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Kim JH, Lee Y, Nam CM, Kwon YJ, Lee JW. Impact of cardiometabolic risk factors for metabolic dysfunction-associated steatotic liver disease on mortality. Nutr Metab Cardiovasc Dis 2025; 35:103965. [PMID: 40187915 DOI: 10.1016/j.numecd.2025.103965] [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: 11/16/2024] [Revised: 02/14/2025] [Accepted: 02/25/2025] [Indexed: 04/07/2025]
Abstract
BACKGROUND AND AIMS Metabolic dysfunction-associated steatotic liver disease (MASLD) is a potential independent risk factor for cardiovascular disease (CVD)-associated and all-cause mortalities as they share common risk factors. We investigated the association between cardiometabolic risk factors for MASLD and CVD-associated and all-cause mortality risks in middle-aged and older Korean adults. METHODS AND RESULTS We used data from the Korean Genome and Epidemiology Study, a population-based prospective cohort study. Five cardiometabolic risk factors were assessed. MASLD was defined as liver steatosis with a fatty liver index (FLI) ≥60 and at least one cardiometabolic risk factor. The non-MASLD group included individuals with a FLI <60 or FLI ≥60 without cardiometabolic risk factors. The primary outcomes were CVD-associated and all-cause mortalities. Cox proportional hazard models were used to evaluate the association between cardiometabolic risk factors for MASLD and mortalities, adjusting for covariates. Multivariable Cox regression analysis revealed that the MASLD group had increased CVD-associated and all-cause mortality risks compared to the non-MASLD group. The presence of three or more and one or more cardiometabolic risk factors significantly increased the CVD-associated and all-cause mortality rate, respectively. The combination of hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), and high glucose concentrations significantly increased both CVD-associated (hazard ratio [HR] 3.64; 95 % confidence interval [CI] 1.44-9.22; p = 0.006) and all-cause (HR 4.57; 95 % CI: 1.74-12.05; p = 0.002) mortality risks. CONCLUSION Cardiometabolic risk factors for MASLD are strongly associated with higher CVD-associated and all-cause mortality risks, highlighting the need to manage hypertriglyceridemia, low HDL-C, and high glucose concentrations.
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Affiliation(s)
- Jung-Hwan Kim
- Department of Family Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea
| | - Yaeji Lee
- Department of Biostatistics and Computing, Yonsei University, Seoul, 03722, Republic of Korea
| | - Chung-Mo Nam
- Department of Health Informatics and Biostatistics, Graduate School of Public Health, Yonsei University, Seoul, 03722, Republic of Korea
| | - Yu-Jin Kwon
- Department of Family Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, 16995, Republic of Korea.
| | - Ji-Won Lee
- Department of Family Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea; Institute for Innovation in Digital Healthcare, Yonsei University, Seoul, 03722, Republic of Korea.
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Ludusanu A, Tanevski A, Ciuntu BM, Bobeica RL, Chiran DA, Stan CI, Radu VD, Boiculese VL, Tinica G. European System for Cardiac Operative Risk Evaluation II and Liver Dysfunction. Biomedicines 2025; 13:154. [PMID: 39857738 PMCID: PMC11762396 DOI: 10.3390/biomedicines13010154] [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: 12/08/2024] [Revised: 12/31/2024] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
Background: The importance of liver dysfunction in predicting mortality in patients undergoing cardiovascular surgery is an important topic due to the general desire to improve current risk scores such as EUROSCORE II (European System for Cardiac Operative Risk Evaluation), with EUROSCORE III being currently under development. The model for End-Stage Liver Disease (MELD) Score has already proven its utility in predicting outcomes for patients undergoing abdominal, cardiovascular or urological surgery. In the present study, we want to see its usefulness in proving the postoperative mortality in patients undergoing coronary artery bypass surgery. Methods: This was a retrospective study, and it included 185 patients, with 93 survivors being randomly chosen from a total of 589 surviving patients using age, emergency and the weight of cardiac procedures as criteria to match the 92 deceased patients during hospitalization in the postoperative period who underwent coronary artery bypass grafting (CABG) alone or CABG and other concomitant cardiovascular interventions during a 10-year period of time. We calculated for all these patients, at the time of admission, the MELD Score and EUROSCORE II, and we analyzed the predictive performance of the two scores and their constituents. Results: In the multivariable model, patients with a MELD Score ≥ 5.54 had a 2.38-fold increased risk of death (95% C.I.: 1.43-3.96, p = 0.001), while those with a EUROSCORE ≥ 10.37 had a 8.66-fold increased risk of death (95% C.I.: 3.09-24.29, p < 0.001). After combining the two scores, the conditional scenario achieved a high overall accuracy of 84.32% (p < 0.001) in predicting mortality. Conclusions: Patients with a MELD Score ≥ 5.54, had good sensitivity and a very good specificity in terms of mortality prediction, but the conditional scenario, leveraging both risk scores, i.e., the MELD Score and EUROSCORE, offers the highest utility in terms of enhancing mortality prediction regarding these patients.
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Affiliation(s)
- Andreea Ludusanu
- Department of Morphofunctional Sciences I—Anatomy, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania; (A.L.); (D.A.C.); (C.I.S.)
| | - Adelina Tanevski
- Department of General Surgery, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania; (A.T.); (B.M.C.)
| | - Bogdan Mihnea Ciuntu
- Department of General Surgery, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania; (A.T.); (B.M.C.)
| | - Razvan Lucian Bobeica
- Department of Urology, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania;
| | - Dragos Andrei Chiran
- Department of Morphofunctional Sciences I—Anatomy, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania; (A.L.); (D.A.C.); (C.I.S.)
| | - Cristinel Ionel Stan
- Department of Morphofunctional Sciences I—Anatomy, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania; (A.L.); (D.A.C.); (C.I.S.)
| | - Viorel Dragos Radu
- Department of Urology, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania;
| | - Vasile Lucian Boiculese
- Biostatistics, Department of Preventive Medicine and Interdisciplinarity, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania;
| | - Grigore Tinica
- Cardiac Surgery, University of Medicine and Pharmacy “Gr. T. Popa”, 700115 Iasi, Romania;
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Hayat U, Kamal F, Kamal MU, Mirza W, Ahmad TA, Gangwani MK, Dahiya DS, Ali H, Naidoo SF, Humayun S, Okut H, Aziz M. Disparities in the Prevalence of Hospitalizations and In-Hospital Mortality Due to Acute Myocardial Infarction Among Patients with Non-Alcoholic Fatty Liver Disease: A Nationwide Retrospective Study. J Clin Med 2024; 13:6946. [PMID: 39598090 PMCID: PMC11595205 DOI: 10.3390/jcm13226946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 11/16/2024] [Accepted: 11/17/2024] [Indexed: 11/29/2024] Open
Abstract
Background: Non-alcoholic liver disease (NAFLD) may be associated with cardiovascular diseases; however, only a few studies have analyzed this relationship. We aimed to assess the epidemiologic data and the association between NAFLD and acute myocardial infarction (AMI) in the United States. Methods: The National Inpatient Sample (NIS) database 2016-2019 was queried using ICD10-CM diagnostic codes to identify hospitalizations of AMI + NAFLD. Essential demographic variables were analyzed to determine the disparities in the prevalence of AMI hospitalizations and deaths among NAFLD patients. Univariate and multivariate logistic regression models determined the association between NAFLD and AMI hospitalizations and death. Results: Among the total 5450 NAFLD patients hospitalized with AMI, 5.11% (279) died. Females were less likely to be admitted and die due to AMI than males. Younger patients (<50) were less likely to be hospitalized and die than those ≥50. Compared to the white population, black patients were less likely; however, Hispanics, Asians, and Pacific Islanders were more likely to be hospitalized. Race was not found to affect hospital mortality. On multivariate analysis, NAFLD was associated with higher odds of AMI hospitalization [OR 1.55, 95% CI 1.51-1.60, p < 0.01] and death [OR 1.96, 95% CI 1.74-2.21, p < 0.01]. Conclusions: Older white males with NAFLD had a higher prevalence of AMI hospitalizations and mortality.
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Affiliation(s)
- Umar Hayat
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18705, USA; (W.M.); (T.A.A.); (S.F.N.); (S.H.)
| | - Faisal Kamal
- Department of Internal Medicine, Division of Gastroenterology, Thomas Jefferson University, Philadelphia, PA 19107, USA;
| | | | - Wasique Mirza
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18705, USA; (W.M.); (T.A.A.); (S.F.N.); (S.H.)
| | - Tariq A. Ahmad
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18705, USA; (W.M.); (T.A.A.); (S.F.N.); (S.H.)
| | - Manesh K. Gangwani
- Department of Internal Medicine, University of Toledo, Toledo, OH 43614, USA;
| | - Dushyant S. Dahiya
- Department of Gastroenterology and Hepatology, The University of Kansas School of Medicine, Kansas City, KS 66103, USA;
| | - Hassam Ali
- Department of Gastroenterology, ECU Health Medical Center, Greenville, NC 27858, USA;
| | - Shiva F. Naidoo
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18705, USA; (W.M.); (T.A.A.); (S.F.N.); (S.H.)
| | - Sara Humayun
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18705, USA; (W.M.); (T.A.A.); (S.F.N.); (S.H.)
| | - Hayrettin Okut
- Department of Population and Public Health, University of Kansas, Wichita, KS 67214, USA;
| | - Muhammad Aziz
- Department of Gastroenterology, Bon Secours Mercy Health, Toledo, OH 43608, USA;
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Lonardo A, Ballestri S, Baffy G, Weiskirchen R. Liver fibrosis as a barometer of systemic health by gauging the risk of extrahepatic disease. METABOLISM AND TARGET ORGAN DAMAGE 2024; 4. [DOI: 10.20517/mtod.2024.42] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
This review article proposes the theory that liver fibrosis, the abnormal accumulation of excessive extracellular matrix, is not just an indicator of liver disease but also a negative reflection of overall systemic health. Liver fibrosis poses a heavy financial burden on healthcare systems worldwide and can develop due to chronic liver disease from various causes, often due to sustained inflammation. Liver fibrosis may not generate symptoms and become apparent only when it reaches the stage of cirrhosis and is associated with clinically significant portal hypertension and leads to decompensation events or promotes the development of hepatocellular carcinoma. While chronic viral hepatitis and excessive alcohol consumption were once the primary causes of chronic liver disease featuring fibrosis, this role is now increasingly taken over by metabolic dysfunction-associated steatotic liver disease (MASLD). In MASLD, endothelial dysfunction is an essential component in pathogenesis, promoting the development of liver fibrosis, but it is also present in endothelial cells of other organs such as the heart, lungs, and kidneys. Accordingly, liver fibrosis is a significant predictor of liver-related outcomes, as well as all-cause mortality, cardiovascular risk, and extrahepatic cancer. Physicians should be aware that individuals seeking medical attention for reasons unrelated to liver health may also have advanced fibrosis. Early identification of these at-risk individuals can lead to a more comprehensive assessment and the use of various treatment options, both approved and investigational, to slow or reverse the progression of liver fibrosis.
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Gu X, Gao D, Zhou X, Ding Y, Shi W, Park J, Wu S, He Y. Association between fatty liver index and cardiometabolic multimorbidity: evidence from the cross-sectional national health and nutrition examination survey. Front Cardiovasc Med 2024; 11:1433807. [PMID: 39301498 PMCID: PMC11411361 DOI: 10.3389/fcvm.2024.1433807] [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: 05/16/2024] [Accepted: 08/13/2024] [Indexed: 09/22/2024] Open
Abstract
Background Metabolic dysfunction associated steatotic liver disease (MASLD) contributes to the cardiometabolic diseases through multiple mechanisms. Fatty liver index (FLI) has been formulated as a non-invasive, convenient, and cost-effective approach to estimate the degree of MASLD. The current study aims to evaluate the correlation between FLI and the prevalent cardiometabolic multimorbidity (CMM), and to assess the usefulness of FLI to improve the detection of the prevalent CMM in the general population. Methods 26,269 subjects were enrolled from the National Health and Nutrition Examination Survey 1999-2018. FLI was formulated based on triglycerides, body mass index, γ -glutamyltransferase, and waist circumference. CMM was defined as a history of 2 or more of diabetes mellitus, stroke, myocardial infarction. Results The prevalence of CMM was 10.84%. With adjustment of demographic, anthropometric, laboratory, and medical history covariates, each standard deviation of FLI leaded to a 58.8% risk increase for the prevalent CMM. The fourth quartile of FLI had a 2.424 times risk for the prevalent CMM than the first quartile, and a trend towards higher risk was observed. Smooth curve fitting showed that the risk for prevalent CMM increased proportionally along with the elevation of FLI. Subgroup analysis demonstrated that the correlation was robust in several conventional subpopulations. Receiver-operating characteristic curve analysis revealed an incremental value of FLI for detecting prevalent CMM when adding it to conventional cardiometabolic risk factors (Area under the curve: 0.920 vs. 0.983, P < 0.001). Results from reclassification analysis confirmed the improvement from FLI. Conclusion Our study demonstrated a positive, linear, and robust correlation between FLI and the prevalent CMM, and our findings implicate the potential usefulness of FLI to improve the detection of prevalent CMM in the general population.
