Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Nonalcoholic Fatty Liver Disease-Evidence for a Thrombophilic State?

Author(s): Margaret Spinosa and Jonathan G. Stine*

Volume 26, Issue 10, 2020

Page: [1036 - 1044] Pages: 9

DOI: 10.2174/1381612826666200131101553

Price: $65


Nonalcoholic fatty liver disease is the leading cause of liver disease worldwide. It has expansive extrahepatic morbidity and mortality including increased rates of both cardiovascular disease and venous thromboembolism. Derangements in primary, secondary and tertiary hemostasis are found in nonalcoholic fatty liver disease independent of those ascribed to end-stage liver disease. The abnormalities across all stages of hemostasis explain the increased rates of clinically relevant thrombotic events, including pulmonary embolism, deep vein thrombosis and portal vein thrombosis, which on an epidemiologic basis appears to be independent of obesity and other traditional venous thromboembolic risk factors. However, given the complex interaction between obesity, body composition and nonalcoholic fatty liver disease and the potential for exercise to benefit all three, more research is needed to further define the role of each in contributing to the prohemostatic state of nonalcoholic fatty liver disease in order to improve patient oriented outcomes.

Keywords: Thrombosis, nonalcoholic steatohepatitis, liver transplantation, hypercoagulable, exercise, thromboembolic.

Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64(1): 73-84.
[] [PMID: 26707365]
Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA 2015; 313(22): 2263-73.
[] [PMID: 26057287]
Health, United States , 2017: Obesity and Overweight. Maryland: Hyatsville . 2017.
Wong RJ, Aguilar M, Cheung R, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology 2015; 148(3): 547-55.
[] [PMID: 25461851]
Cholankeril G, Wong RJ, Hu M, et al. Liver Transplantation for nonalcoholic steatohepatitis in the US: temporal trends and outcomes. Dig Dis Sci 2017; 62(10): 2915-22.
[] [PMID: 28744836]
Noureddin M, Vipani A, Bresee C, et al. NASH Leading cause of liver transplant in women: updated analysis of indications for liver transplant and ethnic and gender variances. Am J Gastroenterol 2018; 113(11): 1649-59.
[] [PMID: 29880964]
Younossi ZM, Blissett D, Blissett R, et al. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology 2016; 64(5): 1577-86.
[] [PMID: 27543837]
Zeb I, Li D, Budoff MJ, et al. Nonalcoholic fatty liver disease and incident cardiac events: the multi-ethnic study of atherosclerosis. J Am Coll Cardiol 2016; 67(16): 1965-6.
[] [PMID: 27102512]
Francque SM, van der Graaff D, Kwanten WJ. Non-alcoholic fatty liver disease and cardiovascular risk: Pathophysiological mechanisms and implications. J Hepatol 2016; 65(2): 425-43.
[] [PMID: 27091791]
Stine JG, Shah NL, Argo CK, Pelletier SJ, Caldwell SH, Northup PG. Increased risk of portal vein thrombosis in patients with cirrhosis due to nonalcoholic steatohepatitis. Liver Transpl 2015; 21(8): 1016-21.
[] [PMID: 25845711]
Stine JG, Niccum BA, Zimmet AN, et al. Increased risk of venous thromboembolism in hospitalized patients with cirrhosis due to non-alcoholic steatohepatitis. Clin Transl Gastroenterol 2018; 9(3): 140.
[] [PMID: 29511162]
Stine JG, Argo CK, Pelletier SJ, Maluf DG, Caldwell SH, Northup PG. Advanced non-alcoholic steatohepatitis cirrhosis: A high-risk population for pre-liver transplant portal vein thrombosis. World J Hepatol 2017; 9(3): 139-46.
[] [PMID: 28217250]
Bunn HF, Furie B. Overview of Hemostasis(Chapter 13)Pathophysiology of blood disorders. Second Edition. 2017.
Konkle B. Bleeding and Thrombosis (Chapter 61). In: Harrison’s Principles of Internal Medicine. 20th Edition.
Gale AJ. Continuing education course #2: current understanding of hemostasis. Toxicol Pathol 2011; 39(1): 273-80.
[] [PMID: 21119054]
Cesari M, Pahor M, Incalzi RA. Plasminogen activator inhibitor-1 (PAI-1): a key factor linking fibrinolysis and age-related subclinical and clinical conditions. Cardiovasc Ther 2010; 28(5): e72-91.
[] [PMID: 20626406]
Chapin JC, Hajjar KA. Fibrinolysis and the control of blood coagulation. Blood Rev 2015; 29(1): 17-24.
[] [PMID: 25294122]
Tripodi A. Thrombin generation assay and its application in the clinical laboratory. Clin Chem 2016; 62(5): 699-707.
[] [PMID: 26955824]
Chantarangkul V, Clerici M, Bressi C, Giesen PL, Tripodi A. Thrombin generation assessed as endogenous thrombin potential in patients with hyper- or hypo-coagulability. Haematologica 2003; 88(5): 547-54.
[PMID: 12745274]
Takaya H, Uemura M, Fujimura Y, et al. ADAMTS13 activity may predict the cumulative survival of patients with liver cirrhosis in comparison with the Child-Turcotte-Pugh score and the Model for End-Stage Liver Disease score. Hepatol Res 2012; 42(5): 459-72.
[] [PMID: 22292786]
Tripodi A. Liver disease and hemostatic (dys)function. Semin Thromb Hemost 2015; 41(5): 462-7.
[] [PMID: 26080306]
Hollestelle MJ, Geertzen HG, Straatsburg IH, van Gulik TM, van Mourik JA. Factor VIII expression in liver disease. Thromb Haemost 2004; 91(2): 267-75.
[] [PMID: 14961153]
Terraube V, O’Donnell JS, Jenkins PV. Factor VIII and von Willebrand factor interaction: biological, clinical and therapeutic importance. Haemophilia 2010; 16(1): 3-13.
[] [PMID: 19473409]
Tripodi A, Primignani M, Lemma L, Chantarangkul V, Mannucci PM. Evidence that low protein C contributes to the procoagulant imbalance in cirrhosis. J Hepatol 2013; 59(2): 265-70.
[] [PMID: 23583273]
Tripodi A, Primignani M, Chantarangkul V, et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology 2009; 137(6): 2105-11.
[] [PMID: 19706293]
Tripodi A, Primignani M, Lemma L, et al. Detection of the imbalance of procoagulant versus anticoagulant factors in cirrhosis by a simple laboratory method. Hepatology 2010; 52(1): 249-55.
[] [PMID: 20578143]
Blanchard RA, Furie BC, Jorgensen M, Kruger SF, Furie B. Acquired vitamin K-dependent carboxylation deficiency in liver disease. N Engl J Med 1981; 305(5): 242-8.
[] [PMID: 6165889]
Leebeek FW, Rijken DC. The Fibrinolytic Status in liver diseases. Semin Thromb Hemost 2015; 41(5): 474-80.
[] [PMID: 26049070]
Northup PG, Argo CK, Shah N, Caldwell SH. Hypercoagulation and thrombophilia in nonalcoholic fatty liver disease: mechanisms, human evidence, therapeutic implications, and preventive implications. Semin Liver Dis 2012; 32(1): 39-48.
[] [PMID: 22418887]
Targher G, Bertolini L, Rodella S, et al. NASH predicts plasma inflammatory biomarkers independently of visceral fat in men. Obesity (Silver Spring) 2008; 16(6): 1394-9.
[] [PMID: 18369343]
Verrijken A, Francque S, Mertens I, et al. Prothrombotic factors in histologically proven nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology 2014; 59(1): 121-9.
[] [PMID: 24375485]
Chang ML, Hsu CM, Tseng JH, et al. Plasminogen activator inhibitor-1 is independently associated with non-alcoholic fatty liver disease whereas leptin and adiponectin vary between genders. J Gastroenterol Hepatol 2015; 30(2): 329-36.
[] [PMID: 25091195]
Tripodi A. Tests of coagulation in liver disease. Clin Liver Dis 2009; 13(1): 55-61.
[] [PMID: 19150309]
Van Thiel DH, George M, Mindikoğlu AL, Baluch MH, Dhillon S. Coagulation and fibrinolysis in individuals with advanced liver disease. Turk J Gastroenterol 2004; 15(2): 67-72.
[PMID: 15334312]
Van Thiel DH, George M, Fareed J. Low levels of thrombin activatable fibrinolysis inhibitor (TAFI) in patients with chronic liver disease. Thromb Haemost 2001; 85(4): 667-70.
[] [PMID: 11341503]
Gresele P, Binetti BM, Branca G, et al. TAFI deficiency in liver cirrhosis: relation with plasma fibrinolysis and survival. Thromb Res 2008; 121(6): 763-8.
[] [PMID: 17915296]
Chandler WL. A kinetic model of the circulatory regulation of tissue plasminogen activator. Thromb Haemost 1991; 66(3): 321-8.
[] [PMID: 1746003]
Potze W, Siddiqui MS, Sanyal AJ. Vascular disease in patients with nonalcoholic fatty liver disease. Semin Thromb Hemost 2015; 41(5): 488-93.
[] [PMID: 26049073]
Tripodi A, Fracanzani AL, Primignani M, et al. Procoagulant imbalance in patients with non-alcoholic fatty liver disease. J Hepatol 2014; 61(1): 148-54.
[] [PMID: 24657400]
Park Y, Schoene N, Harris W. Mean platelet volume as an indicator of platelet activation: methodological issues. Platelets 2002; 13(5-6): 301-6.
[] [PMID: 12189016]
Bath PM, Butterworth RJ. Platelet size: measurement, physiology and vascular disease. Blood Coagul Fibrinolysis 1996; 7(2): 157-61.
[] [PMID: 8735807]
Ozhan H, Aydin M, Yazici M, et al. Mean platelet volume in patients with non-alcoholic fatty liver disease. Platelets 2010; 21(1): 29-32.
[] [PMID: 19947902]
Celikbilek M, Gürsoy S, Deniz K, Karaman A, Zararsiz G, Yurci A. Mean platelet volume in biopsy-proven non-alcoholic fatty liver disease. Platelets 2013; 24(3): 194-9.
[] [PMID: 22646469]
Khaspekova SG, Ziuriaev IT, Iakushkin VV, et al. [Mean platelet volume: interactions with platelet aggregation activity and glycoprotein IIb-IIIa and Ib expression levels]. Biomed Khim 2014; 60(1): 94-108.
[] [PMID: 24749250]
Haschek and Rooseaux’s Handbook of Toxicologic Pathology. 3rd ed. 2013.
Madan SA, Fida N, Barman P, et al. Frailty assessment in advanced heart failure. J Card Fail 2016; 22(10): 840-4.
[] [PMID: 26883168]
Braekkan SK, Mathiesen EB, Njølstad I, Wilsgaard T, Størmer J, Hansen JB. Mean platelet volume is a risk factor for venous thromboembolism: the Tromsø Study, Tromsø, Norway. J Thromb Haemost 2010; 8(1): 157-62.
[] [PMID: 19496920]
Sansanayudh N, Anothaisintawee T, Muntham D, McEvoy M, Attia J, Thakkinstian A. Mean platelet volume and coronary artery disease: a systematic review and meta-analysis. Int J Cardiol 2014; 175(3): 433-40.
[] [PMID: 25017904]
Lombardi AM, Fabris R, Berti de Marinis G, et al. Defective ADAMTS13 synthesis as a possible consequence of NASH in an obese patient with recurrent thrombotic thrombocytopenic purpura. Eur J Haematol 2014; 92(6): 497-501.
[] [PMID: 24460705]
Kotronen A, Joutsi-Korhonen L, Sevastianova K, et al. Increased coagulation factor VIII, IX, XI and XII activities in non-alcoholic fatty liver disease. Liver Int 2011; 31(2): 176-83.
[] [PMID: 21134109]
Potze W, Siddiqui MS, Boyett SL, et al. Preserved hemostatic status in patients with non-alcoholic fatty liver disease. J Hepatol 2016; 65(5): 980-7.
[] [PMID: 27302378]
Skurk T, Hauner H. Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1. Int J Obes Relat Metab Disord 2004; 28(11): 1357-64.
[] [PMID: 15356668]
Assy N, Bekirov I, Mejritsky Y, Solomon L, Szvalb S, Hussein O. Association between thrombotic risk factors and extent of fibrosis in patients with non-alcoholic fatty liver diseases. World J Gastroenterol 2005; 11(37): 5834-9.
[] [PMID: 16270394]
Cigolini M, Targher G, Agostino G, Tonoli M, Muggeo M, De Sandre G. Liver steatosis and its relation to plasma haemostatic factors in apparently healthy men--role of the metabolic syndrome. Thromb Haemost 1996; 76(1): 69-73.
[] [PMID: 8819254]
Stine JG, Northup PG. Coagulopathy before and after liver transplantation: from the hepatic to the systemic circulatory systems. Clin Liver Dis 2017; 21(2): 253-74.
[] [PMID: 28364812]
Meltzer ME, Lisman T, Doggen CJ, de Groot PG, Rosendaal FR. Synergistic effects of hypofibrinolysis and genetic and acquired risk factors on the risk of a first venous thrombosis. PLoS Med 2008; 5(5): e97
[] [PMID: 18462012]
Meltzer ME, Lisman T, de Groot PG, et al. Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1. Blood 2010; 116(1): 113-21.
[] [PMID: 20385790]
Prins MH, Hirsh J. A critical review of the evidence supporting a relationship between impaired fibrinolytic activity and venous thromboembolism. Arch Intern Med 1991; 151(9): 1721-31.
[] [PMID: 1888237]
Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44(4): 865-73.
[] [PMID: 17006923]
Ekstedt M, Hagström H, Nasr P, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 2015; 61(5): 1547-54.
Söderberg C, Stål P, Askling J, et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology 2010; 51(2): 595-602.
[] [PMID: 20014114]
Adams LA, Lymp JF, St Sauver J, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005; 129(1): 113-21.
[] [PMID: 16012941]
Kotronen A, Yki-Järvinen H. Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol 2008; 28(1): 27-38.
[] [PMID: 17690317]
VanWagner LB, Rinella ME. Extrahepatic manifestations of nonalcoholic fatty liver disease. Curr Hepatol Rep 2016; 15(2): 75-85.
Ong JP, Pitts A, Younossi ZM. Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. J Hepatol 2008; 49(4): 608-12.
[] [PMID: 18682312]
Targher G, Arcaro G. Non-alcoholic fatty liver disease and increased risk of cardiovascular disease. Atherosclerosis 2007; 191(2): 235-40.
[] [PMID: 16970951]
Wang X, Li J, Riaz DR, Shi G, Liu C, Dai Y. Outcomes of liver transplantation for nonalcoholic steatohepatitis: a systematic review and meta-analysis. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 2014; 12(3): 394-402. e1.
Vanwagner LB, Bhave M, Te HS, Feinglass J, Alvarez L, Rinella ME. Patients transplanted for nonalcoholic steatohepatitis are at increased risk for postoperative cardiovascular events. Hepatology 2012; 56(5): 1741-50.
[] [PMID: 22611040]
Malik SM, deVera ME, Fontes P, Shaikh O, Ahmad J. Outcome after liver transplantation for NASH cirrhosis. Am J Transplant 2009; 9(4): 782-93.
[] [PMID: 19344467]
Lee SB, Park GM, Lee JY, et al. Association between non-alcoholic fatty liver disease and subclinical coronary atherosclerosis: An observational cohort study. J Hepatol 2018; 68(5): 1018-24.
[] [PMID: 29274406]
Green DJ, Jones H, Thijssen D, Cable NT, Atkinson G. Flow-mediated dilation and cardiovascular event prediction: does nitric oxide matter? Hypertension (Dallas, Tex : 1979) 2011; 57(3): 363-9.
Yeboah J, Sutton-Tyrrell K, Mcburnie MA, Burke GL, Herrington DM, Crouse JR. Association between brachial artery reactivity and cardiovascular disease status in an elderly cohort: the cardiovascular health study. Atherosclerosis 2008; 197(2): 768-76.
Herrington DM, Fan L, Drum M, et al. Brachial flow-mediated vasodilator responses in population-based research: methods, reproducibility and effects of age, gender and baseline diameter. J Cardiovasc Risk 2001; 8(5): 319-28.
[] [PMID: 11702039]
Inaba Y, Chen JA, Bergmann SR. Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis. Int J Cardiovasc Imaging 2010; 26(6): 631-40.
[] [PMID: 20339920]
Gonzalez-Paredes FJ, Hernández Mesa G, Morales Arraez D, et al. Contribution of cyclooxygenase end products and oxidative stress to intrahepatic endothelial dysfunction in early non-alcoholic fatty liver disease. PLoS One 2016; 11(5)e0156650
[] [PMID: 27227672]
Pugh CJ, Spring VS, Kemp GJ, et al. Exercise training reverses endothelial dysfunction in nonalcoholic fatty liver disease. Am J Physiol Heart Circ Physiol 2014; 307(9): H1298-306.
[] [PMID: 25193471]
Pugh CJ, Sprung VS, Jones H, et al. Exercise-induced improvements in liver fat and endothelial function are not sustained 12 months following cessation of exercise supervision in nonalcoholic fatty liver disease. International journal of obesity 2016; 40(12): 1927-30.
Sapmaz F, Uzman M, Basyigit S, et al. Steatosis grade is the most important risk factor for development of endothelial dysfunction in NAFLD. Medicine (Baltimore) 2016; 95(14): e3280
[] [PMID: 27057890]
Thakur ML, Sharma S, Kumar A, et al. Nonalcoholic fatty liver disease is associated with subclinical atherosclerosis independent of obesity and metabolic syndrome in Asian Indians. Atherosclerosis 2012; 223(2): 507-11.
[] [PMID: 22748277]
Federico A, Dallio M, Masarone M, Persico M, Loguercio C. The epidemiology of non-alcoholic fatty liver disease and its connection with cardiovascular disease: role of endothelial dysfunction. Eur Rev Med Pharmacol Sci 2016; 20(22): 4731-41.
[PMID: 27906428]
Wanless IR, Shiota K. The pathogenesis of nonalcoholic steatohepatitis and other fatty liver diseases: a four-step model including the role of lipid release and hepatic venular obstruction in the progression to cirrhosis. Semin Liver Dis 2004; 24(1): 99-106.
[] [PMID: 15085490]
Wanless IR, Wong F, Blendis LM, Greig P, Heathcote EJ, Levy G. Hepatic and portal vein thrombosis in cirrhosis: possible role in development of parenchymal extinction and portal hypertension. Hepatology 1995; 21(5): 1238-47.
[PMID: 7737629]
Stine JG, Intagliata N, Northup PG, Caldwell SH. Nonalcoholic fatty liver disease, portal vein thrombosis and coagulation: more questions than answers? Transplantation 2017; 101(8): e281-2.
[] [PMID: 28471888]
Stine JG, Wang J, Shah PM, et al. Decreased Portal Vein Velocity is Predictive of the Development of Portal Vein Thrombosis: a Matched Case-Control Study. Liver international : official journal of the International Association for the Study of the Liver 2017.
[] [PMID: 28632958]
Di Minno MN, Tufano A, Rusolillo A, Di Minno G, Tarantino G. High prevalence of nonalcoholic fatty liver in patients with idiopathic venous thromboembolism. World J Gastroenterology : WJG 2010; 16(48): 6119-22.
[] [PMID: 21182227]
Balta G, Altay C, Gurgey A. PAI-1 gene 4G/5G genotype: A risk factor for thrombosis in vessels of internal organs. Am J Hematol 2002; 71(2): 89-93.
[] [PMID: 12353306]
Stein PD, Beemath A, Olson RE. Obesity as a risk factor in venous thromboembolism. Am J Med 2005; 118(9): 978-80.
[] [PMID: 16164883]
Yang G, De Staercke C, Hooper WC. The effects of obesity on venous thromboembolism: A review. Open J Prev Med 2012; 2(4): 499-509.
[] [PMID: 26236563]
Severinsen MT, Kristensen SR, Johnsen SP, Dethlefsen C, Tjønneland A, Overvad K. Anthropometry, body fat, and venous thromboembolism: a Danish follow-up study. Circulation 2009; 120(19): 1850-7.
[] [PMID: 19858417]
El-Sayed MS, El-Sayed Ali Z, Ahmadizad S. Exercise and training effects on blood haemostasis in health and disease: an update. Sports Med 2004; 34(3): 181-200.
[] [PMID: 14987127]
Womack CJ, Nagelkirk PR, Coughlin AM. Exercise-induced changes in coagulation and fibrinolysis in healthy populations and patients with cardiovascular disease. Sports Med 2003; 33(11): 795-807.
[] [PMID: 12959620]
van Stralen KJ, Le Cessie S, Rosendaal FR, Doggen CJ. Regular sports activities decrease the risk of venous thrombosis. J Thromb Haemost 2007; 5(11): 2186-92.
[] [PMID: 17697136]
Kupchak BR, Creighton BC, Aristizabal JC, et al. Beneficial effects of habitual resistance exercise training on coagulation and fibrinolytic responses. Thromb Res 2013; 131(6): e227-34.
[] [PMID: 23510721]
Killewich LA, Macko RF, Montgomery PS, Wiley LA, Gardner AW. Exercise training enhances endogenous fibrinolysis in peripheral arterial disease. J Vasc Surg 2004; 40(4): 741-5.
[] [PMID: 15472603]
Francis RM, Romeyn CL, Coughlin AM, Nagelkirk PR, Womack CJ, Lemmer JT. Age and aerobic training status effects on plasma and skeletal muscle tPA and PAI-1. Eur J Appl Physiol 2014; 114(6): 1229-38.
[] [PMID: 24604072]
Stratton JR, Chandler WL, Schwartz RS, et al. Effects of physical conditioning on fibrinolytic variables and fibrinogen in young and old healthy adults. Circulation 1991; 83(5): 1692-7.
[] [PMID: 1902407]
de Geus EJ, Kluft C, de Bart AC, van Doornen LJ. Effects of exercise training on plasminogen activator inhibitor activity. Med Sci Sports Exerc 1992; 24(11): 1210-9.
[] [PMID: 1435172]
el-Sayed MS. Effects of high and low intensity aerobic conditioning programs on blood fibrinolysis and lipid profile. Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 1996; 7(4): 484-90.
Sudi KM, Gallistl S, Tröbinger M, et al. The influence of weight loss on fibrinolytic and metabolic parameters in obese children and adolescents. J Pediatr Endocrinol Metab 2001; 14(1): 85-94.
[] [PMID: 11220710]
Nagelkirk PR, Scalzo R, Harber M, Kaminsky LA. The influence of acute resistance training and body composition on coagulation and fibrinolytic activity in low-risk women. Int J Sports Med 2010; 31(7): 458-62.
[] [PMID: 20432198]
Pollock ML, Franklin BA, Balady GJ, et al. AHA Science Advisory. Resistance exercise in individuals with and without cardiovascular disease: benefits, rationale, safety, and prescription: An advisory from the Committee on Exercise, Rehabilitation, and Prevention, Council on Clinical Cardiology, American Heart Association; Position paper endorsed by the American College of Sports Medicine. Circulation 2000; 101(7): 828-33.
[] [PMID: 10683360]
Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology 2018; 67(1): 328-57.
[] [PMID: 28714183]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy