2009, Número 1
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Med Int Mex 2009; 25 (1)
Hígado graso no alcohólico: un encuadre didáctico para un problema latente (primera parte)
Córdova PVH, Alemán OG, Cantú GA
Idioma: Español
Referencias bibliográficas: 120
Paginas: 38-57
Archivo PDF: 423.09 Kb.
RESUMEN
El hígado graso no alcohólico es un padecimiento poco reconocido, pero con elevada frecuencia por su asociación con el síndrome metabólico (predominantemente obesidad y diabetes mellitus). En México, cada día encontramos más pacientes con cirrosis hepática y que en su momento cursaron con la enfermedad sin establecerse el diagnóstico adecuado, situación capaz de transformar su historia natural. Este trabajo define la enfermedad de hígado graso no alcohólico, sus causas y mecanismos fisiopatológicos que la generan, con la finalidad de establecer rutas diagnósticas, ofrecer diferentes abordajes terapéuticos y conocer las complicaciones en la población adulta. Se realizó un exhaustivo análisis de bibliografías seleccionadas por médicos con conocimientos en metodología de la investigación, para ofrecer un documento que contemple las aportaciones más relevantes del tema en los años recientes. Se analizaron más de novecientas citas bibliográficas y espacios electrónicos, para finalmente incluir el material contenido sólo en quinientas siete referencias. Se citan, también, trabajos realizados por investigadores mexicanos y se anexan diversas sugerencias de los autores en cuanto al tratamiento dietético y farmacológico, en una experiencia con 97 pacientes tratados durante cuatro años.
REFERENCIAS (EN ESTE ARTÍCULO)
Salama RH, Nassar AY, Nafady AA, Mohamed HH. A novel therapeutic drug (copper nicotinic acid complex) for non-alcoholic fatty liver. Liver Int 2007;27(4):454-64.
Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003;37(5):1202-19.
Dixon JB, Bhathal PS, O’Brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 2001;122 (3):91-100.
Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis. Med Clin North Am 1996;80(5):1147-66.
Harrison SA, Neuschwander-Tetri BA. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Clin Liver Dis 2004;8(4):861-79.
McCullough AJ. The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin Liver Dis 2004;8(3):521-33.
Falck-Ytter Y, Younossi ZM, Marchesini G, McCullough AJ. Clinical features and natural history of nonalcoholic steatosis syndromes. Semin Liver Dis 2001;21(1):17-26.
Nair S, Cope K, Risby TH, Diehl AM. Obesity and female gender increase breath ethanol concentration and potential implications for the pathogenesis of nonalcoholic steato hepatitis. Am J Gastroenterol 2001;96(4):1200-4.
Méndez-Sánchez N, Chávez-Tapia NC, Uribe M. Hígado graso no alcohólico. Nuevos conceptos. Rev Invest Clín 2004;56(1):72-82.
Brunt EM. Alcoholic and nonalcoholic steatohepatitis. Clin Liver Dis 2002;6(2):399-420.
Westwater JO, Fainer D. Liver impairment in the obese. Gastroenterology 1958;34(4):686-93.
Peters RL, Gay T, Reynolds TB. Post-jejunoileal bypass hepatic disease. Its similarity to alcoholic hepatic disease. Am J Clin Pathol 1975;63(3):318-31.
Adler M, Schaffner F. Fatty liver hepatitis and cirrhosis in obese patients. Am J Med 1979;67(5):811-6.
Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980;55(7):434-8.
Ong JP, Younossi ZM. Approach to the diagnosis and treatment of nonalcoholic fatty liver disease. Clin Liver Dis 2005;9(4):617- 34.
McAvoy NC, Ferguson JW, Campbell IW, Hayes PC. Nonalcoholic fatty liver disease: natural history, pathogenesis and treatment. Br J Diabetes Vasc Dis 2006;6:251-60.
Ong JP, Younossi ZM. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis 2007;11(1);1-16.
Ruhl CE, Everhart JE. Epidemiology of nonalcoholic fatty liver Clin Liver Dis 2004;8(3):501-19.
Nugent C, Younossi ZM. Evaluation and management of obesity-related nonalcoholic fatty liver disease. Nat Clin Pract Gastroenterol Hepatol 2007;4(8):432-41.
Bayard M, Holt J, Boroughs E. Nonalcoholic fatty liver disease. Am Fam Physician 2006;73(11):1961-8.
Angelico F, Del Ben M, Conti R, Francioso S, et al. Insulin resistance, the metabolic syndrome and nonalcoholic fatty liver disease. J Clin Endocrinol Metabol 2005;90(3):1578-82.
Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults 2001. Executive summary of the Third Report of the National Cholesterol Education Program (VCEP). Expert Panel on Detection, Evaluation and Treatment of High Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285(2):484-97.
Diehl AM, Goodman Z, Ishak KG. Alcohol-like liver disease in nonalcoholics. A clinical and histologic comparison with alcohol- induced liver injury. Gastroenterology 1988;95(4):1056- 62.
Lee RG. Nonalcoholic steatohepatitis: a study of 49 patients. Hum Pathol 1989;20(6):594-8.
Powell EE, Cooksley WGE, Hanson R, Searle J, et al. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 1990;11(1):74-80.
Bacon BR, Farahvash MJ, Janney CG, Neuschwander-Tetri BA. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology 1994;107(4):1103-9.
Laurin J, Lindor KD, Crippin JS, Gossard A, et al. Ursodeoxycholic acid or clobifrate in the treatment of nonalcohol-induced steatohepatitis: a pilot study. Hepatology 1996;23(6):1464-7.
Matteoni CA, Younossi ZM, Gramlich T, Boparai N, et al. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999;116(6):1413-9.
Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with non-alcoholic steatohepatitis. Hepatology 1999;30(6):1356-62.
Cortez-Pinto H, Camilu ME, Baptista A, DeOliveira AG, De- Moura MC. Nonalcoholic fatty liver: another feature of the metabolic syndrome? Clin Nutr 1999;18(6):353-8.
Wilner IR, Waters B, Patil SR, Reuben A, et al. Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease. Am J Gastroenterol 2001;96(10):2957-61.
Chitturi S, Abeygunasekera S, Farrell GC, Holmes-Walker J, et al. NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology 2002;35(2):373-9.
Marchesini G, Bugianesi E, Forlani G, Cerrelli F, et al. Nonalcoholic fatty liver, steatohepatitis and the metabolic syndrome. Hepatology 2003;37(4):917-23.
Harrison SA, Oliver DA, Torgerson S, Hayashi P, Neuschwander- Tetri B. NASH: clinical assessment of 501 patients from two separate academic medical centers with validation of a clinical scoring system for advanced hepatic fibrosis. Hepatology 2003;34:511.
Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 2003;124(7):71- 79.
Fishbein M, Cox S. Non-alcoholic fatty liver disease in a toddler. Clin Pediatr (Phila) (2004);43(5):483-5.
Chitturi S, Weltman M, Farrell GC, McDonald D, et al. HFE mutations, hepatic iron, and fibrosis: ethnic-specific association of NASH with C282Y but not with fibrotic severity. Hepatology 2002;36(1):142-9.
Choudhury J, Sanyal JA. Clinical aspects of fatty liver disease. Semin Liver Dis 2004;24(4):349-62.
Balistreri WF. Nonalcoholic fatty liver disease: insights and controversies. [en línea]. Medscape Today (2006). Dirección URL:< http://www.medscape.com/viewarticle/536326>.
Caldwell SH, Hespenheide EE. Obesity and cryptogenic cirrhosis. In: Leuschner U, James O, Dancygier H, editors. Falk symposium: steatohepatitis (ASH and NASH). Volume 121. 1st ed. Norwell: Kluwer Academic Publishers, 2001;pp:151.
Reaven GM. Banting lecture 1988. Role of insulin resistance in human diabetes. Diabetes 1988;37(12):1595-607.
Marchesini G, Brizi M, Bianchi G, Tomassetti S, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001;50(8):1844-50
Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med 1998;15(7):539-53.
Marchesini G, Marzocchi R. Metabolic syndrome and NASH. Clin Liver Dis 2007;11(1);105-17.
Marceau P, Biron S, Hould FS, Marceau S, et al. Liver pathology and the metabolic syndrome X in severe obesity. J Clin Endocrinol Metab 1999;84(5):1513-7.
Kadayifci A, Merriman RB, Bass NM. Medical treatment of nonalcoholic steatohepatitis. Clin Liver Dis 2007;11(1);119-40.
Cecil RL, Benett JC, Goldman L. Cecil textbook of medicine. 22st ed. Philadelphia: Saunders WB, 2004.
Feldman M, Friedman LS, Sleiisinger MH. Sleisinger and Fordtran: enfermedades gastrointestinales y hepáticas. 7a ed. Buenos Aires: Editorial Médica Panamericana, 2004.
Sundaram V, Northup G, Nadkarmi M. Metabolic syndrome is a major risk factor for NAFLD among patients with non-insulin dependent diabetes mellitus. Gastroenterology 2006;130:824.
Haynes P, Liangpunsakul S, Chalasani N. Nonalcoholic fatty liver disease in individuals with severe obesity. Clin Liver Dis 2004;8(3):535-47.
Choudhury J, Sanyal AJ. Insulin resistance and the pathogenesis of nonalcoholic fatty liver disease. Clin Liver Dis 2004;8(3):575-94.
World Health Organization. Core indicator. [en línea]. dirección URL: .
Villa AR, Escobedo MH, Méndez- Sánchez N. Estimación y proyección de la prevalencia de obesidad en México a través de la mortalidad por enfermedades asociadas. Gac Med Mex 2004;140(Supl. 2):S21-25.
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):475-83.
Ong JP, Elariny H, Collantes R, Younoszai A, et al. Predictors of nonalcoholic steatohepatitis and advanced fibrosis in morbidly obese patients. Obes Surg 2005;15(3):310-5.
Boza C, Riquelme A, Ibañez L, Duarte I, et al. Predictors of nonalcoholic steatohepatitis (NASH) in obese patients undergoing gastric bypass. Obes Surg 2005;15(8):1148-53.
Xanthakos S, Miles L, Bucuvalas J, Daniels S, et al. Histologic spectrum of nonalcoholic fatty liver disease in morbidly obese adolescents. Clin Gastroenterol Hepatol 2006;4(2):226-32.
Furuya CK, de Oliveira CP, de Mello ES, Faintuch J, et al. Effects of bariatric surgery on nonalcoholic fatty liver disease: preliminary findings after 2 years. J Gastroenterol Hepatol 2007;22(4):510-4.
Kroh M, Liu R, Chand B. Laparoscopic bariatric surgery: what else are we uncovering? Liver pathology and preoperative indicators of advanced liver disease in morbidly obese patients. Surg Endosc 2007;21(11):1957-60.
Rocha R, Cotrim HP, Carvalho FM, Siqueira AC, et al. Body mass index and waist circumference in non-alcoholic fatty liver disease. J Hum Nutr Diet 2005;18(5):365-70.
Sharma AM, Staels B. Peroxisome proliferator-activated receptor and adipose tissue-understanding obesity-related changes in regulation of lipid and glucose metabolism. J Clin Endocrinol Metab 2007;92(2):386-95.
Luyckx FH, Scheen AJ, Desaive C, Dewé W, et al. Effects of gastroplasty on body weight and related biological abnormalities in morbid obesity. Diabetes Metab 1998;24(4):355-61.
King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care 1998;21(9):1414-31.
Gaceta de Comunicación Interna de la Secretaría de Salud. [en línea]. Dirección URL: .
Harada-Shiba M, Takagi A, Miyamoto Y, Tsushima M, et al. Clinical features and genetic analysis of autosomal recessive hypercholesterolemia. J Clin Endocrinol Metab 2003;88(6):2541- 7.
Struben VM, Hespenheide EE, Caldwell S. Nonalcoholic steatohepatitis and cryptogenic cirrhosis within kindreds. Am J Med 2000;108(1):9-13.
Sreekumar R, Rosado B, Rasmussen D, Charlton M. Hepatic gene expression in histologically progressive nonalcoholic steatohepatitis. Hepatology 2003;38(1):244-51.
Younossi ZM, Gorreta F, Ong JP, Schlauch K, et al. Hepatic gene expression in patients with obesity-related non-alcoholic steatohepatitis. Liver Int 2005;25(4):760-71.
Chiappini F, Barrier A, Saffroy R, Domart MC, et al. Exploration of global gene expression in human liver steatosis by highdensity oligonucleotide microarray. Lab Invest 2006;86(2):154- 65.
Gallagher EP, Gardner JL, Barber DS. Several glutathione S-transferase isozymes that protect against oxidative injury are expressed in human liver mitochondria. Biochem Pharmacol 2006;71(11):1619-28.
Younossi ZM, Baranova A, Ziegler K, Del Giacco L, et al. A genomic and proteomic study of the spectrum of nonalcoholic fatty liver disease. Hepatology 2005;42(3):665-74.
T aniai M, Hashimoto E, Tobari M. Hepatic gene expression in patients with NASH in relation to hepatic fibrosis. Gastroenterology 2006;130(4 Suppl. 2):767.
Day CP. The potential role of genes in nonalcoholic fatty liver disease. Clin Liver Dis 2004;8(3):673-91.
Edmison J, McCollough AJ. Pathogenesis of non-alcoholic steatohepatitis: human data. Clin Liver Dis 2007;11(1):75-104.
Partin JS, Partin JC, Schubert WK, McAdams AJ. Liver ultrastructure in abetalipoproteinemia: evolution of micronodular cirrhosis. Gastroenterology 1974;67(1):107-18.
Bernard S, Touzet S, Personne I, Lapras V, et al. Association between microsomal triglyceride transfer protein gene polymorphism and the biological features of liver steatosis in patients with type II diabetes. Diabetologia 2000;43(8):995-9.
Tarugi P, Lonardo A, Ballarini G, Grisendi A, et al. Fatty liver in heterozygous hypobetalipoproteinemia caused by a novel truncated form of apolipoprotein B. Gastroenterology 1996;111(4):1125-33.
Ogata H, Akagi K, Baba M, Nagamatsu A, et al. Fatto liver in a case with heterozygous familial hypobetalipoproteinemia. Am J Gastroenterol 1997;92(2):339-42.
Diehl AM. Hepatic complications of obesity. Gastroenterol Clin North Am 2005;34(1):45-61.
Ebihara K, Kusakabe T, Masuzaki H, Kobayashi N, et al. Gene and phenotype analysis of congenital generalized lipodystrophy in japanese: a novel homozygous nonsense mutation in seipin gene. J Clin Endocrinol Metab 2004;89(5):2360-4.
Kronenberg HK, Melmed S, Polonsky KS, Larsen PR. Williams textbook of endocrinology. 11th ed. Oxford: Elsevier, 2007.
Stephen A. Geller, Lydia M. Petrovic. Biopsy interpretation of the liver. 1st ed. Philadelphia: Lippincott, Williams and Wilkins, 2004.
Kliegman RM, Behrman RE, Jenson HB, Stanton BF, Nelson textbook of pediatrics. 18th ed. Philadelphia: Saunders WB, 2007;pp:590.
Stravitz RT, Sanyal A. Drug induced steatohepatitis. Clin Liver Dis 2003;7(2):435-51.
Diccionario de especialidades farmacéuticas. [en línea]. Dirección URL: .
Koniaris LG. McKillop IH, Schwartz SI, Zimmers TA. Liver regeneration. J Am Coll Surg 2003;197(4):634-59.
Poucell S, Ireton J, Valencia-Mayoral P, Downar E, et al. Amiodarone-associated phospholipidosis and fibrosis of the liver. Light, immunohistochemical, and electron microscopic studies. Gastroenterology 1984;86(5 Pt. 1):926-36.
Itoh S, Igarashi M, Tsukada Y, Ichinoe A. Nonalcoholic fatty liver with alcoholic hyalin after long term glucocorticoid therapy. Acta Hepatogastroenterol 1977;24(6):415-8.
Seki K, Minami Y, Nishikawa M, Kawata S, et al. "Nonalcoholic steatohepatitis" induced by massive doses of synthetic estrogen. Gastroenterol Jpn 1983;18(3):197-203.
Pessayre D, Bichara M, Degott C, Potet F, et al. Perhexiline maleate-induced cirrhosis. Gastroenterology 1979;76(1):170-7.
Fortgang IS, relistos PC, Chaisson RE, Moore RD. Hepatomegaly and steatosis in HIV-infected patients receiving nucleoside analog antiretroviral therapy. Am J Gastroenterol 1995;90(9):1433-6.
Ogedegbe AO, Sulkowski MS. Antiretroviral-associated liver injury. Clin Liver Dis 2003;7(2):475-99.
George DK, Goldwurm S, MacDonald GA, Cowley LL, et al. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis. Gastroenterology 1998;114(2):311-8.
Younossi ZM, Gramlich T, Bacon BR, Matteoni CA, et al. Hepatic iron and nonalcoholic fatty liver disease. Hepatology 1999;30(4):847-50.
Moirand R, Mortaji AM, Loreal O, Paillard F, et al. A new syndrome of liver iron overload with normal transferrin saturation. Lancet 1997;349(9045):95-97.
Bonkovsky HL, Jawaid Q, Tortorelli K, LeClair P, et al. Nonalcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis. J Hepatol 1999;31(3):421-9.
Mendler MH, Turlin B, Moirand R, Jouanolle AM, et al. Insulin resistance-associated hepatic iron overload. Gastroenterology 1999;117(5):1155-63.
Fargion S, Mattioli M, Fracanzani AL, Sampietro M, et al. Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis. Am J Gastroenterol 2001;96(8):2448-55.
Hamilton DL, Vest TK, Brown BS, Shah AN, et al. Liver injury with alcoholic like hyalin after gastroplasty for morbid obesity. Gastroenterology 1983;85(3):722-6.
Peters RL. Hepatic morphologic changes after jejunoileal bypass. Prog Liver Dis 1979;6:581-94.
Wigg A, Roberts-Thomson I, Dymock R, McCarthy P, et al. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor α in the pathogenesis of non-alcoholic steatohepatitis. Gut 2001;48(2):206-11.
Grimm IS, Schindler W, Haluszka O. Steatohepatitis and fatal hepatic failure after biliopancreatic diversion. Am J Gastroenterol 1992;88(2):775-9.
Craig RM, Neumann T, Jeejeebhoy KN, Yokoo H. Severe hepatocellular reaction resembling alcoholic hepatitis with cirrhosis after massive small bowel resection and prolonged total parenteral nutrition. Gastroenterology 1980;79(1):131-7.
Fleming CR. Hepatobiliary complications in adults receiving nutrition support. Dig Dis 1994;12(4):191-8.
Nazim M, Stamp G, Hodgson HJ. Non-alcoholic steatohepatitis associated with small intestinal diverticulosis and bacterial overgrowth. Hepatogastroenterology 1989;36(5):349-51.
Riordan SM, Duncombe VM, Thomas MC, Nagree A, et al. Small intestinal bacterial overgrowth, intestinal permeability, and non-alcoholic steatohepatitis. Gut 2002;50(1):136-8.
Treiber G, Weigt J, Kolfenbach S. The role of bacterial overgrowth in patients with NAFLD. Gastroenterology 2006;130(4 Suppl. 2):823-7.
Van Steenbergen W, Lanckmans S. Liver disturbances in obesity and diabetes mellitus. Int J Obes Relat Metab Disord 1995;19(Suppl. 3):27-36.
Setji TL, Holland ND, Sanders LL, Pereira KC, et al. Nonalcoholic steatohepatitis and nonalcoholic fatty liver disease in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91(5):1741-7.
Kinkhabwala SV, Futterweit W. Nonalcoholic fatty liver disease in lean, overweight, and obese women with polycystic ovary syndrome. Poster presentation at the 3rd Annual Meeting of the Androgen Excess Society, San Diego, CA, 2005, p 13 (Poster 9).
Redinger RN. The physiology of adiposity. J Ky Med Assoc 2008;106(2):53-62.
Sevastianova K, Sutinen J, Kannisto K, Hamsten A, et al. Adipose tissue inflammation and liver fat in patients with highly active antiretroviral therapy-associated lipodystrophy. Am J Physiol Endocrinol Metab 2008;295:E85-91.
Kimura H, Kako M, Yo K, Oda T. Alcoholic hyalins (mallory bodies) in a case of Weber-Christian disease: electron microscopic observations of liver involvement. Gastroenterology 1980;78(4):807-12.
Moraes AJ, Soares PM, Zapata AL, Lotito AP, et al. Panniculitis in childhood and adolescence. Pediatr Int 2006;48(1):48- 53.
Levy ML, Lifshifz O. Weber-Christian disease. [en línea]. E Medicine (2006). Dirección URL: .
Chuang CC, Cheng YF, Chang HP, Lin CZ. Madelung's disease. J Chin Med Assoc 2004;67(11):591-4.
Plotnicov NA, Babayev TA, Lamberg MA, Altonen M, Syrjanen SM. Madelung's disease (benign symmetric lipomatosis). Oral Surg Oral Med Oral Pathol 1988;66(2):171-5.
Carranza MC, Simón MA, Torres A, Romero B, Calle C. Changes in the mechanism of action of insulin on fatty tissue accumulations in lipomas, Madelung's lipomatosis and liposarcoma. An Med Interna 1992;9(12):598-602.
Cave M, Deaciuc I, Mendez C, Song Z, et al. Nonalcoholic fatty liver disease: predisposing factors and the role of nutrition. J Nutr Biochem 2007;18(3):184-95.
Narchi H. Idiopathic copper toxicosis. J Pediatr 2000;137(3):440