-290. [DOI: 10.1007/978-3-031-30866-6_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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25
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Yang S, Ye Z, Liu M, Zhang Y, Wu Q, Zhou C, Zhang Z, He P, Zhang Y, Li H, Liu C, Qin X. Association of serum uric acid with all-cause and cardiovascular mortality among adults with nonalcoholic fatty liver disease. Clin Endocrinol (Oxf) 2023; 98:49-58. [PMID: 35968564 DOI: 10.1111/cen.14810] [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: 04/14/2022] [Revised: 08/05/2022] [Accepted: 08/09/2022] [Indexed: 12/13/2022]
Abstract
AIM The association between serum uric acid (SUA) and mortality from cardiovascular diseases (CVDs) in nonalcoholic fatty liver disease (NAFLD) participants remains uncertain. We aim to investigate the relations of SUA with the risk of CVD mortality among adults with and without NAFLD. METHODS Using data from National Health and Nutrition Examination Survey (NHANES) 1999-2014, a total of 17,858 participants were recruited. Of these, 5767 had a US Fatty Liver Index (USFLI) ≥30 and were classified as having NAFLD. Death information was obtained from the National Death Index until 2015. RESULTS During a mean follow-up of 8.3 years, 427 participants died from CVD. Overall, there was a positive association between SUA and CVD mortality among participants with NAFLD (per SD μmol/L increment, adjusted hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.16-1.68). Accordingly, among those with NAFLD, when SUA was assessed as quartiles, compared with those in the first quartile, a significantly higher risk of CVD mortality was found in participants in the fourth quartile (adjusted HR, 2.69; 95% CI, 1.51-4.80). However, there was no significant association between SUA and CVD mortality among participants without NAFLD (per SD μmol/L increment, adjusted HR, 1.01; 95% CI, 0.83-1.22). Similar trends were found for all-cause mortality. Similar results were also found when using FLI ≥ 60 to define NAFLD. CONCLUSIONS In a large and nationally representative sample of US adults, a higher SUA was significantly associated with a higher risk of CVD mortality among participants with NAFLD, but not in those without NAFLD.
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Affiliation(s)
- Sisi Yang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Ziliang Ye
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Mengyi Liu
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Yanjun Zhang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Qimeng Wu
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Chun Zhou
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Zhuxian Zhang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Panpan He
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Yuanyuan Zhang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Huan Li
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
| | - Chengzhang Liu
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
- Institute of Biomedicine, Anhui Medical University, Hefei, China
| | - Xianhui Qin
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
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Babak O, Lapshyna K, Prosolenko K, Chernyak A, Goptsiy O. Evaluation of MACK-3 parameters, metabolic and fibrotic characteristics of non-alcoholic fatty liver disease patients with hypertension. Minerva Gastroenterol (Torino) 2022; 68:415-420. [PMID: 34929996 DOI: 10.23736/s2724-5985.21.02982-x] [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: 12/15/2022]
Abstract
BACKGROUND Non-alcoholic steatohepatitis (NASH) is an inflammatory subtype of non-alcoholic fatty liver disease (NAFLD) and recent non-invasive test, MACK-3, demonstrated good diagnostic characteristics for fibrosis in several studies. The aim of our study was to assess the liver state using the non-invasive MACK-3 Test, and its link with liver fibrosis stage, inflammatory activity, steatosis, and metabolic markers in NAFLD patients with hypertension (HT). METHODS Thirty adult NAFLD patients with HT, aged 30 to 60 years (mean age 46.36±5.1 years) were included in our study. The control group consisted of 20 healthy volunteers. In addition to basic laboratory tests and ultrasonographic examination, validated non-invasive fibrosis test were performed. MACK-3 was calculated using the online calculator with the following variables: fasting glucose, fasting insulin, aspartate aminotransferase (AST) and cytokeratin 18 (CK18). RESULTS All NAFLD patients with HT were characterized with increased liver enzymatic activity, lipid profile, increased levels of insulin and HOMA-IR˂0.001. MACK-3 parameters were positively correlated with thymol test = 0.45 (P<0.013), with aspartataminotransferase (AST) = 0.38 (P<0.03) and alanineaminotransferase (ALT) - =0.38 (P<0.03), with the stage of Fibrotest activity = 0.25 (P<0.018) and steatosis = 0.76 (P<0.001). CONCLUSIONS MACK-3 parameters associations with hepatic enzymatic activity, steatosis and activity stage suggest this test as a promising for screening use in such patients and requires further studies.
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Affiliation(s)
- Oleg Babak
- Kharkiv National Medical University, Kharkiv, Ukraine
| | | | | | - Arkadiy Chernyak
- GI "National Institute of Therapy named by L.T. Malaya NAMNU, " Kharkiv, Ukraine
| | - Olena Goptsiy
- Kharkiv National Medical University, Kharkiv, Ukraine
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Zhang GH, Yuan TH, Yue ZS, Wang L, Dou GR. The presence of diabetic retinopathy closely associated with the progression of non-alcoholic fatty liver disease: A meta-analysis of observational studies. Front Mol Biosci 2022; 9:1019899. [PMID: 36458094 PMCID: PMC9706004 DOI: 10.3389/fmolb.2022.1019899] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 11/01/2022] [Indexed: 07/30/2023] Open
Abstract
Background and Objective: Although growing evidence indicates that non-alcoholic fatty liver disease is related to diabetic retinopathy (DR), research results significantly vary. Therefore, we conducted a meta-analysis to assess the association between the progression of non-alcoholic fatty liver disease and the onset of DR. Methods: PubMed, Embase, and Cochrane databases were searched until 7 November 2021. Combined odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association. Results: We identified 18 studies involving 12,757 patients. The pooled effect assessment showed that liver fibrosis was positively correlated with DR (OR = 1.69, 95%CI 1.30-2.20; p < 0.0001); non-alcoholic fatty liver disease was not associated with the risk of DR (OR = 1.15, 95%CI 0.75-1.76; p = 0.51); non-alcoholic fatty liver disease was positively correlated with DR in patients with type 1 diabetes (OR = 2.96, 95%CI 1.48-5.94; p = 0.002). In patients with type 2 diabetes, there was no association between non-alcoholic fatty liver disease and DR (OR = 0.92, 95%CI 0.59-1.43; p = 0.70). Subgroup analysis showed no correlation in both Asian and Caucasian races. Conclusion: There is a significant correlation between liver fibrosis and DR. This suggests that the ocular examination of DR could be helpful in predicting whether patients with non-alcoholic fatty liver disease would progress to liver fibrosis.
