Obesity, Visceral Fat, and NAFLD: Querying the Role of Adipokines in the Progression of Nonalcoholic Fatty Liver Disease

M S Mirza, M S Mirza

Abstract

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of clinicopathologic conditions ranging from steatosis alone to nonalcoholic steatohepatitis (NASH), with varying risks for progression to cirrhosis and hepatocellular carcinoma. There is mounting evidence that NAFLD not only complicates obesity, but also perpetuates its metabolic consequences. Critical event that leads to progressive liver injury in NAFLD is unknown. Obesity reflects a generalized proinflammatory state with its increased inflammatory markers like C reactive protein, IL-6, IL-8, IL-10, PAI-1, TNF-α, and hepatocyte growth factor. The elevated production of these adipokines is increasingly considered to be important in the development of diseases linked to obesity and the metabolic syndrome. Disordered cytokine production is likely to play a role in the pathogenesis of NAFLD. There is no effective treatment for NAFLD, though weight loss may halt disease progression and revert histological changes, the underlying mechanism remaining elusive. All stages of the disease pathway from prevention, early identification/diagnosis, and treatment require an understanding of the pathogenesis of liver injury in NAFLD.

References

    1. Seidell JC. Epidemiology of obesity. Seminars in Vascular Medicine. 2005;5(1):3–14.
    1. The World Health Organization. WHO Technical Report Series 894. Geneva, Switzerland: 2000. Preventing and managing the global epidemic.
    1. Kral JG, Schaffner F, Pierson RN, Wang J. Body fat topography as an independent predictor of fatty liver. Metabolism. 1993;42(5):548–551.
    1. Ramsey-Stuart G. Hepatic steatosis and morbid obesity. Obesity Surgery. 1993;3(2):157–159.
    1. van Steenbergen W, Lanckmans S. Liver disturbances in obesity and diabetes mellitus. International Journal of Obesity. 1995;19(supplement 1):S27–S36.
    1. Wolf AM, Busch B, Kuhlmann HW, Beisiegel U. Histological changes in the liver of morbidly obese patients: correlation with metabolic parameters. Obesity Surgery. 2005;15(2):228–237.
    1. Youssef WI, McCullough AJ. Steatohepatitis in obese individuals. Best Practice and Research in Clinical Gastroenterology. 2002;16(5):733–747.
    1. Festi D, Colecchia A, Sacco T, Bondi M, Roda E, Marchesini G. Hepatic steatosis in obese patients: clinical aspects and prognostic significance. Obesity Reviews. 2004;5(1):27–42.
    1. Lyon CJ, Law RE, Hsueh WA. Minireview: adiposity, inflammation, and atherogenesis. Endocrinology. 2003;144(6):2195–2200.
    1. Mora S, Pessin JE. An adipocentric view of signaling and intracellular trafficking. Diabetes/Metabolism Research and Reviews. 2002;18(5):345–356.
    1. Brunt EM. Nonalcoholic steatohepatitis. Seminars in Liver Disease. 2004;24(1):3–20.
    1. Lonardo A. Fatty liver and nonalcoholic steatohepatitis: where do we stand and where are we going? Digestive Diseases. 1999;17(2):80–89.
    1. Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003;37(4):917–923.
    1. Marceau P, Biron S, Hould FS, et al. Liver pathology and the metabolic syndrome X in severe obesity. Journal of Clinical Endocrinology and Metabolism. 1999;84(5):1513–1517.
    1. Alberti KGMM, Zimmet P, Shaw J. The metabolic syndrome—a new worldwide definition. Lancet. 2005;366(9491):1059–1062.
    1. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2005;365(9468):1415–1428.
    1. Matsuzawa Y, Funahashi T, Nakamura T. Molecular mechanism of metabolic syndrome X: contribution of adipocytokines·adipocyte-derived bioactive substances. Annals of the New York Academy of Sciences. 1999;892:146–154.
    1. Unger RH. Lipid overload and overflow: metabolic trauma and the metabolic syndrome. Trends in Endocrinology and Metabolism. 2003;14(9):398–403.
    1. Cases JA, Gabriely I, Ma XH, et al. Physiological increase in plasma leptin markedly inhibits insulin secretion in vivo. Diabetes. 2001;50(2):348–352.
