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Wu Y, Liu S, Fan Z, Tian Y, Zhang L, Liu S. Establishment and Validation of a Blood Test-based Nomogram to Diagnose Patients with AFP-negative HCC. Curr Cancer Drug Targets 2024; 24:556-564. [PMID: 38178672 DOI: 10.2174/0115680096264770231113103930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 09/05/2023] [Accepted: 09/25/2023] [Indexed: 01/06/2024]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide. Alpha-protein (AFP) is the most widely used blood biomarker for HCC. However, elevated serum AFP is only observed in part of HCC. AIMS This study aimed to develop an efficient nomogram model to distinguish patients with alpha- protein-negative HCC and liver cirrhosis. OBJECTIVES A total of 1130 patients (508 HCC patients + 622 cirrhosis patients) were enrolled in the training cohort. A total of 244 HCC patients and 246 cirrhosis patients were enrolled in the validation cohort. METHODS A total of 41 parameters about blood tests were analyzed with logistic regression. The nomogram was based on independent factors and validated both internally and externally. RESULTS Independent factors were eosinophils %, hemoglobin concentration distribution width, fibrinogen, platelet counts, total bile acid, and mitochondria aspartate aminotransferase. The calibration curve for the probability of HCC showed good agreement between prediction by nomogram and actual observation. The concordance index was 0.851. In the validation cohort, the nomogram distinguished HCC from liver cirrhosis with an area under the curve of receiver operating characteristic of 0.754. CONCLUSION This proposed nomogram was an accurate and useful method to distinguish patients with AFP-negative HCC from liver cirrhosis.
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Affiliation(s)
- Yujing Wu
- The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, 83 Jintang Road, Hedong District, Tianjin, 300170, China
| | - Shuang Liu
- The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, 83 Jintang Road, Hedong District, Tianjin, 300170, China
| | - Zhijuan Fan
- The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, 83 Jintang Road, Hedong District, Tianjin, 300170, China
| | - Yaqiong Tian
- The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, 83 Jintang Road, Hedong District, Tianjin, 300170, China
| | - Lei Zhang
- The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, 83 Jintang Road, Hedong District, Tianjin, 300170, China
| | - Shuye Liu
- The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, 83 Jintang Road, Hedong District, Tianjin, 300170, China
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2
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Lambooy S, Heida A, Joschko C, Nakladal D, van Buiten A, Kloosterhuis N, Huijkman N, Gerding A, van de Sluis B, Henning R, Deelman L. Selective Hepatic Cbs Knockout Aggravates Liver Damage, Endothelial Dysfunction and ROS Stress in Mice Fed a Western Diet. Int J Mol Sci 2023; 24:ijms24087019. [PMID: 37108182 PMCID: PMC10138434 DOI: 10.3390/ijms24087019] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 04/07/2023] [Accepted: 04/08/2023] [Indexed: 04/29/2023] Open
Abstract
Cystathionine-β-synthase (CBS) is highly expressed in the liver, and deficiencies in Cbs lead to hyperhomocysteinemia (HHCy) and disturbed production of antioxidants such as hydrogen sulfide. We therefore hypothesized that liver-specific Cbs deficient (LiCKO) mice would be particularly susceptible to the development of non-alcoholic fatty liver disease (NAFLD). NAFLD was induced by a high-fat high-cholesterol (HFC) diet; LiCKO and controls were split into eight groups based on genotype (con, LiCKO), diet (normal diet, HFC), and diet duration (12 weeks, 20 weeks). LiCKO mice displayed intermediate to severe HHCy. Plasma H2O2 was increased by HFC, and further aggravated in LiCKO. LiCKO mice fed an HFC diet had heavier livers, increased lipid peroxidation, elevated ALAT, aggravated hepatic steatosis, and inflammation. LiCKO mice showed decreased L-carnitine in the liver, but this did not result in impaired fatty acid oxidation. Moreover, HFC-fed LiCKO mice demonstrated vascular and renal endothelial dysfunction. Liver and endothelial damage correlated significantly with systemic ROS status. In conclusion, this study demonstrates an important role for CBS in the liver in the development of NAFLD, which is most probably mediated through impaired defense against oxidative stress.
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Affiliation(s)
- Sebastiaan Lambooy
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands
| | - Andries Heida
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands
| | - Christian Joschko
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands
| | - Dalibor Nakladal
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands
| | - Azuwerus van Buiten
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands
| | - Niels Kloosterhuis
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands
| | - Nicolette Huijkman
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands
| | - Albert Gerding
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands
| | - Bart van de Sluis
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands
| | - Robert Henning
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands
| | - Leo Deelman
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands
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Murphy WA, Adiwidjaja J, Sjöstedt N, Yang K, Beaudoin JJ, Spires J, Siler SQ, Neuhoff S, Brouwer KLR. Considerations for Physiologically Based Modeling in Liver Disease: From Nonalcoholic Fatty Liver (NAFL) to Nonalcoholic Steatohepatitis (NASH). Clin Pharmacol Ther 2023; 113:275-297. [PMID: 35429164 PMCID: PMC10083989 DOI: 10.1002/cpt.2614] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 04/05/2022] [Indexed: 01/27/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD), representing a clinical spectrum ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), is rapidly evolving into a global pandemic. Patients with NAFLD are burdened with high rates of metabolic syndrome-related comorbidities resulting in polypharmacy. Therefore, it is crucial to gain a better understanding of NAFLD-mediated changes in drug disposition and efficacy/toxicity. Despite extensive clinical pharmacokinetic data in cirrhosis, current knowledge concerning pharmacokinetic alterations in NAFLD, particularly at different stages of disease progression, is relatively limited. In vitro-to-in vivo extrapolation coupled with physiologically based pharmacokinetic and pharmacodynamic (IVIVE-PBPK/PD) modeling offers a promising approach for optimizing pharmacologic predictions while refining and reducing clinical studies in this population. Use of IVIVE-PBPK to predict intra-organ drug concentrations at pharmacologically relevant sites of action is particularly advantageous when it can be linked to pharmacodynamic effects. Quantitative systems pharmacology/toxicology (QSP/QST) modeling can be used to translate pharmacokinetic and pharmacodynamic data from PBPK/PD models into clinically relevant predictions of drug response and toxicity. In this review, a detailed summary of NAFLD-mediated alterations in human physiology relevant to drug absorption, distribution, metabolism, and excretion (ADME) is provided. The application of literature-derived physiologic parameters and ADME-associated protein abundance data to inform virtual NAFLD population development and facilitate PBPK/PD, QSP, and QST predictions is discussed along with current limitations of these methodologies and knowledge gaps. The proposed methodologic framework offers great potential for meaningful prediction of pharmacological outcomes in patients with NAFLD and can inform both drug development and clinical practice for this population.
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Affiliation(s)
- William A Murphy
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Jeffry Adiwidjaja
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Simulations Plus, Inc., Lancaster, California, USA
| | - Noora Sjöstedt
- Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
| | - Kyunghee Yang
- DILIsym Services Division, Simulations Plus Inc., Research Triangle Park, North Carolina, USA
| | - James J Beaudoin
- DILIsym Services Division, Simulations Plus Inc., Research Triangle Park, North Carolina, USA
| | | | - Scott Q Siler
- DILIsym Services Division, Simulations Plus Inc., Research Triangle Park, North Carolina, USA
| | | | - Kim L R Brouwer
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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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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Gangopadhyay A, Ibrahim R, Theberge K, May M, Houseknecht KL. Non-alcoholic fatty liver disease (NAFLD) and mental illness: Mechanisms linking mood, metabolism and medicines. Front Neurosci 2022; 16:1042442. [PMID: 36458039 PMCID: PMC9707801 DOI: 10.3389/fnins.2022.1042442] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 10/21/2022] [Indexed: 09/26/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world and one of the leading indications for liver transplantation. It is one of the many manifestations of insulin resistance and metabolic syndrome as well as an independent risk factor for cardiovascular disease. There is growing evidence linking the incidence of NAFLD with psychiatric illnesses such as schizophrenia, bipolar disorder and depression mechanistically via genetic, metabolic, inflammatory and environmental factors including smoking and psychiatric medications. Indeed, patients prescribed antipsychotic medications, regardless of diagnosis, have higher incidence of NAFLD than population norms. The mechanistic pharmacology of antipsychotic-associated NAFLD is beginning to emerge. In this review, we aim to discuss the pathophysiology of NAFLD including its risk factors, insulin resistance and systemic inflammation as well as its intersection with psychiatric illnesses.
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Affiliation(s)
| | | | | | | | - Karen L. Houseknecht
- Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME, United States
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Prysyazhnyuk V, Sydorchuk L, Sydorchuk R, Prysiazhniuk I, Bobkovych K, Buzdugan I, Dzuryak V, Prysyazhnyuk P. Glutathione-S-transferases genes-promising predictors of hepatic dysfunction. World J Hepatol 2021; 13:620-633. [PMID: 34239698 PMCID: PMC8239493 DOI: 10.4254/wjh.v13.i6.620] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/06/2021] [Accepted: 06/03/2021] [Indexed: 02/06/2023] Open
Abstract
One of the most commonly known genes involved in chronic diffuse liver diseases pathogenesis are genes that encodes the synthesis of glutathione-S-transferase (GST), known as the second phase enzyme detoxification system that protects against endogenous oxidative stress and exogenous toxins, through catalisation of glutathione sulfuric groups conjugation and decontamination of lipid and deoxyribonucleic acid oxidation products. The group of GST enzymes consists of cytosolic, mitochondrial and microsomal fractions. Recently, eight classes of soluble cytoplasmic isoforms of GST enzymes are widely known: α-, ζ-, θ-, κ-, μ-, π-, σ-, and ω-. The GSTs gene family in the Human Gene Nomenclature Committee, online database recorded over 20 functional genes. The level of GSTs expression is considered to be a crucial factor in determining the sensitivity of cells to a broad spectrum of toxins. Nevertheless, human GSTs genes have multiple and frequent polymorphisms that include the complete absence of the GSTM1 or the GSTT1 gene. Current review supports the position that genetic polymorphism of GST genes is involved in the pathogenesis of various liver diseases, particularly non-alcoholic fatty liver disease, hepatitis and liver cirrhosis of different etiology and hepatocellular carcinoma. Certain GST allelic variants were proven to be associated with susceptibility to hepatological pathology, and correlations with the natural course of the diseases were subsequently postulated.
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Affiliation(s)
- Vasyl Prysyazhnyuk
- Department of Propedeutics of Internal Diseases, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Larysa Sydorchuk
- Department of Family Medicine, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Ruslan Sydorchuk
- Department of Surgery, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Iryna Prysiazhniuk
- Department of Internal Medicine and Invectious Diseases, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Kateryna Bobkovych
- Department of Propedeutics of Internal Diseases, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Inna Buzdugan
- Department of Internal Medicine and Invectious Diseases, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Valentina Dzuryak
- Department of Family Medicine, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Petro Prysyazhnyuk
- Department of Medical and Pharmaceutical Chemistry, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
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Hannawi S, Hannawi H, Alokaily F, Al Salmi I. Variables associated with subclinical atherosclerosis among rheumatoid arthritis patients of Gulf Cooperative Council countries. Saudi Med J 2020; 41:128-137. [PMID: 32020145 PMCID: PMC7841633 DOI: 10.15537/smj.2020.2.24900] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVES To evaluate the cardiovascular disease (CVD) as demonstrated by carotid intima-media thickness (cIMT) and the cluster risk factors of CVD including traditional and non-traditional, urinary functions, iron buildup, and hemorheology in rheumatoid arthritis (RA) patients of Gulf Cooperative Council (GCC) countries. METHODS Carotid intima-media thickness was obtained from 216 RA patients, free of atherosclerotic diseases. The correlation between cIMT and the possible CVD risk factors was carried out using regression analysis. Results: The mean cIMT was observed as 0.58±0.11 mm. Mean age was 48±13 years. Univariate analysis revealed a positive association (p less than 0.05) between cIMT and age, body mass index, systolic blood pressure (SBp), and diastolic blood pressure, c-reactive protein (CRP), triglycerides (TG), low-density lipoprotein (LDL), erythrocyte sedimentation rate (ESR), hemoglobin (Hb), hematocrit (Hct), mean cell volume, platelet, monocytes, eosinophils, ferritin, creatinine, and uric acid. Negative relationship was observed between cIMT and glomerular filtration rate (GFR), transferrin, and high-density lipoprotein. Multiple linear regression analysis exhibited a positive association between cIMT and the age, LDL, eosinophil, SBp, and the ESR, whereas, negative connection with the GFR and transferrin. Conclusion: In this study, we found that the eosinophils, and low transferrin, are the potential candidates for the CVD risk factors in RA patients. Fasting blood glucose level was also observed to be a significant risk factor in diabetic as well as non-diabetic RA. The remaining CVD risk factors in RA patients of GCC countries including older age, high SBp, ESR, LDL, and low GFR were similar to the international population.
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Affiliation(s)
- Suad Hannawi
- Department-Al Baraha Hospital, Ministry of Health and Prevention, Dubai, United Arab Emirates. E-mail.
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Prysyazhnyuk VP, Rossokha ZI, Gorovenko NG. Variation in particular biochemical indicators, cytokine and adipokine profiles of the blood, and the structural and functional parameters of the liver in patients with nonalcoholic fatty liver disease and different genotypes by the polymorphic locus A313G of the GSTP1 gene. CYTOL GENET+ 2017. [DOI: 10.3103/s0095452717060111] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Dinani A, Sanyal A. Nonalcoholic fatty liver disease: implications for cardiovascular risk. Cardiovasc Endocrinol 2017; 6:62-72. [PMID: 31646122 PMCID: PMC6768515 DOI: 10.1097/xce.0000000000000126] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Accepted: 03/23/2017] [Indexed: 12/20/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic in the USA affecting ∼30% of the population. It has been closely linked to metabolic syndrome and type 2 diabetes, with strong implications for cardiovascular disease (CVD). This review focuses on the relationship between NAFLD and CVD and the proposed interactions interlinking these two diseases. This appraisal also discusses treatments targeting NAFLD in the context of CVD. NAFLD is a multisystem disease and ultimately the goals of therapy are to ameliorate CVD and prevent coronary artery disease morbidity and mortality.
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Affiliation(s)
- Amreen Dinani
- Department of Gastroenterology and Hepatology, NewYork-Presbyterian Brooklyn Methodist, NewYork-Presbyterian Healthcare System, Brooklyn, New York
| | - Arun Sanyal
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA
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Association of hematocrit and pre-hypertension among Chinese adults: the CRC study. Cell Biochem Biophys 2016; 71:1123-8. [PMID: 25476140 DOI: 10.1007/s12013-014-0318-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Elevated blood pressure is regarded as an independent risk factor for cardiovascular diseases and diabetes. We examined the relation between hematocrit and pre-hypertension as well as the effect of sex, obesity, fasting glucose, and lipids in Chinese adults. The study samples were from a community-based health examination survey in China and included a total of 2,3691 patients with blood pressure in normal range. The odds ratios [ORs, 95 % confidence interval (CI)] of pre-hypertension across increasing quartiles of hematocrit were 1.000, 1.176 (1.050-1.318), 1.213 (1.081-1.363), and 1.364 (1.209-1.540) (P for trend < 0.001), when adjusted for age, sex, body mass index, glutamic-pyruvic transaminase, glutamic-oxalocetie transaminase, serum uric acid, glucose, and lipids. Associations were significant in both men and women, but not in individuals older than 60 years. In addition, low-density lipoprotein cholesterol significantly interacted with hematocrit (P for interaction <0.024). The associations were more evident in patients with low (P < 0.001) and median LDL-C levels (P < 0.013) than those with high glucose levels. Hematocrit was associated with pre-hypertension, and was independent of metabolic risk factors. These associations were not significant in older individuals and low-density lipoprotein cholesterol may modify these associations.
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Zhao HY, Li J, Xu M, Wang TG, Sun WW, Chen Y, Bi YF, Wang WQ, Ning G. Elevated whole blood viscosity is associated with insulin resistance and non-alcoholic fatty liver. Clin Endocrinol (Oxf) 2015; 83:806-11. [PMID: 25823525 DOI: 10.1111/cen.12776] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2014] [Revised: 01/08/2015] [Accepted: 03/19/2015] [Indexed: 01/06/2023]
Abstract
BACKGROUND Accumulating evidences demonstrate that abnormalities in whole blood viscosity (WBV) have been implicated in insulin resistance which may lead to non-alcoholic fatty liver disease (NAFLD). However, epidemiological studies exploring the association between WBV and NAFLD were not available. OBJECTIVE Our objective was to evaluate the association between WBV levels and risk of prevalent NAFLD. DESIGN This was a cross-sectional population-based study performed in Shanghai, China. PATIENTS A total of 8673 participants aged 40 years or older were included. MEASUREMENTS WBV was calculated from haematocrit and plasma protein concentration, at a shear rate of 208(-1) s, by a validated equation. NAFLD was diagnosed by hepatic ultrasound after the exclusion of alcohol abuse and other liver diseases. Insulin resistance (IR) was assessed by homeostasis model assessment (HOMA-IR). RESULTS The overall prevalence of NAFLD was 30·2% in this population. With the increase of WBV level, participants have larger waist circumference (WC), more severe insulin resistance and the prevalence of NAFLD increased significantly with elevated WBV quartiles. Compared with those in the lowest quartiles, adults in the highest quartile of WBV levels have higher prevalence of NAFLD (adjusted odds ratio 1·77, 95% confidence interval [CI] 1·48-2·13) and IR (2·72, 95% CI 2·26-3·27). CONCLUSIONS Elevated WBV is associated with prevalence of NAFLD and IR in middle-aged and elderly Chinese population.
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Affiliation(s)
- Hong-yan Zhao
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, The National Clinical Research Center for Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai, China
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
| | - Jing Li
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, The National Clinical Research Center for Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai, China
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
| | - Min Xu
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, The National Clinical Research Center for Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai, China
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
| | - Tian-ge Wang
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, The National Clinical Research Center for Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai, China
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
| | - Wan-wan Sun
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, The National Clinical Research Center for Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai, China
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
| | - Ying Chen
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, The National Clinical Research Center for Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai, China
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
| | - Yu-fang Bi
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, The National Clinical Research Center for Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai, China
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
| | - Wei-qing Wang
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, The National Clinical Research Center for Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai, China
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
| | - Guang Ning
- Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, The National Clinical Research Center for Metabolic Diseases of Ministry of Health, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, E-Institute of Shanghai Universities, Shanghai, China
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
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Zhang Y, Zhang T, Zhang C, Tang F, Zhong N, Li H, Song X, Lin H, Liu Y, Xue F. Identification of reciprocal causality between non-alcoholic fatty liver disease and metabolic syndrome by a simplified Bayesian network in a Chinese population. BMJ Open 2015; 5:e008204. [PMID: 26395497 PMCID: PMC4593152 DOI: 10.1136/bmjopen-2015-008204] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVES It remains unclear whether non-alcoholic fatty liver disease (NAFLD) is a cause or a consequence of metabolic syndrome (MetS). We proposed a simplified Bayesian network (BN) and attempted to confirm their reciprocal causality. SETTING Bidirectional longitudinal cohorts (subcohorts A and B) were designed and followed up from 2005 to 2011 based on a large-scale health check-up in a Chinese population. PARTICIPANTS Subcohort A (from NAFLD to MetS, n=8426) included the participants with or without NAFLD at baseline to follow-up the incidence of MetS, while subcohort B (from MetS to NAFLD, n=16,110) included the participants with or without MetS at baseline to follow-up the incidence of NAFLD. RESULTS Incidence densities were 2.47 and 17.39 per 100 person-years in subcohorts A and B, respectively. Generalised estimating equation analyses demonstrated that NAFLD was a potential causal factor for MetS (relative risk, RR, 95% CI 5.23, 3.50 to 7.81), while MetS was also a factor for NAFLD (2.55, 2.23 to 2.92). A BN with 5 simplification strategies was used for the reciprocal causal inference. The BN's causal inference illustrated that the total effect of NAFLD on MetS (attributable risks, AR%) was 2.49%, while it was 19.92% for MetS on NAFLD. The total effect of NAFLD on MetS components was different, with dyslipidemia having the greatest (AR%, 10.15%), followed by obesity (7.63%), diabetes (3.90%) and hypertension (3.51%). Similar patterns were inferred for MetS components on NAFLD, with obesity having the greatest (16.37%) effect, followed by diabetes (10.85%), dyslipidemia (10.74%) and hypertension (7.36%). Furthermore, the most important causal pathway from NAFLD to MetS was that NAFLD led to elevated GGT, then to MetS components, while the dominant causal pathway from MetS to NAFLD began with dyslipidaemia. CONCLUSIONS The findings suggest a reciprocal causality between NAFLD and MetS, and the effect of MetS on NAFLD is significantly greater than that of NAFLD on MetS.
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Affiliation(s)
- Yongyuan Zhang
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, Shandong, China
- Medical Department, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Tao Zhang
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, Shandong, China
| | - Chengqi Zhang
- Health Management Center, Shandong Provincial QianFoShan Hospital, Jinan, Shandong, China
| | - Fang Tang
- Health Management Center, Shandong Provincial QianFoShan Hospital, Jinan, Shandong, China
| | - Nvjuan Zhong
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, Shandong, China
| | - Hongkai Li
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, Shandong, China
| | - Xinhong Song
- Health Management Center, Shandong Provincial QianFoShan Hospital, Jinan, Shandong, China
| | - Haiyan Lin
- Health Management Center, Shandong Provincial QianFoShan Hospital, Jinan, Shandong, China
| | - Yanxun Liu
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, Shandong, China
| | - Fuzhong Xue
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, Shandong, China
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Liu H, Lu HY. Nonalcoholic fatty liver disease and cardiovascular disease. World J Gastroenterol 2014; 20:8407-8415. [PMID: 25024598 PMCID: PMC4093693 DOI: 10.3748/wjg.v20.i26.8407] [Citation(s) in RCA: 83] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2013] [Revised: 01/04/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) are two diseases that are common in the general population. To date, many studies have been conducted and demonstrate a direct link between NAFLD and CVD, but the exact mechanisms for this complex relationship are not well established. A systematic search of the PubMed database revealed that several common mechanisms are involved in many of the local and systemic manifestations of NAFLD and lead to an increased cardiovascular risk. The possible mechanisms linking NAFLD and CVD include inflammation, oxidative stress, insulin resistance, ectopic adipose tissue distribution, dyslipidemia, endothelial dysfunction, and adiponectin, among others. The clinical implication is that patients with NAFLD are at an increased risk of CVD and should undergo periodic cardiovascular risk assessment.
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Jin YZ, Zheng DH, Duan ZY, Lin YZ, Zhang XY, Wang JR, Han S, Wang GF, Zhang YJ. Relationship Between Hematocrit Level and Cardiovascular Risk Factors in a Community-Based Population. J Clin Lab Anal 2014; 29:289-93. [PMID: 24849556 DOI: 10.1002/jcla.21767] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Accepted: 03/17/2014] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND This study aimed to determine the relationship between hematocrit (HCT) levels and cardiovascular risk factors in a community-based population of middle-aged adults. METHODS From April 2011 to February 2012, a total of 1,884 middle-aged adults were selected from a community-based population in China. Blood and urine samples were collected for routine blood and urine tests, and measurement of plasma glucose and lipid levels. Baseline information including traditional cardiovascular risk factors was obtained by standard questionnaire to analyze. We evaluated the distribution of the HCT values for middle-aged adults with or without cardiovascular risk factors. There were 548 males and 1,336 females in this study. The mean age of all subjects was 54.7 ± 6.7 years. There were 1,209 subjects with risk factors and 675 without risk factors. RESULTS The HCT levels in subjects with risk factors were higher than those without risk factors (P = 0.005). According to a simplified tool for evaluation of the 10-year risk of ischemic cardiovascular diseases (CVDs) in Chinese populations, all subjects were divided into four groups: the ultralow-risk group (1,367, 72.6%), low-risk group (232, 12.3%), intermediate-risk group (201, 10.7%), and high-risk/ultrahigh-risk group (84, 4.4%). Compared with HCT levels in the ultralow-risk group, significant differences were found in the low-risk, intermediate-risk, and high-risk/ultrahigh-risk groups (all P < 0.05). CONCLUSION Our results indicate that elevated HCT levels may be positively associated with cardiovascular risk factors. Thus, the combination of HCT values and cardiovascular risk factors may enable early diagnosis of CVDs.
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Affiliation(s)
- Yuan-Ze Jin
- Department of Cardiology, Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China
| | - Dong-Han Zheng
- Department of Cardiology, Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China
| | - Zhi-Ying Duan
- Department of Cardiology, Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China
| | - Ying-Zi Lin
- Department of Cardiology, Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China
| | - Xue-Ying Zhang
- Department of Cardiology, Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China
| | - Jing-Ru Wang
- Department of Cardiology, Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China
| | - Shuo Han
- Department of Cardiology, Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China
| | - Guo-Feng Wang
- Department of Cardiology, Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China
| | - Yi-Jing Zhang
- Department of Cardiology, Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China
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15
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Fan JG. Epidemiology of alcoholic and nonalcoholic fatty liver disease in China. J Gastroenterol Hepatol 2013; 28 Suppl 1:11-7. [PMID: 23855290 DOI: 10.1111/jgh.12036] [Citation(s) in RCA: 209] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/20/2013] [Indexed: 12/12/2022]
Abstract
The prevalence of patients presenting with fatty liver disease (FLD) in China has approximately doubled over the past two decades. At present, FLD, which is typically diagnosed by imaging, is highly prevalent (≈ 27% urban population) in China and is mainly related to obesity and metabolic syndrome (MetS). However, the percentage of alcoholic liver disease (ALD) among patients with chronic liver diseases in clinic is increasing as well, and a synergetic effect exists between heavy alcohol drinking and obesity in ALD. Prevalence figures reveal regional variations, with a median prevalence of ALD and nonalcoholic FLD (NAFLD) of 4.5% and 15.0%, respectively. The prevalence of NAFLD in children is 2.1%, although the prevalence increases to 68.2% among obese children. With the increasing pandemic of obesity and MetS in the general population, China is likely to harbor an increasing reservoir of patients with FLD. The risk factors for FLD resemble to those of Caucasian counterparts, but the ethnic-specific definitions of obesity and MetS are more useful in assessment of Chinese people. Therefore, FLD/NAFLD has become a most common chronic liver disease in China. Public health interventions are needed to halt the worldwide trend of obesity and alcohol abuse to ameliorate liver injury and to improve metabolic health.
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Affiliation(s)
- Jian-Gao Fan
- Department of Gastroenterology, Shanghai Key Laboratory of Children's Digestion and Nutrition, Xin-Hua Hospital Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
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Stark H, Schuster S. Comparison of various approaches to calculating the optimal hematocrit in vertebrates. J Appl Physiol (1985) 2012; 113:355-67. [DOI: 10.1152/japplphysiol.00369.2012] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
An interesting problem in hemorheology is to calculate that volume fraction of erythrocytes (hematocrit) that is optimal for transporting a maximum amount of oxygen. If the hematocrit is too low, too few erythrocytes are present to transport oxygen. If it is too high, the blood is very viscous and cannot flow quickly, so that oxygen supply to the tissues is again reduced. These considerations are very important, since oxygen transport is an important factor for physical performance. Here, we derive theoretical optimal values of hematocrit in vertebrates and collect, from the literature, experimentally observed values for 57 animal species. It is an interesting question whether optimal hematocrit theory allows one to calculate hematocrit values that are in agreement with the observed values in various vertebrate species. For this, we first briefly review previous approaches in that theory. Then we check which empirical or theoretically derived formulas describing the dependence of viscosity on concentration in a suspension lead to the best agreement between the theoretical and observed values. We consider both spatially homogeneous and heterogeneous distributions of erythrocytes in the blood and also possible extensions, like the influence of defective erythrocytes and cases where some substances are transported in the plasma. By discussing the results, we critically assess the power and limitations of optimal hematocrit theory. One of our goals is to provide a systematic overview of different approaches in optimal hematocrit theory.
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Affiliation(s)
- Heiko Stark
- Department of Bioinformatics, Friedrich-Schiller University, Jena, Germany
| | - Stefan Schuster
- Department of Bioinformatics, Friedrich-Schiller University, Jena, Germany
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