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Affiliation(s)
- Guo-heng Zhang
- Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- Department of Ophthalmology, 942 Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Yin’chuan, China
| | - Tian-hao Yuan
- Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- Department of The Cadet Team 6 of School of Basic Medicine, Fourth Military Medical University, Xi’an, China
| | - Zhen-sheng Yue
- Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Lin Wang
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Guo-Rui Dou
- Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an, China
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A Meta-Analysis on the Global Prevalence, Risk factors and Screening of Coronary Heart Disease in Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol 2022; 20:2462-2473.e10. [PMID: 34560278 DOI: 10.1016/j.cgh.2021.09.021] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/04/2021] [Accepted: 09/10/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Cardiovascular disease remains the leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Studies examining the association of coronary heart disease (CHD) and NAFLD are cofounded by various cardiometabolic factors, particularly diabetes and body mass index. Hence, we seek to explore such association by investigating the global prevalence, independent risk factors, and influence of steatosis grade on manifestation of CHD among patients with NAFLD. METHODS Two databases, Embase and Medline, were utilized to search for articles relating to NAFLD and CHD. Data including, but not limited to, continent, diagnostic methods, baseline characteristics, prevalence of CHD, CHD severity, NAFLD severity, and risk factors were extracted. RESULTS Of the 38 articles included, 14 reported prevalence of clinical coronary artery disease (CAD) and 24 subclinical CAD. The pooled prevalence of CHD was 44.6% (95% confidence interval [CI], 36.0%-53.6%) among 67,070 patients with NAFLD with an odds ratio of 1.33 (95% CI, 1.21%-1.45%; P < .0001). The prevalence of CHD was higher in patients with moderate to severe steatosis (37.5%; 95% CI, 15.0%-67.2%) than those with mild steatosis (29.6%; 95% CI, 13.1%-54.0%). The pooled prevalence of subclinical and clinical CAD was 38.7% (95% CI, 29.8%-48.5%) and 55.4% (95% CI, 39.6%-70.1%), respectively. CONCLUSION Steatosis was found to be related with CHD involvement, with moderate to severe steatosis related to clinical CAD. Early screening and prompt intervention for CHD in NAFLD are warranted for holistic care in NAFLD.
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Koullias ES, Koskinas J. Pharmacotherapy for Non-alcoholic Fatty Liver Disease Associated with Diabetes Mellitus Type 2. J Clin Transl Hepatol 2022; 10:965-971. [PMID: 36304499 PMCID: PMC9547270 DOI: 10.14218/jcth.2021.00564] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 04/14/2022] [Accepted: 04/27/2022] [Indexed: 12/04/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and diabetes mellitus type 2 commonly coexist as a manifestation of metabolic syndrome. The presence of diabetes promotes the progression of simple fatty liver to non-alcoholic steatohepatitis (NASH) and cirrhosis, and the presence of NAFLD increases the risk of diabetic complications. This coexistence affects a large part of the population, imposing a great burden on health care systems worldwide. Apart from diet modification and exercise, recent advances in the pharmacotherapy of diabetes offer new prospects regarding liver steatosis and steatohepatitis improvement, enriching the existing algorithm and supporting a multifaceted approach to diabetic patients with fatty liver disease. These agents mainly include members of the families of glucagon-like peptide-1 analogues and the sodium-glucose co-transporter-2 inhibitors. In addition, agents acting on more than one receptor simultaneously are presently under study, in an attempt to further enhance our available options.
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Affiliation(s)
- Emmanouil S. Koullias
- Correspondence to: Emmanouil S. Koullias, 2nd Department of Internal Medicine, National and Kapodistrian University of Athens, Ampelokipoi, Athens, Greece. ORCID: https://orcid.org/0000-0002-4037-7123. Tel: +69-4-5631-395, E-mail:
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The Protective Effects of Corn Oligopeptides on Acute Alcoholic Liver Disease by Inhibiting the Activation of Kupffer Cells NF-κB/AMPK Signal Pathway. Nutrients 2022; 14:nu14194194. [PMID: 36235846 PMCID: PMC9572984 DOI: 10.3390/nu14194194] [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: 08/29/2022] [Revised: 09/25/2022] [Accepted: 09/27/2022] [Indexed: 11/05/2022] Open
Abstract
Alcohol can cause injury and lead to an inflammatory response in the liver. The NF-κB/AMPK signaling pathway plays a vital role in regulating intracellular inflammatory cytokine levels. In this study, corn oligopeptides (CPs), as the research objects, were obtained from corn gluten meal, and their regulation of the activation of the Kupffer cell NF-κB/AMPK signal pathway induced by LPS was investigated. Results showed that ALT, AST, and inflammatory cytokines in mice serum after the administration of CPs at 0.2, 0.4, and 0.8 g/kg of body weight displayed a distinct (p < 0.05) reduction. On the other hand, the CPs also inhibited the expression of recognized receptor CD14 and TLR4, down-regulated P-JNK, P-ERK, and P-p-38, and thus inhibited inflammatory cytokine levels in Kupffer cells (KCs). Furthermore, four kinds of dipeptides with a leucine residue at the C-terminus that might exhibit down-regulated inflammatory cytokines in the NF-κB/AMPK signaling pathway functions were detected using HPLC-MS/MS. These results indicated that CPs have a potential application value in acute alcoholic liver disease.
