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Muñoz-Restrepo AM, Navas MC, Daza J, Girala M, Ridruejo E, Gerken G, Teufel A. Prevention in Hepatology. J Pers Med 2024; 14:132. [PMID: 38392566 PMCID: PMC10890057 DOI: 10.3390/jpm14020132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Revised: 01/01/2024] [Accepted: 01/09/2024] [Indexed: 02/24/2024] Open
Abstract
The prevention of liver disease has improved significantly in the last few decades, to the point that it can now be considered a true success story. The wide variety of interventions, including comprehensive vaccination strategies, novel medications, lifestyle changes, and even preventive surgeries, have reduced the morbidity and mortality of chronic liver diseases. However, the prevalence of chronic liver diseases is increasing worldwide. Currently, fatty liver disease alone is estimated to be present in as much as 30% of the adult population. Furthermore, there is a trend towards increasing incidences of chronic hepatitis B, and a global lack of success in efforts to eliminate chronic hepatitis C. Thus, improving and efficiently rolling out existing and successful prevention strategies for chronic liver diseases will play an essential role in healthcare throughout the upcoming decades. In this review, we summarize the current options and concepts for preventing chronic liver diseases, highlight their limitations, and provide an outlook on probable future developments to improve awareness, integrated care, and the analysis of big data.
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Affiliation(s)
- Ana-Maria Muñoz-Restrepo
- Department of Medicine II, Division of Hepatology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (A.-M.M.-R.); (J.D.)
- Grupo Gastrohepatología, Facultad de Medicina, Universidad de Antioquia, UdeA, Calle 70 # 52-21, Medellin 050010, Colombia;
| | - Maria-Cristina Navas
- Grupo Gastrohepatología, Facultad de Medicina, Universidad de Antioquia, UdeA, Calle 70 # 52-21, Medellin 050010, Colombia;
| | - Jimmy Daza
- Department of Medicine II, Division of Hepatology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (A.-M.M.-R.); (J.D.)
| | - Marcos Girala
- Department of Hepatology, Universidad Nacional de Asunción, San Lorenzo 111421, Paraguay;
| | - Ezequiel Ridruejo
- Hepatology Section, Department of Medicine, Center for Medical Education and Clinical Research, Norberto Quirno CEMIC, Buenos Aires 1431, Argentina;
| | - Guido Gerken
- Department of Gastroenterology, University Hospital Essen, 45147 Essen, Germany;
| | - Andreas Teufel
- Department of Medicine II, Division of Hepatology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (A.-M.M.-R.); (J.D.)
- Clinical Cooperation Unit Healthy Metabolism, Center for Preventive Medicine, and Digital Health (CPD), Medical Faculty Mannheim, Heidelberg University, 69117 Mannheim, Germany
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Chew NW, Muthiah MD, Sanyal AJ. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: pathophysiology and implications for cardiovascular disease. CARDIOVASCULAR ENDOCRINOLOGY AND METABOLISM 2023:137-173. [DOI: 10.1016/b978-0-323-99991-5.00003-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Dar SH, Rahim M, Hosseini DK, Sarfraz K. Impact of liver cirrhosis on ST-elevation myocardial infarction related shock and interventional management, a nationwide analysis. World J Hepatol 2022; 14:766-777. [PMID: 35646267 PMCID: PMC9099112 DOI: 10.4254/wjh.v14.i4.766] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 01/04/2022] [Accepted: 03/07/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Critical care is rapidly evolving with significant innovations to decrease hospital stays and costs. To our knowledge, there is limited data on factors that affect the length of stay and hospital charges in cirrhotic patients who present with ST-elevation myocardial infarction-related cardiogenic shock (SRCS). AIM To identify the factors that increase inpatient mortality, length of stay, and total hospital charges in patients with liver cirrhosis (LC) compared to those without LC. METHODS This study includes all adults over 18 from the National Inpatient Sample 2017 database. The study consists of two groups of patients, including SRCS with LC and without LC. Inpatient mortality, length of stay, and total hospital charges are the primary outcomes between the two groups. We used STATA 16 to perform statistical analysis. The Pearson's chi-square test compares the categorical variables. Propensity-matched scoring with univariate and multivariate logistic regression generated the odds ratios for inpatient mortality, length of stay, and resource utilization. RESULTS This study includes a total of 35798453 weighted hospitalized patients from the 2017 National Inpatient Sample. The two groups are SRCS without LC (n = 758809) and SRCS with LC (n = 11920). The majority of patients were Caucasian in both groups (67% vs 72%). The mean number of patients insured with Medicare was lower in the LC group (60% vs 56%) compared to the other group, and those who had at least three or more comorbidities (53% vs 90%) were significantly higher in the LC group compared to the non-LC group. Inpatient mortality was also considerably higher in the LC group (28.7% vs 10.63%). Length of Stay (LOS) is longer in the LC group compared to the non-LC group (9 vs 5.6). Similarly, total hospital charges are higher in patients with LC ($147407.80 vs $113069.10, P ≤ 0.05). Inpatient mortality is lower in the early percutaneous coronary intervention (PCI) group (OR: 0.79 < 0.11), however, it is not statistically significant. Both early Impella (OR: 1.73 < 0.05) and early extracorporeal membrane oxygenation (ECMO) (OR: 3.10 P < 0.05) in the LC group were associated with increased mortality. Early PCI (-2.57 P < 0.05) and Impella (-3.25 P < 0.05) were also both associated with shorter LOS compared to those who did not. Early ECMO does not impact the LOS; however, it does increase total hospital charge (addition of $24717.85, P < 0.05). CONCLUSION LC is associated with a significantly increased inpatient mortality, length of stay, and total hospital charges in patients who develop SRCS. Rural and Non-teaching hospitals have significantly increased odds of extended hospital stays and higher adjusted total hospital charges. The Association of LC with worse outcomes outlines the essential need to monitor these patients closely and treat them early on with higher acuity care. Patients with early PCI had both shorter LOS and reduced inpatient mortality, while early Impella was associated with increased mortality and shorter LOS. Early ECMO is associated with increased mortality and higher total hospital charges. This finding should affect the decision to follow through with interventional management in this cohort of patients as it is associated with poor outcomes and immense resource utilization.
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Affiliation(s)
- Sophia Haroon Dar
- Internal Medicine, Hackensack University Medical Center, Hackensack, NJ 07601, United States.
| | - Mehek Rahim
- Internal Medicine, Hackensack University Medical Center, Hackensack, NJ 07601, United States
| | - Davood K Hosseini
- Internal Medicine, Hackensack University Medical Center, Hackensack, NJ 07601, United States
| | - Khurram Sarfraz
- Internal Medicine, Hackensack University Medical Center, Hackensack, NJ 07601, United States
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Association between Non-alcoholic Fatty Liver Disease and the Severity of Coronary Artery Stenosis in Eastern Chinese Population. HEPATITIS MONTHLY 2022. [DOI: 10.5812/hepatmon.122772] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: The present study aimed to investigate the relationship of non-alcoholic fatty liver disease (NAFLD) with the severity and extent of coronary stenotic lesions calculated by the Gensini score. In addition, the ability of Fibrosis-4 (FIB4) score to differentiate coronary artery calcification (CAC) and its severity is assessed. Methods: The current retrospective study was performed on a total of 342 patients examined between January and December 2016 in an affiliated hospital of Jiaxing University, Zhejiang, China. The study used liver ultrasonography for the assessment of NAFLD. Furthermore, the FIB4 and Gensini scores were used to predict hepatic fibrosis risk and the severity of coronary stenotic lesions. Results: The present study revealed that the serum levels of triglycerides, fasting glucose, alanine aminotransferase, and uric acid were significantly higher in patients with NAFLD than in participants without NAFLD (P < 0.001, P < 0.001, P = 0.032, and P = 0.002). Moreover, cases with NAFLD had a higher percentage of diabetes mellitus and hypertension (P < 0.001 and 0.001) than those without NAFLD. It was noted that the level of high-density lipoprotein was lower in patients with NAFLD than in participants without NAFLD (P = 0.006). In addition, we observed that the Gensini score was higher in patients with NAFLD than in participants without NAFLD (P = 0.033). It was found that 27.3%, 25.8%, 45.7%, and 56.3% of the participants had NAFLD in control, single, double, and multi lesion groups, respectively, and the difference was statistically significant (P = 0.008). The number of diseased vessels in patients with severe NAFLD was higher than in the control group (P < 0.001). It was also evident that the number of affected vessels significantly increased (P = 0.010 and P = 0.001) with the stages of NAFLD predicted by the FIB4 and Gensini scores. Furthermore, the Gensini score in patients with moderate and severe NAFLD was higher than in the control group (P = 0.013 and P = 0.019). We also conducted univariate logistic regression analyses to examine the relationship of CAC with FIB4 scores, and it was not significant (P = 0.191). Conclusions: The present study showed a positive relationship between NAFLD severity and coronary stenotic lesions in the eastern Chinese population. Furthermore, it was found that the higher the degree of FIB4 score, the higher the risk of CAC in patients with NAFLD. Therefore, assessing NAFLD severity using the FIB4 score may be useful for differentiating the patients at a higher risk of CAC. However, further prospective studies are required to establish the link between the FIB4 score and CAC.
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Sharma D, Gotlieb N, Farkouh ME, Patel K, Xu W, Bhat M. Machine Learning Approach to Classify Cardiovascular Disease in Patients With Nonalcoholic Fatty Liver Disease in the UK Biobank Cohort. J Am Heart Assoc 2022; 11:e022576. [PMID: 34927450 PMCID: PMC9075189 DOI: 10.1161/jaha.121.022576] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 11/12/2021] [Indexed: 12/18/2022]
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide. Cardiovascular disease (CVD) is the leading cause of mortality among patients with NAFLD. The aim of our study was to develop a machine learning algorithm integrating clinical, lifestyle, and genetic risk factors to identify CVD in patients with NAFLD. Methods and Results We created a cohort of patients with NAFLD from the UK Biobank, diagnosed according to proton density fat fraction from magnetic resonance imaging data sets. A total of 400 patients with NAFLD with subclinical atherosclerosis or clinical CVD, defined by disease codes, constituted cases and 446 NAFLD cases with no CVD constituted controls. We evaluated 7 different supervised machine learning approaches on clinical, lifestyle, and genetic variables for identifying CVD in patients with NAFLD. The most significant clinical and lifestyle variables observed by the predictive modeling were age (59 years [54.00-63.00 years]), hypertension (145 mm Hg [134.0-156.0 mm Hg] and 85 mm Hg [79.00-93.00 mm Hg]), waist circumference (98 cm [95.00-105.00 cm]), and sedentary lifestyle, defined as time spent watching TV >4 h/d. In the genetic data, single-nucleotide polymorphisms in IL16 and ANKLE1 gene were most significant. Our proposed ensemble-based integrative machine learning model achieved an area under the curve of 0.849 using the random forest modeling for CVD prediction. Conclusions We propose a machine learning algorithm that identifies CVD in patients with NAFLD through integration of significant clinical, lifestyle, and genetic risk factors. These patients with NAFLD at higher risk of CVD should be flagged for screening and aggressive treatment of their cardiometabolic risk factors to prevent cardiovascular morbidity and mortality.