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Affiliation(s)
- Xinsheng Gu
- Department of Cardiology, Shanghai Eighth People's Hospital, Shanghai, China
| | - Di Gao
- Department of Cardiology, Shanghai Eighth People's Hospital, Shanghai, China
| | - Xinjian Zhou
- Department of Intensive Care Unit, Shanghai Eighth People's Hospital, Shanghai, China
| | - Yueyou Ding
- Department of Cardiology, Shanghai Eighth People's Hospital, Shanghai, China
| | - Wenrui Shi
- Department of Cardiology, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China
| | - Jieun Park
- School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Shaohui Wu
- Department of Cardiology, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China
| | - Yue He
- Department of Cardiology, Shanghai Eighth People's Hospital, Shanghai, China
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Wang D, Zhou BY, Xiang L, Chen XY, Feng JX. Alanine aminotransferase as a risk marker for new-onset metabolic dysfunction-associated fatty liver disease. World J Gastroenterol 2024; 30:3132-3139. [PMID: 39006380 PMCID: PMC11238669 DOI: 10.3748/wjg.v30.i25.3132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 05/07/2024] [Accepted: 06/13/2024] [Indexed: 07/01/2024] Open
Abstract
In this editorial, we comment on the article by Chen et al. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a global public health burden whose incidence has risen concurrently with overweight and obesity. Given its detrimental health impact, early identification of at-risk individuals is crucial. MAFLD diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy, imaging, or blood biomarkers, and one of the following conditions: Overweight/ obesity, type 2 diabetes mellitus, or metabolic dysregulation. However, in large-scale epidemiological studies, liver biopsies are not feasible. The application of techniques such as ultrasonography, computed tomography, magnetic resonance imaging, and magnetic resonance spectroscopy is restricted by their limited sensitivity, low effectiveness, high costs, and need for specialized software. Blood biomarkers offer several advantages, particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are impractical. Analysis of cumulative effects of excess high-normal blood alanine aminotransferase (ALT) levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging methods. Accordingly, investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring, enabling timely intervention and management and improving patient outcomes.
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Affiliation(s)
- Di Wang
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Bing-Yan Zhou
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Lei Xiang
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Xu-Yong Chen
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Jie-Xiong Feng
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Mellemkjær A, Kjær MB, Haldrup D, Grønbæk H, Thomsen KL. Management of cardiovascular risk in patients with metabolic dysfunction-associated steatotic liver disease. Eur J Intern Med 2024; 122:28-34. [PMID: 38008609 DOI: 10.1016/j.ejim.2023.11.012] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 11/06/2023] [Accepted: 11/08/2023] [Indexed: 11/28/2023]
Abstract
The novel term Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is proposed to replace non-alcoholic fatty liver disease (NAFLD) to highlight the close association with the metabolic syndrome. MASLD encompasses patients with liver steatosis and at least one of five cardiometabolic risk factors which implies that these patients are at increased risk of cardiovascular disease (CVD). Indeed, the prevalence of CVD in MASLD patients is increased and CVD is recognized as the most common cause of death in MASLD patients. We here present an update on the pathophysiology of CVD in MASLD, discuss the risk factors, and suggest screening for CVD in patients with MASLD. Currently, there is no FDA-approved pharmacological treatment for MASLD, and no specific treatment recommended for CVD in patients with MASLD. Thus, the treatment strategy is based on weight loss and a reduction and treatment of CVD risk factors. We recommend screening of MASLD patients for CVD using the SCORE2 system with guidance to specific treatment algorithms. In all patients with CVD risk factors, lifestyle intervention to induce weight loss through diet and exercise is recommended. Especially a Mediterranean diet may improve hyperlipidemia and if further treatment is needed, statins should be used as first-line treatment. Further, anti-hypertensive drugs should be used to treat hypertension. With the epidemic of obesity and type 2 diabetes mellitus (T2DM) the risk of MASLD and CVD is expected to increase, and preventive measures, screening, and effective treatments are highly needed to reduce morbidity and mortality in MASLD patients.
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Affiliation(s)
- Anders Mellemkjær
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Mikkel Breinholt Kjær
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - David Haldrup
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Henning Grønbæk
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
| | - Karen Louise Thomsen
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Hooshmand Gharabagh L, Shargh A, Mohammad Hosseini Azar MR, Esmaeili A. Comparison between the effect of Empagliflozin and Pioglitazone added to metformin in patients with type 2 diabetes and nonalcoholic fatty liver disease. Clin Res Hepatol Gastroenterol 2024; 48:102279. [PMID: 38159676 DOI: 10.1016/j.clinre.2023.102279] [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: 12/01/2023] [Revised: 12/23/2023] [Accepted: 12/28/2023] [Indexed: 01/03/2024]
Abstract
BACKGROUND/AIMS Non-alcoholic fatty liver disease (NAFLD), defined as the accumulation of >5% fat in the liver, is the most frequently co-exist disease with diabetics up to 70%. Current study was conducted to compare efficacy of combination therapy of empagliflozin (EMPA) or pioglitazone (PGZ) with metformin (MET) in patients with T2DM and NAFLD. METHODS In this open label, prospective clinical trial, sixty patients were randomly assigned to receive EMPA 10 mg/day or PGZ 30 mg/day in combination Metformin (at least 1500 mg) for six months. NAFLD grade and liver stiffness were defined and measured at the beginning and after 6 months. As the secondary outcomes, anthropometric characteristics, lipid profile, plasma glucose test, and liver enzymes test were measured at the baseline and endpoint. RESULTS The results showed that both combination therapy with EMPA+ MET or PGZ+MET significantly reversed fibrosis stage of NAFLD (P<0.05). Significant reduction in lipid profile test, and liver enzymes test were seen in both groups (P<0.05). However, the greater reduction in waist circumference was observed in EMPA groups compared to PGZ (-4.4 ± 2.39 vs -2.05±1.28, p<0.001), meanwhile weight and BMI decreased significantly only in the patients receiving EMPA (-5.78 ± 3.6 kg vs 0.93 ± 0.33 kg and -2.01± 3.19 kg/m2 vs 0.33 ± 0.12 kg/m2, respectively, P<0.001). CONCLUSION combination of EMPA or PGZ with metformin equally improved liver fibrosis stage and stiffness in T2DM patients with NAFLD. The improvements of laboratory tests were observed in the both groups, while, regarding weight reduction, only the regimen containing EMPA was effective.
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Affiliation(s)
- Laya Hooshmand Gharabagh
- Department of Internal Medicine, School of Medicine, Urmia University of Medical Sciences, Imam Khomeini Hospital, Urmia, Iran.
| | - Ali Shargh
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | | | - Ayda Esmaeili
- Department of Clinical Pharmacy, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran; Experimentaland Applied Pharmaceutical Sciences Research Center, Urmia University of Medical Sciences, Urmia, Iran.
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Niu Y, Wang G, Feng X, Niu H, Shi W. Significance of fatty liver index to detect prevalent ischemic heart disease: evidence from national health and nutrition examination survey 1999-2016. Front Cardiovasc Med 2023; 10:1171754. [PMID: 37900562 PMCID: PMC10600492 DOI: 10.3389/fcvm.2023.1171754] [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: 02/22/2023] [Accepted: 09/25/2023] [Indexed: 10/31/2023] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) contributes to the development of ischemic heart disease via multiple mechanisms. Fatty liver index (FLI) has been proposed as an accurate, convenient, and economic surrogate of the severity of NAFLD. Our present study aims to assess the association between FLI and the prevalent IHD and to evaluate the potential value of FLI to refine the detection of prevalent IHD in the general population. Methods Our work recruited 32,938 subjects from the National Health and Nutrition Examination Survey 1999-2016. IHD was diagnosed according to the subjects' self-report. FLI was determined based on triglycerides, BMI, γ-glutamyltransferase, and waist circumference. Results 2,370 (7.20%) subjects were diagnosed with IHD. After adjustment of age, sex, race, current smoking, current drinking, PIR, BMI, WC, TC, TG, GGT, Scr, FPG, SBP, anti-hypertensive therapy, anti-diabetic therapy, and lipid-lowering therapy, one standard deviation increase of FLI resulted in a 27.0% increment of the risk of prevalent IHD. In the quartile analysis, we observed a 1.684 times risk of prevalent IHD when comparing the fourth quartile with the first quartile, and there was a trend towards higher risk across the quartiles. The smooth curve fitting displayed a linear relationship between FLI and the presence of IHD without any threshold or saturation effect. Subgroup analysis revealed a robust association in conventional cardiovascular subpopulations, and the association could be more prominent in female subjects and diabetes patients. ROC analysis demonstrated an incremental value of FLI for detecting prevalent IHD after introducing it to conventional cardiovascular risk factors (AUC: 0.823 vs. 0.859, P for comparison <0.001). Also, results from reclassification analysis implicated that more IHD patients could be correctly identified by introducing FLI into conventional cardiovascular risk factors (continuous net reclassification index: 0.633, P < 0.001; integrated discrimination index: 0.034, P < 0.001). Conclusion The current analysis revealed a positive and linear relationship between FLI and the prevalent IHD. Furthermore, our findings suggest the incremental value of FLI to refine the detection of prevalent IHD in the general population.
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Affiliation(s)
- Yuyu Niu
- Department of Cardiovascular Medicine, First People's Hospital of Xinxiang City and The Fifth Affiliated Hospital of Xinxiang Medical College, Xinxiang, China
| | - Guifang Wang
- Department of Cardiovascular Medicine, First People's Hospital of Xinxiang City and The Fifth Affiliated Hospital of Xinxiang Medical College, Xinxiang, China
| | - Xianjun Feng
- Department of Cardiovascular Medicine, First People's Hospital of Xinxiang City and The Fifth Affiliated Hospital of Xinxiang Medical College, Xinxiang, China
| | - Hongyi Niu
- Sanquan College, Xinxiang Medical University, Xinxiang, China
| | - Wenrui Shi
- Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
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Sonaglioni A, Cerini F, Cerrone A, Argiento L, Nicolosi GL, Rigamonti E, Lombardo M, Rumi MG, Viganò M. Liver stiffness measurement identifies subclinical myocardial dysfunction in non-advanced non-alcoholic fatty liver disease patients without overt heart disease. Intern Emerg Med 2022; 17:1425-1438. [PMID: 35302179 DOI: 10.1007/s11739-022-02966-2] [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: 01/02/2022] [Accepted: 02/26/2022] [Indexed: 12/14/2022]
Abstract
Patients with non-advanced non-alcoholic fatty liver disease (NAFLD) have an increased cardiovascular risk. The present study was designed to evaluate the relationship between liver stiffness measurement (LSM) by transient elastography (TE) and myocardial deformation indices of all cardiac chambers in NAFLD patients without overt heart disease. All consecutive NAFLD patients diagnosed with LSM < 12.5 kPa on TE between September 2021 and December 2021 entered the study. All participants underwent blood tests, TE and two-dimensional (2D) transthoracic echocardiography (TTE) implemented with speckle-tracking echocardiography (STE) analysis of left ventricular (LV) global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS), right ventricular (RV) GLS, left atrial (LA) total global strain (TGSA) and right atrial (RA) TGSA. Main independent predictors of impaired LV-GLS (defined as absolute value less negative than - 20%) were evaluated. A total of 92 NAFLD patients (54.0 ± 11.1 years, 50% males) were prospectively analyzed. Mean LSM was 6.2 ± 2.4 kPa. Fibroscan results revealed that 76.1% of patients had F0-F1, 5.4% F2 and 18.5% F3 liver fibrosis. Despite normal biventricular systolic function on 2D-TTE, LV-GLS, LV-GCS and LV-GRS, RV-GLS, LA-TGSA and RA-TGSA were reduced in 64.1%, 38.0%, 38.0%, 31.5%, 39.1% and 41.3% of patients, respectively. Body mass index (BMI) (OR 1.76, 95% CI 1.18-2.64), neutrophil-to-lymphocyte ratio (NLR) (OR 4.93, 95% CI 1.15-31.8) and LSM (OR 9.26, 95% CI 2.24-38.3) were independently associated to impaired LV-GLS. BMI ≥ 29.3 kg/m2, NLR ≥ 1.8 and LSM ≥ 5.5 kPa were the best cut-off values for detecting outcome. LSM ≥ 5.5 kPa identifies NAFLD patients with subclinical myocardial dysfunction.