    1. Seufert J. Leptin effects on pancreatic β-cell gene expression and function. Diabetes. 2004;53(1):152–158.
    1. Zimmet PZ, Alberti KGMM, Shaw J. A new IDF worldwide definition of the metabolic syndrome: the rationale and the results. Diabetes Voice. 2005;50(3):31–33.
    1. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. Journal of the American Medical Association. 2002;287(3):356–359.
    1. Arner P. Regional adiposity in man. Journal of Endocrinology. 1997;155(11):191–192.
    1. Arner P. Differences in lipolysis between human subcutaneous and omental adipose tissues. Annals of Medicine. 1995;27(4):435–438.
    1. Wajchenberg BL. Subcutaneous and visceral adipose tissue: Their relation to the metabolic syndrome. Endocrine Reviews. 2000;21(6):697–738.
    1. Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology. 2004;145(5):2273–2282.
    1. Dusserre E, Moulin P, Vidal H. Differences in mRNA expression of the proteins secreted by the adipocytes in human subcutaneous and visceral adipose tissues. Biochimica Biophysica Acta. 2000;1500(1):88–96.
    1. Lihn AS, Bruun JM, He G, Pedersen SB, Jensen PF, Richelsen B. Lower expression of adiponectin mRNA in visceral adipose tissue in lean and obese subjects. Molecular and Cellular Endocrinology. 2004;219(1-2):9–15.
    1. Schaffler A, Scholmerich J, Buchler C. Mechanisms of disease: adipocytokines and visceral adipose tissue—emerging role in nonalcoholic fatty liver disease. Nature Clinical Practice Gastroenterology and Hepatology. 2005;2(6):273–280.
    1. Montague CT, Prins JB, Sanders L, et al. Depot-related gene expression in human subcutaneous and omental adipocytes. Diabetes. 1998;47(9):1384–1391.
    1. van Harmelen V, Dicker A, Rydén M, et al. Increased lipolysis and decreased leptin production by human omental as compared with subcutaneous preadipocytes. Diabetes. 2002;51(7):2029–2036.
    1. Bruun JM, Lihn AS, Madan AK, et al. Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. implication of nonadipose cells in adipose tissue. American Journal of Physiology Endocrinology and Metabolism. 2004;286(1):E8–E13.
    1. Bruun JM, Lihn AS, Pedersen SB, Richelsen B. Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): implication of macrophages resident in the AT. Journal of Clinical Endocrinology and Metabolism. 2005;90(4):2282–2289.
    1. Sethi JK, Vidal-Puig A. Visfatin: the missing link between intra-abdominal obesity and diabetes? Trends in Molecular Medicine. 2005;11(8):344–347.
    1. Lefebvre AM, Laville M, Vega N, et al. Depot-specific differences in adipose tissue gene expression in lean and obese subjects. Diabetes. 1998;47(1):98–103.
    1. Montague CT, Prins JB, Sanders L, Digby JE, O’Rahilly S. Depot- and sex-specific differences in human leptin mRNA expression. Diabetes. 1997;46(3):342–347.
    1. Yang RZ, Lee MJ, Hu H, et al. Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. American Journal of Physiology. 2006;290(6):E1253–E1261.
    1. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single topic conference. Hepatology. 2003;37(5):1202–1219.
    1. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. American Journal of Gastroenterology. 1999;94(9):2467–2474.
    1. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Chang Liu Y, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116(6):1413–1419.
    1. Angelico F, Del Ben M, Conti R, et al. Non-alcoholic fatty liver syndrome: a hepatic consequence of common metabolic diseases. Journal of Gastroenterology and Hepatology. 2003;18(5):588–594.
    1. Pagano G, Pacini G, Musso G, et al. Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association. Hepatology. 2002;35(2):367–372.
    1. Chitturi S, Abeygunasekera S, Farrell GC, et al. NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology. 2002;35(2):373–379.
    1. Freedland ES. Role of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome: implications for controlling dietary carbohydrates: a review. Nutrition and Metabolism. 2004;1(12):1–24.
    1. Kissebah AH, Krakower GR. Regional adiposity and morbidity. Physiological Reviews. 1994;74(4):761–811.
    1. Arner P. Not all fat is alike. Lancet. 1998;351(9112):1301–1302.
    1. Kissebah AH, Vydelingum N, Murray R, Evans DJ, Hartz AJ, Kalkhoff RK. Relation of body fat distribution to metabolic complications of obesitof obesity. The Journal of Clinical Endocrinology Metabolism. 1982;54(2):254–260.