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Affiliation(s)
- Divya Sharma
- Department of BiostatisticsPrincess Margaret Cancer CentreUniversity Health NetworkTorontoOntarioCanada
| | - Neta Gotlieb
- Division of Adult GastroenterologyUniversity Health NetworkToronto General HospitalTorontoOntarioCanada
| | - Michael E. Farkouh
- Peter Munk Cardiac Centre, Heart and Stroke Richard Lewar CentreUniversity of TorontoOntarioCanada
| | - Keyur Patel
- Division of GastroenterologyUniversity Health NetworkToronto General HospitalTorontoOntarioCanada
| | - Wei Xu
- Department of BiostatisticsPrincess Margaret Cancer CentreUniversity Health NetworkTorontoOntarioCanada
- Biostatistics DivisionDalla Lana School of Public HealthUniversity of TorontoOntarioCanada
| | - Mamatha Bhat
- Department of MedicineMulti‐Organ Transplant ProgramToronto General HospitalTorontoOntarioCanada
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Møller S, Kimer N, Kronborg T, Grandt J, Hove JD, Barløse M, Gluud LL. Nonalcoholic Fatty Liver Disease and Cardiovascular Disease: Overlapping Mechanisms. Semin Liver Dis 2021; 41:235-247. [PMID: 33992031 DOI: 10.1055/s-0041-1725022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) denotes a condition with excess fat in the liver. The prevalence of NAFLD is increasing, averaging > 25% of the Western population. In 25% of the patients, NAFLD progresses to its more severe form: nonalcoholic steatohepatitis and >25% of these progress to cirrhosis following activation of inflammatory and fibrotic processes. NAFLD is associated with obesity, type 2 diabetes, and the metabolic syndrome and represents a considerable and increasing health burden. In the near future, NAFLD cirrhosis is expected to be the most common cause for liver transplantation. NAFLD patients have an increased risk of developing cardiovascular disease as well as liver-related morbidity. In addition, hepatic steatosis itself appears to represent an independent cardiovascular risk factor. In the present review, we provide an overview of the overlapping mechanisms and prevalence of NAFLD and cardiovascular disease.
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Affiliation(s)
- Søren Møller
- Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.,Department of Clinical Medicine, University of Copenhagen, Denmark
| | - Nina Kimer
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Denmark.,Bridge Translational Excellence Program, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark
| | - Thit Kronborg
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Denmark
| | - Josephine Grandt
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Denmark
| | - Jens Dahlgaard Hove
- Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.,Department of Cardiology, Copenhagen University Hospital, Hvidovre, Denmark
| | - Mads Barløse
- Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark
| | - Lise Lotte Gluud
- Department of Clinical Medicine, University of Copenhagen, Denmark.,Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Denmark
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Robertson M, Chung W, Liu D, Seagar R, O'Halloran T, Koshy AN, Horrigan M, Farouque O, Gow P, Angus P. Cardiac Risk Stratification in Liver Transplantation: Results of a Tiered Assessment Protocol Based on Traditional Cardiovascular Risk Factors. Liver Transpl 2021; 27:1007-1018. [PMID: 33606328 DOI: 10.1002/lt.26025] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 12/14/2020] [Accepted: 12/17/2020] [Indexed: 01/13/2023]
Abstract
Coronary artery disease (CAD) confers increased perioperative risk in patients undergoing liver transplantation (LT). Although routine screening for CAD is recommended, there are limited data on the effectiveness of screening strategies. We evaluated the safety and efficacy of a 3-tiered cardiac risk-assessment protocol that stratifies patients based on age and traditional cardiac risk factors. We peformed a single-center, prospective, observational study of consecutive adult patients undergoing LT assessment (2010-2017). Patients were stratified into low-risk (LR), intermediate-risk (IR), or high-risk (HR) cardiac groups and received standardized investigations with selective use of transthoracic echocardiography (TTE), dobutamine stress echocardiography (DSE), computed tomography coronary angiography (CTCA), and coronary angiography (CA). Primary outcomes were cardiac events (CEs) and cardiovascular death up to 30 days after LT. Overall, 569 patients were included, with 76 patients identified as LR, 256 as IR, and 237 as HR. Cardiac risk factors included diabetes mellitus (26.0%), smoking history (47.3%), hypertension (17.8%), hypercholesterolemia (7.2%), family (17.0%) or prior history of heart disease (6.0%), and obesity (27.6%). Of the patients, 42.0% had ≥2 risk factors. Overall compliance with the protocol was 90.3%. Abnormal findings on TTE, DSE, and CTCA were documented in 3, 23, and 44 patients, respectively, and 12 patients were not listed for transplantation following cardiac assessment (1 LR, 2 IR, and 9 HR). Moderate or severe CAD was identified in 25.4% of HR patients on CTCA following a normal DSE. CEs were recorded in 7 patients (1.2%), with 2 cardiovascular deaths (0.4%). Cardiac risk stratification based on traditional cardiac risk factors with the selective use of DSE, CTCA, and CA is a safe and feasible approach that results in a low perioperative cardiac event rate.
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Affiliation(s)
- Marcus Robertson
- Liver Transplant Unit, Austin Hospital, Heidelberg, Victoria, Australia.,Department of Medicine, University of Melbourne, Heidelberg, Victoria, Australia
| | - William Chung
- Liver Transplant Unit, Austin Hospital, Heidelberg, Victoria, Australia
| | - Dorothy Liu
- Liver Transplant Unit, Austin Hospital, Heidelberg, Victoria, Australia
| | - Rosemary Seagar
- Liver Transplant Unit, Austin Hospital, Heidelberg, Victoria, Australia
| | - Tess O'Halloran
- Liver Transplant Unit, Austin Hospital, Heidelberg, Victoria, Australia
| | - Anoop N Koshy
- Department of Medicine, University of Melbourne, Heidelberg, Victoria, Australia.,Department of Cardiology, Austin Hospital, Heidelberg, Victoria, Australia
| | - Mark Horrigan
- Department of Cardiology, Austin Hospital, Heidelberg, Victoria, Australia
| | - Omar Farouque
- Department of Cardiology, Austin Hospital, Heidelberg, Victoria, Australia
| | - Paul Gow
- Liver Transplant Unit, Austin Hospital, Heidelberg, Victoria, Australia.,Department of Medicine, University of Melbourne, Heidelberg, Victoria, Australia
| | - Peter Angus
- Liver Transplant Unit, Austin Hospital, Heidelberg, Victoria, Australia.,Department of Medicine, University of Melbourne, Heidelberg, Victoria, Australia
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Afolabi PR, Scorletti E, Calder PC, Byrne CD. Factors independently associated with cardiorespiratory fitness in patients with non-alcoholic fatty liver disease. Liver Int 2020; 40:2998-3007. [PMID: 32706931 DOI: 10.1111/liv.14618] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 07/16/2020] [Accepted: 07/17/2020] [Indexed: 02/13/2023]
Abstract
UNLABELLED Low cardiorespiratory fitness (CRF) is associated with non-alcoholic fatty liver disease (NAFLD) and low CRF is an important risk factor for cardiovascular disease. The factors that influence CRF in NAFLD are poorly understood and it has been suggested that reduced hepatic mitochondrial function (HMF) may be linked to low CRF. Therefore, our aim was to determine the factors associated with CRF in NAFLD. METHODS Ninety-seven patients with NAFLD were studied. CRF was assessed by treadmill testing and expressed as maximal O2 consumption (VO2 peak) per lean body mass. HMF was assessed by the 13 C-ketoisocaproate breath test. Multivariable linear regression modelling was undertaken to test the independence of associations with CRF. RESULTS Mean (SD) age was 51 (13) years and 61% were men. With CRF as the outcome, age (B coefficient -0.3, 95%CI -0.4, -0.2, P < .0001), total body fat mass (B coefficient -0.2, 95%CI -0.3, -0.05, P = .01), type 2 diabetes mellitus (T2DM) (B coefficient -3.6, 95%CI -1.1, -6.1, P = .005), smoking status (B coefficient -5.7, 95%CI -1.9, -9.5, P = .004), serum γ-glutamyl transferase (GGT) (B coefficient -0.04, 95%CI -0.05, -0.02, P < .0001), HMF (B coefficient -0.5, 95%CI -0.8, -0.1, P = .01) and diastolic function (B coefficient 0.1, 95%CI 0.05, 0.13, P < .0001) were independently associated with CRF. This model explained 60% of the total variance in CRF (R2 = 0.6, P < .0001); and this model with GGT alone explained 24% of the variance in CRF. CONCLUSIONS In patients with NAFLD, HMF is independently associated with CRF and a model with GGT alone explained most of the variance in CRF.
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Affiliation(s)
- Paul R Afolabi
- National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.,School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Eleonora Scorletti
- National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.,School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.,Department of Gastroenterology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
| | - Philip C Calder
- National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.,School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Christopher D Byrne
- National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.,School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
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Arslan U, Yenerçağ M. Relationship between non-alcoholic fatty liver disease and coronary heart disease. World J Clin Cases 2020; 8:4688-4699. [PMID: 33195636 PMCID: PMC7642538 DOI: 10.12998/wjcc.v8.i20.4688] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 09/17/2020] [Accepted: 09/25/2020] [Indexed: 02/05/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease and considered a liver manifestation of metabolic syndrome. It is in close relationship with insulin resistance, obesity, diabetes mellitus, all of which increase risk of cardiovascular disease (CVD). Besides, many studies point out that NAFLD independently contributes to the development of atherosclerosis and CHD. On the other hand, CVDs are the leading cause of death in NAFLD patients. Many pathophysiological changes and molecular mechanisms play an important role in NAFLD for CVD formation. Atherosclerosis is common in NAFLD, which also mainly contributes to the CVD formation and CHD. Many studies linking atherosclerotic CHD and NAFLD are present in the literature. Subclinical CHD, mainly detected by coronary computed tomography views, have been detected more common in NAFLD patients. Presence of NAFLD has been found to be more common in patients with severe CHD and in stable CHD, NAFLD has been found to be associated with more diffuse disease. In acute coronary syndromes, especially in acute myocardial infarction, patients with NAFLD have been found to have poor prognosis when compared with NAFLD free patients. In this review, our aim is to evaluate the relationship between NAFLD and CHD in detail and go over the pathophysiological mechanisms underlying this relationship.
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Affiliation(s)
- Ugur Arslan
- Department of Cardiology, University of Health Sciences Samsun Training and Research Hospital, Samsun 55400, Turkey
| | - Mustafa Yenerçağ
- Department of Cardiology, University of Health Sciences Samsun Training and Research Hospital, Samsun 55400, Turkey
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10
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Nonalcoholic Fatty Liver Disease, Male Sexual Dysfunction, and Infertility: Common Links, Common Problems. Sex Med Rev 2020; 8:274-285. [DOI: 10.1016/j.sxmr.2019.01.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 12/28/2018] [Accepted: 01/14/2019] [Indexed: 12/18/2022]
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Abstract
BACKGROUND AND AIM Accumulating clinical and epidemiologic evidence indicates that nonalcoholic fatty liver disease (NAFLD) is not only associated with liver-related morbidity and mortality, but also with a greater risk of coronary heart disease (CHD). However, there is currently no diagnostic parameter for NAFLD that has been determined to reliably indicate the presence of CHD as a co-morbidity. We evaluated the liver stiffness and visceral fat thickness of NAFLD patients ultrasonographically to explore the relationship between liver stiffness, visceral fat thickness, and CHD, aiming to find explore the relationship between the liver stiffness and CHD. METHODS We enrolled 120 consecutive patients who had been initially diagnosed with CHD on the basis of their symptoms. All patients underwent coronary angiography or computed tomography angiography, and were classified into a CHD group and a non-CHD group on the basis of the results. All patients underwent liver ultrasonography, shear-wave elastography, and visceral fat thickness measurement. RESULTS NAFLD and visceral fat thickness were significantly positively correlated with CHD and Gensini score (P<0.001). Multivariate regression showed that age, male, cholesterol, liver stiffness, and visceral fat thickness were determinants of CHD. Age, cholesterol, liver stiffness, and visceral fat thickness cut-off points for the prediction of CHD were above 50 years old [area under the curve (AUC): 0.678; sensitivity, 87%; specificity, 42.6%], >3.76 mmol/L (AUC: 0.687; sensitivity, 68.4%; specificity, 64.8%), >6.1 kPa (AUC: 0.798; sensitivity, 50%; specificity, 92.6%), and >7.41 cm (AUC: 0.694; sensitivity, 52.6%; specificity, 87%), respectively. Compared with the use of age, gender, and cholesterol (model 1), the addition of the liver stiffness cut-off to model 1 resulted in a stronger predictive value (P=0.005). CONCLUSIONS High-grade NAFLD is more present in symptomatic CHD. The higher degree of liver stiffness in patients with NAFLD, the higher risk of CHD in these NAFLD patients.
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12
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Baysal M, Ortaburun Y, Soylu AR, Yılmaztepe MA, Baysal S, Umit E, Umit H, Tezel A, Muzaffer Demir A. Autonomic and diastolic dysfunction association with quality of life impairment in cirrhotic patients. Arab J Gastroenterol 2020; 21:32-36. [PMID: 32088164 DOI: 10.1016/j.ajg.2020.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 07/24/2019] [Accepted: 01/26/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND AND STUDY AIMS Cirrhosis is a multisystem disorder characterized by hyperdynamic circulation which can progress to multiple organ dysfunctions. Recent studies have demonstrated autonomic dysfunction and cirrhotic cardiomyopathy including diastolic dysfunction, systolic dysfunction with electrophysiologic abnormalities in patients with cirrhosis. Due to the long and complicated course of the disease, health related quality of life is affected. We aimed to evaluate the frequency of diastolic dysfunction and autonomic dysfunction in cirrhosis, and the effects on health-related quality of life. PATIENTS AND METHODS Hundred cirrhotic patients were enrolled in the study. According to the Child-Pugh classification 35 patients were of Child A, 36 of Child B and 29 of Child C. The proportion of autonomic dysfunction was 52%, and diastolic dysfunction 51%. Autonomic dysfunction was diagnosed using bedside maneuvers and tests; diastolic dysfunction was diagnosed using the E/A ratio in echocardiographic findings. Health-related quality of life measurements was obtained from an SF-36 questionnaire. RESULTS Patients with advanced Child-Pugh classifications were found to have significantly lower health-related quality of life values (p < 0.05). Likewise, health-related quality of life values were observed to be significantly lower in patients with autonomic dysfunction (p < 0.05). No significant difference was found in health related quality of life measurements between patients with and without diastolic dysfunction. CONCLUSION Our study showed that autonomic dysfunction and diastolic dysfunction are found in patients with cirrhosis. Further studies are needed to assess the effects of autonomic dysfunction and diastolic dysfunction on health-related quality of life.
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Affiliation(s)
- Mehmet Baysal
- Department of Internal Medicine, Trakya University, Medical Faculty, Edirne, Turkey.
| | - Yıldız Ortaburun
- Department of Internal Medicine, Trakya University, Medical Faculty, Edirne, Turkey
| | - Ali Rıza Soylu
- Department of Gastroenterology, Trakya University, Medical Faculty, Edirne, Turkey
| | | | - Serap Baysal
- Department of Public Health, Trakya University, Medical Faculty, Edirne, Turkey
| | - Elif Umit
- Department of Haematology, Trakya University, Medical Faculty, Edirne, Turkey
| | - Hasan Umit
- Department of Gastroenterology, Trakya University, Medical Faculty, Edirne, Turkey
| | - Ahmet Tezel
- Department of Gastroenterology, Trakya University, Medical Faculty, Edirne, Turkey
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Ismaiel A, Dumitraşcu DL. Cardiovascular Risk in Fatty Liver Disease: The Liver-Heart Axis-Literature Review. Front Med (Lausanne) 2019; 6:202. [PMID: 31616668 PMCID: PMC6763690 DOI: 10.3389/fmed.2019.00202] [Citation(s) in RCA: 118] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 08/27/2019] [Indexed: 12/14/2022] Open
Abstract
According to the World Health Organization, cardiovascular disease (CVD) remains the leading cause of death worldwide, accounting for approximately 18 million deaths per year. Nevertheless, the worldwide prevalence of metabolic diseases, such as type 2 diabetes mellitus, obesity, and non-alcoholic fatty liver disease (NAFLD), also known to be common risk factors for CVD, have dramatically increased over the last decades. Chronic alcohol consumption is a major cause of chronic liver diseases (CLD) as well as being a major health care cost expenditure accounting for the spending of tremendous amounts of money annually. NAFLD has become one of the major diseases plaguing the world while standing as the most common cause of liver disease in the Western countries by representing about 75% of all CLD. Currently, the most common cause of death in NAFLD remains to be CVD. Several mechanisms have been suggested to be responsible for associating FLD with CVD through several mechanisms including low-grade systemic inflammation, oxidative stress, adipokines, endoplasmic reticulum stress, lipotoxicity and microbiota dysbiosis which may also be influenced by other factors such as genetic and epigenetic variations. Despite of all this evidence, the exact mechanisms of how FLD can causally contribute to CVD are not fully elucidated and much remains unknown. Moreover, the current literature supports the increasing evidence associating FLD with several cardiovascular (CV) adverse events including coronary artery disease, increased subclinical atherosclerosis risk, structural alterations mainly left ventricular hypertrophy, increased epicardial fat thickness, valvular calcifications including aortic valve sclerosis and mitral annular calcification and functional cardiac modifications mainly diastolic dysfunction in addition to cardiac arrhythmias such as atrial fibrillation and ventricular arrythmias and conduction defects including atrioventricular blocks and bundle branch blocks. Patients with FLD should be evaluated and managed accordingly in order to prevent further complications. Possible management methods include non-pharmacological strategies including life style modifications, pharmacological therapies as well as surgical management. This review aims to summarize the current state of knowledge regarding the pathophysiological mechanisms linking FLD with an increased CV risk, in addition to associated CV adverse events and current management modalities.
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Affiliation(s)
- Abdulrahman Ismaiel
- Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- 2nd Department of Internal Medicine, Cluj-Napoca, Romania
| | - Dan L. Dumitraşcu
- Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- 2nd Department of Internal Medicine, Cluj-Napoca, Romania
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14
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Patel SS, Lin FP, Rodriguez VA, Bhati C, John BV, Pence T, Siddiqui MB, Sima AP, Abbate A, Reichman T, Siddiqui MS. The relationship between coronary artery disease and cardiovascular events early after liver transplantation. Liver Int 2019; 39:1363-1371. [PMID: 30848862 PMCID: PMC6620133 DOI: 10.1111/liv.14092] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2018] [Revised: 01/29/2019] [Accepted: 03/01/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Cardiovascular complications are major contributors to mortality at liver transplantation (LT). However, the impact of coronary artery disease (CAD) on these complications is not well-understood as the literature is limited by non-invasive assessment of CAD, which is suboptimal in patients with cirrhosis. Thus, the current study evaluated cardiovascular events at LT stratified according to the presence and severity of CAD quantified on coronary angiography. METHODS All patients who had LT from January 2010 to January 2017 were evaluated (N = 348), but analysis was restricted to patients who had coronary angiography prior to LT (N = 283). Protocol coronary angiography was performed in all patients' ages >50 years, history of CAD, abnormal cardiac stress test or risk factors for CAD. The primary outcome was a cardiovascular composite outcome including myocardial infraction (MI), cardiac arrest, stroke, cardiac death, heart failure or arrhythmia occurring within 4 weeks after LT. RESULTS CAD was present in 92(32.5%) patients and 32(11.3%) had obstructive CAD. During the study period, 72(25.4%) patients met the primary cardiovascular outcome, the most common being arrhythmia (N = 59 or 20.8%). Non-ST elevation MI occurred in 11(3.9%) of patients. A total of 10 deaths (3.5%) occurred, of which 6(2.1%) were attributable to cardiac death. There was no evidence of a relationship between the presence and severity of CAD and composite cardiovascular events. In multiple regression modelling, only diabetes [OR 2.62, 95%CI (1.49, 4.64), P < 0.001] was associated with the likelihood of having a cardiovascular event. CONCLUSION Cardiovascular disease mortality is the most important contributor of early mortality after LT but is not related to the severity of CAD.
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Affiliation(s)
- Samarth S. Patel
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University (VCU)
| | | | | | - Chandra Bhati
- Division of Transplant Surgery, Department of Surgery, VCU
| | - Binu V. John
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University (VCU)
- Division of Gastroenterology and Hepatology, Hunter-Holmes McGuire Veterans Affairs Medical Center
| | | | - Mohammad B Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University (VCU)
| | | | - Antonio Abbate
- Division Cardiology, Department of Internal Medicine, VCU
| | | | - Mohammad S. Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University (VCU)
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15
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Zhang MF, Liu YX, Jiang KY, Niu HM, Jiang JL, Dong ST, Wang X, Wang DF, Meng SN. Alteration of UDP-glucuronosyltransferase 1a1, 1a7 and P-glycoprotein expression in hepatic fibrosis rats and the impact on pharmacokinetics of puerarin. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2019; 52:264-271. [PMID: 30599907 DOI: 10.1016/j.phymed.2018.06.024] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Revised: 04/13/2018] [Accepted: 06/18/2018] [Indexed: 06/09/2023]
Abstract
BACKGROUND Puerarin, derived from a traditional Chinese herb Pueraria lobata (Willd.) Ohwi which was distributed globally and planted in most parts of China, has been extensively applied in patients with cardiovascular diseases in China. Yet a considerable proportion of the patients were accompanied with liver illnesses simultaneously because of all sorts of reasons. HYPOTHESIS/PURPOSE It had been implied by some previous research that the absorption and the metabolism of puerarin were susceptible to liver issues due to changed P-gp and Ugt1a level, but pharmacokinetics of puerarin under such conditions were few concerned. Our study aimed to make sure whether and how much the behavior of puerarin in vivo was affected by hepatic diseases, and to explore the potential mechanisms. METHODS A CCl4 induced rat model of hepatic fibrosis (HF) was prepared and verified. Single low/high doses of oral and intravenous administration of puerarin to HF and normal rats were performed. Pharmacokinetics of puerarin were determined by a validated HPLC method. The expression of P-gp, Ugt1a1, and Ugt1a7 in both liver and intestines were determined by quantitative RT-PCR and Western blot analysis respectively. RESULTS The systemic exposure of puerarin in HF rats of experimental groups were found decreased remarkably except for that of the high dose intravenous group. Moreover, the expression of P-gp, Ugt1a1, and Ugt1a7 in liver and intestines of HF rats were figured out increased. CONCLUSION The results indicated that the HF originated overexpression of Ugt1a1, Ugt1a7, and P-gp level played important roles in pharmacokinetics of puerarin, suggested the clinical regimen of puerarin based on normal populations might be inappropriate for patients with chronic liver diseases. It was implied drugs whose absorption or elimination were related to P-gp, Ugt1a1, or Ugt1a7 might also be affected by hepatic illnesses.
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Affiliation(s)
- Mao-Fan Zhang
- Department of Pharmaceutics, School of Pharmacy, China Medical University, Shenyang, Liaoning, China
| | - Yi-Xuan Liu
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Kun-Yu Jiang
- Department of Pharmaceutics, School of Pharmacy, China Medical University, Shenyang, Liaoning, China
| | - Hui-Min Niu
- Department of Pharmaceutics, School of Pharmacy, China Medical University, Shenyang, Liaoning, China
| | - Jia-Lei Jiang
- Department of Pharmaceutics, School of Pharmacy, China Medical University, Shenyang, Liaoning, China
| | - Song-Tao Dong
- Department of Pharmaceutics, School of Pharmacy, China Medical University, Shenyang, Liaoning, China
| | - Xin Wang
- Department of Pharmaceutics, School of Pharmacy, China Medical University, Shenyang, Liaoning, China
| | - Di-Fei Wang
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
| | - Sheng-Nan Meng
- Department of Pharmaceutics, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.
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Buckley AJ, Thomas EL, Lessan N, Trovato FM, Trovato GM, Taylor-Robinson SD. Non-alcoholic fatty liver disease: Relationship with cardiovascular risk markers and clinical endpoints. Diabetes Res Clin Pract 2018; 144:144-152. [PMID: 30170074 DOI: 10.1016/j.diabres.2018.08.011] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 08/08/2018] [Accepted: 08/14/2018] [Indexed: 02/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common diagnosis and is increasing in prevalence worldwide. NAFLD is usually asymptomatic at presentation; progression of the disease is unpredictable, leading to the development of a variety of techniques for screening, diagnosis and risk stratification. Clinical methods in current use include serum biomarker panels, hepatic ultrasound, magnetic resonance imaging, and liver biopsy. NAFLD is strongly associated with the metabolic syndrome, and the most common cause of death for people with the condition is cardiovascular disease. Whether NAFLD is an independent cardiovascular risk factor needs exploration. NAFLD has been associated with surrogate markers of cardiovascular disease such as carotid intima-media thickness, the presence of carotid plaque, brachial artery vasodilatory responsiveness and CT coronary artery calcification score. There is no effective medical treatment for NAFLD and evidence is lacking regarding the efficacy of interventions in mitigating cardiovascular risk. Health care professionals managing patients with NAFLD should tackle the issue with early identification of risk factors and aggressive modification. Current management strategies therefore comprise lifestyle change, with close attention to known cardiovascular risk factors.
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Affiliation(s)
- Adam J Buckley
- Imperial College London, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine London, United Kingdom; Imperial College London Diabetes Centre, Research Department, Abu Dhabi, United Arab Emirates.
| | - E Louise Thomas
- University of Westminster, Department of Life Sciences, London, United Kingdom.
| | - Nader Lessan
- Imperial College London, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine London, United Kingdom; Imperial College London Diabetes Centre, Research Department, Abu Dhabi, United Arab Emirates.
| | - Francesca M Trovato
- University of Catania, Department of Clinical and Experimental Medicine, Catania, Italy
| | - Guglielmo M Trovato
- University of Catania, Department of Clinical and Experimental Medicine, Catania, Italy
| | - Simon D Taylor-Robinson
- Imperial College London, Division of Integrative Systems Medicine and Digestive Health, Department of Surgery and Cancer, London, United Kingdom.
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17
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Impact of Allograft Steatosis on Cardiovascular Outcomes. CURRENT TRANSPLANTATION REPORTS 2018. [DOI: 10.1007/s40472-018-0205-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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18
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Patel SS, Guzman LA, Lin FP, Pence T, Reichman T, John B, Celi FS, Liptrap E, Bhati C, Siddiqui MS. Utilization of aspirin and statin in management of coronary artery disease in patients with cirrhosis undergoing liver transplant evaluation. Liver Transpl 2018; 24:872-880. [PMID: 29624871 DOI: 10.1002/lt.25067] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2018] [Revised: 03/12/2018] [Accepted: 03/22/2018] [Indexed: 12/12/2022]
Abstract
Coronary artery disease (CAD) assessment is a vital part of liver transplantation (LT) evaluation, as it allows for identification and medical optimization prior to transplantation. Although aspirin and statins are standard of care for CAD, they are not universally used in cirrhosis due to concerns about adverse events. Per protocol, coronary angiography was performed as part of the LT evaluation in all patients over the age of 50 years or with CAD risk factors, even if they were younger than 50. Optimal CAD medical management was defined as the use of both statin and aspirin, unless a contraindication was documented. Impact of these medications on hepatic decompensation, renal function, gastrointestinal bleeding, and need for transfusion was evaluated. CAD was detected in 84/228 (36.8%) patients. Lipid profile was similar in patients with and without CAD. In patients with CAD, statins were started in 19 (23%), while aspirin was used in 30 (36%) patients. In patients with obstructive or multivessel CAD, statin therapy was used only in 41% and 65%, respectively. Statins were more likely to be prescribed in patients with diabetes (32% versus 15%, P = 0.05) and history of dyslipidemia (38% versus 15%, P = 0.02). Use of statin therapy was not linked to hepatic decompensation, hospitalization, or rise in Model for End-Stage Liver Disease (MELD). Similarly, use of aspirin therapy was not associated with increased risk acute variceal hemorrhage, gastrointestinal bleeding, or worsening anemia. In conclusion, in decompensated cirrhosis, lipid profile alone is unable to risk stratify patients with CAD. Statin and aspirin appear to be safe. However, they are significantly underutilized for the management of CAD in this patient population. Liver Transplantation 24 872-880 2018 AASLD.
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Affiliation(s)
- Samarth S Patel
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
| | - Luis A Guzman
- Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
| | - Fei-Pi Lin
- School of Medicine, Virginia Commonwealth University, Richmond, VA
| | - Taylor Pence
- School of Medicine, Virginia Commonwealth University, Richmond, VA
| | - Trevor Reichman
- Division of Transplant Surgery, Department of Surgery, Virginia Commonwealth University, Richmond, VA
| | - Binu John
- Division of Gastroenterology and Hepatology, Hunter-Holmes McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA
| | - Francesco S Celi
- Division of Endocrinology, Diabetes and Metabolism, Virginia Commonwealth University, Richmond, VA
| | - Erika Liptrap
- Division of Transplant Surgery, Department of Surgery, Virginia Commonwealth University, Richmond, VA
| | - Chandra Bhati
- Division of Transplant Surgery, Department of Surgery, Virginia Commonwealth University, Richmond, VA
| | - Mohammad S Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
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19
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Gitman M, Albertz M, Nicolau-Raducu R, Aniskevich S, Pai SL. Cardiac diseases among liver transplant candidates. Clin Transplant 2018; 32:e13296. [PMID: 29804298 DOI: 10.1111/ctr.13296] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/20/2018] [Indexed: 11/29/2022]
Abstract
Improvements in early survival after liver transplant (LT) have allowed for the selection of LT candidates with multiple comorbidities. Cardiovascular disease is a major contributor to post-LT complications. We performed a literature search to identify the causes of cardiac disease in the LT population and to describe techniques for diagnosis and perioperative management. As no definite guidelines for preoperative assessment (except for pulmonary heart disease) are currently available, we recommend an algorithm for preoperative cardiac work-up.
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Affiliation(s)
- Marina Gitman
- Department of Anesthesiology, University of Illinois Hospital, Chicago, IL, USA
| | - Megan Albertz
- Department of Anesthesiology, Children's Hospital Colorado, Aurora, CO, USA
| | | | - Stephen Aniskevich
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Sher-Lu Pai
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, FL, USA
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20
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Patel SS, Nabi E, Guzman L, Abbate A, Bhati C, Stravitz RT, Reichman T, Matherly SC, Driscoll C, Lee H, Luketic VA, Sterling RK, Sanyal AJ, Patel V, Levy M, Siddiqui MS. Coronary artery disease in decompensated patients undergoing liver transplantation evaluation. Liver Transpl 2018; 24:333-342. [PMID: 29328556 DOI: 10.1002/lt.25012] [Citation(s) in RCA: 82] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Revised: 09/30/2017] [Accepted: 12/20/2017] [Indexed: 02/06/2023]
Abstract
Coronary artery disease (CAD) is an important contributor to morbidity and mortality in patients undergoing liver transplantation (LT). However, the current literature is limited by sampling bias and nondefinitive assessment of CAD. The current study examines the prevalence of CAD via per protocol coronary angiography and its relationship to etiology of liver disease in patients undergoing liver transplantation evaluation (LTE). Data on 228 patients were prospectively collected who had coronary angiography as part of LTE between 2011 and 2014. Coronary angiography was done in all patients age ≥50 years or with CAD risk factors. CAD was defined as any coronary artery stenosis, whereas stenosis ≥ 70% in distribution of 1 or 3 major coronary arteries was considered as single- or triple-vessel disease. CAD was detected in 36.8% of patients, with the highest prevalence among nonalcoholic steatohepatitis (NASH) patients with cirrhosis (52.8%). Prevalence of single-vessel disease was higher among patients with NASH compared with hepatitis C virus (HCV) and alcoholic cirrhosis (15.1% versus 4.6% versus 6.6%; P = 0.02). Similarly, patients with NASH were more likely to have triple-vessel disease when compared with HCV and alcoholic cirrhosis (9.4% versus 0.9% versus 0%; P = 0.001). While adjusting for traditional risk factors for CAD, only NASH as etiology of liver disease remained significantly associated with CAD. Complications from diagnostic coronary angiography or percutaneous coronary intervention were low (2.6%). In conclusion, patients undergoing LTE have a high prevalence of CAD, which varies widely depending on etiology of liver cirrhosis. The procedural complications from coronary angiography are low. Liver Transplantation 24 333-342 2018 AASLD.
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Affiliation(s)
- Samarth S Patel
- Divisions of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Richmond, VA
| | - Eiman Nabi
- Divisions of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Richmond, VA
| | - Luis Guzman
- Cardiology, Department of Internal Medicine, Richmond, VA
| | - Antonio Abbate
- Cardiology, Department of Internal Medicine, Richmond, VA
| | - Chandra Bhati
- Transplant Surgery, Department of Surgery, Virginia Commonwealth University, Richmond, VA
| | - Richard T Stravitz
- Divisions of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Richmond, VA
| | - Trevor Reichman
- Transplant Surgery, Department of Surgery, Virginia Commonwealth University, Richmond, VA
| | - Scott C Matherly
- Divisions of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Richmond, VA
| | - Carolyn Driscoll
- Divisions of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Richmond, VA
| | - Hannah Lee
- Divisions of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Richmond, VA
| | - Velimir A Luketic
- Divisions of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Richmond, VA
| | - Richard K Sterling
- Divisions of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Richmond, VA
| | - Arun J Sanyal
- Divisions of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Richmond, VA
| | - Vaishali Patel
- Divisions of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Richmond, VA
| | - Marlon Levy
- Transplant Surgery, Department of Surgery, Virginia Commonwealth University, Richmond, VA
| | - Mohammad Shadab Siddiqui
- Divisions of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Richmond, VA
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21
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Adams LA, Anstee QM, Tilg H, Targher G. Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut 2017; 66:1138-1153. [PMID: 28314735 DOI: 10.1136/gutjnl-2017-313884] [Citation(s) in RCA: 791] [Impact Index Per Article: 98.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Revised: 02/14/2017] [Accepted: 02/16/2017] [Indexed: 02/07/2023]
Abstract
Key physiological functions of the liver, including glucose and lipid metabolism, become disturbed in the setting of non-alcoholic fatty liver disease (NAFLD) and may be associated with a systemic inflammatory 'milieu' initiated in part by liver-secreted cytokines and molecules. Consequently, the pathophysiological effects of NAFLD extend beyond the liver with a large body of clinical evidence demonstrating NAFLD to be independently associated with both prevalent and incident cardiovascular disease (CVD), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). The magnitude of risk of developing these extrahepatic diseases parallels the underlying severity of NAFLD, such that patients with non-alcoholic steatohepatitis (NASH) appear to be at greater risk of incident CVD, CKD and T2DM than those with simple steatosis. Other modifiers of risk may include genetic variants (eg, patatin-like phospholipase domain-containing 3 and trans-membrane 6 superfamily member 2 polymorphisms), visceral adipose tissue accumulation, dietary intake and the gut microbiome. Emerging data also suggest that NAFLD may be a risk factor for colonic neoplasia and reduced bone mineral density, especially among men. Importantly, improvement/resolution of NAFLD is associated with a reduced incidence of T2DM and improved kidney function, adding weight to causality and suggesting liver focused treatments may reduce risk of extrahepatic complications. Awareness of these associations is important for the clinicians such that CVD risk factor management, screening for T2DM and CKD are part of the routine management of patients with NAFLD.
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Affiliation(s)
- Leon A Adams
- School of Medicine and Pharmacology, The University of Western Australia, Nedlands, Western Australia, Australia
| | - Quentin M Anstee
- Faculty of Medical Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK.,Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology & Metabolism, Medical University Innsbruck, Innsbruck, Austria
| | - Giovanni Targher
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
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Ballestri S, Nascimbeni F, Baldelli E, Marrazzo A, Romagnoli D, Lonardo A. NAFLD as a Sexual Dimorphic Disease: Role of Gender and Reproductive Status in the Development and Progression of Nonalcoholic Fatty Liver Disease and Inherent Cardiovascular Risk. Adv Ther 2017; 34:1291-1326. [PMID: 28526997 PMCID: PMC5487879 DOI: 10.1007/s12325-017-0556-1] [Citation(s) in RCA: 394] [Impact Index Per Article: 49.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) spans steatosis through nonalcoholic steatohepatis, cirrhosis, and hepatocellular carcinoma (HCC) associated with striking systemic features and excess cardiovascular and liver-related mortality. The pathogenesis of NAFLD is complex and multifactorial. Endocrine derangements are closely linked with dysmetabolic traits. For example, in animal and human studies, female sex is protected from dysmetabolism thanks to young individuals' ability to partition fatty acids towards ketone body production rather than very low density lipoprotein (VLDL)-triacylglycerol, and to sex-specific browning of white adipose tissue. Ovarian senescence facilitates both the development of massive hepatic steatosis and the fibrotic progression of liver disease in an experimental overfed zebrafish model. Consistently, estrogen deficiency, by potentiating hepatic inflammatory changes, hastens the progression of disease in a dietary model of nonalcoholic steatohepatitis (NASH) developing in ovariectomized mice fed a high-fat diet. In humans, NAFLD more often affects men; and premenopausal women are equally protected from developing NAFLD as they are from cardiovascular disease. It would be expected that early menarche, definitely associated with estrogen activation, would produce protection against the risk of NAFLD. Nevertheless, it has been suggested that early menarche may confer an increased risk of NAFLD in adulthood, excess adiposity being the primary culprit of this association. Fertile age may be associated with more severe hepatocyte injury and inflammation, but also with a decreased risk of liver fibrosis compared to men and postmenopausal status. Later in life, ovarian senescence is strongly associated with severe steatosis and fibrosing NASH, which may occur in postmenopausal women. Estrogen deficiency is deemed to be responsible for these findings via the development of postmenopausal metabolic syndrome. Estrogen supplementation may at least theoretically protect from NAFLD development and progression, as suggested by some studies exploring the effect of hormonal replacement therapy on postmenopausal women, but the variable impact of different sex hormones in NAFLD (i.e., the pro-inflammatory effect of progesterone) should be carefully considered.
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Affiliation(s)
- Stefano Ballestri
- Azienda USL di Modena, Pavullo Hospital, Pavullo nel Frignano, Italy
| | - Fabio Nascimbeni
- Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
| | - Enrica Baldelli
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Alessandra Marrazzo
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Dante Romagnoli
- Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
| | - Amedeo Lonardo
- Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
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23
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Mangi MA, Rehman H, Minhas AM, Rafique M, Bansal V, Constantin J. Non-Alcoholic Fatty Liver Disease Association with Cardiac Arrhythmias. Cureus 2017; 9:e1165. [PMID: 28507837 PMCID: PMC5429146 DOI: 10.7759/cureus.1165] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become a public health burden all over the world. A significant percentage of the patients with NAFLD have a co-existing metabolic syndrome that is a risk factor for cardiovascular disease. Clinical as well as epidemiological research shows that NAFLD is not simply related to liver-related morbidity and mortality but is also associated with an elevated risk of coronary heart disease (CHD), irregularities of cardiac function as well as cardiac structure, valvular heart disease, and arrhythmias. Animal studies suggest that NAFLD by itself exacerbates systemic/hepatic insulin resistance, leads to atherogenic dyslipidemia and generates a number of pro-inflammatory, pro-coagulant and profibrogenic mediators which play an essential role in the pathophysiology of cardiac abnormalities including arrhythmias. Hence, it is suggested that the patients with NAFLD may derive benefit from intensive monitoring and treatment methods to reduce the risk of CHD along with other cardiac/arrhythmic complications. The intent of this clinical review is to sum up the quickly increasing body of evidence that provides support for a robust relationship between NAFLD and cardiac arrhythmias and to present the putative biological mechanisms underlying this correlation.
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Affiliation(s)
| | - Hiba Rehman
- GME Internal Medicine, Orange Park Medical Center
| | | | | | - Vikas Bansal
- Critical Care Medicine , Mayo Clinic Jacksonville, Fl
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24
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Mangi MA, Minhas AM, Rehman H, Pathan F, Liang H, Beidas S. Association of Non-alcoholic Fatty Liver Disease with Conduction Defects on Electrocardiogram. Cureus 2017; 9:e1107. [PMID: 28439482 PMCID: PMC5400518 DOI: 10.7759/cureus.1107] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a leading cause of liver disease in developed countries. The association of NAFLD with conduction defects is unknown. The aim of our study was to find whether an association exists between conduction defects and NAFLD. METHODS This is a case-control retrospective study of 700 patients admitted to Orange Park Medical Center, Orange Park, Florida from 2009 to 2015. Patients with a history of alcohol use, congenital heart disease, infiltrative malignancy, and myocarditis were excluded from the study. NAFLD was diagnosed by detection of hepatic steatosis on abdominal ultrasound or computerized tomography (CT) scan. Electrocardiograms (EKGs) were performed on all 700 patients and were interpreted by a cardiologist. Univariate logistic regression was used to assess the association between NAFLD and the variables of demographics, clinical characteristics, medicine use, EKG changes, and conduction defects, while multivariate logistic regression with backward elimination method was performed to determine if NAFLD is one of the most important risk factors for conduction defects. RESULTS The study population included 408 patients with NAFLD and 292 patients with No-NAFLD. A total of 155 conduction defects occurred in 140 patients; conduction defects included 25.7% (36) patients with first degree block, 2.1% (three) patients with Mobitz type 1 block, 41.4% (58) patients with right bundle branch block (RBBB), 17.9% (25) patients with left bundle branch block (LBBB), 11.4% (16) patients with bifascicular block, and 12.1% (17) patients with nonspecific intraventricular block. Multivariate logistic regression with backward elimination method identified six risk factors for conduction defects; these included NAFLD (odds ratio (OR) 2.38; 95% confidence interval (CI) 1.51-3.73, p<0.0001), hypertrophy (OR 2.52; 95% CI 1.57-4.05, p=0.0001), congestive heart failure (CHF) (OR 3.05; 95%CI 1.46-6.38, p=0.0031), male sex (OR 1.79; 95%CI 1.19-2.69, p=0.0051), diabetes mellitus (OR 1.63; 95% CI 1.08-2.47, p=0.02), and age (OR 1.04; 95% CI 1.02-1.06, p<0.0001). CONCLUSION NAFLD is associated with conduction defects. Prospective randomized trials are needed to demonstrate that NAFLD causes conduction defects.
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Affiliation(s)
| | | | - Hiba Rehman
- GME Internal Medicine, Orange Park Medical Center
| | | | - Hong Liang
- GME Internal Medicine, North Florida Regional Medical Center/CyberKnife at North Florida
| | - Sary Beidas
- GME Internal Medicine, Orange Park Medical Center
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Hogan BJ, Gonsalkorala E, Heneghan MA. Evaluation of coronary artery disease in potential liver transplant recipients. Liver Transpl 2017; 23:386-395. [PMID: 27875636 DOI: 10.1002/lt.24679] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2016] [Accepted: 11/08/2016] [Indexed: 12/12/2022]
Abstract
Improvements in the management of patients undergoing liver transplantation (LT) have resulted in a significant increase in survival in recent years. Cardiac disease is now the leading cause of early mortality, and the stress of major surgery, hemodynamic shifts, and the possibilities of hemorrhage or reperfusion syndrome require the recipient to have good baseline cardiac function. The prevalence of coronary artery disease (CAD) is increasing in LT candidates, especially in those with nonalcoholic fatty liver disease. In assessing LT recipients, we suggest a management paradigm of "quadruple assessment" to include (1) history, examination, and electrocardiogram; (2) transthoracic echocardiogram; (3) functional testing; and (4) where appropriate, direct assessment of CAD. The added value of functional testing, such as cardiopulmonary exercise testing, has been shown to be able to predict posttransplant complications independently of the presence of CV disease. This approach gives the assessment team the greatest chance of detecting and preventing complications related to CAD. Liver Transplantation 23 386-395 2017 AASLD.
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Affiliation(s)
- Brian J Hogan
- Institute of Liver Studies, King's College Hospital, National Health Service Foundation Trust, London, UK
| | - Enoka Gonsalkorala
- Institute of Liver Studies, King's College Hospital, National Health Service Foundation Trust, London, UK
| | - Michael A Heneghan
- Institute of Liver Studies, King's College Hospital, National Health Service Foundation Trust, London, UK
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Mikolasevic I, Milic S, Turk Wensveen T, Grgic I, Jakopcic I, Stimac D, Wensveen F, Orlic L. Nonalcoholic fatty liver disease - A multisystem disease? World J Gastroenterol 2016; 22:9488-9505. [PMID: 27920470 PMCID: PMC5116593 DOI: 10.3748/wjg.v22.i43.9488] [Citation(s) in RCA: 135] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 08/30/2016] [Accepted: 10/19/2016] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians.
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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: 175] [Impact Index Per Article: 19.4] [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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Calzada E, Onguka O, Claypool SM. Phosphatidylethanolamine Metabolism in Health and Disease. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2015; 321:29-88. [PMID: 26811286 DOI: 10.1016/bs.ircmb.2015.10.001] [Citation(s) in RCA: 319] [Impact Index Per Article: 31.9] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Phosphatidylethanolamine (PE) is the second most abundant glycerophospholipid in eukaryotic cells. The existence of four only partially redundant biochemical pathways that produce PE, highlights the importance of this essential phospholipid. The CDP-ethanolamine and phosphatidylserine decarboxylase pathways occur in different subcellular compartments and are the main sources of PE in cells. Mammalian development fails upon ablation of either pathway. Once made, PE has diverse cellular functions that include serving as a precursor for phosphatidylcholine and a substrate for important posttranslational modifications, influencing membrane topology, and promoting cell and organelle membrane fusion, oxidative phosphorylation, mitochondrial biogenesis, and autophagy. The importance of PE metabolism in mammalian health has recently emerged following its association with Alzheimer's disease, Parkinson's disease, nonalcoholic liver disease, and the virulence of certain pathogenic organisms.
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Affiliation(s)
- Elizabeth Calzada
- Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ouma Onguka
- Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Steven M Claypool
- Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Mariani S, Fiore D, Basciani S, Persichetti A, Contini S, Lubrano C, Salvatori L, Lenzi A, Gnessi L. Plasma levels of SIRT1 associate with non-alcoholic fatty liver disease in obese patients. Endocrine 2015; 49:711-6. [PMID: 25358448 DOI: 10.1007/s12020-014-0465-x] [Citation(s) in RCA: 94] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2014] [Accepted: 10/23/2014] [Indexed: 01/14/2023]
Abstract
Sirtuins (SIRTs) are master metabolic regulators with protective roles against obesity and obesity-associated metabolic disorders, including non-alcoholic fatty liver disease (NAFLD) and type-2 diabetes. We aimed to ascertain whether there is a relationship between serum SIRT1 and liver steatosis severity in obese patients. Seventy-two obese patients (BMI ≥ 30 kg/m(2)), 18 males and 54 females, mean age 39.66 ± 12.34 years, with ultrasonographic evidence of NAFLD, were studied. BMI, transaminases, insulin, HOMA-index, HbA1c, body composition (DXA), plasma SIRT1 levels (ELISA) and representative measures of metabolic syndrome (waist circumference, fasting plasma glucose, blood pressure, HDL-cholesterol, triglycerides) and inflammation (ESR, CRP, fibrinogen) were evaluated. Thirty healthy lean patients were included as controls. SIRT1 was significantly lower in severe liver steatosis obese group compared to the mild steatosis group, both had lower SIRT1 plasma values compared to control lean patients (P = 0.0001). SIRT1 showed an inverse correlation with liver steatosis and HbA1c in univariate analysis (ρ = -0.386; P = 0.001; ρ = -0.300; P = 0.01, respectively). Multiple linear regression analysis showed that liver steatosis was the independent correlate of SIRT1 even after adjustment for potentially relevant variables (β = -0.442; P = 0.003). Serum SIRT1 might be a novel clinical/biochemical parameter associated with fat liver infiltration. Further studies in larger cohorts are warranted.
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Affiliation(s)
- Stefania Mariani
- Department of Experimental Medicine, Section of Medical Pathophysiology Food Science and Endocrinology, Sapienza University of Rome, 00161, Rome, Italy
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Bhala N, George J. The Burden of Non-alcoholic Fatty Liver Disease (NAFLD) in the Asia Pacific Region. ACTA ACUST UNITED AC 2015. [DOI: 10.1007/s11901-015-0264-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol 2015; 62:S47-64. [PMID: 25920090 DOI: 10.1016/j.jhep.2014.12.012] [Citation(s) in RCA: 2108] [Impact Index Per Article: 210.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 11/06/2014] [Accepted: 12/09/2014] [Indexed: 12/11/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that is predicted to become also the most frequent indication for liver transplantation by 2030. Over the last decade, it has been shown that the clinical burden of NAFLD is not only confined to liver-related morbidity and mortality, but there is now growing evidence that NAFLD is a multisystem disease, affecting extra-hepatic organs and regulatory pathways. For example, NAFLD increases risk of type 2 diabetes mellitus (T2DM), cardiovascular (CVD) and cardiac diseases, and chronic kidney disease (CKD). Although the primary liver pathology in NAFLD affects hepatic structure and function to cause morbidity and mortality from cirrhosis, liver failure and hepatocellular carcinoma, the majority of deaths among NAFLD patients are attributable to CVD. This narrative review focuses on the rapidly expanding body of clinical evidence that supports the concept of NAFLD as a multisystem disease. The review discusses the factors involved in the progression of liver disease in NAFLD and the factors linking NAFLD with other extra-hepatic chronic diseases, such as T2DM, CVD, cardiac diseases and CKD. The review will not discuss NAFLD treatments as these are discussed elsewhere in this issue of the Journal. For this review, PubMed was searched for articles using the keywords "non-alcoholic fatty liver disease" or "fatty liver" combined with "diabetes", "cardiovascular (or cardiac) disease", "cardiovascular mortality" or "chronic kidney disease" between 1990 and 2014. Articles published in languages other than English were excluded.
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Affiliation(s)
- Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK; Southampton National Institute for Health Research, Biomedical Research Centre, University Hospital Southampton, UK.
| | - Giovanni Targher
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
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Del Ben M, Polimeni L, Brancorsini M, Di Costanzo A, D'Erasmo L, Baratta F, Loffredo L, Pastori D, Pignatelli P, Violi F, Arca M, Angelico F. Non-alcoholic fatty liver disease, metabolic syndrome and patatin-like phospholipase domain-containing protein3 gene variants. Eur J Intern Med 2014; 25:566-570. [PMID: 24947770 DOI: 10.1016/j.ejim.2014.05.012] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2014] [Revised: 05/10/2014] [Accepted: 05/23/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease was traditionally interpreted as a condition which may progress to liver-related complications. However, the increased mortality is primarily a result of cardiovascular diseases. It has been suggested that fatty liver can be considered as the hepatic consequence of the metabolic syndrome. The aim was to describe the different clinical presentations of non-alcoholic fatty liver disease on the basis of the patatin-like phospholipase domain-containing protein3 (PNPLA3) rs738409 gene variant. METHODS Fatty liver was defined by ultrasonographic Hamaguchi's criteria in 211 consecutive subjects with non-alcoholic fatty liver disease. The rs738409 polymorphism was determined by TaqMan assays. Metabolic syndrome was defined according to ATPIII modified criteria. RESULTS Prevalence of PNPLA3-148II, PNPLA3-148IM, and PNPLA3-148MM genotypes was 45.0%, 40.7%, and 14.3% respectively. Prevalence of metabolic syndrome progressively increased with the severity of liver steatosis (from 52.5% to 65.2%, and 82.3% respectively, p<0.01). The PNPLA3-148MM group had significantly lower mean serum triglycerides (p<0.001), Framingham cardiovascular risk score (p<0.01) and lower prevalence of metabolic syndrome (p<0.05) and its components. Age and HOMA-IR were positive independent predictors of metabolic syndrome, while a negative independent association was found between metabolic syndrome and the homozygotes PNPLA3 I148M variant. CONCLUSIONS We suggest a lower prevalence of MetS and reduced cardiovascular risk in NAFLD patients with PNPLA3MM genotype.
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Affiliation(s)
- M Del Ben
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - L Polimeni
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - M Brancorsini
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - A Di Costanzo
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - L D'Erasmo
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - F Baratta
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - L Loffredo
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - D Pastori
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - P Pignatelli
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - F Violi
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - M Arca
- Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy
| | - F Angelico
- Department of Public Health and Infectious Disease, Sapienza University, Rome, Italy.
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Elsheikh E, Younoszai Z, Otgonsuren M, Hunt S, Raybuck B, Younossi ZM. Markers of endothelial dysfunction in patients with non-alcoholic fatty liver disease and coronary artery disease. J Gastroenterol Hepatol 2014; 29:1528-34. [PMID: 25587619 DOI: 10.1111/jgh.12549] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Tripodi A, Fracanzani AL, Primignani M, Chantarangkul V, Clerici M, Mannucci PM, Peyvandi F, Bertelli C, Valenti L, Fargion S. Procoagulant imbalance in patients with non-alcoholic fatty liver disease. J Hepatol 2014; 61:148-54. [PMID: 24657400 DOI: 10.1016/j.jhep.2014.03.013] [Citation(s) in RCA: 150] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Revised: 02/09/2014] [Accepted: 03/10/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is characterized by increased risk of cardiovascular events and liver-fibrosis. Both could be explained by a procoagulant-imbalance that was surmised but never directly demonstrated. We investigated 113 patients with varying histological liver damage [steatosis (n=32), steatohepatitis (n=51), metabolic-cirrhosis (n=30)], 54 with alcoholic/viral-cirrhosis and 179 controls. METHODS Plasma was evaluated for levels of pro- and anti-coagulants, and for thrombin-generation assessed as endogenous-thrombin-potential (ETP) with and without thrombomodulin or Protac® as protein C activators. The procoagulant-imbalance was defined as ETP-ratio (with-to-without thrombomodulin) or as Protac®-induced-coagulation-inhibition (PICI%). High ETP-ratios or low PICI% indicate resistance to thrombomodulin or Protac® and hence a procoagulant-imbalance. RESULTS ETP-ratio increased from controls [0.57 (0.11-0.89)] to steatosis [0.72 (0.33-0.86)] and metabolic-cirrhosis [0.80 (0.57-0.95)], (p<0.001), the latter being comparable to that for alcoholic/viral-cirrhosis [0.80 (0.57-0.95) vs. 0.80 (0.44-0.96)]. Factor VIII (a potent procoagulant for thrombin-generation) increased from steatosis [99% (71-150)] to metabolic-cirrhosis [157% (64-232)], p<0.001. Protein C (a powerful anticoagulant) decreased from steatosis [103% (77-228)] to metabolic-cirrhosis [77 (17-146)], p<0.001. As a consequence, factor VIII-to-protein C ratio increased from steatosis [0.96 (0.36-1.60)] to metabolic-cirrhosis [2.05 (0.81-12.1)], p<0.001 and was correlated with the ETP-ratio (rho=0.543, p<0.001). Similar results were obtained for PICI%. Patients with procoagulant-imbalance detected as ETP-ratio greater or PICI% lower than the median value of controls tended to have a higher risk of metabolic-syndrome, higher intima-media thickness, fibrosis, steatosis or lobular inflammation, all considered clinical manifestations of NAFLD. CONCLUSION NAFLD is characterized by a procoagulant-imbalance progressing from the less severe (steatosis) to the most severe form of the disease (metabolic-cirrhosis). This imbalance appears to result from increased factor VIII and reduced protein C and might play a role in the risk of cardiovascular events and liver-fibrosis commonly observed in NAFLD.
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Affiliation(s)
- Armando Tripodi
- Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano, Italy; IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.
| | - Anna L Fracanzani
- Metabolic Liver Diseases Center, Department of Pathophysiology and Transplantation, Section of Internal Medicine, Università degli Studi di Milano, Italy; IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy
| | - Massimo Primignani
- First Division of Gastroenterology; IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy
| | - Veena Chantarangkul
- Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano, Italy; IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy
| | - Marigrazia Clerici
- Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano, Italy; IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy
| | | | - Flora Peyvandi
- Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano, Italy; IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy
| | - Cristina Bertelli
- Metabolic Liver Diseases Center, Department of Pathophysiology and Transplantation, Section of Internal Medicine, Università degli Studi di Milano, Italy; IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy
| | - Luca Valenti
- Metabolic Liver Diseases Center, Department of Pathophysiology and Transplantation, Section of Internal Medicine, Università degli Studi di Milano, Italy; IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy
| | - Silvia Fargion
- Metabolic Liver Diseases Center, Department of Pathophysiology and Transplantation, Section of Internal Medicine, Università degli Studi di Milano, Italy; IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy
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Munteanu MA, Mircea PA. From NAFLD to Cardiovascular Disease. Is it (Still) the Metabolic Syndrome? ACTA ACUST UNITED AC 2014; 87:80-6. [PMID: 26528002 PMCID: PMC4620846 DOI: 10.15386/cjmed-277] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2014] [Accepted: 06/04/2014] [Indexed: 12/28/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in developed countries. The incidence of NAFLD in the general population is 30–38% deppending on the geographical area and the diagnostic method used. NAFLD is considered to be the liver manifestation of the metabolic syndrome. A better understanding of the natural evolution would have practical consequences related mainly to the need of early and aggressive diagnosis, active monitoring and therapeutic solutions. Cardiovascular disease appears to be the main cause of death in these patients. The mechanisms linking NAFLD with cardiovascular disease are not fully understood yet, but attention was focused primarily on insulin resistance. The visceral adipose tissue, the epicardial adipose tissue, the systemic inflammatory response syndrome, the lipid profile, the procoagulants factors, the oxidative stress, and type 2 diabetes mellitus, they all might play a role in the link between NAFLD and cardiovascular disease. Currently, there isn’t any medication specifically recommended for the treatment of NAFLD. Although the mechanisms underlying the association between NAFLD and cardiovascular disease are not fully known, attention must be paid to this association, given that these patients are more likely to die due to heart disease rather than liver disease.
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Affiliation(s)
- Mihai Alexandru Munteanu
- Department of Internal Medicine, 1 Medical Clinic - Internal Medicine, Cardiology and Gastroenterology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Petru Adrian Mircea
- Department of Internal Medicine, 1 Medical Clinic - Internal Medicine, Cardiology and Gastroenterology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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Byrne CD, Targher G. Ectopic fat, insulin resistance, and nonalcoholic fatty liver disease: implications for cardiovascular disease. Arterioscler Thromb Vasc Biol 2014; 34:1155-61. [PMID: 24743428 DOI: 10.1161/atvbaha.114.303034] [Citation(s) in RCA: 124] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Ectopic fat accumulation in the liver causes nonalcoholic fatty liver disease (NAFLD), which is the most common cause of chronic liver disease in Western countries. Ectopic liver lipid, particularly diacylglycerol, exacerbates hepatic insulin resistance, promotes systemic inflammation, and increases risk of developing both type 2 diabetes mellitus and cardiovascular disease. Increasing evidence suggests that NAFLD is an emerging risk factor for cardiovascular disease, and although there are currently no licensed treatments for NAFLD per se, current evidence suggests that statin treatment is safe in NAFLD. Presently, there is insufficient evidence to indicate that statins or other cardioprotective agents, such as angiotensin receptor blockers, are effective in treating NAFLD. In this brief narrative review, we discuss the diagnosis of NAFLD and the role of ectopic liver fat to cause insulin resistance and to increase risk of both type 2 diabetes mellitus and cardiovascular disease. For this review, PubMed was searched for articles using the key words non-alcoholic fatty liver disease or fatty liver combined with diabetes risk, cardiovascular risk, and cardiovascular mortality between 1990 and 2014. Articles published in languages other than English were excluded.
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Affiliation(s)
- Christopher D Byrne
- From Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, United Kingdom (C.D.B.); Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton, United Kingdom (C.D.B.); and Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy (G.T.).
| | - Giovanni Targher
- From Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, United Kingdom (C.D.B.); Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton, United Kingdom (C.D.B.); and Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy (G.T.)
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Ballestri S, Lonardo A, Bonapace S, Byrne CD, Loria P, Targher G. Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease. World J Gastroenterol 2014; 20:1724-1745. [PMID: 24587651 PMCID: PMC3930972 DOI: 10.3748/wjg.v20.i7.1724] [Citation(s) in RCA: 200] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Revised: 10/30/2013] [Accepted: 11/18/2013] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has emerged as a public health problem of epidemic proportions worldwide. Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease (CHD), abnormalities of cardiac function and structure (e.g., left ventricular dysfunction and hypertrophy, and heart failure), valvular heart disease (e.g., aortic valve sclerosis) and arrhythmias (e.g., atrial fibrillation). Experimental evidence suggests that NAFLD itself, especially in its more severe forms, exacerbates systemic/hepatic insulin resistance, causes atherogenic dyslipidemia, and releases a variety of pro-inflammatory, pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications. Collectively, these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications. The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular, cardiac and arrhythmic complications, to briefly examine the putative biological mechanisms underlying this association, and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications.
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Choi DH, Lee SJ, Kang CD, Park MO, Choi DW, Kim TS, Lee W, Cho BR, Kim YH, Lee BK, Ryu DR, Lee JW. Nonalcoholic fatty liver disease is associated with coronary artery disease in Koreans. World J Gastroenterol 2013; 19:6453-6457. [PMID: 24151364 PMCID: PMC3801316 DOI: 10.3748/wjg.v19.i38.6453] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Revised: 08/12/2013] [Accepted: 08/20/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether nonalcoholic fatty liver disease (NAFLD) affects coronary artery disease (CAD) and identify candidate mediators.
METHODS: Patients who underwent coronary angiography were consecutively recruited. The patients were classified into four groups by coronary artery stenosis: A, insignificant; B, one-vessel disease; C, two-vessel disease; and D, three-vessel disease. Abdominal ultrasonography was performed to determine the presence of a fatty liver and categorize by grade: 0, no evidence; 1, mild; 2, moderate; and 3, severe. We measured not only known CAD risk factors, but also serum insulin, HOMA-index, adiponectin, interleukin-6, tumor necrosis factor-α and high-sensitivity C-reactive protein levels.
RESULTS: Of the 134 patients who met the inclusion criteria, 82 (61.2%) had ultrasonographically diagnosed NAFLD. Among the 46 patients with CAD, 37 (80.4%) had evidence of a fatty liver. The two groups (A vs B-D) were significantly different in terms of age, total cholesterol, triglycerides, low-density lipoprotein levels and fatty liver. Coronary artery stenosis was strongly associated with fatty liver in a grade-dependent manner (P = 0.025). In binary logistic regression, NAFLD was a significant independent predictor of CAD (P = 0.03, OR = 1.685; 95%CI: 1.051-2.702). Among the candidate mediators, the serum adiponectin level showed a trend toward lowering based on CAD progression (P = 0.071).
CONCLUSION: NAFLD is an independent risk factor for CAD in a grade-dependent manner. Moreover, adiponectin might be related to the pathogenesis of NAFLD.
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Ballestri S, Meschiari E, Baldelli E, Musumeci FE, Romagnoli D, Trenti T, Zennaro RG, Lonardo A, Loria P. Relationship of serum fetuin-A levels with coronary atherosclerotic burden and NAFLD in patients undergoing elective coronary angiography. Metab Syndr Relat Disord 2013; 11:289-295. [PMID: 23600632 DOI: 10.1089/met.2012.0149] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) patients are prone to coronary artery disease (CAD). Fetuin-A inhibits arterial calcification, induces insulin resistance, and is increased in NAFLD. Data on fetuin-A levels in CAD are conflicting. We tried to ascertain whether NAFLD and CAD are associated and if fetuin-A predicts CAD and/or NAFLD. METHODS CAD was diagnosed by ≥50% stenosis in coronary arteries and NAFLD by ultrasound imaging in the absence of any other liver disease. Seventy patients who underwent elective coronarography at our hospital were recruited in this cross-sectional study. Twenty-four patients had no CAD (9 with and 15 without NAFLD) and 46 had CAD (20 with and 26 without NAFLD). Standard anthropometric indices and metabolic parameters were recorded. Fetuin-A was determined by enzyme-linked immunosorbent assay (ELISA). Visceral fat thickness and visceral/subcutaneous fat ratio were assessed by ultrasonography. RESULTS NAFLD was not associated with CAD, probably owing to the limited series. Fetuin-A was significantly lower, whereas visceral fat thickness and visceral/subcutaneous fat ratio were higher in patients with CAD versus those without CAD. Younger age and higher body mass index (BMI), waist circumference, triglycerides, fasting glucose, homeostasis model assessment, spleen area, subcutaneous fat thickness, and prevalence of metabolic derangements were associated with NAFLD. At multivariate analysis, elevated fetuin-A levels were an independent negative predictor of CAD [odds ratio (OR)=0.995, P=0.049]. Fetuin-A was an independent predictor of NAFLD (OR=1.005, P=0.036) in the model including BMI. CONCLUSIONS This prospective cross-sectional study demonstrates high fetuin-A levels to be independently associated with NAFLD and a lower risk of coronarographically diagnosed CAD.
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Affiliation(s)
- Stefano Ballestri
- Department of Internal Medicine, Endocrinology, Metabolism and Geriatrics, Operating Unit of Internal Medicine and Metabolism, University of Modena and Reggio Emilia, AUSL Modena, Modena, Italy
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Jung DH, Shim JY, Lee HR, Moon BS, Park BJ, Lee YJ. Relationship between non-alcoholic fatty liver disease and pulmonary function. Intern Med J 2013; 42:541-6. [PMID: 22181832 DOI: 10.1111/j.1445-5994.2011.02644.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND It has been observed that non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease and insulin resistance. Pulmonary function is also known to be related with cardiovascular disease and metabolic syndrome. AIMS The objective of this study was to investigate the association between NAFLD and pulmonary function. METHODS We performed a cross-sectional study to examine the association of NAFLD based on abdominal sonographic findings and pulmonary function in 2119 Korean men between the ages of 30 and 75. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) were compared according to the presence of NAFLD. Univariate and multivariate logistic regression analyses were conducted to evaluate the relationship of NAFLD with FVC and FEV(1) as pulmonary function tests. RESULTS The subjects with NAFLD had lower FVC and FEV(1) than their non-steatotic counterparts, and FVC and FEV(1) gradually decreased according to the grade of hepatic steatosis. After adjusting for age, body mass index, smoking status, blood pressure, fasting plasma glucose, total cholesterol, hypertension, diabetes, triglyceride and high-density lipoprotein cholesterol, the FVC and FEV(1) were found to be inversely associated with the presence of NAFLD. CONCLUSION NAFLD was independently associated with reduced pulmonary function, and the severity of NAFLD was inversely correlated with pulmonary function.
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Affiliation(s)
- D-H Jung
- Department of Family Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
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Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 2013; 10:330-44. [PMID: 23507799 DOI: 10.1038/nrgastro.2013.41] [Citation(s) in RCA: 1312] [Impact Index Per Article: 109.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
NAFLD is a spectrum of progressive liver disease that encompasses simple steatosis, NASH, fibrosis and, ultimately, cirrhosis. NAFLD is recognized as the hepatic component of the metabolic syndrome, as these conditions have insulin resistance as a common pathophysiological mechanism. Therefore, NAFLD is strongly associated with type 2 diabetes mellitus and abdominal obesity. As lifestyles have become increasingly sedentary and dietary patterns have changed, the worldwide prevalence of NAFLD has increased dramatically and is projected to be the principal aetiology for liver transplantation within the next decade. Importantly, a growing body of clinical and epidemiological evidence suggests that NAFLD is associated not only with liver-related morbidity and mortality, but also with an increased risk of developing both cardiovascular disease and type 2 diabetes mellitus. This article reviews the evidence that suggests NAFLD is a multisystem disease and the factors that might determine interindividual variation in the development and progression of its major hepatic and extrahepatic manifestations (principally type 2 diabetes mellitus and cardiovascular disease).
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Affiliation(s)
- Quentin M Anstee
- Liver Research Group, Institute of Cellular Medicine, The Medical School, Newcastle University, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK
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Sirota JC, McFann K, Targher G, Chonchol M, Jalal DI. Association between nonalcoholic liver disease and chronic kidney disease: an ultrasound analysis from NHANES 1988-1994. Am J Nephrol 2012; 36:466-71. [PMID: 23128368 DOI: 10.1159/000343885] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2012] [Accepted: 09/28/2012] [Indexed: 12/20/2022]
Abstract
BACKGROUND/AIMS Nonalcoholic fatty liver disease (NAFLD) has been proposed to contribute to chronic kidney disease (CKD) independently of traditional cardiometabolic risk factors. We hypothesized that NAFLD is associated with CKD and that greater severity of NAFLD is associated with higher odds of CKD. METHODS A cross-sectional analysis of 11,469 adults who participated in the National Health and Nutrition Examination Survey (NHANES) 1988-1994. NAFLD was defined by ultrasonographic detection of steatosis in the absence of other liver diseases. CKD was defined as an estimated glomerular filtration rate of ≤60 ml/min/1.73 m(2) or the presence of albuminuria in subjects with an estimated glomerular filtration rate of >60 ml/min/1.73 m(2). RESULTS 2,891 (25.4%) patients in the cohort had CKD. The prevalence of NAFLD was higher in individuals with CKD compared to those without CKD (42.2 vs. 34.5%, p < 0.0001). NAFLD was associated with CKD in unadjusted logistic regression analysis (OR = 1.47, 95% CI: 1.29-1.67, p < 0.0001). Adjustment for demographics and components of metabolic syndrome attenuated this relationship (OR = 1.04, 95% CI: 0.88-1.23, p = 0.64). Moderate and severe NAFLD on ultrasound were increasingly associated with prevalent CKD in unadjusted analysis, but not after adjustment for metabolic syndrome components. CONCLUSION After adjusting for features of metabolic syndrome, ultrasound-diagnosed NAFLD is not associated with prevalent CKD among US adults. Aggressive public health efforts are needed to prevent and treat metabolic syndrome.
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Affiliation(s)
- Jeffrey C Sirota
- University of Colorado at Denver Health Sciences Center, Aurora, USA
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world. It is closely associated with metabolic syndrome. The alarming epidemics of diabetes and obesity have fueled an increasing prevalence of NAFLD, particularly among these high-risk groups. Histologically, NAFLD encompasses a disease spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury, inflammation, and variable degrees of fibrosis on liver biopsy. Non-alcoholic steatohepatitis can progress to cirrhosis in a fraction of patients. There is currently little understanding of risk factors for disease progression and the disease pathogenesis has not been fully defined. Liver biopsy remains the gold standard for diagnosis. Weight loss, dietary modification, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established. There are no well-established pharmacological agents for treatment of NASH, although this is a subject of ongoing research.
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Abstract
Cardiac and hepatic fat are associated with insulin resistance and impaired suppression of lipolysis, ultimately leading to lipotoxicity. In the heart the lipotoxic effect translates into an impairment of energetic and mechanical efficiency, whereas in the liver a fibrogenic response is favored by the abundance of inflammatory cells. These features precede, and likely contribute to, left ventricular overload and cardiac hypertrophy through mechanisms similar to the ones observed in the progression of liver damage in nonalcoholic fatty liver disease (NAFLD). Collectively these findings suggest the presence of complex and intertwined interrelationships between NAFLD, myocardial steatosis, and coronary artery disease.
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Abstract
NAFLD is very common in the general population and its prevalence is increasing worldwide in parallel with the increasing incidences of obesity and metabolic diseases, mainly type 2 diabetes. In some cases, however, the diagnosis of NAFLD remains uncertain because other causes of liver disease are not easy to exclude in patients who are diagnosed with NAFLD after a biochemical or ultrasonographic analysis. Several studies have documented a strong association between NAFLD and traditional and nontraditional risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD). Accordingly, patients with NAFLD have an increased prevalence and incidence of both CVD and CKD. It is reasonable to believe that NAFLD, CVD and CKD share common risk factors (such as visceral obesity, insulin resistance, dysglycaemia, dyslipidaemia and hypertension) and therefore that NAFLD might simply be a marker rather than a causal risk factor of CVD and CKD. In this context, the identification of NAFLD might be an additional clinical feature to improve the stratification of patients for their risk of CVD and CKD. Growing evidence suggests that in patients with NAFLD, especially if NASH is present, several molecules released from the steatotic and inflamed liver might have pathogenic roles in the development of atherosclerosis and kidney damage. If these findings are confirmed by further studies, NAFLD could become a target for the prevention and treatment of CVD and CKD. NAFLD, whatever its role (marker or causal risk factor), is therefore a clinical condition that deserves greater attention from gastroenterologists, endocrinologists, cardiologists and nephrologists, as well as internists and general practitioners.
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Bhatia LS, Curzen NP, Calder PC, Byrne CD. Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor? Eur Heart J 2012; 33:1190-200. [PMID: 22408036 DOI: 10.1093/eurheartj/ehr453] [Citation(s) in RCA: 344] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population worldwide and may confer increased cardiometabolic risk with consequent adverse cardiovascular outcomes independent of traditional cardiovascular risk factors and the metabolic syndrome. It is characterized almost universally by insulin resistance and is strongly associated with type 2 diabetes and obesity. Non-alcoholic fatty liver disease is a marker of pathological ectopic fat accumulation combined with a low-grade chronic inflammatory state. This results in several deleterious pathophysiological processes including abnormal glucose, fatty acid and lipoprotein metabolism, increased oxidative stress, deranged adipokine profile, hypercoaguability, endothelial dysfunction, and accelerated progression of atherosclerosis. This ultimately leads to a dysfunctional cardiometabolic phenotype with cardiovascular mortality representing the main mode of premature death in NAFLD. This review is aimed at introducing NAFLD to the clinical cardiologist by discussing in-depth the evidence to date linking NAFLD with cardiovascular disease, reviewing the likely mechanisms underlying this association, as well as summarizing from a cardiologist's perspective, current and potential future treatment options for this increasingly prevalent disease.
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Affiliation(s)
- Lokpal S Bhatia
- National Institute of Health Research Biomedical Research Unit, Southampton University Hospitals NHS Trust, Southampton General Hospital, Tremona Road, Southampton, UK.
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Decreased circulating endothelial progenitor cell levels and function in patients with nonalcoholic fatty liver disease. PLoS One 2012; 7:e31799. [PMID: 22359630 PMCID: PMC3280999 DOI: 10.1371/journal.pone.0031799] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2011] [Accepted: 01/19/2012] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVES Nonalcoholic fatty liver disease (NAFLD) is associated with advanced atherosclerosis and a higher risk of cardiovascular disease. Increasing evidence suggests that injured endothelial monolayer is regenerated by circulating bone marrow derived-endothelial progenitor cells (EPCs), and levels of circulating EPCs reflect vascular repair capacity. However, the relation between NAFLD and EPC remains unclear. Here, we tested the hypothesis that patients with nonalcoholic fatty liver disease (NAFLD) might have decreased endothelial progenitor cell (EPC) levels and attenuated EPC function. METHODS AND RESULTS A total of 312 consecutive patients undergoing elective coronary angiography because of suspected coronary artery disease were screened and received examinations of abdominal ultrasonography between July 2009 and November 2010. Finally, 34 patients with an ultrasonographic diagnosis of NAFLD, and 68 age- and sex-matched controls without NAFLD were enrolled. Flow cytometry with quantification of EPC markers (defined as CD34(+), CD34(+)KDR(+), and CD34(+)KDR(+)CD133(+)) in peripheral blood samples was used to assess circulating EPC numbers. The adhesive function, and migration, and tube formation capacities of EPCs were also determined in NAFLD patients and controls. Patients with NAFLD had a significantly higher incidence of metabolic syndrome, previous myocardial infarction, hyperuricemia, and higher waist circumference, body mass index, fasting glucose and triglyceride levels. In addition, patients with NAFLD had significantly decreased circulating EPC levels (all P<0.05), attenuated EPC functions, and enhanced systemic inflammation compared to controls. Multivariate logistic regression analysis showed that circulating EPC level (CD34(+)KDR(+) [cells/10(5) events]) was an independent reverse predictor of NAFLD (Odds ratio: 0.78; 95% confidence interval: 0.69-0.89, P<0.001). CONCLUSIONS NAFLD patients have decreased circulating EPC numbers and functions than those without NAFLD, which may be one of the mechanisms to explain atherosclerotic disease progression and enhanced cardiovascular risk in patients with NAFLD.
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Maurantonio M, Ballestri S, Odoardi MR, Lonardo A, Loria P. Treatment of atherogenic liver based on the pathogenesis of nonalcoholic fatty liver disease: a novel approach to reduce cardiovascular risk? Arch Med Res 2011; 42:337-353. [PMID: 21843565 DOI: 10.1016/j.arcmed.2011.08.004] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2011] [Accepted: 07/18/2011] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD), which spans a spectrum of conditions ranging from simple steatosis to progressive nonalcoholic steatohepatitis (NASH), is the most common chronic liver disease and a relevant public health issue. The prevalence of NAFLD depends on adiposity, age, gender and ethnicity. The natural history of liver disease in those with NAFLD critically depends on liver histological changes. However, cardiovascular mortality is increased in NAFLD, particularly in middle-aged adults. Against such a background, this review consists of three sections. First, data on NAFLD as a novel mechanism of increased cardiovascular risk via hyperinsulinism, pro-thrombotic potential, and subclinical inflammation are summarized. Next, the role of atherogenic liver in the development of manifestations of oxidative stress and atherosclerosis is emphasized. Finally, whether and how treating NAFLD will mechanistically result in reduced cardiovascular risk through ameliorated metabolic syndrome is discussed.
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Affiliation(s)
- Mauro Maurantonio
- Department of Internal Medicine, Endocrinology, Metabolism and Geriatrics, Nuovo Ospedale Civile Sant'Agostino-Estense di Modena, University of Modena and Reggio Emilia, Modena, Italy.
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Chitturi S, Wong VWS, Farrell G. Nonalcoholic fatty liver in Asia: Firmly entrenched and rapidly gaining ground. J Gastroenterol Hepatol 2011; 26 Suppl 1:163-72. [PMID: 21199528 DOI: 10.1111/j.1440-1746.2010.06548.x] [Citation(s) in RCA: 116] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming an important chronic liver disorder in Asia. Prevalence figures show regional variations but at least 10% of the general population in Asia have fatty liver. Fatty liver can develop with relatively small changes in weight (2-3 kg), often with increasing central adiposity. The metabolic syndrome may precede or follow NAFLD. Overt diabetes is present in one-third of cases but when oral glucose tolerance tests are performed, a further third of individuals have impaired glucose tolerance or diabetes. Natural history data are still scarce but cases of advanced hepatic fibrosis and hepatocellular carcinoma are now regularly reported. Many cases of cryptogenic cirrhosis are also attributable to NAFLD. Histological progression has been demonstrated for patients with NASH as well as for those with hepatic steatosis alone. Genetic factors may in part contribute to the rise in NAFLD. Polymorphisms within apolipoprotein C3 (APOC3) gene have been linked to NAFLD in lean Indian men. Although a number of other polymorphisms involving genes controlling adipose distribution, insulin signalling, adipokine responses and hepatic fibrosis have been reported, these studies have been underpowered. Transient elastography could help in detecting and monitoring hepatic fibrosis but further refinements in technique are necessary for obese individuals. Of the biomarkers, hyaluronic acid and cytokeratin-18 fragment testing show promise as markers of hepatic fibrosis and NASH, respectively. Lifestyle alterations including dietary changes and increased physical activity remain the cornerstone of management. Attention should be paid to prevention through public education of campaigns addressing the increase in both adult and childhood obesity.
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