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Affiliation(s)
- Andrea Sonaglioni
- Division of Cardiology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy.
| | - Federica Cerini
- Division of Hepatology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
- University of Milan, Milan, Italy
| | - Antonio Cerrone
- Division of Hepatology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
- University of Milan, Milan, Italy
| | - Lorenzo Argiento
- Division of Hepatology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
- University of Milan, Milan, Italy
| | | | - Elisabetta Rigamonti
- Division of Cardiology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
| | - Michele Lombardo
- Division of Cardiology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
| | - Maria Grazia Rumi
- Division of Hepatology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
- University of Milan, Milan, Italy
| | - Mauro Viganò
- Division of Hepatology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
- University of Milan, Milan, Italy
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11
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Hagström H, Kechagias S, Ekstedt M. Risk for hepatic and extra-hepatic outcomes in nonalcoholic fatty liver disease. J Intern Med 2022; 292:177-189. [PMID: 34118091 DOI: 10.1111/joim.13343] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is defined by presence of steatosis in more than 5% of liver cells. The gold standard for diagnosis is liver biopsy, but this is seldom achieved due to costs and risk for side effects, and that is why the diagnosis is mostly made based on a combination of radiology and exclusion of other liver diseases. Disease severity staging can be noninvasively achieved with radiological exams such as elastography or blood-based markers that usually have lower sensitivity and specificity. NAFLD is today the most common chronic liver disease globally with a prevalence estimated to be 25%. Fortunately, for many persons NAFLD is an incidental finding with a good prognosis. Whilst a major focus has been on liver-related outcomes in NAFLD, there has recently been an increased interest in extrahepatic consequences of NAFLD. The most commonly studied outcomes include cardiovascular disease and cancer. The risk of adverse outcomes generally differs according to the baseline fibrosis stage. There is a five-time higher risk of liver-related events in NAFLD patients with fibrosis stage 3 as compared to those with no or little fibrosis. Meanwhile, the presence of nonalcoholic steatohepatitis (NASH) does not seem to influence prognosis in addition to fibrosis stage. Patients with NAFLD clearly have a higher risk for cardiovascular outcomes compared to the general population, with a recent meta-analysis indicating a 37% increased hazard for cardiovascular events as opposed to individuals without NAFLD. The risk of liver cancer is increased, which is mostly driven by presence of cirrhosis, but the increased risk is present also in patients without cirrhosis, and to a greater extent than for other chronic liver disease. Around one-third of patients with NAFLD and liver cancer do not have cirrhosis. Additionally, the risk of extrahepatic malignancies is thought to be moderately increased, with most evidence for a link between NAFLD and colorectal cancer where the risk is approximately 50% higher compared to patients without NAFLD. A particularly salient point is if NAFLD can be considered an independent risk factor for outcomes. Many studies have not been able to adjust for key confounders, or suffer from different forms of bias. The clinical problem is nevertheless to identify persons with an increased risk for adverse hepatic and extrahepatic outcomes. We here discuss the evidence linking NAFLD to severe hepatic and extrahepatic outcomes.
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Affiliation(s)
- Hannes Hagström
- Division of Hepatology, Department of Upper GI diseases, Karolinska University Hospital, Stockholm, Sweden.,Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.,Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden
| | - Stergios Kechagias
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Mattias Ekstedt
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
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12
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Tapper EB, Fleming C, Rendon A, Fernandes J, Johansen P, Augusto M, Nair S. The Burden of Nonalcoholic Steatohepatitis: A Systematic Review of Epidemiology Studies. GASTRO HEP ADVANCES 2022; 1:1049-1087. [PMID: 39131247 PMCID: PMC11307414 DOI: 10.1016/j.gastha.2022.06.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 06/30/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims Nonalcoholic steatohepatitis (NASH) is associated with increased mortality and risk of complications but is often asymptomatic and under-recognized. A systematic review of NASH epidemiology was conducted to provide information on the burden of NASH and highlight important evidence gaps for future research. Methods Medline, EMBASE, and Cochrane Library databases were searched for English-language publications published from 2010 to January 2022 that reported on natural history, risk factors, comorbidities, and complications of a NASH population or subpopulation. Results Overall, 173 publications were included. NASH was shown to have a variable disease course and high prevalence of comorbid disease. Although many patients progressed to cirrhosis and end-stage liver disease, disease regression or resolution was reported in up to half of patients in some studies. Reported risk factors for disease progression or resolution included levels of (or changes in) serum fibrosis markers, liver enzymes, and platelets. The presence of NASH increased the risk of liver cirrhosis and other serious diseases such as hepatocellular carcinoma, colorectal cancer, chronic kidney disease, and cardiovascular disease. In 2017, NASH was responsible for ∼118,000 cirrhosis deaths globally, and an increasing proportion of patients are receiving liver transplantation for NASH in Europe and the United States. Consolidation of data was hampered by heterogeneity across the studies in terms of patient populations, follow-up time, and outcomes measured. Conclusion NASH is associated with significant morbidity and mortality, an increased risk of comorbidities, and imposes an increasing burden among liver transplantation recipients. Longer studies with harmonized study criteria are required to better understand the impact of NASH on patient outcomes.
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Affiliation(s)
- Elliot B. Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | | | - Adriana Rendon
- Global Medical Affairs, Novo Nordisk A/S, Søborg, Denmark
| | - João Fernandes
- Payer Evidence Generation, Novo Nordisk A/S, Søborg, Denmark
| | - Pierre Johansen
- Novo Nordisk Denmark A/S, Region North & West Europe, Ørestad, Denmark
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13
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OUP accepted manuscript. Eur J Cardiothorac Surg 2022; 62:6575310. [DOI: 10.1093/ejcts/ezac128] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 01/31/2022] [Accepted: 02/23/2022] [Indexed: 11/13/2022] Open
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14
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Yu X, Zhang H, Pan J, Zou L, Tang L, Miao H, Zheng P, Xing L. Jiang Zhi Granule protects immunological barrier of intestinal mucosa in rats with non-alcoholic steatohepatitis. PHARMACEUTICAL BIOLOGY 2021; 59:1359-1368. [PMID: 34915801 PMCID: PMC8725831 DOI: 10.1080/13880209.2021.1979594] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 08/09/2021] [Accepted: 09/07/2021] [Indexed: 06/14/2023]
Abstract
CONTEXT Jiang Zhi Granule (JZG) is known to improve hepatic function, reduce liver fat deposition and inflammation in non-alcoholic fatty liver disease (NAFLD). OBJECTIVE To determine the protective mechanism of JZG on immunological barrier of intestinal mucosa in rats with diet-induced non-alcoholic steatohepatitis (NASH). MATERIALS AND METHODS A Sprague-Dawley (SD) model of NASH was established using a high-fat diet and 1% dextran sulphate sodium (DSS) through drinking water. The rats were randomized into four groups and treated for four weeks, respectively, including normal control (NC), model control (MC), positive control (PC) and JZG. Mesenteric lymph nodes (MLNs) cells were isolated and cultured to assess a potential disruption of the enteric immune barrier. Also, investigation of intestinal mucosal dendritic cell-toll-like-receptor-myeloid differentiation primary response 88 (DC-TLR-MyD88) signalling pathway in vitro was examined. RESULTS The lethal concentration 50 (LD50) of JZG was greater than 5 g/kg, while its inhibitory concentration 50 (IC50) was 1359 μg/mL in HepG2. In JZG group, the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), malondialdehyde (MDA), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and serum endotoxin were significantly (p < 0.01) reduced. In contrast, plasma concentrations of high-density lipoprotein cholesterol (HDL-C) and superoxide dismutase (SOD) were increased. Furthermore, proinflammatory factor, interferon-γ (IFN-γ)+ from CD4+ T cells in DSS-induced NASH rats increased significantly (p < 0.01) compared to NC group. Importantly, JZG treatment substantially decreased (p < 0.01) the relative expressions of TLR-44 and MyD88. CONCLUSIONS JZG treatment may protect immunological barrier of intestinal mucosa in NASH individual.
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Affiliation(s)
- Xiao Yu
- Department II of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Haiyan Zhang
- Department II of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jielu Pan
- Department II of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lu Zou
- Experiment Center for Teaching & Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ling Tang
- Department II of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hongyu Miao
- Department II of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Peiyong Zheng
- Department II of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lianjun Xing
- Department II of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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15
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Comeglio P, Sarchielli E, Filippi S, Cellai I, Guarnieri G, Morelli A, Rastrelli G, Maseroli E, Cipriani S, Mello T, Galli A, Bruno BJ, Kim K, Vangara K, Papangkorn K, Chidambaram N, Patel MV, Maggi M, Vignozzi L. Treatment potential of LPCN 1144 on liver health and metabolic regulation in a non-genomic, high fat diet induced NASH rabbit model. J Endocrinol Invest 2021; 44:2175-2193. [PMID: 33586025 PMCID: PMC8421272 DOI: 10.1007/s40618-021-01522-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 01/27/2021] [Indexed: 12/14/2022]
Abstract
PURPOSE Low free testosterone (T) level in men is independently associated with presence and severity of Non-Alcoholic Steatohepatitis (NASH). The histological and molecular effects of oral testosterone prodrug LPCN 1144 treatment on hepatic fibrosis and NASH features are unknown. A metabolic syndrome-induced NASH model in rabbits consuming high fat diet (HFD) has been previously used to assess treatment effects of injectable T on hepatic fibrosis and NASH features. Here we present results on LPCN 1144 in this HFD-induced, NASH preclinical model. METHODS Male rabbits were randomly assigned to five groups: regular diet (RD), HFD, HFD + 1144 vehicle (HFD + Veh), HFD + 1144 (1144), and HFD + 1144 + α-tocopherol (1144 + ALPHA). Rabbits were sacrificed after 12 weeks for liver histological, biochemical and genetic analyses. Histological scores were obtained through Giemsa (inflammation), Masson's trichrome (steatosis and ballooning), and Picrosirius Red (fibrosis) staining. RESULTS Compared to RD, HFD and HFD + Veh significantly worsened NASH features and hepatic fibrosis. Considering HFD and HFD + Veh arms, histological and biomarker features were not significantly different. Both 1144 and 1144 + ALPHA arms improved mean histological scores of NASH as compared to HFD arm. Importantly, percentage of fibrosis was improved in both 1144 (p < 0.05) and 1144 + ALPHA (p = 0.05) treatment arms vs. HFD. Both treatment arms also reduced HFD-induced inflammation and fibrosis mRNA markers. Furthermore, 1144 treatments significantly improved HFD-induced metabolic dysfunctions. CONCLUSIONS Histological and biomarker analyses demonstrate that LPCN 1144 improved HFD-induced hepatic fibrosis and NASH biochemical, biomolecular and histochemical features. These preclinical findings support a therapeutic potential of LPCN 1144 in the treatment of NASH and of hepatic fibrosis.
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Affiliation(s)
- P Comeglio
- Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy
| | - E Sarchielli
- Section of Human Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - S Filippi
- Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy
| | - I Cellai
- Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy
| | - G Guarnieri
- Section of Human Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - A Morelli
- Section of Human Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - G Rastrelli
- Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy
| | - E Maseroli
- Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy
| | - S Cipriani
- Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy
| | - T Mello
- Gastroenterology Unit, Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - A Galli
- Gastroenterology Unit, Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - B J Bruno
- Lipocine Inc., Salt Lake City, Utah, 84088, USA
| | - K Kim
- Lipocine Inc., Salt Lake City, Utah, 84088, USA
| | - K Vangara
- Lipocine Inc., Salt Lake City, Utah, 84088, USA
| | | | | | - M V Patel
- Lipocine Inc., Salt Lake City, Utah, 84088, USA
| | - M Maggi
- Endocrinology Unit, Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
- I.N.B.B. (Istituto Nazionale Biostrutture E Biosistemi), Rome, Italy
| | - L Vignozzi
- Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy.
- I.N.B.B. (Istituto Nazionale Biostrutture E Biosistemi), Rome, Italy.