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Shibata Y, Fukuda T, Nobeyama Y, Asahina A. Evaluation of nonalcoholic fatty liver disease in Japanese patients with psoriasis: Chest CT imaging for screening purposes. J Dermatol 2022; 49:1263-1267. [PMID: 36074651 DOI: 10.1111/1346-8138.16564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 07/20/2022] [Accepted: 08/15/2022] [Indexed: 11/26/2022]
Abstract
Psoriasis patients have been reported to have a higher prevalence of nonalcoholic fatty liver disease (NAFLD), therefore detection at an early stage is important since it may progress to hepatic cirrhosis or hepatocellular carcinoma. We evaluated liver fat accumulation in patients with moderate to severe psoriasis by chest computed tomography (CT). The images were taken for screening purposes prior to the start of any biologics. The prevalence of NAFLD in patients with psoriasis vulgaris, psoriatic arthritis, and control subjects was 19.4%, 33.3% and 9.8%, respectively (P = 0.004). The mean CT score in psoriasis patients was significantly lower (51.684 ± 12.778) than that in control subjects (61.204 ± 9.498, P < 0.001). Multivariate logistic regression analysis showed that only CT scores were associated with the presence of psoriasis (P = 0.001). No significant relationship was observed between the Psoriasis Activity and Severity Index scores and CT scores of psoriasis patients (P = 0.055), suggesting that the presence of psoriasis may contribute to the pathogenesis of NAFLD. By analysis of chest CT imaging, our study successfully assessed liver fat accumulation. Chest CT is a useful diagnostic tool for the quantitative measurement of fat accumulated in the liver, enabling the early noninvasive detection of NAFLD and early therapeutic intervention.
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Affiliation(s)
- Yuka Shibata
- Dermatology, Jikei University School of Medicine, Tokyo, Japan
| | - Takeshi Fukuda
- Radiology, Jikei University School of Medicine, Tokyo, Japan
| | | | - Akihiko Asahina
- Dermatology, Jikei University School of Medicine, Tokyo, Japan
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The effects of vitamin B12 supplementation on metabolic profile of patients with non-alcoholic fatty liver disease: a randomized controlled trial. Sci Rep 2022; 12:14047. [PMID: 35982162 PMCID: PMC9388548 DOI: 10.1038/s41598-022-18195-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 08/08/2022] [Indexed: 11/09/2022] Open
Abstract
The present study is the first effort to evaluate the effects of vitamin B12 supplementation on the serum level of liver enzymes, homocysteine, grade of hepatic steatosis, and metabolic profiles in patients with non-alcoholic fatty liver disease (NAFLD). Forty patients with NAFLD were enrolled in a double-blind placebo-controlled trial to receive either one oral tablet of vitamin B12 (1000 µg cyanocobalamin) or a placebo per day for 12 weeks. We investigated serum levels of homocysteine, aminotransferases, fasting blood glucose (FBG), lipids, malondialdehyde (MDA), and homeostasis model assessment of insulin resistance (HOMA-IR). The grade of liver steatosis and fibrosis was measured by real-time 2-dimensional shear wave elastography. Vitamin B12 supplementation significantly decreased serum levels of homocysteine compared to placebo (medians: - 2.1 vs. - 0.003 µmol/l; P = 0.038). Although serum alanine transaminase (ALT) in the vitamin B12 group decreased significantly, this change did not reach a significant level compared to the placebo group (medians: - 7.0 vs. 0.0 IU/l; P > 0.05). Despite the significant within-group decrease in FBG, MDA, and liver steatosis in the vitamin B12 group, between-group comparisons did not reveal any significant difference. Vitamin B12 supplementation might decrease serum levels of homocysteine in patients with NAFLD. The fasting blood glucose and serum levels of MDA were significantly improved in the trial group who received vitamin B12. However, these changes did not reach a significant level compared to the placebo group. In this respect, further studies with larger sample sizes, different doses, and types of vitamin B12 will reveal additional evidence.Trial Registration: At http://irct.ir/ as IRCT20120718010333N5 on December 25, 2019.
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Czapla-Iskrzycka A, Świątkowska-Stodulska R, Sworczak K. Comorbidities in Mild Autonomous Cortisol Secretion - A Clinical Review of Literature. Exp Clin Endocrinol Diabetes 2022; 130:567-576. [PMID: 35817047 DOI: 10.1055/a-1827-4113] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Mild autonomous cortisol secretion (mACS) is a state of cortisol excess usually associated with existence of adrenal incidentaloma. Because of the lack of symptoms of the disease, the biochemical evaluation is the most important to determine a diagnosis. However, scientific societies have different diagnostic criteria for mACS, which makes the treatment of this disease and using results of original papers in daily practice more difficult. Chronic hypercortisolemic state, even if mild, may lead to diseases that are mostly connected with overt Cushing's syndrome. Some of them can cause a higher mortality of patients with mACS and those problems need to be addressed. In this review we describe the comorbidities associated with mACS: cardiovascular disorders, arterial hypertension, diabetes mellitus, insulin resistance, dyslipidemia, obesity, metabolic syndrome, non-alcoholic fatty liver disease, vertebral fractures and osteoporosis. The point of this paper is to characterise them and determine if and how these conditions should be managed. Two databases - PubMed and Web of Science were searched. Even though the evidence are scarce, this is an attempt to lead clinicians through the problems associated with this enigmatic condition.
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Affiliation(s)
- Aleksandra Czapla-Iskrzycka
- Department of Endocrinology and Internal Medicine, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland
| | - Renata Świątkowska-Stodulska
- Department of Endocrinology and Internal Medicine, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland
| | - Krzysztof Sworczak
- Department of Endocrinology and Internal Medicine, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland
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Sex hormone binding globulin as a potential drug candidate for liver-related metabolic disorders treatment. Biomed Pharmacother 2022; 153:113261. [PMID: 35738176 DOI: 10.1016/j.biopha.2022.113261] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/30/2022] [Accepted: 06/06/2022] [Indexed: 11/29/2022] Open
Abstract
Sex hormone binding globulin (SHBG) is a hepatokine that binds to circulating steroid hormones (testosterone, oestradiol) to regulate their concentration in the bloodstream. Recently SHBG was recognized as an essential biomarker for metabolic syndrome (MetS) and hepatic steatosis development. At the hepatic level, the production of SHBG is mainly regulated by sex steroids and thyroxine. Studies of various research groups, including ours, showed that SHBG could be considered a reliable marker of insulin resistance and, therefore, can serve as a predictor of type 2 diabetes. Moreover, increased levels of circulating pro-inflammatory mediators strongly correlate with lowered serum levels of SHBG. This review paper emphasizes the role of SHBG as a potential drug candidate in the course of various metabolic dysfunctions, including non-alcoholic fatty liver disease (NAFLD), obesity, diabetes mellitus and insulin resistance. The studies related to SHBG and its role in the course of metabolic disorders are very limited. Here, we have summarized the most current knowledge about SHBG and its mechanism of action, indicating a novel concept for its possible therapeutic application in the management framework of commonly occurring metabolic dysfunctions.
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Papagiouvanni I, Theodorakopoulou MP, Sarafidis P, Sinakos E, Goulis I. Peripheral endothelial and microvascular damage in liver cirrhosis: a systematic review and meta-analysis. Microcirculation 2022; 29:e12773. [PMID: 35652811 DOI: 10.1111/micc.12773] [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: 02/18/2022] [Revised: 04/13/2022] [Accepted: 05/25/2022] [Indexed: 11/29/2022]
Abstract
OBJECTIVE This is the first systematic review and meta-analysis of studies using any available functional method to examine differences in peripheral endothelial function between cirrhotic and non-cirrhotic individuals. METHODS Literature search involved PubMed, Web-of-Science and Scopus databases, as well as grey literature sources. We included studies in adult subjects evaluating endothelial function with any semi-invasive or non-invasive functional method in patients with and without liver cirrhosis. RESULTS From 3378 records initially retrieved, 15 studies with a total of 570 participants were included in the final quantitative meta-analysis. In 6 studies examining endothelial function with flow-mediated-dilatation no differences between patients with cirrhosis and controls were evident (WMD: 1.33, 95%CI [-2.87, 5.53], I2 =97%, p<0.00001). Among studies assessing differences in endothelial-dependent or endothelial-independent vasodilation with venous-occlusion-plethysmography, there were no significant differences between the two groups. When pooling all studies together, regardless of the technique used, no significant difference in endothelial function between cirrhotic patients and controls was observed(SMD: 0.79, 95%CI[-0.04, 1.63], I2=94%, p<0.00001). CONCLUSIONS No differences in peripheral endothelial function assessed with semi-invasive or non-invasive functional methods exist between cirrhotic and non-cirrhotic subjects. The increasing co-existence of cardiovascular risk factors leading to impaired vascular reactivity in cirrhotic patients may partly explain these findings.
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Affiliation(s)
- Ioanna Papagiouvanni
- 1Fourth Department of Internal Medicine, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Marieta P Theodorakopoulou
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Pantelis Sarafidis
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Emmanouil Sinakos
- 1Fourth Department of Internal Medicine, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Ioannis Goulis
- 1Fourth Department of Internal Medicine, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Baars T, Gieseler RK, Patsalis PC, Canbay A. Towards harnessing the value of organokine crosstalk to predict the risk for cardiovascular disease in non-alcoholic fatty liver disease. Metabolism 2022; 130:155179. [PMID: 35283187 DOI: 10.1016/j.metabol.2022.155179] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 02/25/2022] [Accepted: 03/07/2022] [Indexed: 12/13/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Importantly, NAFLD increases the risk for cardiovascular disease (CVD). A causal relationship has been substantiated. Given the pandemic proportions of NAFLD, a reliable scoring system for predicting the risk of NAFLD-associated CVD is an urgent medical need. We here review cumulative evidence suggesting that systemically released organokines - especially certain adipokines, hepatokines, and cardiokines - may serve this purpose. The underlying rationale is that these signalers directly communicate between white adipose tissue, liver, and heart as key players in the pathogenesis of NAFLD and resultant CVD events. Moreover, evidence suggests that these organ-specific cytokines are secreted in a biologically predetermined, cascade-like pattern. Consequently, upon pinpointing organokines of relevance, we sketch requirements to establish an algorithm predictive of the CVD risk in patients with NAFLD. Such an algorithm, as to be consolidated in the form of an applicable equation, may be improved continuously by machine learning. To the best of our knowledge, such an option has not yet been considered. Establishing and implementing a reliable algorithm for determining the NAFLD-associated CVD risk has the potential to save many NAFLD patients from life-threatening CVD events.
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Affiliation(s)
- Theodor Baars
- Department of Internal Medicine, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany; Section of Metabolic and Preventive Medicine, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany
| | - Robert K Gieseler
- Department of Internal Medicine, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany; Laboratory of Immunology and Molecular Biology, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany
| | - Polykarpos C Patsalis
- Department of Internal Medicine, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany; Section of Cardiology and Internal Emergency Medicine, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany
| | - Ali Canbay
- Department of Internal Medicine, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany; Section of Hepatology and Gastroenterology, University Hospital, Knappschaftskrankenhaus, Ruhr University Bochum, 44892 Bochum, Germany.
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The role of Dobutamine stress echocardiography in patients evaluated for liver transplant to predict latent cardiac disease. JOURNAL OF LIVER TRANSPLANTATION 2022. [DOI: 10.1016/j.liver.2022.100093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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Ogresta D, Mrzljak A, Cigrovski Berkovic M, Bilic-Curcic I, Stojsavljevic-Shapeski S, Virovic-Jukic L. Coagulation and Endothelial Dysfunction Associated with NAFLD: Current Status and Therapeutic Implications. J Clin Transl Hepatol 2022; 10:339-355. [PMID: 35528987 PMCID: PMC9039716 DOI: 10.14218/jcth.2021.00268] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 09/24/2021] [Accepted: 10/08/2021] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is closely related to insulin resistance, type 2 diabetes mellitus and obesity. It is considered a multisystem disease and there is a strong association with cardiovascular disease and arterial hypertension, which interfere with changes in the coagulation system. Coagulation disorders are common in patients with hepatic impairment and are dependent on the degree of liver damage. Through a review of the literature, we consider and discuss possible disorders in the coagulation cascade and fibrinolysis, endothelial dysfunction and platelet abnormalities in patients with NAFLD.
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Affiliation(s)
- Doris Ogresta
- Department of Gastroenterology and Hepatology, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
| | - Anna Mrzljak
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia
- Department of Medicine, University of Zagreb, School of Medicine, Zagreb, Croatia
| | - Maja Cigrovski Berkovic
- Department for Endocrinology, Diabetes and Pharmacology, University Hospital Dubrava, Zagreb, Croatia
- Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb
- Department of Pharmacology, Faculty of Medicine, University of JJ Strossmayer, Osijek, Croatia
| | - Ines Bilic-Curcic
- Department of Pharmacology, Faculty of Medicine, University of JJ Strossmayer, Osijek, Croatia
- Department of Diabetes, Endocrinology and Metabolism Disorders, University Hospital Osijek, Osijek, Croatia
| | | | - Lucija Virovic-Jukic
- Department of Gastroenterology and Hepatology, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
- Department of Medicine, University of Zagreb, School of Medicine, Zagreb, Croatia
- Correspondence to: Lucija Virović-Jukić, University of Zagreb School of Medicine, Department of Medicine; Department of Gastroenterology and Hepatology, Sestre Milosrdnice University Hospital Center, Vinogradska cesta 29, Zagreb 10000, Croatia. ORCID: https://orcid.org/0000-0002-6350-317X. Tel: +385-1-3787178, Fax: +385-1-3787448, E-mail:
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Guo XF, Wang C, Yang T, Ma WJ, Zhai J, Zhao T, Xu TC, Li J, Liu H, Sinclair AJ, Li D. Concentrated fish oil ameliorates non-alcoholic fatty liver disease by regulating FGF21-adiponectin axis. Nutrition 2022; 99-100:111659. [DOI: 10.1016/j.nut.2022.111659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 03/14/2022] [Accepted: 03/15/2022] [Indexed: 10/18/2022]
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Guo XF, Wang C, Yang T, Ma WJ, Zhai J, Zhao T, Xu TC, Li J, Liu H, Sinclair AJ, Li D. The effects of fish oil plus vitamin D3 intervention on non-alcoholic fatty liver disease: a randomized controlled trial. Eur J Nutr 2022; 61:1931-1942. [DOI: 10.1007/s00394-021-02772-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 12/03/2021] [Indexed: 01/10/2023]
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The Association between Serum Uric Acid Levels and 10-Year Cardiovascular Disease Risk in Non-Alcoholic Fatty Liver Disease Patients. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19031042. [PMID: 35162067 PMCID: PMC8834479 DOI: 10.3390/ijerph19031042] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 01/10/2022] [Accepted: 01/17/2022] [Indexed: 02/04/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) and serum uric acid (SUA) levels are risk factors for developing cardiovascular disease (CVD). Additionally, previous studies have suggested that high SUA levels increase the risk of having NAFLD. However, no study has investigated the relationship between SUA and CVD risk in NAFLD. This study analyzed the relationship between SUA and CVD in NAFLD. Data for this study used the 2016–2018 Korean National Health and Nutrition Examination Survey, which represents the Korean population. A total of 11,160 NAFLD patients were included. Participants with hepatic steatosis index ≥ 30 were considered to have NAFLD. Ten-year CVD risk was estimated using an integer-based Framingham risk score. Estimated 10-year CVD risk ≥ 20% was considered high risk. Multiple logistic regression was conducted to calculate the odds ratios (ORs) associated with SUA level and CVD risk. High CVD risk OR increases by 1.31 (95% CI 1.26–1.37) times per 1 mg/dL of SUA. After adjustment, SUA still had an increased risk (OR 1.44; 95% CI 1.38–1.51) of CVD. Compared with the lowest SUA quartile group, the highest quartile group showed a significantly higher risk of having CVD before (OR 2.76; 95% CI 2.34–3.25) and after (OR 4.01; 95% CI 3.37–4.78) adjustment. SUA is independently associated with CVS risk in NAFLD.
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Xu C, Li H, Tang CK. Sterol Carrier Protein 2: A promising target in the pathogenesis of atherosclerosis. Genes Dis 2022; 10:457-467. [DOI: 10.1016/j.gendis.2021.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 11/21/2021] [Accepted: 12/01/2021] [Indexed: 10/19/2022] Open
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Yardeni D, Toledano R, Novack V, Shalev A, Wolak A, Rotman Y, Etzion O. The Association of Alanine Aminotransferase Levels With Myocardial Perfusion Imaging and Cardiovascular Morbidity. J Cardiovasc Pharmacol Ther 2022; 27:10742484221074585. [PMID: 35077243 PMCID: PMC8840806 DOI: 10.1177/10742484221074585] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
INTRODUCTION Studies suggest that non-alcoholic fatty liver disease (NAFLD) is associated with an independent risk of cardiovascular disease (CVD). We utilized a large cohort of patients undergoing myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) to determine the association between alanine aminotransferase (ALT) as a surrogate marker for presumed NAFLD, and the presence of myocardial ischemia and mortality. METHODS We retrospectively assessed SPECT-MPI results and medical records of individuals evaluated between 1997 and 2008. We excluded patients with known non-NAFLD liver diseases, ALT values <17 or >340 U/L and absent liver tests. Elevated ALT cases were classified as presumed NAFLD. The primary endpoint was abnormal SPECT-MPI. Secondary endpoints included cardiac death, acute myocardial infarction and all-cause mortality. RESULTS Of 26,034 patients who underwent SPECT-MPI, 11,324 met inclusion criteria. 1635 (14.4%) patients had elevated ALT. SPECT-MPI results did not differ significantly between subjects with elevated ALT and controls. Elevated ALT was associated with increased risk for the composite endpoint of cardiac death or acute myocardial infarction at 5-year follow-up (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.01-1.67) and in all-cause mortality (HR 1.27, CI 1.02-1.58) but only in patients with normal SPECT-MPI. CONCLUSIONS The long-term mortality of patients with abnormal SPECT-MPI is not modulated by ALT, likely reflecting an already high risk and established CVD. However, patients with normal SPECT-MPI are at increased risk for a future cardiac event if they have an elevated ALT level, suggesting an important role for NAFLD in earlier stages of CVD.
