Abstract
Objective:
To study the relationship between elevated liver tests and high sensitive C-reactive protein (hs-CRP), as potential markers of liver inflammation and non-alcoholic steatohepatitis (NASH), with anthropometric and laboratory parameters in overweight patients, especially the relationship with visceral adipose tissue (VAT).
Methods:
Patients presenting to the obesity clinic were prospectively included. Detailed anthropometry, computed tomography (CT)-measured VAT, liver tests (aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT)) and hs-CRP were assessed, along with an extended series of biochemical parameters.
Results:
All 480 patients (gender distribution male (M)/female (F) (10/90%)) with complete data were included. Mean age was 39±13 years, mean BMI 34.5±6.0 kg m−2. In 37.3% of the patients one or more of the liver tests were elevated. VAT was positively related to AST (r=0.18, P<0.001), ALT (r=0.29, P<0.001), ALP (r=0.16, P<0.01) and GGT (r=0.39, P<0.001). Comparing subjects with high (VAT⩾113 cm2) vs low (VAT<113 cm2) VAT levels, significant differences were noted for AST (26±12 vs 24±12 U l−1, P=0.003), ALT (37±21 vs 31±21 U l−1, P<0.001), ALP (76±20 vs 71±18 U l−1, P=0.008), GGT (33±20 vs 25±15 U l−1, P<0.001) and hs-CRP (0.62±0.43 vs 0.52±0.48 mg dl−1, P<0.001). After correction for BMI the difference in AST and ALP between the high vs low VAT group disappeared. The differences for ALT and GGT remained significant (P=0.008 and P<0.001 respectively). After correction for hs-CRP the four different liver tests remained significantly higher in the high VAT group. A stepwise multiple regression analysis revealed that every single liver test has his own most important determinant; VAT and hs-CRP for AST, insulin resistance calculated with homeostasis model assessment (HOMA-IR) and hs-CRP for ALT and ALP, and triglycerides and VAT for GGT.
Conclusion:
In overweight and obese patients, liver tests, especially ALT and GGT, are associated with visceral fat mass. After correction for BMI and hs-CRP, ALT and GGT are significantly higher in patients with increased VAT, thereby supporting evidence for a potential key role of VAT in the pathogenesis of non-alcoholic fatty liver disease (NAFLD).
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References
Brunt EM . Nonalcoholic steatohepatitis: pathologic features and differential diagnosis. Semin Diagn Pathol 2005; 22: 330–338.
Angulo P . Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 1221–1231.
Angulo P . Obesity and nonalcoholic fatty liver disease. Nutr Rev 2007; 65: S57–S63.
Ruhl CE, Everhart JE . Epidemiology of nonalcoholic fatty liver. Clin Liver Dis 2004; 8: 501–519.
Eguchi Y, Eguchi T, Mizuta T, Ide Y, Yasutake T, Iwakiri R et al. Visceral fat accumulation and insulin resistance are important factors in nonalcoholic fatty liver disease. J Gastroenterol 2006; 41: 462–469.
Utzschneider KM, Kahn SE . The role of insulin resistance in nonalcholic fatty liver disease. J Clin Endocrinol Metab 2006; 91: 4753–4761.
Ford ES . Body mass index, diabetes and C-reactive protein among US adults. Diabetes Care 1999; 22: 1971–1979.
Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB . Elevated C-reactive protein levels in overweight and obese adults. JAMA 1999; 282: 2131–2135.
Van Gaal LF, Mertens IL, De Block CE . Mechanisms linking obesity with cardiovascular disease. Nature 2006; 444: 875–880.
Park HS, Park JY, Yu R . Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6. Diabetes Res Clin Pract 2005; 69: 29–35.
Saijo Y, Kiyota N, Kawasaki Y, Miyazaki Y, Kashimura J, Fukuda M et al. Relationship between C-reactive protein and visceral adipose tissue in healthy Japanese subjects. Diabetes Obes Metab 2004; 6: 249–258.
Forouhi NG, Sattar N, McKeigue PM . Relation of C-reactive protein to body fat distribution and features of the metabolic syndrome in Europeans and South Asians. Int J Obes Relat Metab Disord 2001; 25: 1327–1331.
Lemieux I, Pascot A, Prud’homme D, Almeras N, Bogaty P, Nadeau A et al. Elevated C-reactive protein: another component of the atherothrombotic profile of abdominal obesity. Arterioscler Thromb Vasc Biol 2001; 21: 961–967.
Fasshauer M, Paschke R . Regulation of adipocytkines and insulin resistance. Diabetologia 2003; 46: 1594–1603.
Anty R, Bekri S, Luciani N, Saint-Paul MC, Dahman M, Iannelli A et al. The inflammatory C-reactive protein is increased in both liver and adipose tissue in severely obese patients independently from metabolic syndrome, Type 2 diabetes, and NASH. Am J Gastroenterol 2006; 101: 1–10.
Ouchi N, Kihara S, Funahashi T, Nakamura T, Nishida M, Kumada M et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation 2003; 107: 671–674.
Calabro P, Chang DW, Willerson JT, Yeh ETH . Release of C-reactive protein in response to inflammatory cytokines by human adipocytes: linking obesity to vascular inflammation. J Am Coll Cardiol 2005; 46: 1112–1113.
Lyon CJ, Law RE, Hsueh WA . Mini-review: adiposity, inflammation, and atherogenesis. Endocrinology 2003; 144: 2195–2200.
World Health Organization (WHO). Obesity: preventing and managing the global epidemic. WHO: Geneva, 1998. WHO/NUT/NCD/98 1.
American Diabetes Association. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 2003; 26: 3160–3167.
Wong VW, Wong GL, Tsang SW, Hui AY, Chan AW, Choi PC et al. Metabolic and histological features of non-alcoholic fatty liver disease patients with different serum alanine aminotransferase levels. Aliment Pharmacol Ther 2009; 29: 387–396.
Lukaski HC, Johnson PE, Bolonchuk WW, Lykken GI . Assessment of fat-free mass using bioelectrical impedance measurements of the human body. Am J Clin Nutr 1985; 41: 810–817.
Deurenberg P, Weststrate JA, Hautvast JGAJ . Changes in fat-free mass during weight loss measured by bioelectrical impedance and by densitometry. Am J Clin Nutr 1989; 49: 33–36.
van der Kooy K, Seidell JC . Techniques for the measurement of visceral vat: a practical guide. Int J Obes Relat Metab Disord 1993; 17: 187–196.
Sobhonslidsuk A, Jongjirasiri S, Thakkinstian A, Wisedopas N, Bunnag P, Puavilai G . Visceral fat and insulin resistance as predictors of non-alcoholic steatohepatitis. World J Gastroenterol 2007; 13: 3614–3618.
Friedewald WT, Levy RI, Fredrickson DS . Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and β-cell function from fasting glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.
St-Pierre J, Lemieux I, Perron P, Brisson D, Santuré M, Vohl MC et al. Relation of the ‘hypertriglyceridemic waist’ phenotype to earlier manifestations of coronary artery disease in patients with glucose intolerance and type 2 diabetes mellitus. Am J Cardiol 2007; 99: 369–373.
Lemieux I, Pascot A, Couillard C, Lamarche B, Tchernof A, Alméras N et al. Hypertriglyceridemic waist: a marker of the atherogenic metabolic traid (hyperinsulinemia; hyperapolipoprotein B; small dense LDL) in men? Circulation 2000; 102: 179–184.
Omagari K, Kadokawa Y, Masuda J, Egawa I, Sawa T, Hazama H et al. Fatty liver in non-alcoholic non-overweight Japanese adults: incidence and clinical characteristics. J Gastroenterol Hepatol 2002; 17: 1098–1105.
Bellentani S, Saccoccio G, Masutti F, Crocè LS, Brandi G, Sasso F et al. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 2000; 132: 112–117.
Schindhelm RK, Diamant M, Dekker JM, Tushuizen ME, Teerlink T, Heine RJ . Alanine aminotransferase as a marker of non-alcoholic fatty liver disease in relation to type 2 diabetes mellitus and cardiovascular disease. Diabetes Metab Res Rev 2006; 22: 437–443.
Stranges S, Dorn JM, Muti P, Freudenheim JL, Farinaro E, Russell M et al. Body fat distribution, relative weight, and liver enzyme levels: a population-based study. Hepatology 2004; 39: 754–763.
Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 2002; 137: 1–10.
Kerner A, Avizohar O, Sella R, Bartha P, Zinder O, Markiewicz W et al. Association between elevated liver enzymes and C-reactive protein: possible hepatic contribution to systemic inflammation in the metabolic syndrome. Arterioscler Thromb Vasc Biol 2005; 25: 193–197.
Targher G, Bertolini L, Scala L, Zoppini G, Zenari L, Falezza G . Non-alcoholic hepatic steatosis and its relation to increased plasma biomarkers of inflammation and endothelial dysfunction in non-diabetic men. Role of visceral adipose tissue. Diabet Med 2005; 22: 1354–1358.
Day CP, James OF . Steatohepatitis: a tale of two ‘hits’? Gastroenterology 1998; 114: 842–845.
Park SH, Kim BI, Yun JW, Kim JW, Park DI, Cho YK et al. Insulin resistance and C-reactive protein as independent risk factors for non-alcoholic fatty liver disease in non-obese Asian men. J Gastroenterol Hepatol 2004; 19: 694–698.
van der Poorten D, Milner KL, Hui J, Hodge A, Trenell MI, Kench JG et al. Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatology 2008; 48: 449–457.
Acknowledgements
This work is part of the project ‘Hepatic and adipose tissue and functions in the metabolic syndrome’ (HEPADIP), which is supported by the European Commission as an Integrated Project under the 6th Framework Programme (Contract LSHM-CT-2005–018734).
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Verrijken, A., Francque, S., Mertens, I. et al. Visceral adipose tissue and inflammation correlate with elevated liver tests in a cohort of overweight and obese patients. Int J Obes 34, 899–907 (2010). https://doi.org/10.1038/ijo.2010.4
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DOI: https://doi.org/10.1038/ijo.2010.4
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