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16
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Hepatic Interactions in Atherosclerotic Heart Disease. Am J Med Sci 2021; 363:104-113. [PMID: 34547286 DOI: 10.1016/j.amjms.2021.07.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 04/19/2021] [Accepted: 07/16/2021] [Indexed: 12/20/2022]
Abstract
Atherosclerotic heart disease remains a major cause of morbidity and mortality worldwide. The past few decades have seen the emergence of chronic inflammation as a mediator of atherosclerosis. Although the heart and vascular system remain the organ systems most affected in the atherosclerotic process, chronic inflammation and ischemia trigger a systemic multi-organ response. The liver is a critical organ for systemic hemostasis and recent developments have established an important role of the liver in response to atherosclerosis and myocardial ischemia. In addition, the rapid emergence of systemic liver diseases has unraveled a pathophysiological link with heart disease with therapeutic implications. In this review, we explore the relationship between the liver and the heart in myocardial ischemia, describe epidemiological associations between various liver pathologies and coronary heart disease, and elucidate practical challenges in the clinical management of patients with concomitant coronary heart disease and hepatic abnormalities.
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17
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De Matteis C, Cariello M, Graziano G, Battaglia S, Suppressa P, Piazzolla G, Sabbà C, Moschetta A. AST to Platelet Ratio Index (APRI) is an easy-to-use predictor score for cardiovascular risk in metabolic subjects. Sci Rep 2021; 11:14834. [PMID: 34290320 PMCID: PMC8295377 DOI: 10.1038/s41598-021-94277-3] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 07/05/2021] [Indexed: 02/06/2023] Open
Abstract
Visceral obesity is characterized by a low-grade inflammatory systemic state that contributes to the genesis of non-alcoholic fatty liver disease (NAFLD), frequently associated with liver fibrosis. Non-invasive serum markers have recently emerged as reliable, easy-to-use scores to predict liver fibrosis. NAFLD is often linked to metabolic and cardiovascular risk. Thus, in this cross-sectional study, we investigated in a population of 1225 subjects if AST to Platelet Ratio Index (APRI), one of the non-invasive liver fibrosis serum markers, can predict cardiovascular risk (CVR). APRI has been previously validated as an efficient score to predict liver fibrosis in viral hepatitis patients with a cut-off of 0.5 for fibrosis and 1.5 for cirrhosis. Our study showed that APRI significantly correlates with CVR and determines, when elevated, a significant increase in CVR for both genders, especially females. This spike in CVR, observed when APRI is elevated, is relatively high in patients in the age of 51–65 years, but it is significantly higher in younger and premenopausal women, approaching risk values usually typical of men at the same age. Taken together, our data highlighted the role of APRI as a reliable predictor easy-to-use score for CVR in metabolic patients.
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Affiliation(s)
- Carlo De Matteis
- INBB, National Institute for Biostructures and Biosystems, Viale delle Medaglie d'Oro 305, 00136, Rome, Italy
| | - Marica Cariello
- INBB, National Institute for Biostructures and Biosystems, Viale delle Medaglie d'Oro 305, 00136, Rome, Italy
| | - Giusi Graziano
- INBB, National Institute for Biostructures and Biosystems, Viale delle Medaglie d'Oro 305, 00136, Rome, Italy
| | - Stefano Battaglia
- Clinica Medica "Cesare Frugoni", Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124, Bari, Italy.,Depatment of Tissues and Organs Transplantation and Cellular Therapies, "Aldo Moro" University of Bari, Bari, Italy
| | - Patrizia Suppressa
- Clinica Medica "Cesare Frugoni", Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124, Bari, Italy
| | - Giuseppina Piazzolla
- Clinica Medica "Cesare Frugoni", Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124, Bari, Italy
| | - Carlo Sabbà
- Clinica Medica "Cesare Frugoni", Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124, Bari, Italy
| | - Antonio Moschetta
- INBB, National Institute for Biostructures and Biosystems, Viale delle Medaglie d'Oro 305, 00136, Rome, Italy. .,Clinica Medica "Cesare Frugoni", Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124, Bari, Italy.
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18
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Tutunchi H, Naeini F, Ebrahimi-Mameghani M, Mobasseri M, Naghshi S, Ostadrahimi A. The association of the steatosis severity, NAFLD fibrosis score and FIB-4 index with atherogenic dyslipidaemia in adult patients with NAFLD: A cross-sectional study. Int J Clin Pract 2021; 75:e14131. [PMID: 33683797 DOI: 10.1111/ijcp.14131] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 02/26/2021] [Accepted: 03/02/2021] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVES Obesity and dyslipidaemia are the major risk factors for non-alcoholic fatty liver disease (NAFLD), and are known to increase cardiovascular disease (CVD), which is the leading cause of death in NAFLD patients. The present cross-sectional study aimed to investigate associations among severity of hepatic steatosis, NAFLD fibrosis score and atherogenic lipid profile. METHODS A total of 265 patients with NAFLD confirmed by ultrasonographic findings were included. The NAFLD fibrosis score and the fibrosis-4 (FIB-4) index were used to classify the probability of fibrosis as low, intermediate and high probability. Serum lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured, and then TC/HDL-C, LDL-C/HDL-C, TG/HDL-C and non HDL-C/HDL-C ratios were determined. Fasting blood sugar (FBS), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also assessed. The homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. RESULTS The severity of hepatic steatosis was positively correlated with TC/HDL-C (r = 0.29, P = .002), LDL-C/HDL-C (r = 0.32, P < .001), TG/HDL-C (r = 0.36, P < .001) and non-HDL-C/HDL-C (r = 0.24, P = .001) ratios. Similarly, these parameters were positively correlated with NAFLD fibrosis score and FIB-4 index (P < .05). In addition, alanine aminotransferase and aspartate aminotransferase levels were positively correlated with TG/HDL-C ratio (r = 0.31, P = .003; and r = 0.27, P = .001 respectively). With increasing the severity of hepatic steatosis and NAFLD fibrosis score, the mean of all lipid ratios increased significantly (P < .01 and P < .05, respectively). Importantly, after controlling for potential confounders including age, gender, physical activity level, body mass index, waist circumference and HOMA-IR, the severity of steatosis, NAFLD fibrosis score and FIB-4 index remained independent predictors of atherogenic lipid profile. CONCLUSIONS Severity of hepatic steatosis, NAFLD fibrosis score and FIB-4 index were significantly correlated with atherogenic lipid profile. As NAFLD is high among patients with metabolic risk factors for CVD, their dyslipidaemia should be aggressively managed.
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Affiliation(s)
- Helda Tutunchi
- Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Naeini
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran university of medical science, Tehran, Iran
| | - Mehrangiz Ebrahimi-Mameghani
- Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- School of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Majid Mobasseri
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sina Naghshi
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran university of medical science, Tehran, Iran
| | - Alireza Ostadrahimi
- Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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19
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Cao YX, Zhang M, Zhang HW, Jin JL, Liu HH, Zhang Y, Guo YL, Wu NQ, Zhu CG, Xu RX, Gao Y, Dong Q, Sun J, Li JJ. Impact of liver fibrosis score on prognosis in patients with previous myocardial infarction: A prospective cohort study. Liver Int 2021; 41:1294-1304. [PMID: 33389804 DOI: 10.1111/liv.14780] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 11/24/2020] [Accepted: 12/21/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Liver fibrosis score (LFS) has been used for predicting the cardiovascular outcomes (CVOs) in diverse populations. However, the association of LFS with CVOs in patients with previous myocardial infarction (MI) remains undetermined. We aimed to examine the prognostic value of LFS in patients with prior MI in a prospective cohort. METHODS A total of 3718 patients with previous MI were consecutively enrolled from March 2009 to January 2019. Five LFSs including the fibrosis-4 (FIB-4) score, non-alcohol fatty liver disease fibrosis score (NFS), Forns score, HUI score and BARD score were used. The CVOs covered major adverse cardiac event (MACEs), cardiovascular mortality and all-cause mortality. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS During a mean follow-up of 47.4 ± 24.8 months, 431 (11.6%) MACEs occurred. Kaplan-Meier analysis demonstrated that higher LFSs resulted in a significantly higher probability of CVOs. Compared to the lowest score group, multivariable-adjusted HRs (95% CIs) of the highest group of FIB-4, NFS, Forns score, HUI score and BARD score were 1.75 (1.32-2.33), 2.37 (1.70-3.33), 2.44 (1.61-3.73), 1.58 (1.16-2.14) and 1.27 (1.03-1.57) respectively. These LFSs were also independent predictors of cardiovascular mortality and all-cause mortality. Similar results were observed across subgroups analysis. The addition of LFSs to a prediction model significantly increased the C-statistic for CVOs. CONCLUSIONS The present study firstly demonstrated that LFS could be used as a risk stratification tool for predicting CVOs in patients with previous MI, which should be evaluated further.
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Affiliation(s)
- Ye-Xuan Cao
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- Department of Cardiology, Beijing Chaoyang Hospital Affiliated to Capital University of Medical Science, Beijing, China
| | - Meng Zhang
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Hui-Wen Zhang
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Jing-Lu Jin
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Hui-Hui Liu
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yan Zhang
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yuan-Lin Guo
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Na-Qiong Wu
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Cheng-Gang Zhu
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Rui-Xia Xu
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Ying Gao
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Qian Dong
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Jing Sun
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Jian-Jun Li
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
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Nonalcoholic fatty liver disease (NAFLD) severity is associated to a nonhemostatic contribution and proinflammatory phenotype of platelets. Transl Res 2021; 231:24-38. [PMID: 33171266 DOI: 10.1016/j.trsl.2020.11.003] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 10/16/2020] [Accepted: 11/03/2020] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease and ranges from simple steatosis to nonalcoholic steatohepatitis. Recently, a platelet role in NAFLD pathogenesis and progression has been reported in mouse models and in patients. We investigated whether platelets are involved in liver and systemic inflammation processes in NAFLD. In this exploratory study we recruited 24 consecutive patients with biopsy-proven diagnosis of NAFLD and 17 healthy volunteers. We measured plasma levels of inflammatory markers by ELISA. We investigated hemostatic and inflammatory transcripts in circulating platelets and leukocytes from NAFLD patients. We analyzed platelet and neutrophil extracellular traps (NET) accumulations in liver sinusoids using CD42 and H3 citrullinated histones immunohistochemical staining on liver biopsies. NAFLD patients had increased inflammation markers and lipolysaccharides plasma levels. We found significant increase of inflammatory transcripts in circulating platelets and not in leukocytes of NAFLD subjects compared with healthy controls. We demonstrated increased intrahepatic platelet accumulation that correlated with NAFLD activity score (NAS) score and intrahepatic neutrophil extracellular traps (NET) formation in liver biopsies of NAFLD patients. NET formation was higher in livers with higher NAS and inflammation scores. The presence of low-grade systemic inflammation and proinflammatory changes of circulating platelets indicate that platelets participate on systemic inflammatory changes associated with NAFLD. Liver platelet accumulation and liver NET formation, together with low-grade endotoxemia, suggest that platelets may act to protect the liver from invading microorganisms by favoring local NET formation.
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21
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Nurmawati L, Sulchan M, Fatimah-Muis S, Djagat Purnomo H, Djamiatun K, Ardiaria M, Karlowee V. The effect of single clove Black garlic on the hemostasis status and lipid profile in male Sprague Dawley rats with non-alcoholic fatty liver disease. POTRAVINARSTVO 2021. [DOI: 10.5219/1516] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) patients have alteration in hemostasis components. Thus, including excess expression of plasminogen activator inhibitor-1 (PAI-1), causing fibrinolysis disorders; the majority of these patients are hypercoagulable state prone to thrombosis. Some evidence suggests that garlic and garlic supplements have antithrombotic and anti-inflammatory properties. Besides, garlic stimulates fibrinolytic activity and normalizes plasma lipid imbalances. Black garlic is processed garlic that is produced through natural aging at a controlled temperature (70 °C) and high humidity (90%) for several days, without other additives. This study aimed to prove the effect of single clove black garlic (SCBG) (Allium sativum Linn) on PAI-1 levels and lipid profiles of NAFLD rats induced by a high-fat fructose diet (HFFD) containing 1.25% cholesterol and 0.5% cholic acid.The rats were then divided into healthy control group (K1+); NAFLD control group without treatment (K2+); 0.9 mg simvastatin treatment group (K1-); 45 mg metformin treatment group (K2-); SCBG 450 mg per 200g BW (X1); 900 mg per 200 g BW (X2); and 1350 mg per 200 g BW (X3). All treatments were administered for 4 weeks via oral gavage. As a result, significant differences in PAI-1 levels and lipid profiles between groups after the administration (p = 0.001) were noted and also by simvastatin and metformin, respectively. There was a correlation between PAI-1 and lipid profile of SCBG treatment. In conclusion, the administration of SCBG (1350 mg per 200 g BB per day) for 4 weeks had a significant effect on PAI-1 levels, and the lipid profiles in Sprague Dawley rats modeled NAFLD (p = 0.001). SCBG has provided benefits that can be useful in the management of NAFLD but it’s not equivalent to medicine.