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Affiliation(s)
- David Yardeni
- Department of Gastroenterology and Liver Diseases, Soroka University Medical Center, Beer-Sheva, Israel
| | - Ronen Toledano
- Clinical Research Center, Soroka University Medical Center, Beer-Sheva, Israel
| | - Victor Novack
- Clinical Research Center, Soroka University Medical Center, Beer-Sheva, Israel
| | - Aryeh Shalev
- Cardiology Department, Soroka University Medical Center, Beer-Sheva, Israel
| | - Arik Wolak
- Cardiology Department, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Yaron Rotman
- Liver & Energy Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Ohad Etzion
- Department of Gastroenterology and Liver Diseases, Soroka University Medical Center, Beer-Sheva, Israel
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Liu J, Duan S, Wang C, Wang Y, Peng H, Niu Z, Yao S. Optimum non-invasive predictive indicators for metabolic dysfunction-associated fatty liver disease and its subgroups in the Chinese population: A retrospective case-control study. Front Endocrinol (Lausanne) 2022; 13:1035418. [PMID: 36531447 PMCID: PMC9751395 DOI: 10.3389/fendo.2022.1035418] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 11/15/2022] [Indexed: 12/04/2022] Open
Abstract
OBJECTIVE Metabolic dysfunction-associated fatty liver disease (MAFLD) affects 25% of the population without approved drug therapy. According to the latest consensus, MAFLD is divided into three subgroups based on different diagnostic modalities, including Obesity, Lean, and Type 2 diabetes mellitus (T2DM) MAFLD subgroups. This study aimed to find out the optimum non-invasive metabolism-related indicators to respectively predict MAFLD and its subgroups. DESIGN 1058 Chinese participants were enrolled in this study. Anthropometric measurements, laboratory data, and ultrasonography features were collected. 22 metabolism-related indexes were calculated, including fatty liver index (FLI), lipid accumulation product (LAP), waist circumference-triglyceride index (WTI), etc. Logistic regression analyzed the correlation between indexes and MAFLD. Receiver operating characteristics were conducted to compare predictive values among 22 indicators for screening the best indicators to predict MAFLD in different subgroups. RESULTS FLI was the best predictor with the maximum odds ratio (OR) values of overall MAFLD (OR: 6.712, 95%CI: 4.766-9.452, area under the curve (AUC): 0.879, P < 0.05) and T2DM MAFLD subgroup (OR: 14.725, 95%CI: 3.712-58.420, AUC: 0.958, P < 0.05). LAP was the best predictor with the maximum OR value of Obesity MAFLD subgroup (OR: 2.689, 95%CI: 2.182-3.313, AUC: 0.796, P < 0.05). WTI was the best predictor with the maximum OR values of Lean MAFLD subgroup (OR: 3.512, 95%CI: 2.286-5.395, AUC: 0.920, P < 0.05). CONCLUSION The best predictors of overall MAFLD, Obesity, Lean, and T2DM MAFLD subgroups were respectively FLI, LAP, WTI, and FLI.
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Affiliation(s)
- Jing Liu
- Graduate School, Peking Union Medical College, Beijing, China
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Shaojie Duan
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Che Wang
- School of Qi Huang, Beijing University of Chinese Medicine, Beijing, China
| | - Yutong Wang
- School of Qi Huang, Beijing University of Chinese Medicine, Beijing, China
| | - Hongye Peng
- Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zuohu Niu
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Shukun Yao
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
- *Correspondence: Shukun Yao,
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45
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Li W, Shen Y, Gong X, Zhang XB, Yuan L. Highly Selective Fluorescent Probe Design for Visualizing Hepatic Hydrogen Sulfide in the Pathological Progression of Nonalcoholic Fatty Liver. Anal Chem 2021; 93:16673-16682. [PMID: 34842411 DOI: 10.1021/acs.analchem.1c04246] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Hydrogen sulfide (H2S), emerging as an important gaseous signal, has attracted more and more attention for its key role in chronic fatty liver diseases. However, lacking tools for H2S-specific in situ detection, the changes of endogenous hepatic H2S levels in the pathological progression of chronic liver diseases are still unclear. To this end, we adopted a strategy of combining molecular probe design and nanofunctionalization to develop a highly selective near-infrared (NIR) fluorescent probe, which allows in vivo real-time monitoring of hepatic H2S levels in the process of nonalcoholic fatty liver disease (NAFLD). As a proof of strategy demonstration, we first designed NIR molecular probes for H2S sensing through chemical design and probe screening and then loaded molecular probes into mesoporous silicon nanomaterials (MSNs) with surface encapsulation using poly(ethylene glycol) to construct a highly selective probe MSN@CSN@PEG, with significantly improved selectivity and photostability. Moreover, MSN@CSN@PEG exhibited high selectivity and sensitivity for endogenous H2S in cells and tumors in vivo, eliminating the interference of a high concentration of biothiols and sulfhydryl proteins. Furthermore, the probe was applied to in situ intravital imaging and systematic assessment of hepatic H2S levels in different stages of NAFLD for the first time, which may offer a promising tool for the future study of fatty liver diseases and other chronic liver diseases.
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Affiliation(s)
- Wei Li
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China
| | - Yang Shen
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China
| | - Xiangyang Gong
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China
| | - Xiao-Bing Zhang
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China
| | - Lin Yuan
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China
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Lak HM, Chawla S, Gajulapalli RD, Verma BR, Vural AF, Gad M, Nair R, Shekhar S, Quintini C, Menon KN, Yun J, Burns D, Reed GW, Puri R, Harb S, Krishnaswamy A, Fares M, Kapadia SR. Outcomes After Transfemoral Transcatheter Aortic Valve Implantation With a SAPIEN 3 Valve in Patients With Cirrhosis of the Liver (a Tertiary Care Center Experience). Am J Cardiol 2021; 160:75-82. [PMID: 34583810 DOI: 10.1016/j.amjcard.2021.08.043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 08/10/2021] [Accepted: 08/16/2021] [Indexed: 01/06/2023]
Abstract
Little is known about the utility of transcatheter aortic valve implantation (TAVI) in patients with cirrhosis of the liver, and their outcomes have not been studied extensively in literature. We performed a retrospective analysis of patients with severe symptomatic aortic stenosis (AS) who underwent transfemoral TAVI with a SAPIEN 3 valve at our institution between April 2015 and December 2018. We identified 32 consecutive patients with evidence of cirrhosis of the liver on imaging (including ultrasound and/or computed tomography) and patients with severe symptomatic AS who underwent transfemoral TAVI with a SAPIEN 3 valve. Among 1,028 patients, 32 had cirrhosis of the liver and 996 constituted the control group without cirrhosis. Mean age in the cirrhosis group was 74.5 years compared with 81.2 years in the control group. Baseline variables were comparable between the groups. Compared with the noncirrhotic group, patients with cirrhosis had a similar 1-year mortality (12% vs 12%, p = 1), a lower 30-day new pacemaker after TAVI rate (6% vs 9%, p = 0.85), a higher 30-day and 1-year readmission rate for heart failure (11% vs 1% and 12% vs 5%, p = 0.12, respectively), and a similar 1-year major adverse cardiac and cerebrovascular event rate (15% vs 14%, p = 0.98). In conclusion, patients with severe AS with concomitant liver cirrhosis who underwent TAVI demonstrated comparable outcomes to their noncirrhotic counterparts.
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47
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Lee SB, Park BJ, Lee YJ, Jung DH. Early Chronic Kidney Disease (G1-G3a) in Combination with Steatosis as a Predictor of Incident Ischemic Heart Disease: A Longitudinal Study in Non-Diabetic Koreans. Biomedicines 2021; 9:biomedicines9101358. [PMID: 34680475 PMCID: PMC8533481 DOI: 10.3390/biomedicines9101358] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/25/2021] [Accepted: 09/28/2021] [Indexed: 12/26/2022] Open
Abstract
Hepatic steatosis and chronic kidney disease (CKD) in the advanced stages are closely related to cardiovascular diseases. Despite the potential connection between early CKD (G1-G3a) and hepatic steatosis on cardiometabolic risks, few studies have revealed their causal link to ischemic heart disease (IHD). We prospectively investigated the combined effect of CKD in earlier stages and hepatic steatosis on incident IHD risk in large-scale, non-diabetic Koreans. Data were assessed from 16,531 participants without diabetes from the Health Risk Assessment Study (HERAS) and Korea Health Insurance Review and Assessment (HIRA) data. We divided the study population into four groups according to the existence of early CKD and hepatic steatosis: controls, early CKD only, hepatic steatosis only, and both early CKD and hepatic steatosis. We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional-hazard regression models over a 50-month period. During the follow-up period, 326 (2.0%) patients developed IHD. HRs of IHD in the four groups were 1.00 (controls), 1.26 (95% CI 0.72–2.19), 1.19 (95% CI 0.90–1.57) and 1.76 (95% CI 1.04–2.97), respectively, after adjusting for potential confounding variables. Even less than stage 3A, CKD could precede and predict IHD in patients with hepatic steatosis.
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Affiliation(s)
- Sung-Bum Lee
- Department of Health Check-up, Yongin Severance Hospital, Yongin-si 16995, Korea;
| | - Byoung-Jin Park
- Department of Family Medicine, Yongin Severance Hospital, Yongin-si 16995, Korea;
| | - Yong-Jae Lee
- Department of Family Medicine, Gangnam Severance Hospital, Seoul 06273, Korea;
| | - Dong-Hyuk Jung
- Department of Family Medicine, Yongin Severance Hospital, Yongin-si 16995, Korea;
- Correspondence:
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48
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Prediction of Cardiovascular Risk Using Nonalcoholic Fatty Liver Disease Scoring Systems. Healthcare (Basel) 2021; 9:healthcare9070899. [PMID: 34356275 PMCID: PMC8303122 DOI: 10.3390/healthcare9070899] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 07/09/2021] [Accepted: 07/12/2021] [Indexed: 11/16/2022] Open
Abstract
This study aimed to determine whether nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for CVD and to identify the most useful NAFLD diagnostic tool for predicting CVD. Data from a total of 23,376 Korean adults without established CVD were analyzed. Cardiovascular risk was calculated using the Framingham Risk Score (FRS) 2008. The presence of NAFLD was defined as moderate-to-severe fatty liver disease diagnosed by ultrasonography. Scores for fatty liver were calculated using four NAFLD scoring systems (Fatty Liver Index, FLI; Hepatic Steatosis Index, HSI; Simple NAFLD Score, SNS; Comprehensive NAFLD Score, CNS), and were compared and analyzed according to cardiovascular risk group. Using the FRS, 67.4% of participants were considered to be at low risk of CVD, 21.5% at intermediate risk, and 11.1% at high risk. As the risk of CVD increased, both the prevalence of NAFLD and the score from each NAFLD scoring system increased significantly (p < 0.001). In the unadjusted analysis, the CNS had the strongest association with high CVD risk; in the adjusted analysis, the FLI score was most strongly associated with high CVD risk. Fatty liver is an important independent risk factor for CVD. Therefore, the available NAFLD scoring systems could be utilized to predict CVD.
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49
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Dietrich CF, Shi L, Löwe A, Dong Y, Potthoff A, Sparchez Z, Teufel A, Guth S, Koch J, Barr RG, Cui XW. Conventional ultrasound for diagnosis of hepatic steatosis is better than believed. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 60:1235-1248. [PMID: 34171931 DOI: 10.1055/a-1491-1771] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
BACKGROUND Hepatic steatosis is a condition frequently encountered in clinical practice, with potential progression towards fibrosis, cirrhosis, and hepatocellular carcinoma. Detection and staging of hepatic steatosis are of most importance in nonalcoholic fatty liver disease (NAFLD), a disease with a high prevalence of more than 1 billion individuals affected. Ultrasound (US) is one of the most used noninvasive imaging techniques used in the diagnosis of hepatic steatosis. Detection of hepatic steatosis with US relies on several conventional US parameters, which will be described. US is the first-choice imaging in adults at risk for hepatic steatosis. The use of some scoring systems may add additional accuracy especially in assessing the severity of hepatic steatosis. SUMMARY In the presented paper, we discuss screening and risk stratification, ultrasound features for diagnosing hepatic steatosis, B-mode criteria, focal fatty patterns and Doppler features of the hepatic vessels, and the value of the different US signs for the diagnosis of liver steatosis including classifying the severity of steatosis using different US scores. Limitations of conventional B-mode and Doppler features in the evaluation of hepatic steatosis are also discussed, including those in grading and assessing the complications of steatosis, namely fibrosis and nonalcoholic steatohepatitis. KEY MESSAGES Ultrasound is the first-line imaging examination for the screening and follow-up of patients with liver steatosis. The use of some scoring systems may add additional accuracy in assessing the severity of steatosis. Conventional B-mode and Doppler ultrasound have limitations in grading and assessing the complications of steatosis.
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Affiliation(s)
- Christoph F Dietrich
- Department Allgemeine Innere Medizin, Kliniken Hirslanden, Beau Site, Salem und Permanence, Bern, Switzerland
| | - Long Shi
- Department of Ultrasound, Jingmen No. 2 People's Hospital, Jingmen, Hubei, China
| | - Axel Löwe
- Department Allgemeine Innere Medizin, Kliniken Hirslanden, Beau Site, Salem und Permanence, Bern, Switzerland
| | - Yi Dong
- Ultrasound Department, Zhongshan Hospital Fudan University, Shanghai, China
| | - Andrej Potthoff
- Gastroenterology and Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Zeno Sparchez
- Department of Internal Medicine-Gastroenterology, University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Andreas Teufel
- Division of Hepatology, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Sabine Guth
- Conradia Medical Prevention Hamburg, Hamburg, Deutschland
| | - Jonas Koch
- Department Allgemeine Innere Medizin, Kliniken Hirslanden, Beau Site, Salem und Permanence, Bern, Switzerland
| | - Richard G Barr
- Northeastern Ohio Medical University, Southwoods Imaging, Youngstown, OH, USA
| | - Xin-Wu Cui
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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50
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Esenboğa K, Kurtul A, Nazman H, Tekin CG, Özyüncü N, Tan TS, Tutar E, Turhan ST. Evaluation of the Impact of Ranolazine Treatment on Liver Function Tests in Patients With Coronary Heart Disease and Nonalcoholic Fatty Liver Disease. Angiology 2021; 73:73-78. [PMID: 33823622 DOI: 10.1177/00033197211005590] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common liver pathology in the developed world. Nonalcoholic fatty liver disease is associated with a higher risk of cardiovascular disease. We investigated the impact of ranolazine on liver tests in patients with NAFLD and coronary artery disease (CAD). Patients who had established CAD and NAFLD (as assessed by raised serum transaminase activity, sonographic criteria, and the absence of any other obvious liver disease) were allocated to "on ranolazine" (n = 40) or "not on ranolazine" (n = 35) groups. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured in all patients at baseline and at the end of the study. After 6 months of ranolazine treatment, both ALT and AST activities were significantly lower in patients in the "on ranolazine" group compared with "not on ranolazine" patients (change from baseline: ALT, -11.0 ± 1.7 IU/L, P < .001; AST, -5.2 ± 1.9 IU/L, P =.009). In conclusion, the present study showed that treatment with ranolazine for 6 months led to a significant reduction in the activities of both serum aminotransferases in patients with stable CAD and NAFLD.
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Affiliation(s)
- Kerim Esenboğa
- 324508Ankara University Faculty of Medicine, Department of Cardiology, Ankara, Turkey
| | - Alparslan Kurtul
- 111335Hatay Mustafa Kemal University Faculty of Medicine, Department of Cardiology, Hatay, Turkey
| | - Hüseyin Nazman
- Department of Cardiology, Sivas Numune State Hospital, Sivas, Turkey
| | - Cemre Gül Tekin
- 324508Ankara University Faculty of Medicine, Department of Cardiology, Ankara, Turkey
| | - Nil Özyüncü
- 324508Ankara University Faculty of Medicine, Department of Cardiology, Ankara, Turkey
| | - Türkan Seda Tan
- 324508Ankara University Faculty of Medicine, Department of Cardiology, Ankara, Turkey
| | - Eralp Tutar
- 324508Ankara University Faculty of Medicine, Department of Cardiology, Ankara, Turkey
| | - Sibel Tekin Turhan
- 324508Ankara University Faculty of Medicine, Department of Cardiology, Ankara, Turkey
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