    1. Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD. Splanchnic lipolysis in human obesity. Journal of Clinical Investigation. 2004;113(11):1582–1588.
    1. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. Journal of Clinical Endocrinology and Metabolism. 2004;89(6):2548–2556.
    1. Park KS, Rhee BD, Lee HK, Koh CS, Min HK. Intraabdominal fat is associated with decreased insulin sensitivity in healthy young men. Metabolism. 1991;40(6):600–603.
    1. Bergstrom RW, Newell-Morris LL, Leonetti DL, Shuman WP, Wahl PW, Fujimoto WY. Association of elevated fasting C-peptide level and increased intra-abdominal fat distribution with development of NIDDM in Japanese-American men. Diabetes. 1990;39(1):104–111.
    1. Couillard C, Bergeron N, Prud’Homme D, et al. Postprandial triglyceride response in visceral obesity in men. Diabetes. 1998;47(6):953–960.
    1. Hauner H. Biology of obesity—secretory factors from human adipose tissue and their functional role. Proceedings of the Nutrition Society. 2005;64(2):163–169.
    1. Lundgren M, Buren J, Ruge T, Myrnas T, Eriksson JW. Glucocorticoids down-regulate glucose uptake capacity and insulin-signaling proteins in omental but not subcutaneous human adipocytes. Journal of Clinical Endocrinology and Metabolism. 2004;89(6):2989–2997.
    1. Giorgino F, Laviola L, Eriksson JW. Regional differences of insulin action in adipose tissue: insights from in vivo and in vitro studies. Acta Physiologica Scandinavica. 2005;183(1):13–30.
    1. Garaulet M, Hernandez-Morante JJ, Lujan J, Tebar FJ, Zamora S. Relationship between fat cell size and number and fatty acid composition in adipose tissue from different fat depots in overweight/obese humans. International Journal of Obesity. 2006:1–7.
    1. Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. Journal of Clinical Endocrinology and Metabolism. 1998;83(3):847–850.
    1. Van Harmelen V, Reynisdottir S, Eriksson P, et al. Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes. 1998;47(6):913–917.
    1. Van Harmelen V, Rohrig K, Hauner H. Comparison of proliferation and differentiation capacity of human adipocyte precursor cells from the omental and subcutaneous adipose tissue depot of obese subjectss. Metabolism. 2004;53(5):632–637.
    1. Wajchenberg BL, Giannella-Neto D, da Silva MER, Santos RF. Depot-specific hormonal characteristics of subcutaneous and visceral adipose tissue and their relation to the metabolic syndrome. Hormone and Metabolic Research. 2002;34(11-12):616–621.
    1. Mohamed-Ali V, Pinkney JH, Coppack SW. Adipose tissue as an endocrine and paracrine organ. International Journal of Obesity. 1998;22(12):1145–1158.
    1. Arner P. Regulation of lipolysis in fat cells. Diabetes Reviews. 1996;4(4):450–463.
    1. Martin ML, Jensen MD. Effects of body fat distribution on regional lipolysis in obesity. Journal of Clinical Investigation. 1991;88(2):609–613.
    1. Marin P, Andersson B, Ottosson M, et al. The morphology and metabolism of intraabdominal adipose tissue in men. Metabolism. 1992;41(11):1242–1248.
    1. Ostman J, Arner P, Engfeldt P, Kager L. Regional differences in the control of lipolysis in human adipose tissue. Metabolism. 1979;28(12):1198–1205.
    1. Wahrenberg H, Lonnqvist F, Arner P. Mechanisms underlying regional differences in lipolysis in human adipose tissue. Journal of Clinical Investigation. 1989;84(2):458–467.
    1. Bolinder J, Kager L, Ostman J, Arner P. Differences at the receptor and postreceptor levels between human omental and subcutaneous adipose tissue in the action of insulin on lipolysis. Diabetes. 1983;32(2):117–123.
    1. Richelsen B, Pedersen SB, Moller-Pedersen T, Bak JF. Regional differences in triglyceride breakdown in human adipose tissue: effects of catecholamines, insulin, and prostaglandin e2. Metabolism. 1991;40(9):990–996.
    1. Rebuffe-Scrive M, Bronnegard M, Nilsson A, Eldh J, Gustafsson JA, Bjorntorp P. Steroid hormone receptors in human adipose tissues. Journal of Clinical Endocrinology and Metabolism. 1990;71(5):1215–1219.