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22
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Su H, Liu D, Shao J, Li Y, Wang X, Gao Q. Aging Liver: Can Exercise be a Better Way to Delay the Process than Nutritional and Pharmacological Intervention? Focus on Lipid Metabolism. Curr Pharm Des 2021; 26:4982-4991. [PMID: 32503400 DOI: 10.2174/1381612826666200605111232] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 05/18/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Nowadays, the world is facing a common problem that the population aging process is accelerating. How to delay metabolic disorders in middle-aged and elderly people, has become a hot scientific and social issue worthy of attention. The liver plays an important role in lipid metabolism, and abnormal lipid metabolism may lead to liver diseases. Exercise is an easily controlled and implemented intervention, which has attracted extensive attention in improving the health of liver lipid metabolism in the elderly. This article reviewed the body aging process, changes of lipid metabolism in the aging liver, and the mechanism and effects of different interventions on lipid metabolism in the aging liver, especially focusing on exercise intervention. METHODS A literature search was performed using PubMed-NCBI, EBSCO Host and Web of Science, and also a report from WHO. In total, 143 studies were included from 1986 to 15 February 2020. CONCLUSION Nutritional and pharmacological interventions can improve liver disorders, and nutritional interventions are less risky relatively. Exercise intervention can prevent and improve age-related liver disease, especially the best high-intensity interval training intensity and duration is expected to be one of the research directions in the future.
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Affiliation(s)
- Hao Su
- The School of Sport Science, Beijing Sport University, Beijing, China
| | - Dongsen Liu
- The School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Jia Shao
- The Graduate School, Beijing Sport University, Beijing, China
| | - Yinuo Li
- The Graduate School, Beijing Sport University, Beijing, China
| | - Xiaoxia Wang
- The School of Physical Education and Art Education, Beijing Technology and Business University, Beijing, China
| | - Qi Gao
- The School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing, China
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23
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Ramadan MS, Russo V, Nigro G, Durante-Mangoni E, Zampino R. Interplay between Heart Disease and Metabolic Steatosis: A Contemporary Perspective. J Clin Med 2021; 10:1569. [PMID: 33917867 PMCID: PMC8068259 DOI: 10.3390/jcm10081569] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 03/26/2021] [Accepted: 04/03/2021] [Indexed: 12/12/2022] Open
Abstract
The liver-heart axis is a growing field of interest owing to rising evidence of complex bidirectional interplay between the two organs. Recent data suggest non-alcoholic fatty liver disease (NAFLD) has a significant, independent association with a wide spectrum of structural and functional cardiac diseases, and seems to worsen cardiovascular disease (CVD) prognosis. Conversely, the effect of cardiac disease on NAFLD is not well studied and data are mostly limited to cardiogenic liver disease. We believe it is important to further investigate the heart-liver relationship because of the tremendous global health and economic burden the two diseases pose, and the impact of such investigations on clinical decision making and management guidelines for both diseases. In this review, we summarize the current knowledge on NAFLD diagnosis, its systemic manifestations, and associations with CVD. More specifically, we review the pathophysiological mechanisms that govern the interplay between NAFLD and CVD and evaluate the relationship between different CVD treatments and NAFLD progression.
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Affiliation(s)
- Mohammad Said Ramadan
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
| | - Vincenzo Russo
- Department of Translational Medical Sciences, AORN Ospedali dei Colli-Monaldi Hospital, 80131 Naples, Italy; (V.R.); (G.N.)
- Cardiology Unit, AORN Ospedali dei Colli-Monaldi Hospital, 80131 Naples, Italy
| | - Gerardo Nigro
- Department of Translational Medical Sciences, AORN Ospedali dei Colli-Monaldi Hospital, 80131 Naples, Italy; (V.R.); (G.N.)
- Cardiology Unit, AORN Ospedali dei Colli-Monaldi Hospital, 80131 Naples, Italy
| | - Emanuele Durante-Mangoni
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
- Infectious and Transplant Medicine Unit, AORN Ospedali dei Colli-Monaldi Hospital, 80131 Naples, Italy;
| | - Rosa Zampino
- Infectious and Transplant Medicine Unit, AORN Ospedali dei Colli-Monaldi Hospital, 80131 Naples, Italy;
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
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24
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Choudhary N, Saraf N, Kuchay M, Kasliwal R. The association between nonalcoholic fatty liver disease and cardiovascular disease: A window of opportunity. JOURNAL OF CLINICAL AND PREVENTIVE CARDIOLOGY 2021. [DOI: 10.4103/jcpc.jcpc_31_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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25
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Kang KW, Ok M, Lee SK. Leptin as a Key between Obesity and Cardiovascular Disease. J Obes Metab Syndr 2020; 29:248-259. [PMID: 33342767 PMCID: PMC7789022 DOI: 10.7570/jomes20120] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 12/03/2020] [Accepted: 12/13/2020] [Indexed: 12/14/2022] Open
Abstract
Obesity increases the risk of cardiovascular disease through various influencing factors. Leptin, which is predominantly secreted by adipose tissue, regulates satiety homeostasis and energy balance, and influences cardiovascular functions directly and indirectly. Leptin appears to play a role in heart protection in leptin-deficient and leptin-receptor-deficient rodent model experiments. Hyperleptinemia or leptin resistance in human obesity influences the vascular endothelium, cardiovascular structure and functions, inflammation, and sympathetic activity, which may lead to cardiovascular disease. Leptin is involved in many processes, including signal transduction, vascular endothelial function, and cardiac structural remodeling. However, the dual (positive and negative) regulator effect of leptin and its receptor on cardiovascular disease has not been completely understood. The protective role of leptin signaling in cardiovascular disease could be a promising target for cardiovascular disease prevention in obese patients.
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Affiliation(s)
- Ki-Woon Kang
- Division of Cardiology, Department of Internal Medicine, Eulji University School of Medicine, Daejeon, Korea
| | - Minho Ok
- Department of Cardiovascular Pharmacology, Mokpo National University, Mokpo, Korea
| | - Seong-Kyu Lee
- Division of Endocrinology, Department of Internal Medicine, Daejeon, Korea.,Department of Biochemistry-Molecular Biology, Eulji University School of Medicine, Daejeon, Korea
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26
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Shabalala SC, Dludla PV, Mabasa L, Kappo AP, Basson AK, Pheiffer C, Johnson R. The effect of adiponectin in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and the potential role of polyphenols in the modulation of adiponectin signaling. Biomed Pharmacother 2020; 131:110785. [PMID: 33152943 DOI: 10.1016/j.biopha.2020.110785] [Citation(s) in RCA: 93] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 09/16/2020] [Accepted: 09/17/2020] [Indexed: 02/08/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, as it affects up to 30 % of adults in Western countries. Moreover, NAFLD is also considered an independent risk factor for cardiovascular diseases. Insulin resistance and inflammation have been identified as key factors in the pathophysiology of NAFLD. Although the mechanisms associated with the development of NAFLD remain to be fully elucidated, a complex interaction between adipokines and cytokines appear to play a crucial role in the development of this condition. Adiponectin is the most common adipokine known to be inversely linked with insulin resistance, lipid accumulation, inflammation and NAFLD. Consequently, the focus has been on the use of new therapies that may enhance hepatic expression of adiponectin downstream targets or increase the serum levels of adiponectin in the treatment NAFLD. While currently used therapies show limited efficacy in this aspect, accumulating evidence suggest that various dietary polyphenols may stimulate adiponectin levels, offering potential protection against the development of insulin resistance, inflammation and NAFLD as well as associated conditions of metabolic syndrome. As such, this review provides a better understanding of the role polyphenols play in modulating adiponectin signaling to protect against NAFLD. A brief discussion on the regulation of adiponectin during disease pathophysiology is also covered to underscore the potential protective effects of polyphenols against NAFLD. Some of the prominent polyphenols described in the manuscript include aspalathin, berberine, catechins, chlorogenic acid, curcumin, genistein, piperine, quercetin, and resveratrol.
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Affiliation(s)
- Samukelisiwe C Shabalala
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa; Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, University of Zululand, KwaDlangezwa, 3886, South Africa
| | - Phiwayinkosi V Dludla
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa; Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, 60131, Italy
| | - Lawrence Mabasa
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa
| | - Abidemi P Kappo
- Department of Biochemistry, Faculty of Science, University of Johannesburg, Auckland Park, 2006, South Africa
| | - Albertus K Basson
- Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, University of Zululand, KwaDlangezwa, 3886, South Africa
| | - Carmen Pheiffer
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa; Department of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa
| | - Rabia Johnson
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa; Department of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa.
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27
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St-Amand R, Ngo Sock ÉT, Quinn S, Lavoie JM, St-Pierre DH. Two weeks of western diet disrupts liver molecular markers of cholesterol metabolism in rats. Lipids Health Dis 2020; 19:192. [PMID: 32825820 PMCID: PMC7442981 DOI: 10.1186/s12944-020-01351-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 07/20/2020] [Indexed: 12/20/2022] Open
Abstract
Background The present study was designed to test the hypothesis that in the liver, excessive fat accumulation impairs cholesterol metabolism mainly by altering the low-density lipoprotein-receptor (LDL-R) pathway. Method Young male Wistar rats were fed standard (SD), high fat (HFD; 60% kcal) or Western (WD; 40% fat + 35% sucrose (17.5% fructose)) diets for 2 or 6 weeks. Results Weight gain (~ 40 g) was observed only following 6 weeks of the obesogenic diets (P < 0.01). Compared to the 2-week treatment, obesogenic diets tripled fat pad weight (~ 20 vs 7 g) after 6 weeks. Hepatic triglyceride (TG) levels were greater in response to both the WD and HFD compared to the SD (P < 0.01) at 2 and 6 weeks and their concentrations were greater (P < 0.05) in WD than HFD at 2 weeks. Plasma total cholesterol levels were higher (P < 0.05) in animals submitted to WD. After 2 and 6 weeks, liver expression of LDL-R, proprotein convertase subtilisin/kexin 9 (PCSKk9) and sterol regulatory element binding protein 2 (SREBP2), involved in LDL-cholesterol uptake, was lower in animals submitted to WD than in others treated with HFD or SD (P < 0.01). Similarly, low-density lipoprotein-receptor-related protein 1 (LRP1) and acyl-CoA cholesterol acyltransferase-2 (ACAT-2) mRNA levels were lower (P < 0.01) among WD compared to SD-fed rats. Expression of the gene coding the main regulator of endogenous cholesterol synthesis, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR) was reduced in response to WD compared to SD and HFD at 2 (P < 0.001) and 6 (P < 0.05) weeks. Being enriched in fructose, the WD strongly promoted the expression of carbohydrate-response element binding protein (ChREBP) and acetyl-CoA carboxylase (ACC), two key regulators of de novo lipogenesis. Conclusion These results show that the WD promptly increased TG levels in the liver by potentiating fat storage. This impaired the pathway of hepatic cholesterol uptake via the LDL-R axis, promoting a rapid increase in plasma total cholesterol levels. These results indicate that liver fat content is a factor involved in the regulation of plasma cholesterol.
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Affiliation(s)
- Roxane St-Amand
- École de Kinésiologie et des Sciences de l'Activité Physique, Faculté de Médecine, Université de Montréal, Montréal, Canada
| | - Émilienne T Ngo Sock
- École de Kinésiologie et des Sciences de l'Activité Physique, Faculté de Médecine, Université de Montréal, Montréal, Canada
| | - Samantha Quinn
- Department of Exercise Sciences, Université du Québec à Montréal, 141, Avenue Président-Kennedy, C.P. 8888, succursale Centre-Ville, Montréal, Québec, H3C 3P8, Canada
| | - Jean-Marc Lavoie
- École de Kinésiologie et des Sciences de l'Activité Physique, Faculté de Médecine, Université de Montréal, Montréal, Canada
| | - David H St-Pierre
- Department of Exercise Sciences, Université du Québec à Montréal, 141, Avenue Président-Kennedy, C.P. 8888, succursale Centre-Ville, Montréal, Québec, H3C 3P8, Canada.
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28
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Non-alcoholic steatohepatitis and the risk of myocardial infarction: A population-based national study. World J Hepatol 2020. [DOI: 10.4254/wjh.v12.i7.379] [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: 02/07/2023] Open
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29
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Ghoneim S, Dhorepatil A, Shah AR, Ram G, Ahmad S, Kim C, Asaad I. Non-alcoholic steatohepatitis and the risk of myocardial infarction: A population-based national study. World J Hepatol 2020; 12:378-388. [PMID: 32821336 PMCID: PMC7407919 DOI: 10.4254/wjh.v12.i7.378] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Revised: 05/25/2020] [Accepted: 06/10/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a systemic disease with bidirectional relationships with cardiovascular disease (CVD). Non-alcoholic steatohepatitis (NASH) is a more severe subtype of NAFLD. Patients with NASH exhibit more intra and extrahepatic inflammation, procoagulant imbalances and proatherogenic lipid profiles. Whether NASH increases the risk of ischemic heart disease is currently unclear.
AIM To investigate the relationship between acute myocardial infarction (MI) and NASH in a large cohort of subjects in the United States.
METHODS We reviewed data from a large commercial database (Explorys IBM) that aggregates electronic health records from 26 large nationwide healthcare systems. Using systemized nomenclature of clinical medical terms (SNOMED CT), we identified adult with the diagnosis of NASH from 1999-2019. We included patients with the diagnosis of acute MI from 2018-2019. Comorbidities known to be associated with NASH and MI such as obesity, diabetes mellitus, hyperlipidemia, smoking, male gender, and hypertension were collected. Univariable and multivariable analyses were performed to investigate whether NASH is independently associated with the risk of MI.
RESULTS Out of 55099280 patients, 43170 were diagnosed with NASH (0.08%) and 107000 (0.194%) had a MI within 2018-2019. After adjusting for traditional risk factors, NASH conferred greater odds of MI odds ratio (OR) 1.5 [95% confidence interval (CI): 1.40-1.62]. Hyperlipidemia had the strongest association with MI OR 8.39 (95%CI: 8.21-8.58) followed by hypertension OR 3.11 (95%CI: 3.05-3.17) and smoking OR 2.83 (95%CI: 2.79-2.87). NASH had a similar association with MI as the following traditional risk factors like age above 65 years OR 1.47 (95%CI: 1.45-1.49), male gender OR 1.53 (95%CI: 1.51-1.55) diabetes mellitus OR 1.89 (95%CI: 1.86-1.91).
CONCLUSION MI appears to be a prevalent disease in NASH. Patients with NASH may need early identification and aggressive cardiovascular risk modification.
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Affiliation(s)
- Sara Ghoneim
- Department of Internal Medicine, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH 44109, United States
| | - Aneesh Dhorepatil
- Department of Internal Medicine, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH 44109, United States
| | - Aun Raza Shah
- Department of Internal Medicine, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH 44109, United States
| | - Ganesh Ram
- Department of Pain Management, The Schulich School of Medicine and Dentistry, London, Ontario N6A 5C1, Canada
| | - Subhan Ahmad
- Department of Internal Medicine, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH 44109, United States
| | - Chang Kim
- Department of Internal Medicine, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH 44109, United States
| | - Imad Asaad
- Division of Gastroenterology, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH 44109, United States
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Bisaccia G, Ricci F, Mantini C, Tana C, Romani GL, Schiavone C, Gallina S. Nonalcoholic fatty liver disease and cardiovascular disease phenotypes. SAGE Open Med 2020; 8:2050312120933804. [PMID: 32612827 PMCID: PMC7307287 DOI: 10.1177/2050312120933804] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 05/21/2020] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease is increasingly recognized as a major global health problem. Intertwined with diabetes, metabolic syndrome, and obesity, nonalcoholic fatty liver disease embraces a spectrum of liver conditions spanning from steatosis to inflammation, fibrosis, and liver failure. Compared with the general population, the prevalence of cardiovascular disease is higher among nonalcoholic fatty liver disease patients, in whom comprehensive cardiovascular risk assessment is highly desirable. Preclinical effects of nonalcoholic fatty liver disease on the heart include both metabolic and structural changes eventually preceding overt myocardial dysfunction. Particularly, nonalcoholic fatty liver disease is associated with enhanced atherosclerosis, heart muscle disease, valvular heart disease, and arrhythmias, with endothelial dysfunction, inflammation, metabolic dysregulation, and oxidative stress playing in the background. In this topical review, we aimed to summarize current evidence on the epidemiology of nonalcoholic fatty liver disease, discuss the pathophysiological links between nonalcoholic fatty liver disease and cardiovascular disease, illustrate nonalcoholic fatty liver disease-related cardiovascular phenotypes, and finally provide a glimpse on the relationship between nonalcoholic fatty liver disease and cardiac steatosis, mitochondrial (dys)function, and cardiovascular autonomic dysfunction.
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Affiliation(s)
- Giandomenico Bisaccia
- Department of Neuroscience, Imaging and Clinical Sciences, Institute for Advanced Biomedical Technologies, "G. d'Annunzio" University of Chieti and Pescara, Chieti, Italy
| | - Fabrizio Ricci
- Department of Neuroscience, Imaging and Clinical Sciences, Institute for Advanced Biomedical Technologies, "G. d'Annunzio" University of Chieti and Pescara, Chieti, Italy.,Department of Clinical Sciences, Lund University, Malmö, Sweden
| | - Cesare Mantini
- Department of Neuroscience, Imaging and Clinical Sciences, Institute for Advanced Biomedical Technologies, "G. d'Annunzio" University of Chieti and Pescara, Chieti, Italy
| | - Claudio Tana
- Internal Medicine and Critical Subacute Care Unit, Medicine Geriatric-Rehabilitation Department, and Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy
| | - Gian Luca Romani
- Department of Neuroscience, Imaging and Clinical Sciences, Institute for Advanced Biomedical Technologies, "G. d'Annunzio" University of Chieti and Pescara, Chieti, Italy
| | - Cosima Schiavone
- Department of Internistic Ultrasound, "G. d'Annunzio" University of Chieti and Pescara, Chieti, Italy
| | - Sabina Gallina
- Department of Neuroscience, Imaging and Clinical Sciences, Institute for Advanced Biomedical Technologies, "G. d'Annunzio" University of Chieti and Pescara, Chieti, Italy
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Chi ZC. Relationship between non-alcoholic fatty liver disease and cardiovascular disease. Shijie Huaren Xiaohua Zazhi 2020; 28:313-329. [DOI: 10.11569/wcjd.v28.i9.313] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
With the in-depth study of non-alcoholic fatty liver disease (NAFLD), it has been found in recent years that NAFLD is closely related to cardiovascular disease (CVD). It has been proved that NAFLD is not only an important risk factor for CVD, but it is also an important mechanism of atherosclerosis, coronary heart disease, and hypertension in young people. This article reviews the recent progress in the understanding of the relationship between NAFLD and CVD, with an aim to improve the knowledge of CVD physicians on liver disease and provide reference for prevention and treatment of these conditions.
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Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
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Gehrke N, Schattenberg JM. Metabolic Inflammation-A Role for Hepatic Inflammatory Pathways as Drivers of Comorbidities in Nonalcoholic Fatty Liver Disease? Gastroenterology 2020; 158:1929-1947.e6. [PMID: 32068022 DOI: 10.1053/j.gastro.2020.02.020] [Citation(s) in RCA: 135] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 02/05/2020] [Accepted: 02/11/2020] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a global and growing health concern. Emerging evidence points toward metabolic inflammation as a key process in the fatty liver that contributes to multiorgan morbidity. Key extrahepatic comorbidities that are influenced by NAFLD are type 2 diabetes, cardiovascular disease, and impaired neurocognitive function. Importantly, the presence of nonalcoholic steatohepatitis and advanced hepatic fibrosis increase the risk for systemic comorbidity in NAFLD. Although the precise nature of the crosstalk between the liver and other organs has not yet been fully elucidated, there is emerging evidence that metabolic inflammation-in part, emanating from the fatty liver-is the engine that drives cellular dysfunction, cell death, and deleterious remodeling within various body tissues. This review describes several inflammatory pathways and mediators that have been implicated as links between NAFLD and type 2 diabetes, cardiovascular disease, and neurocognitive decline.
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Affiliation(s)
- Nadine Gehrke
- Metabolic Liver Research Program, I. Department of Medicine, University Medical Center, Mainz, Germany.
| | - Jörn M Schattenberg
- Metabolic Liver Research Program, I. Department of Medicine, University Medical Center, Mainz, Germany
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Breuer DA, Pacheco MC, Washington MK, Montgomery SA, Hasty AH, Kennedy AJ. CD8 + T cells regulate liver injury in obesity-related nonalcoholic fatty liver disease. Am J Physiol Gastrointest Liver Physiol 2020; 318:G211-G224. [PMID: 31709830 PMCID: PMC7052570 DOI: 10.1152/ajpgi.00040.2019] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Nonalcoholic steatohepatitis (NASH) has increased in Western countries due to the prevalence of obesity. Current interests are aimed at identifying the type and function of immune cells that infiltrate the liver and key factors responsible for mediating their recruitment and activation in NASH. We investigated the function and phenotype of CD8+ T cells under obese and nonobese NASH conditions. We found an elevation in CD8 staining in livers from obese human subjects with NASH and cirrhosis that positively correlated with α-smooth muscle actin, a marker of hepatic stellate cell (HSC) activation. CD8+ T cells were elevated 3.5-fold in the livers of obese and hyperlipidemic NASH mice compared with obese hepatic steatosis mice. Isolated hepatic CD8+ T cells from these mice expressed a cytotoxic IL-10-expressing phenotype, and depletion of CD8+ T cells led to significant reductions in hepatic inflammation, HSC activation, and macrophage accumulation. Furthermore, hepatic CD8+ T cells from obese and hyperlipidemic NASH mice activated HSCs in vitro and in vivo. Interestingly, in the lean NASH mouse model, depletion and knockdown of CD8+ T cells did not impact liver inflammation or HSC activation. We demonstrated that under obese/hyperlipidemia conditions, CD8+ T cell are key regulators of the progression of NASH, while under nonobese conditions they play a minimal role in driving the disease. Thus, therapies targeting CD8+ T cells may be a novel approach for treatment of obesity-associated NASH.NEW & NOTEWORTHY Our study demonstrates that CD8+ T cells are the primary hepatic T cell population, are elevated in obese models of NASH, and directly activate hepatic stellate cells. In contrast, we find CD8+ T cells from lean NASH models do not regulate NASH-associated inflammation or stellate cell activation. Thus, for the first time to our knowledge, we demonstrate that hepatic CD8+ T cells are key players in obesity-associated NASH.
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Affiliation(s)
- Denitra A. Breuer
- 1Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, North Carolina
| | - Maria Cristina Pacheco
- 2Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - M. Kay Washington
- 2Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Stephanie A. Montgomery
- 4Department of Pathology and Laboratory Medicine and Lineberger Cancer Center, University North Carolina Chapel Hill, Chapel Hill, North Carolina
| | - Alyssa H. Hasty
- 3Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Arion J. Kennedy
- 1Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, North Carolina
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Affiliation(s)
- Matthew T McKenna-Barry
- Hepatology Unit, Beaumont Hospital / Royal College of Surgeons in Ireland, Dublin 9, Republic of Ireland
| | - John D Ryan
- Hepatology Unit, Beaumont Hospital / Royal College of Surgeons in Ireland, Dublin 9, Republic of Ireland
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Olubamwo OO, Virtanen JK, Pihlajamaki J, Mantyselka P, Tuomainen TP. Fatty liver index as a predictor of increased risk of cardiometabolic disease: finding from the Kuopio Ischaemic Heart Disease Risk Factor Study Cohort. BMJ Open 2019; 9:e031420. [PMID: 31492793 PMCID: PMC6731849 DOI: 10.1136/bmjopen-2019-031420] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE Fatty liver disease (FLD), a global epidemic, is also a predictor of cardiometabolic disease (CMD) (type 2 diabetes or cardiovascular disease). Our objective was to examine whether progressive FLD, as assessed by fatty liver index (FLI), predicts increasing future CMD risk compared with relatively stable FLD, among middle-aged men. DESIGN Prospective epidemiological study. SETTING University affiliated research centre in Kuopio, Eastern Finland. PARTICIPANTS Our subjects were 501 men without CMD during the initial 4-year follow-up in the Kuopio Ischaemic Heart Disease Risk Factor Study cohort. OUTCOME MEASURE Over the initial 4-year follow-up, 135 men (26.9%) had a significant (≥10) FLI increase. The association of 4-year FLI increase with incident CMD was analysed in multivariable-adjusted Cox regression models, adjusting for baseline constitutional and lifestyle factors (model 1) and, in addition, metabolic and inflammation biomarker factors (model 2). RESULTS During a mean follow-up of 15 years, 301 new CMD cases occurred. We used subjects with low baseline FLI and no significant 4-year FLI increase as the reference. For subjects with intermediate baseline FLI and significant 4-year FLI increase, the HRs and 95% CIs for incident CMD in model 1 (2.13 (1.45 to 3.13)) and model 2 (1.73 (1.13 to 2.66)) exceeded values for subjects with similar baseline FLI without a significant 4-year change (HRs (95% CIs) were 1.36 (0.94 to 1.97) for model 1 and 1.18 (0.81 to 1.70) for model 2). They approached HRs (95% CI) for subjects who maintained high FLI over the 4 years (HRs (95% CIs) were 2.18 (1.54 to 3.10) in model 1 and 1.85 (1.21 to 2.82) in model 2). CONCLUSION Persons with significant FLI increase are likely with increasing CMD risk. Such persons should be evaluated for progressive FLD and CMD and managed to reduce CMD risk.
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Affiliation(s)
- Olubunmi O Olubamwo
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
| | - Jyrki K Virtanen
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
| | - Jussi Pihlajamaki
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
- Clinical Nutrition and Obesity Center, Kuopio University Hospital, KYS, Kuopio, Finland
| | - Pekka Mantyselka
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
- Primary Health Care Unit, Kuopio University Hospital, Kuopio, Finland
| | - Tomi-Pekka Tuomainen
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
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Cardiovascular Risk in Non-Alcoholic Fatty Liver Disease: Mechanisms and Therapeutic Implications. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16173104. [PMID: 31455011 PMCID: PMC6747357 DOI: 10.3390/ijerph16173104] [Citation(s) in RCA: 128] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2019] [Revised: 08/18/2019] [Accepted: 08/21/2019] [Indexed: 02/06/2023]
Abstract
New evidence suggests that non-alcoholic fatty liver disease (NAFLD) has a strong multifaceted relationship with diabetes and metabolic syndrome, and is associated with increased risk of cardiovascular events, regardless of traditional risk factors, such as hypertension, diabetes, dyslipidemia, and obesity. Given the pandemic-level rise of NAFLD—in parallel with the increasing prevalence of obesity and other components of the metabolic syndrome—and its association with poor cardiovascular outcomes, the question of how to manage NAFLD properly, in order to reduce the burden of associated incident cardiovascular events, is both timely and highly relevant. This review aims to summarize the current knowledge of the association between NAFLD and cardiovascular disease, and also to discuss possible clinical strategies for cardiovascular risk assessment, as well as the spectrum of available therapeutic strategies for the prevention and treatment of NAFLD and its downstream events.
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Porous graphene-black phosphorus nanocomposite modified electrode for detection of leptin. Biosens Bioelectron 2019; 137:88-95. [DOI: 10.1016/j.bios.2019.04.045] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 04/06/2019] [Accepted: 04/23/2019] [Indexed: 12/22/2022]
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Abstract
The health-promoting effects of physical activity to prevent and treat metabolic disorders are numerous. However, the underlying molecular mechanisms are not yet completely deciphered. In recent years, studies have referred to the liver as an endocrine organ, since it releases specific proteins called hepatokines. Some of these hepatokines are involved in whole body metabolic homeostasis and are theorized to participate in the development of metabolic disease. In this regard, the present review describes the role of Fibroblast Growth Factor 21, Fetuin-A, Angiopoietin-like protein 4, and Follistatin in metabolic disease and their production in response to acute exercise. Also, we discuss the potential role of hepatokines in mediating the beneficial effects of regular exercise and the future challenges to the discovery of new exercise-induced hepatokines.
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Affiliation(s)
- Gaël Ennequin
- PEPITE EA4267, EPSI, Université de Bourgogne Franche-Comté , Besançon , France
| | - Pascal Sirvent
- Université Clermont Auvergne, Laboratoire des Adaptations Métaboliques à l'Exercice en conditions Physiologiques et Pathologiques (AME2P), CRNH Auvergne, Clermont-Ferrand , France
| | - Martin Whitham
- School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham , Birmingham , United Kingdom
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Pastore M, Grimaudo S, Pipitone RM, Lori G, Raggi C, Petta S, Marra F. Role of Myeloid-Epithelial-Reproductive Tyrosine Kinase and Macrophage Polarization in the Progression of Atherosclerotic Lesions Associated With Nonalcoholic Fatty Liver Disease. Front Pharmacol 2019; 10:604. [PMID: 31191323 PMCID: PMC6548874 DOI: 10.3389/fphar.2019.00604] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Accepted: 05/14/2019] [Indexed: 12/13/2022] Open
Abstract
Recent lines of evidence highlight the involvement of myeloid-epithelial-reproductive tyrosine kinase (MerTK) in metabolic disease associated with liver damage. MerTK is mainly expressed in anti-inflammatory M2 macrophages where it mediates transcriptional changes including suppression of proinflammatory cytokines and enhancement of inflammatory repressors. MerTK is regulated by metabolic pathways through nuclear sensors including LXRs, PPARs, and RXRs, in response to apoptotic bodies or to other sources of cholesterol. Nonalcoholic fatty liver disease (NAFLD) is one of the most serious public health problems worldwide. It is a clinicopathological syndrome closely related to obesity, insulin resistance, and oxidative stress. It includes a spectrum of conditions ranging from simple steatosis, characterized by hepatic fat accumulation with or without inflammation, to nonalcoholic steatohepatitis (NASH), defined by hepatic fat deposition with hepatocellular damage, inflammation, and accumulating fibrosis. Several studies support an association between NAFLD and the incidence of cardiovascular diseases including atherosclerosis, a major cause of death worldwide. This pathological condition consists in a chronic and progressive inflammatory process in the intimal layer of large- and medium-sized arteries. The complications of advanced atherosclerosis include chronic or acute ischemic damage in the tissue perfused by the affected artery, leading to cellular death. By identifying specific targets influencing lipid metabolism and cardiovascular-related diseases, the present review highlights the role of MerTK in NAFLD-associated atherosclerotic lesions as a potential innovative therapeutic target. Therapeutic advantages might derive from the use of compounds selective for nuclear receptors targeting PPARs rather than LXRs regulating macrophage lipid metabolism and macrophage mediated inflammation, by favoring the expression of MerTK, which mediates an immunoregulatory action with a reduction in inflammation and in atherosclerosis.
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Affiliation(s)
- Mirella Pastore
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Stefania Grimaudo
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Rosaria Maria Pipitone
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Giulia Lori
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Chiara Raggi
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.,Humanitas Clinical and Research Center, Rozzano, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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El Hadi H, Di Vincenzo A, Vettor R, Rossato M. Cardio-Metabolic Disorders in Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2019; 20:ijms20092215. [PMID: 31064058 PMCID: PMC6539803 DOI: 10.3390/ijms20092215] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 04/19/2019] [Accepted: 04/28/2019] [Indexed: 12/16/2022] Open
Abstract
With the progressive epidemics of obesity, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in adults and children. The increasing prevalence and incidence of NAFLD with advanced fibrosis is concerning because patients appear to experience higher non-liver-related morbidity and mortality than the general population. Recent clinical evidence suggests that NAFLD is directly associated with an increased risk of cardio-metabolic disorders. This mini review describes briefly the current understanding of the pathogenesis of NAFLD, summarizing the link between NAFLD and cardio-metabolic complications, focusing mainly upon ischemic stroke, type 2 diabetes mellitus (DM), hypertension, chronic kidney disease (CKD) and cardiac arrhythmias. In addition, it describes briefly the current understanding of the pathogenesis of NAFLD.
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Affiliation(s)
- Hamza El Hadi
- Internal Medicine 3, Department of Medicine DIMED, University of Padova, 35122 Padova, Italy.
- Department of Medicine, Klinikum Rheine, 48431 Rheine, Germany.
| | - Angelo Di Vincenzo
- Internal Medicine 3, Department of Medicine DIMED, University of Padova, 35122 Padova, Italy.
| | - Roberto Vettor
- Internal Medicine 3, Department of Medicine DIMED, University of Padova, 35122 Padova, Italy.
| | - Marco Rossato
- Internal Medicine 3, Department of Medicine DIMED, University of Padova, 35122 Padova, Italy.
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Choudhary NS, Saigal S. Preventive Strategies for Nonalcoholic Fatty Liver Disease After Liver Transplantation. J Clin Exp Hepatol 2019; 9:619-624. [PMID: 31695252 PMCID: PMC6823688 DOI: 10.1016/j.jceh.2019.05.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 05/22/2019] [Indexed: 12/12/2022] Open
Abstract
Post-transplant nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) is common and can be recurrent or de novo. The available data suggest that progression of fibrosis is accelerated in these patients compared to NASH in general population. The long-term data suggest more risk of metabolic syndrome and associated metabolic comorbidities and cardiovascular disease in these patients. The current review focuses on prevalence and prevention/treatment of post-transplant NAFLD or NASH.
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Affiliation(s)
| | - Sanjiv Saigal
- Address for correspondence: Sanjiv Saigal, Director, Hepatology & Liver Transplant, Medanta Institute of Digestive & Hepatobiliary Sciences &Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, PIN 122001, India.
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Choudhary NS, Duseja A. Screening of Cardiovascular Disease in Nonalcoholic Fatty Liver Disease: Whom and How? J Clin Exp Hepatol 2019; 9:506-514. [PMID: 31516267 PMCID: PMC6728527 DOI: 10.1016/j.jceh.2019.02.005] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 02/06/2019] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Patients with NAFLD are at a higher risk of developing cardiovascular disease (CVD). In fact, CVD-related mortality is more common in patients with NAFLD in comparison to liver-related mortality. This association is related to the common metabolic risk factors such as obesity, dyslipidemia, diabetes, and hypertension shared by both NAFLD and CVD, and also there is independent association of NAFLD with CVD because of risk factors such as insulin resistance, systemic inflammation, and atherogenic dyslipidemia. While there is abundant literature on association of NAFLD with CVD, there is sparse literature regarding the screening for CVD in patients with NAFLD. In the current review article, we discuss as to which patients with NAFLD to screen and how to screen for CVD.
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Key Words
- BMI, Body Mass Index
- CAD, Coronary Artery Disease
- CI, Confidence Interval
- CVD, Cardiovascular Disease
- DM, Diabetes Mellitus
- DSE, Dobutamine Stress ECHO
- HDL, High-Density Lipoprotein
- ILTS, International Liver Transplantation Society
- LDL, Low-Density Lipoprotein
- NAFL, Nonalcoholic Fatty Liver
- NAFLD, Nonalcoholic Fatty Liver Disease
- NASH, Nonalcoholic Steatohepatitis
- OR, Odds Ratio
- atherosclerosis
- cirrhosis
- hs-CRP, High-Sensitivity C-Reactive Protein
- metabolic syndrome
- risk scores
- screening
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Affiliation(s)
- Narendra S. Choudhary
- Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity, Gurgaon, Delhi (NCR), India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India,Address for correspondence: Ajay Duseja, DM, FAMS, FAASLD, FACG, FSGEI, Professor, Department of Hepatology, Sector 12, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India. Tel.: +91 172 2756336; fax: +91 0172 2744401.
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Magri-Tomaz L, Melbouci L, Mercier J, Ou Y, Auclair N, Lira FS, Lavoie JM, St-Pierre DH. Two weeks of high-fat feeding disturb lipid and cholesterol molecular markers. Cell Biochem Funct 2018; 36:387-393. [DOI: 10.1002/cbf.3358] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Revised: 08/15/2018] [Accepted: 09/06/2018] [Indexed: 12/19/2022]
Affiliation(s)
- L. Magri-Tomaz
- Département des Sciences de l'Activité Physique; UQAM; Montréal Québec Canada
- Centre de Recherche du CHU Sainte-Justine; Montréal Québec Canada
- Département de Kinésiologie; Université de Montréal; Montréal Québec Canada
| | - L. Melbouci
- Département des Sciences de l'Activité Physique; UQAM; Montréal Québec Canada
- Centre de Recherche du CHU Sainte-Justine; Montréal Québec Canada
| | - J. Mercier
- Département des Sciences de l'Activité Physique; UQAM; Montréal Québec Canada
- Centre de Recherche du CHU Sainte-Justine; Montréal Québec Canada
| | - Ya Ou
- Département des Sciences de l'Activité Physique; UQAM; Montréal Québec Canada
- Centre de Recherche du CHU Sainte-Justine; Montréal Québec Canada
| | - N. Auclair
- Département des Sciences de l'Activité Physique; UQAM; Montréal Québec Canada
- Centre de Recherche du CHU Sainte-Justine; Montréal Québec Canada
| | - F. S. Lira
- Department of Physical Education; State University of São Paulo, Presidente Prudente; São Paulo Brazil
| | - J-M. Lavoie
- Département de Kinésiologie; Université de Montréal; Montréal Québec Canada
| | - D. H. St-Pierre
- Département des Sciences de l'Activité Physique; UQAM; Montréal Québec Canada
- Centre de Recherche du CHU Sainte-Justine; Montréal Québec Canada
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Dyslipidemia is associated with pediatric nonalcoholic fatty liver disease. J Clin Lipidol 2018; 12:981-987. [PMID: 29699915 DOI: 10.1016/j.jacl.2018.03.089] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Revised: 02/20/2018] [Accepted: 03/28/2018] [Indexed: 01/14/2023]
Abstract
BACKGROUND With the increasing prevalence of childhood obesity, nonalcoholic fatty liver disease (NAFLD) has emerged as the most common cause of pediatric chronic liver disorder. Factors underlying the pathophysiology of NAFLD remain poorly defined. OBJECTIVE This study aimed to describe the metabolic characteristics of children with NAFLD differing in race/ethnicity and to test associations between dyslipidemia and NAFLD. METHODS A retrospective chart review was conducted at a tertiary referral university hospital among 309 children with a diagnosis of NAFLD. RESULTS Participants (mean age 12.5 ± 3.4 years) were 64% male, 63% white, 23% Hispanic, and 14% black. Hispanic children were diagnosed with NAFLD at a significantly younger age (10.6 ± 3.1 years, P < .0001) and lower body mass index (31.5 ± 6.8 kg/m2, P < .0001) than their white and black counterparts. For the entire cohort, prevalence of systolic hypertension was 41%, diabetes 14%, elevated cholesterol 42%, elevated non-high-density lipoprotein cholesterol (non-HDL-C) 58%, elevated low-density lipoprotein cholesterol 36%, elevated triglycerides (TG) 88%, and low high-density lipoprotein cholesterol 77%. Whites had elevated non-HDL-C, low-density lipoprotein cholesterol, and TG compared to blacks or Hispanics. Serum TG and non-HDL-C were significantly correlated to alanine aminotransferase (r = 0.18, P = .01; r = 0.16, P = .02), respectively, and persisted after adjusting for age and body mass index. CONCLUSION Cardiometabolic derangements, especially dyslipidemia, are highly prevalent in children with NAFLD and differ based on race/ethnicity. Serum TG and non-HDL-C may play an important role in the pathophysiology of pediatric NAFLD.
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Severity of nonalcoholic fatty liver disease is associated with subclinical cerebro-cardiovascular atherosclerosis risk in Korean men. PLoS One 2018; 13:e0193191. [PMID: 29565984 PMCID: PMC5863945 DOI: 10.1371/journal.pone.0193191] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Accepted: 02/06/2018] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND No studies have reported the relationship between nonalcoholic fatty liver disease (NAFLD) and concurrent cerebral artery and coronary artery atherosclerosis simultaneously. We aimed at determining whether NAFLD, as assessed by ultrasound, is associated with subclinical cerebro-cardio vascular atherosclerosis (CCVA) by multidetector-row computed tomography (MDCT), and high resolution-magnetic resonance angiography (HR-MRA). This cross-sectional study included men in the general Korean population aged 20-70 years. RESULTS A total of 1,652 men participated in the study (normal, n = 835; mild-to-moderate NAFLD, n = 512; severe NAFLD, n = 305). The risk of subclinical CCVA was positively associated with age (odds ratio [OR] 1.068; 1.054-1.081, p < 0.001), body mass index (OR 1.120; 1.08 0-1.162, p < 0.001), hepatic enzyme levels (OR 1.012; 1.001-1.023, p = 0.027; OR 1.006; 1.001-1.012, p = 0.036), fasting glucose (OR 1.021; 1.015-1.027, p < 0.001), triglycerides (OR 1.002; 1.000-1.003, p = 0.016), hypertension (OR 2.836; 2.268-3.546, p < 0.001), and diabetes (OR 2.911; 2.137-3.964, p < 0.001). Also, high-density lipoprotein cholesterol was inversely associated with subclinical CCVA (OR 0.974; 0.965-0.982, p < 0.001). Compared with normal controls, the OR for subclinical CCVA after full adjustment was 1.46 in the mild-to-moderate NAFLD group (95% confidence interval [CI]: 1.10 to 1.93) and 2.04 in the severe NAFLD group (95% CI: 1.44 to 2.89). CONCLUSIONS Our data show that NAFLD is common among Korean men, and NAFLD severity on ultrasonography is associated with subclinical CCVA, as assessed by MDCT, and HR-MRA.
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Gong Z, Tas E, Yakar S, Muzumdar R. Hepatic lipid metabolism and non-alcoholic fatty liver disease in aging. Mol Cell Endocrinol 2017; 455:115-130. [PMID: 28017785 DOI: 10.1016/j.mce.2016.12.022] [Citation(s) in RCA: 99] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Revised: 09/23/2016] [Accepted: 12/16/2016] [Indexed: 02/06/2023]
Abstract
Aging is associated with dysregulation of glucose and lipid metabolism. Various factors that contribute to the dysregulation include both modifiable (e.g. obesity, insulin resistance) and non-modifiable risk factors (age-associated physiologic changes). Although there is no linear relationship between aging and prevalence of non-alcoholic fatty liver disease, current data strongly suggests that advanced age leads to more severe histological changes and poorer clinical outcomes. Hepatic lipid accumulation could lead to significant hepatic and systemic consequences including steatohepatitis, cirrhosis, impairment of systemic glucose metabolism and metabolic syndrome, thereby contributing to age-related diseases. Insulin, leptin and adiponectin are key regulators of the various physiologic processes that regulate hepatic lipid metabolism. Recent advances have expanded our understanding in this field, highlighting the role of novel mediators such as FGF 21, and mitochondria derived peptides. In this review, we will summarize the mediators of hepatic lipid metabolism and how they are altered in aging.
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Affiliation(s)
- Zhenwei Gong
- Department of Pediatrics, University of Pittsburgh School of Medicine, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA 15224, USA; Children's Hospital of Pittsburgh of UPMC, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA 15224, USA
| | - Emir Tas
- Children's Hospital of Pittsburgh of UPMC, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA 15224, USA
| | - Shoshana Yakar
- David B. Kriser Dental Center, Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY 10010, USA
| | - Radhika Muzumdar
- Department of Pediatrics, University of Pittsburgh School of Medicine, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA 15224, USA; Children's Hospital of Pittsburgh of UPMC, One Children's Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA 15224, USA; Department of Cell Biology, University of Pittsburgh School of Medicine, 3500 Terrace Street, 5362 Biomedical Sciences Tower, Pittsburgh, PA 15261, USA.
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Edgerton CA, McGillicuddy JW, DuBay D, Nadig SN. Utilization of the Iliac Artery as Inflow in the Morbidly Obese During Orthotopic Liver Transplantation: A Case Report. Transplant Proc 2017; 49:1624-1627. [PMID: 28838452 DOI: 10.1016/j.transproceed.2017.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 05/13/2017] [Indexed: 11/17/2022]
Abstract
Arterial conduits are a well-recognized technique used in liver transplantation to achieve allograft arterial inflow when conventional hepatic arterial inflow is compromised. Indications for ectopic inflow include native arterial disease at the time of initial transplantation, as well as reconstruction in the setting of thrombotic complications. Although supraceliac or infrarenal aortic reconstructions are preferred approaches, the right common iliac artery represents a viable alternative. We present the case of a morbidly obese patient with occlusive atheromatous plaque at the celiac origin not amenable to preoperative angioplasty who underwent reconstruction with a donor iliac artery conduit to the recipient right common iliac artery. His hepatic arterial inflow remained patent postoperatively with no thrombotic or hemorrhagic complications.
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Affiliation(s)
- C A Edgerton
- Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, Charleston, South Carolina
| | - J W McGillicuddy
- Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, Charleston, South Carolina
| | - D DuBay
- Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, Charleston, South Carolina
| | - S N Nadig
- Department of Surgery, Division of Transplant Surgery, Medical University of South Carolina, Charleston, South Carolina.
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Man E, Cheung PT, Cheung YF. Associations between arterial structure and function and serum levels of liver enzymes in obese adolescents. J Paediatr Child Health 2017; 53:691-697. [PMID: 28383828 DOI: 10.1111/jpc.13528] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Revised: 11/04/2016] [Accepted: 12/11/2016] [Indexed: 11/27/2022]
Abstract
AIM To determine the structural and functional alterations of systemic arteries in obese adolescents and their relationships with adiposity, metabolic and lipid profile, and serum liver enzyme levels. METHODS Carotid intima-media thickness (IMT), carotid stiffness index, and brachial-ankle pulse wave velocity (baPWV) were measured in 56 obese adolescents and 58 lean controls. Obese adolescents had additional liver ultrasound and determination of fasting blood indices of glucose metabolism and lipid profile, and serum levels of liver enzymes. RESULTS Carotid IMT (P < 0.0001), carotid stiffness index (P < 0.0001) and baPWV (P = 0.001) were significantly greater in obese than control subjects. Thirty-seven (66%) obese subjects had fatty liver changes and their aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, and gamma-glutamyl transferase levels were significantly higher than those without (all P < 0.05). Univariate analyses showed positive correlations between serum ALT (r = 0.29, P = 0.03) and alkaline phosphatase (r = 0.28, P = 0.04) levels and carotid IMT, aspartate aminotransferase level and carotid stiffness (r = 0.41, P = 0.002), and gamma-glutamyl transferase level and baPWV (r = 0.34, P = 0.02) in obese subjects. Multivariate linear regression revealed serum ALT level (β = 0.02, P = 0.006) as an independent correlate of carotid stiffness. CONCLUSION Obese adolescents have increased carotid IMT and stiffness, which are associated positively with serum liver enzyme levels.
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Affiliation(s)
- Elim Man
- Division of Paediatrics and Adolescent Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Pik-To Cheung
- Division of Paediatrics and Adolescent Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Yiu-Fai Cheung
- Division of Paediatric Cardiology, Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Pok Fu Lam, Hong Kong
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Silva AKSE, Gomes FODS, Santos Silva BD, Ribeiro EL, Oliveira AC, Araújo SMDR, de Lima IT, Oliveira AGV, Rudnicki M, Abdalla DS, Lima MDCAD, Pitta IDR, Peixoto CA. Chronic LPSF/GQ-02 treatment attenuates inflammation and atherosclerosis development in LDLr−/− mice. Eur J Pharmacol 2016; 791:622-631. [DOI: 10.1016/j.ejphar.2016.09.037] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 08/25/2016] [Accepted: 09/28/2016] [Indexed: 12/12/2022]
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Lonardo A, Sookoian S, Pirola CJ, Targher G. Non-alcoholic fatty liver disease and risk of cardiovascular disease. Metabolism 2016; 65:1136-1150. [PMID: 26477269 DOI: 10.1016/j.metabol.2015.09.017] [Citation(s) in RCA: 177] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Revised: 08/17/2015] [Accepted: 09/19/2015] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases worldwide, causing considerable liver-related mortality and morbidity. During the past decade, it has also become increasingly evident that NAFLD is a multisystem disease that affects many extra-hepatic organ systems, including the heart and the vascular system. In this updated clinical review, we discuss the rapidly expanding body of clinical and epidemiological evidence that supports a strong association of NAFLD with cardiovascular diseases (CVDs) and other functional and structural myocardial abnormalities. We also discuss some recently published data that correlate NAFLD due to specific genetic polymorphisms with the risk of CVDs. Finally, we briefly examine the assessment tools for estimating the global CVD risk in patients with NAFLD as well as the conventional and the more innovative pharmacological approaches for the treatment of CVD risk in this group of patients.
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Affiliation(s)
- Amedeo Lonardo
- Outpatient Liver Clinic and Division of Internal Medicine, Department of Biomedical, Metabolic and Neural Sciences, NOCSAE, Baggiovara, Azienda USL and University of Modena and Reggio Emilia, Modena, Italy
| | - Silvia Sookoian
- Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires-National Scientific and Technical Research Council (CONICET), Ciudad Autónoma de Buenos Aires, Argentina
| | - Carlos J Pirola
- Department of Molecular Genetics and Biology of Complex Diseases, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires-National Scientific and Technical Research Council (CONICET), Ciudad Autónoma de Buenos Aires, Argentina
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
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