    1. Fried SK, Russell CD, Grauso NL, Brolin RE. Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men. Journal of Clinical Investigation. 1993;92(5):2191–2198.
    1. Arner P. Regional differences in protein production by human adipose tissue. Biochemical Society Transactions. 2001;29(2):72–75.
    1. Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue. British Journal of Nutrition. 2004;92(3):347–355.
    1. Yudkin JS, Stehouwer CDA, Emeis JJ, Coppack SW. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19(4):972–978.
    1. Rajala MW, Scherer PE. Minireview: the adipocyte—at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology. 2003;144(9):3765–3773.
    1. Trayhurn P, Wood IS. Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochemical Society Transactions. 2005;33(5):1078–1081.
    1. Yudkin JS. Adipose tissue, insulin action and vascular disease: inflammatory signals. International Journal of Obesity. 2003;27(3):S25–S28.
    1. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW., Jr. Obesity is associated with macrophage accumulation in adipose tissue. Journal of Clinical Investigation. 2003;112(12):1796–1808.
    1. Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. Journal of Clinical Investigation. 2003;112(12):1821–1830.
    1. Haynes P, Liangpunsakul S, Chalasani N. Nonalcoholic fatty liver disease in individuals with severe obesity. Clinics in Liver Disease. 2004;8(3):535–547.
    1. Reid AE. Nonalcoholic steatohepatitis. Gastroenterology. 2001;121(3):710–723.
    1. Gramlich T, Kleiner DE, McCullough AJ, Matteoni CA, Boparai N, Younossi ZM. Pathologic features associated with fibrosis in nonalcoholic fatty liver disease. Human Pathology. 2004;35(2):196–199.
    1. Charlton M. Nonalcoholic fatty liver disease: a review of current understanding and future impact. Clinical Gastroenterology and Hepatology. 2004;2(12):1048–1058.
    1. Abrams GA, Kunde SS, Lazenby AJ, Clements RH. Portal fibrosis and hepatic steatosis in morbidly obese subjects: a spectrum of nonalcoholic fatty liver disease. Hepatology. 2004;40(2):475–483.
    1. Zelman S. The Liver in obesity. Archives of Internal Medicine. 1952;90(4):141–156.
    1. Adler M, Schaffner F. Fatty liver hepatitis and cirrhosis in obese patients. American Journal of Medicine. 1979;67(5):811–816.
    1. Campbell JM, Hunt TK, Karam JH, Forsham PH. Jejunoileal bypass as a treatment of morbid obesity. Archives of Internal Medicine. 1977;137(5):602–610.
    1. Kern WH, Heger AH, Payne JH. Fatty metamorphosis of the liver in morbid obesity. Archives of Pathology and Laboratory Medicine. 1973;96(5):342–346.
    1. Andersen T, Gluud C. Liver morphology in morbid obesity: a literature study. International Journal of Obesity. 1984;8(2):97–106.
    1. Dixon JB, Bhathal PS, O’Brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology. 2001;121(1):91–100.
    1. Adamson L, Bell E, Kaye P, Neal K, Ryder SD, Bennett A. Portal inflammtion in non-alcoholic fatty liver disease—is it a marker of a second hit? Hepatology. 2005;42:p. 615A.
    1. Sanyal AJ. AGA technical review on nonalcoholic fatty liver disease. Gastroenterology. 2002;123(5):1705–1725.
    1. Peters RL, Gay T, Reynolds TB. Post jejunoileal bypass hepatic disease. its similarity to alcoholic hepatic disease. American Journal of Clinical Pathology. 1975;63(3):318–331.
    1. Ludwig J, Viggiano TR, McGill DB, Ott BJ. Nonalcoholic steatohepatitis. mayo clinic experiences with a hitherto unnamed disease. Mayo Clinic Proceedings. 1980;55(7):434–438.
    1. Seki K, Minami Y, Nishikawa M. “Nonalcoholic steatohepatitis” induced by massive doses of synthetic estrogen. Gastroenterologia Japonica. 1983;18(3):197–203.
    1. Novaro GM. Isoniazid and nonalcoholic steatohepatitis. Journal of Clinical Gastroenterology. 1999;28(2):p. 180.
    1. Simon JB, Manley PN, Brien JF, Armstrong PW. Amiodarone hepatotoxicity simulating alcoholic liver disease. New England Journal of Medicine. 1984;311(3):167–172.
    1. Bacon BR, Farahvash MJ, Janney CG, Neuschwander-Tetri BA. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology. 1994;107(4):1103–1109.
    1. McCullough AJ. Update on nonalcoholic fatty liver disease. Journal of Clinical Gastroenterology. 2002;34(3):255–262.
    1. Brallion A, Capron JP, Herve MA, Degot C, Quenum C. Liver in obesity. Gut. 1985;26:133–139.
    1. Garcia-Monzon C, Martin-Perez E, Iacono OL, et al. Characterization of pathogenic and prognostic factors of nonalcoholic steatohepatitis associated obesity. Journal of Hepatology. 2000;33(5):716–724.
    1. Luyckx FH, Desaive C, Thiry A, Dewe W, Scheen AJ, Gielen JE. Liver abnormalities in severly obese subjects. Effects of drastic weight loss after gastroplasty. International Journal of Obesity. 1998;22:222–226.
    1. Caldwell SH, Oelsner DH, Iezzoni JC, Hespenheide EE, Battle EH, Driscoll CJ. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology. 1999;29(3):664–669.
    1. Poonawala A, Nair SP, Thuluvath PJ. Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: a case-control study. Hepatology. 2000;32(4 I):689–692.
    1. Luyckx FH, Lefebvre PJ, Scheen AJ. Non-alcoholic steatohepatitis: association with obesity and insulin resistance, and influence of weight loss. Diabetes and Metabolism. 2000;26(2):98–106.
    1. Day CP, James OFW. Steatohepatitis: a tale of two ’hits’? Gastroenterology. 1998;114(4 I):842–845.
    1. Day CP. Non-alcoholic steatohepatitis (NASH): where are we now and where are we going? Gut. 2002;50(5):585–588.
    1. Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006;43(2):99–112.
    1. Mofrad P, Contos MJ, Haque M, et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology. 2003;37(6):1286–1292.
    1. Powell EE, Cooksley WG, Hanson R, Searle J, Halliday JW, Powell LW. The natural history of non-alcoholic steatohepatitis: a followup study of forty-two patients for up to 21 years. Hepatology. 1990;11:74–80.
    1. Sheth SG, Gordon FD, Chopra S. Nonalcoholic steatohepatitis. Annals of Internal Medicine. 1997;126(2):137–145.
    1. Sonsuz A, Basaranoglu M, Ozbay G. Relationship between aminotransferase levels and histopathological findings in patients with nonalcoholic steatohepatitis. The American Journal of Gastroenterology. 2000;95(5):1370–1371.
    1. Lee RG. Nonalcoholic steatohepatitis: a study of 49 patients. Human Pathology. 1989;20(6):594–598.
    1. Diehl AM, Goodman Z, Ishak KG. Alcohollike liver disease in nonalcoholics. A clinical and histologic comparison with alcohol-induced liver injury. Gastroenterology. 1988;95(4):1056–1062.
    1. Cotler SJ, Kanji K, Keshavarzian A, Jensen DM, Jakate S. Prevalence and significance of autoantibodies in patients with non-alcoholic steatohepatitis. Journal of Clinical Gastroenterology. 2004;38(9):801–804.
    1. Tajiri K, Takenawa H, Yamaoka K, Yamane M, Marumo F, Sato C. Nonalcoholic steatohepatitis masquerading as autoimmune hepatitis. Journal of Clinical Gastroenterology. 1997;25(3):538–540.
    1. Mortele KJ, Ros PR. Imaging of diffuse liver disease. Seminars in Liver Disease. 2001;21(2):195–212.
    1. Mottin CC, Moretto M, Padoin AV, et al. The role of ultrasound in the diagnosis of hepatic steatosis in morbidly obese patients. Obesity Surgery. 2004;14(5):635–637.
    1. Ataseven H, Yildirim MH, Yalniz M, Bahcecioglu H, Celebi S, Ozercan IH. The vaue of ultrasonography and computerized tomograph in estimating the histopatological severity of nonalcoholic steatohepatitis. Gastroenterology in Belgium. 2005;68:221–225.
    1. Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123(3):745–750.
    1. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999;30(6):1356–1362.
    1. Joy D, Thava VR, Scott BB. Diagnosis of fatty liver disease: is biopsy necessary? European Journal of Gastroenterology and Hepatology. 2003;15(5):539–543.
    1. Siegelman ES, Rosen MA. Imaging of hepatic steatosis. Seminars in Liver Disease. 2001;21(1):71–80.
    1. Brunt EM. Nonalcoholic steatohepatitis: definition and pathology. Seminars in Liver Disease. 2001;21(1):3–16.
    1. Neuschwander-Tetri BA. Nonalcoholic steatohepatitis: an evolving diagnosis. Canadian Journal of Gastroenterology. 2000;14(4):321–326.
    1. Shimada M, Hashimoto E, Taniai M, Hasegawa K, Okuda H, Nakanuma Y. Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis. Pathology International. 2001;51:127–131.
    1. Moretto M, Kupski C, Mottin CC, et al. Hepatic steatosis in patients undergoing bariatric surgery and its relationship to body mass index and co-morbidities. Obesity Surgery. 2003;13(4):622–624.
    1. Shalhub S, Parsee A, Gallagher SF, et al. The importance of routine liver biopsy in diagnosing nonalcoholic steatohepatitis in bariatric patients. Obesity Surgery. 2004;14(1):54–59.
    1. Campbell MS, Reddy KR. Review article: the evolving role of liver biopsy. Alimentary Pharmacology and Therapeutics. 2004;20(3):249–259.
    1. Hubscher SG. Role of liver biopsy in the assessment of non-alcoholic fatty liver disease. European Journal of Gastroenterology and Hepatology. 2004;16(11):1107–1115.
    1. Bravo AA, Sheth SG, Chopra S. Liver biopsy. New England Journal of Medicine. 2001;344(7):495–500.
    1. Merriman RB, Ferrel LD, Patti MG, Ostroff JW, Bagetelos K, Aouizerat BE. Histologic correlation of paired right lobe and left lobe liver biopsies in morbidly obese individuals with suspected nonalcoholic fatty liver disease. Hepatology. 2003;38(supplement 1):p. 230A.
    1. Grant A, Neuberger J. Guidelines on the use of liver biopsy in clinical practice. Gut. 1999;45(supplement 4):1–11.
    1. Guido M, Rugge M. Liver biopsy sampling in chronic viral hepatitis. Seminars in Liver Disease. 2004;24(1):89–97.
    1. Geller S, Pitman M. Morphological diagnostic procedures (liver biopsy) In: Burt AD, Portmann BC, McSween RNM, editors. Pathology of the Liver. London, UK: Churchill Livingston; 2002:. pp. 943–960.
    1. Seki S, Sakaguchi H, Kadoya H, et al. Laparoscopic wedge biopsy of the liver with use of an ultrasonically activated scalpel. Digestive Endoscopy. 2001;13(1):17–20.
    1. Gilmore IT, Burroughs A, Murray-Lyon IM, Williams R, Jenkins D, Hopkins A. Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London. Gut. 1995;36(3):437–441.
    1. Piccinino F, Sagnelli E, Pasquale G. Complications following percutaneous liver biopsy. Journal of Hepatology. 1986;2(2):165–173.
    1. Colloredo G, Guido M, Sonzogni A, Leandro G. Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease. Journal of Hepatology. 2003;39(2):239–244.
    1. Maharaj B, Maharaj RJ, Leary WP. Sampling variability and its influence on the diagnostic yield of percutaneous needle biopsy of the liver. Lancet. 1986;1(8480):523–525.
    1. Harrison SA, Torgerson S, Hayashi PH. The natural history of nonalcoholic fatty liver disease: a clinical histopathological study. American Journal of Gastroenterology. 2003;98(9):2042–2047.
    1. Fassio E, Alvarez E, Domínguez N, Landeira G, Longo C. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology. 2004;40(4):820–826.
    1. Ratziu V, Giral P, Charlotte F, Bruckert E, Thibault V, Theodorou I. Liver fibrosis in over weight patients. Gastroenterology. 2000;118:1117–1123.
    1. Propst A, Propst T, Zangerl G, Ofner D, Judmaier G, Vogel W. Prognosis and life expectancy in chronic liver disease. Digestive Diseases and Sciences. 1995;40(8):1805–1815.
    1. Bugianesi E, Leone N, Vanni E, et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology. 2002;123(1):134–140.
    1. Clark JM, Diehl AM. Nonalcoholic fatty liver disease. An underrecognized cause of cryptogenic cirrhosis. Journal of the American Medical Association. 2003;289(22):300–304.
    1. McCullough AJ. The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clinics in Liver Disease. 2004;8(3):521–533.
    1. Dixon JB, Bhathal PS, Hughes NR, O’Brien PE. Nonalcoholic fatty liver disease: improvement in liver histological analysis with weight loss. Hepatology. 2004;39(6):1647–1654.
    1. Eriksson S, Eriksson KF, Bondesson L. Nonalcoholic steatohepatitis in obesity: a reversible condition. Acta Medica Scandinavica. 1986;220(1):83–88.
    1. Andersen T, Gluud C, Franzmann MB, Christoffersen P. Hepatic effects of dietary weight loss in morbidly obese subjects. Journal of Hepatology. 1991;12(2):224–229.
    1. Luyckx FH, Scheen AJ, Desaive C, Dewe W, Gielen JE, Lefebvre PJ. Effects of gastroplasty on body weight and related biological abnormalities in morbid obesity. Diabetes and Metabolism. 1998;24(4):355–361.
    1. Drenick EJ, Simmons F, Murphy JF. Effect on hepatic morphology of treatment of obesity by fasting, reducing diets and small-bowel bypass. New England Journal of Medicine. 1970;282(15):829–834.
    1. Tilg H, Diehl AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. New England Journal of Medicine. 2000;343(20):1467–1476.
    1. Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J. Beyond insulin resistance in NASH: TNF-α or adiponectin? Hepatology. 2004;40(1):46–54.
    1. Choi S, Diehl AM. Role of inflammation in nonalcoholic steatohepatitis. Current Opinion in Gastroenterology. 2005;21(6):702–707.
    1. Atzmon G, Yang XM, Muzumdar R, Ma XH, Gabriely I, Barzilai N. Differential gene expression between visceral and subcutaneous fat depots. Hormone and Metabolic Research. 2002;34(11-12):622–628.
    1. Lyon CJ, Law RE, Hsueh WA. Minireview: adiposity, inflammation, and atherogenesis. Endocrinology. 2003;144(6):2195–2200.
    1. Ziccardi P, Nappo F, Giugliano G, et al. Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation. 2002;105(7):804–809.
    1. Lehrke M, Reilly MP, Millington SC, Iqbal N, Rader DJ, Lazar MA. An inflammatory cascade leading to hyperresistinemia in humans. PLoS Medicine. 2004;1:161–168.
    1. Chitturi S, Farrell G, Frost L, et al. Serum leptin in NASH correlates with hepatic steatosis but not fibrosis: a manifestation of lipotoxicity? Hepatology. 2002;36(2):403–409.
    1. Chalasani N, Crabb DW, Cummings OW, et al. Does leptin play a role in the pathogenesis of human nonalcoholic steatohepatitis? American Journal of Gastroenterology. 2003;98(12):2771–2776.
    1. Angulo P, Alba LM, Petrovic LM, Adams LA, Lindor KD, Jensen MD. Leptin, insulin resistance, and liver fibrosis in human nonalcoholic fatty liver disease. Journal of Hepatology. 2004;41(6):943–949.
    1. Musso G, Gambino R, Durazzo M, et al. Adipokines in NASH: postprandial lipid metabolism as a link between adiponectin and liver disease. Hepatology. 2005;42(5):1175–1183.
    1. Czaja MJ. Liver injury in the setting of steatosis: crosstalk between adipokine and cytokine. Hepatology. 2004;40(1):19–22.
    1. Janke J, Angeli S, Gorzelniak K, Luft FC, Sharma AM. Resistin gene expression in human adipocytes is not related to insulin resistance. Obesity Research. 2002;10(1):1–5.
    1. Pagano C, Soardo G, Pilon C, et al. Increased serum resistin in nonalcoholic fatty liver disease is related to liver disease severity and not to insulin resistance. Journal of Clinical Endocrinology and Metabolism. 2006;91(3):1081–1086.
    1. Tiniakos DG, Vos MB, Brunt EM. Nonalcoholic fatty liver disease. Annual Review of Pathology. 2010;5:145–171.
    1. Van Der Poorten D, Milner KL, Hui J, et al. Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatology. 2008;48(2):449–457.
    1. Guerrero R, Vega GL, Grundy SM, Browning JD. Ethnic differences in hepatic steatosis: an insulin resistance paradox? Hepatology. 2009;49(3):791–801.
    1. Weston SR, Leyden W, Murphy R, Bass NM, Bell BP. Racial and ethnic distribution ofnonalcoholic fatty liver in persons with newly diagnosed chronic liver disease. Hepatology. 2005;41:372–379.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner