Conceptos Categóricos

FACTORES DE RIESGO EN LA ENFERMEDAD HEPATICA GRASA NO ALCOHOLICA

FACTORES DE RIESGO EN LA ENFERMEDAD HEPATICA GRASA NO ALCOHOLICA

(especial para SIIC © Derechos reservados)
La enfermedad hepática grasa no alcohólica es una causa frecuente de hepatopatía crónica, con una prevalencia mundial creciente, que puede progresar a cirrosis y hepatocarcinoma.
alonsolopez9_62716.jpg Autor:
Sonia Alonso López
Columnista Experta de SIIC

Institución:
Hospital Universitario Fundación Alcorcón


Artículos publicados por Sonia Alonso López
Coautores
Conrado M Fernandez Rodriguez* María Luisa Gutiérrez García** 
Doctor en medicina, Hospital Universitario Fundacion Alcorcon, Madrid, España*
Doctora en medicina, Hospital Universitario Fundacion Alcorcon, Madrid, España**
Recepción del artículo
27 de Septiembre, 2015
Aprobación
20 de Abril, 2016
Primera edición
5 de Julio, 2016
Segunda edición, ampliada y corregida
17 de Mayo, 2018

Resumen
La enfermedad hepática grasa no alcohólica puede afectar al 15%-25% de la población, con cifras mayores en pacientes obesos y con diabetes mellitus tipo 2. El principal factor de riesgo es el síndrome metabólico, especialmente la obesidad central. Aunque la mayoría de los pacientes con esteatosis macrovacuolar simple no presentan progresión de su enfermedad, existe un subgrupo que progresa a esteatohepatitis no alcohólica, y aunque se desconocen los factores de riesgo para esta progresión, la mayoría de los estudios reconocen la edad, la presencia de diabetes mellitas tipo 2 y la obesidad como predictores de riesgo independientes de EHNA. La presencia de lesión hepatocelular significativa, como el abalonamiento hepatocitario o la hialina de Mallory y la fibrosis, incrementan significativamente el riesgo de cirrosis. Los pacientes que tienen esta lesión histopatológica presentan una mortalidad de causa hepática superior, si bien no se ha demostrado una mortalidad global aumentada. Aunque la cirrosis secundaria a esteatohepatitis no alcohólica parece tener un pronóstico ligeramente mejor que la secundaria a hepatitis C, en muchas series es la tercera causa de trasplante ortotópico de hígado. La recurrencia postrasplante de la esteatosis, de la esteatohepatitis no alcohólica y de la cirrosis es frecuente. Existe un aumento del riesgo de hepatocarcinoma en pacientes con enfermedad hepática grasa no alcohólica. En la actualidad se recomienda el seguimiento para la detección precoz de este tumor en todos los pacientes con cirrosis criptogénica.

Palabras clave
enfermedad hepática grasa no alcohólica, hepatopatía crónica, esteatohepatitis no alcohólica, esteatosis hepática, cirrosis


Artículo completo

(castellano)
Extensión:  +/-9.52 páginas impresas en papel A4
Exclusivo para suscriptores/assinantes

Abstract
Prevalence of non-alcoholic fatty liver disease (NAFLD) may be 10%-15% worldwide, and these figures are even higher in obese and in type 2 diabetes mellitus patients. The most important risk factor is metabolic syndrome, especially central obesity. Even though the majority of patients with macrovesicular steatohepatitis will not progress to advanced liver disease, a subgroup of patients will evolve to non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Independent risk factors associated with NASH are older age, type 2 diabetes mellitus and obesity. Patients with significant hepatocellular lesion, such as hepatocyte ballooning, Mallory hyalline or fibrosis, have a higher risk of cirrhosis and are more likely to have a high liver-related mortality, although higher global mortality has not been demonstrated. Although NASH related cirrhosis may have better prognosis compared to hepatitis C cirrhosis, recent series suggest that it may be the third cause of liver transplantation. Steatosis, NASH and cirrhosis recurrence post-liver transplantation is common. The risk of hepatocellular carcinoma (HCC) is increased in patients with NAFLD, and all patients with cryptogenic cirrhosis should be screened for HCC.

Key words
nonalcoholic steatohepatitis, hepatic steatosis, nonalcoholic fatty liver disease, chronic liver disease, cirrhosis


Clasificación en siicsalud
Artículos originales > Expertos de Iberoamérica >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: EpidemiologíaGastroenterología
  Relacionadas: Anatomía Patológica,  Salud Pública



Comprar este artículo
Extensión: 9.52 páginas impresas en papel A4

file05.gif (1491 bytes) Artículos seleccionados para su compra



Enviar correspondencia a:
Sonia Alonso López, HOSPITAL UNIVERSITARIO FUNDACION ALCORCON , 28922, Av. Budapest-1, Madrid, España
Bibliografía del artículo
1. Clark JM. The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol 40 (Suppl 1):S5-S10, 2006.
2. Ludwig J, Viaggiano TR, McGill DB, Ott BJ. Nonalcoholic steatohepatitis. Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 55:434-438, 1980.
3. Powell EE, Cooksley WG, Hanson R, Searle J, Halliday JW, Powell LW. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 11:74-80, 1990.
4. Brunt EM. Nonalcoholic steatohepatitis. Semin Liver Dis 24:3-20, 2004.
5. Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, Forlani G, Melchionda N. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 107:450-455, 1999.
6. National Institutes of Health. Third report of the National Cholesterol Education Program expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III). NIH publication. 1-3670, 2001.
7. Falck-Ytter Y, Younossi ZM, Marchesini G, McCullough AJ. Clinical features and natural history of nonalcoholic steatosis syndromes. Semin Liver Dis 21:17-26, 2001.
8. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 37:1202-1219, 2003.
9. McCullough AJ. Update on nonalcoholic fatty liver disease. J Clin Gastroenterology 34:255-262, 2002.
10. Hilden M, Christoffersen P, Juhl E, Dalgaard JB. Liver histology in a 'normal' population-examinations of 503 consecutive fatal traffic casualties. Scand J Gastroenterol 12:593-597, 1977.
11. Ground KE. Liver pathology in aircrew. Aviat Space Environ Med 53:14-18, 1982.
12. Clark, JE, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease: The most common cause of abnormal liver enzymes in the US population. Gastroenterology 120 (Suppl 1):A65, 2001.
13. Clark, JE, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology 122:1649-1657, 2002.
14. Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 124:71-79, 2003.
15. Bellentani S, Saccoccio G, Masutti F, Croce LS, Brandi G, Sasso F, Cristanini G, Tiribelli C. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 132:112-117, 2000.
16. Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study Hepatology 42:44-52, 2005.
17. Pendino GM, Mariano A, Surace P, Caserta CA, Fiorrillo MT, Amante A, Bruno S, Mangano C, Polito I, Cotichini R, Stroffolini T, Mele A. Prevalence and etiology of altered liver tests: a population-based survey in a Mediterranean town. Hepatology 41:1151-1159, 2005.
18. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40:1387-1395, 2004.
19. El-Hassan AY, Ibrahim EM, Al-Mulhim FA, Nabhan AA, Chammas MY. Fatty infiltration of the liver: analysis of prevalence, radiological and clinical features and influence on patient management. Br J Radiol 65:774-8, 1992.
20. Nomura H, Kashiwagi S, Hayashi J, Kajiyama W, Tani S, Goto M. Prevalence of fatty liver in a general population of Okinawa, Japan. Jpn J Med 27:142-149, 1988.
21. Araujo LM, DeOliveira DA, Nunes DS. Liver and biliary ultrasonography in diabetic and non-diabetic obese women. Diabetes Metab 24:458-462, 1998.
22. Caballería L, Pera G, Auladell MA, Torán P, Muñoz L, Miranda D, Alumà A, Casas JD et al. Prevalence and factors associated with the presence of nonalcoholic fatty liver disease in an adult population in Spain. Eur J Gastroenterol Hepatol 22:24-32, 2010.
23. Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, Vianello L et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Int Med 137:1-10, 2002.
24. Lonardo A, Bellini M, Tartoni P, Tondelli E. The bright liver syndrome: prevalence and determinants of a 'bright' liver echo pattern. Ital J Gastroenterol Hepatol 29:351-356, 1997.
25. Zois CD, Baltayiannis GH, Bekiari A, Goussia A, Karayiannis P, Doukas M, Demopoulos D, Mitsellou A, Vougiouklakis T, Mitsi V, Tsianos EV. Steatosis and steatohepatitis in postmortem material from Northwestern Greece. World J Gastroenterol 16:3944-9, 2010.
26. Hasan I, Gani RA, Machmud R et al. Prevalence and risk factors for nonalcoholic fatty liver in Indonesia. J Gastroenterol Hepatol 17 (Suppl):SI54, 2002.
27. Gupte P, Amarapurkar D, Agal S, Baijal R, Kulshrestha P, Pramanik S, Patel N et al. Non-alcoholic steatohepatitis in type 2 diabetes mellitus. Gastroenterol Hepatol 19:854-858, 2004.
28. Del Gaudio A, Boschi L, Del Gaudio GA, Mastrangelo L, Munari D. Liver damage in obese patients. Obese Surg 12:802-804, 2002.
29. Andersen T, Gluud C. Liver morphology in morbid obesity: a literature study. Int J Obes 8:97-106, 1984.
30. Lyznicki JM, Young DC, Riggs JA, Davis RM. Obesity: assessment and management in primary care. Am Fam Physician 63:2185-2196, 2001.
31. Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology 12:1106-1110, 1990.
32. Silverman JF, O´Brien KF, Long S, Leggett N, Khazanie PG, Pories WJ, Norris HT, Caro JF. Liver pathology in morbidly obese patients with and without diabetes. Am J Gastro 85:1349-1355, 1990.
33. Bacon BR, Farahvash MJ, Janney CG, Neuschwander-Tetri BA. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology 107:1103-1109, 1994.
34. Kim HJ, Kim HJ, Lee KE, Kim DJ, Kim SK, Ahn CW, Lim SK et al. Metabolic significance of nonalcoholic fatty liver disease in nonobese, nondiabetic adults. Arch Intern Med 164:2169-2175, 2004.
35. Chitturi S, Abeygunasekera S, Farrell GC, Holmes-Walker J, Hui JM, Fung C, Karim R, et al. NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology 35:373-379, 2002.
36. Omagari K, Kadokawa Y, Masuda J, Egawa I, Sawa T, Hazama H, Ohba K et al. Fatty liver in non-alcoholic non-overweight Japanese adults: incidence and clinical characteristics. J Gastroenterol Hepatol 17:1098-1105, 2002.
37. Kral JG, Schaffner F, Pierson RN Jr, Wang J. Body fat topography as an independent predictor of fatty liver. Metabolism 42:548-551, 1993.
38. Thomas EL, Hamilton G, Patel N, O'Dwyer R, Doré CJ, Goldin RD, Bell JD, Taylor-Robinson SD. Hepatic triglyceride content and its relation to body adiposity: a magnetic resonance imaging and proton magnetic resonance spectroscopy study. Gut 54:122-127, 2005.
39. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 37:917-23, 2003.
40. Bahcecioglu IH, Koruk M, Yilmaz O, Bolukbas C, Bolukbas F, Tuncer I, Atasevent H et al. Demographic and clinicopathological characteristics of nonalcoholic fatty liver disease in the East-Southeastern Anatolia regions in Turkey. Med Princ Pract 15:62-68, 2006.
41. Das K, Das K, Mukherjee PS, Ghosh A, Ghosh S, Mridha AR, Dhibar T, Bhattacharya B, Bhattacharya D, Manna B, Dhali GK, Santra A, Chowdhury A. Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease. Hepatology 51:1593-602, 2010.
42. Teli MR, James OF, Burt AD, Bennett MK, Day CP. The natural history of nonalcoholic fatty liver: a follow-up study. Hepatology 22:1714-1719, 1995.
43. Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999-2000. JAMA 288:1723-1727, 2002.
44. Fernández Rodríguez CM, Alonso López S, López Serrano P. Síndrome metabólico y progresión de la lesión hepática en la infección por el virus de la hepatitis C y el hígado graso no alcohólico. Gastro Hepatol 29(Supl 1):9-14, 2006.
45. Baldridge AD, Perez-Atayde AR, Graeme-Cook F, Higgins L, Lavine JE. Idiopathic steatohepatitis in childhood: a multicenter retrospective study. J Pediatr 127:700-704, 1995.
46. Tominaga K, Kurata JH, Chen YK, Fujimoto E, Miyagawa S, Abe I, Kusano Y. Prevalence of fatty liver in Japanese children and relationship to obesity. An epidemiological ultrasonographic survey. Dig Dis Sci 40:2002-2009, 1995.
47. Rashid M, Roberts EA. Nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr 30:48-53, 2000.
48. Franzese A, Vajro P, Argenziano A, Iannucci MP, Saviano MC, Brunetti F, Rubino A. Liver involvement in obese children. Ultrasonography and liver enzyme levels at diagnosis and during follow-up in an Italian population. Dig Dis Sci 42:1428-1432, 1997.
49. Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL. Overweight and obesity in the United States: prevalence and trends, 1960-1994. Int J Obes Relat Metab Disord 22:39-47, 1998.
50. Caldwell SH, Harris DM, Patrie JT, Hespenheide EE. Is NASH underdiagnosed among African Americans? Am J Gastroenterol 97:1496-1500, 2002.
51. Ruhl CE, Everhart JE. Epidemiology of nonalcoholic fatty liver. Clin Liver Dis 8:501-519, 2004.
52. Weston SR, Leyden W, Murphy R Bass NM, Bell BP, Manos MM, Terrault NA. Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease. Hepatology 41:372-379, 2005.
53. Targher G, Bertolini L, Padovani R, Rodella S, Tessari R, Zenari L, Day Ch, Arcaro G. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 30:1212-8, 2007.
54. Patt CH, Yoo HY, Dibadj K, Flynn J, Thuluvath PJ. Prevalence of transaminase abnormalities in asymptomatic, healthy subjects participating in an executive health-screening program. Dig Dis Sci 48:797-801, 2003.
55. Crespo J, Fernández-Gil P, Hernandez-Guerra M, Cayón A, Mayorga M, Domínguez-Diez A, Fernández-Escalante JC, Pons-Romero F. Are there predictive factors of severe liver fibrosis in morbidly obese patients with non-alcoholic steatohepatitis? Obes Surg 11:254-257, 2001.
56. Dixon JB, Bhathal PS, Jonsson RS, Dixon AF, Powell EE, O'Brien PE. Pro-fibrotic polymorphisms predictive of advanced liver fibrosis in severely obeses. J Hepatol 39:967-971, 2003.
57. Gholam PM, Kotler DP, Flancbaum LJ. Liver pathology in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery. Obes Surg 12:49-51, 2002.
58. Poniachik J, Mancilla C Contreras J, Csendes A, Smok G, Cavada G, Rojas J, Oksenberg D, Burdiles P, Maluenda F, Díaz JC. Obesidad: factores de riesgo para esteatohepatitis. Rev Med Chil 130:731-736, 2002.
59. Beymer C, Kowdley KV, Larson A, Edmonson P, Dellinger EP, Flum DR. Prevalence and predictors of asymptomatic liver disease in patients undergoing gastric bypass surgery. Arch Surg 138:1240-1244, 2003.
60. Ryan CK, Johnson LA, Germin BI, Marcos A. One hundred consecutive hepatic biopsies in the workup of living donors for right lobe liver transplantation. Liver Transpl 8:1114-1122, 2002.
61. Garcia Ureña MA, Colina Ruiz-Delgado F, Moreno GE, Jiménez Romero C, García García I, Loinzaz Segurola C, Gonzalez-Pinto, Gómez Sanz R. Hepatic steatosis in liver transplant donors: common feature of donor population? World J Surg 22:837-844, 1998.
62. Marcos A, Fisher RA, Ham JM, Olzinski AT, Shiffman ML, Sanyal AJ, Luketic VA et al. Selection and outcome of living donors for adult to adult right lobe transplantation. Transplantation 69:2410-2415, 2000.
63. Soejima Y, Shimada M, Suehiro T, Kishikawa K, Yoshizumi T, Hashimoto K, Minagawa R. Use of steatotic graft in living-donor liver transplantation. Transplantation 76:344-348, 2003.
64. Lee JY, Kim KM, Lee SG, Yu E, Lim YS, Lee HC, Chung YH, Lee YS, Suh DJ. Prevalence and risk factors of non-alcoholic fatty liver disease in potential living liver donors in Korea: a review of 589 consecutive liver biopsies in a single center. J Hepatol 47(2):239-44, 2007.
65. Mokdad AH, Ford ES, Bowman BA Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003; 289:76-79
66. Kojima S, Watanabe N, Numata M, Ogawa T, Matsuzaki S.Increase in the prevalence of fatty liver in Japan over the past 12 years: analysis of clinical background. J Gastroenterol 38:954-961, 2003..
67. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 34:274-85, 2011.
68. Solga S, Alkhuraishe AR, Clark JM, Torbenson M, Greenwald A, Diehl AM, Magnuson T.Dietary composition and nonalcoholic fatty liver disease. Dig Dis Sci 49:1578-1583, 2004.
69. Musso G, Gambino R, De Michieli F, Cassader M, Rizzetto M, Durazzo M, Fagà E et al. Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 37:909-916, 2003.
70. Willner IR, Waters B, Patil SR, Reuben A, Morelli J, Riely CA. Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease. Am J Gastroenterol 96:2813-2814, 2001.
71. Tarugi P, Lonardo A, Ballarini G, Grisendi A, Pulvirenti M, Bagni A, Calandra S. Fatty liver in heterozygous hypobetalipoproteinemia caused by a novel truncated form of apolipoprotein B. Gastroenterology 111:1125-1133, 1996.
72. Ogata H, Akagi K, Baba M, Nagamatsu A, Suzuki N, Nomiyama K, Fujishima M. et al. Fatty liver in a case with heterozygous familial hypobetalipoproteinemia. Am J Gastroenterol 92:339-342, 1997.
73. Ludtke A, Genschel J, Brabant G, Bauditz J, Taupitz M, Koch M, Wermke W, Worman HJ, Schmidt HH.Hepatic steatosis in Dunnigan-type familial partial lipodystrophy. Am J Gastroenterol 100:2218-2224, 2005.
74. Huang H, Merriman RB, Chokkalingam AP. Novel genetic markers associated with risk of non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver diseases. Gastroenterology 128(Suppl 2):A-694, 2005.
75. Hyogo H, Iwamoto K, Arihiro K. Glyceraldehyde-derived advanced glycation end products as the predictive factor for the disease progression in nonalcoholic steatohepatitis. Gastroenterology 128(Suppl 2):A-768, 2005.
76. Iwamoto K, Hyogo H, Ajima T. Role of advanced glycation end products (AGE) and their receptors (RAGE) in the pathogenesis of nonalcoholic steatohepatitis (NASH). Gastroenterology 128(suppl 2):A-695, 2005.
77. Trujillo KD, Vizcarra SN, Lopez RO. Non-alcoholic steatohepatitis related to morbid obesity: Genetic and clinical risk factors. Gastroenterology 128(Suppl 2):A-542, 2005.
78. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, Boerwinkle E, Cohen JC, Hobbs HH. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 40:1461-5, 2008.
79. Mendler MH, Turlin B, Moirand R, Jouanolle AM, Sapey T, Guyader D, Le Gall JY et al. Insulin resistance-associated hepatic iron overload. Gastroenterology 117:1155-1163, 1999.
80. Davis RJ, Corvera S Czech MP. Insulin stimulates cellular iron uptake and causes the redistribution of intracellular transferrin receptors to the plasma membrane. J Biol Chem 261:8708-8711, 1986.
81. Fargion S, Dongiovanni P, Guzzo A, Colombo S, Valenti L, Fracanzani AL. Iron and insulin resistance. Alimentary Pharmacology & Therapeutics 22:61-63, 2005.
82. Younossi ZM, Gramlich T, Bacon BR, Matteoni CA, Boparai N, O'Neill R, McCullough AJ. Hepatic iron and nonalcoholic fatty liver disease. Hepatology 30:847-850, 1999.
83. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 37:917-923, 2003.
84. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 30:1356-1362, 1999.
85. George DK, Goldwurm S, MacDonald GA, Cowley LL, Walker NI, Ward PJ, Jazwinska EC,Powell LW. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis. Gastroenterology 114:311-318, 1998.
86. Facchini FS, Hua NW, Stoohs RA. Effect of iron depletion in carbohydrate-intolerant patients with clinical evidence of nonalcoholic fatty liver disease. Gastroenterology 122:931-939, 2002.
87. Valenti L, Fracanzani AL, Fargion S. Effect of iron depletion in patients with nonalcoholic fatty liver disease without carbohydrate intolerance. Gastroenterology 124:866, 2003.
88. Riquelme A, Soza A, Nazal L, Martínez G, Kolbach M, Patillo A, Arellano JM et al. Histological resolution of steatohepatitis after iron depletion. Digest Dis Sci 49:1012-1015, 2004.
89. Jayaraman AK, Clark JM, Solga SF. Iron Stores, ALT and hepatic steatosis in overweight adults with type 2 diabetes. Gastroenterology 128(suppl 2):A-768, 2005.
90. Bloomgarden ZT. Non-alcoholic fatty liver disease and malignancy as complications of insulin resistance. Metabolic Syndrome and Related Disorders 3:316-327, 2005.
91. Kowdley KV, Belt P, Wilson LA, Yeh MM, Neuschwander-Tetri BA, Chalasani N, Sanyal AJ, Nelson JE; NASH Clinical Research Network. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 55:77-85, 2012.
92. Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology 12:1106-1110, 1990.
93. Dixon JB, Bhathal PS, O'Brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 121:91-100, 2001.
94. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology116:1413-1419, 1999.
95. Ratziu V, Giral P, Cralotte F, Bruckert E, Thibault V, Theodorou I, Khalil L et al. Liver fibrosis in overweight patients Gastroenterology 118:1117-1123, 2000.
96. Lee RG. Non-alcoholic steatohepatitis: a study of 49 patients. Human Pathology 20:504-598, 1989.
97. Choudhury J, Sanyal AJ. Clinical aspects of fatty liver diseases. Semin Liver Dis 24:349-362, 2004.
98. Adams L, Lymp J, St. Sauver J. The natural history of nonalcoholic fatty liver disease: A population based cohort study. Hepatology 40:582A, 2004.
99. Day CP. Natural history of NAFLD: remarkably benign in the absence of cirrhosis. Gastroenterology 129:375-378, 2005.
100. Hui JM, Kench JG, Chitturi S, Sud A, Farrell GC, Byth K, Hall P et al. Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C. Hepatology 38:420-427, 2003.
101. Bhala N, Angulo P, van der Poorten D, Lee E, Hui JM, Saracco G, Adams LA, Charatcharoenwitthaya P, Topping JH, Bugianesi E, Day CP, George J. The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. Hepatology 54:1208-16, 2011.
102. Keeffe EB. Liver transplantation: Status and novel approaches to liver replacement. Gastroenterology 120:749-762, 2001.
103. Charlton M, Kasparova P, Weston S, Lindor K, Maor-Kendler Y, Wiesner RH, Rosen CB et al. Frequency of nonalcoholic steatohepatitis as a cause of advanced liver disease. Liver Transpl 7:608-614, 2001.
104. Kim WR, Poterucha JJ, Porayko MK, Dickson ER, Steers JL, Wiesner RH. Recurrence of nonalcoholic steatohepatitis following liver transplantation. Tranplantation 62:1802-1805, 1996.
105. Lawson DH, Gray JM, McKillop C, Clarke J, Lee FD, Patrick RS. Diabetes mellitus and primary hepatocellular carcinoma. Q J Med 61:945-955, 1986.
106. Adami HO, Chow WH, Nyrén O, Berne C, Linet MS, Ekbom A, Wolk A et al J Excess risk of primary liver cancer in patients with diabetes mellitus. J Natl Cancer Inst 88:1472-1477, 1996.
107. Wideroff L, Gridley G, Mellemkjaer L, Chow WH, Linet M, Keehn S, Borch-Johnsen K et al Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst 89:1360-1365, 1997.
108. Fujino Y, Mizoue T, Tokui N, Yoshimura T. Prospective study of diabetes mellitus and liver cancer in Japan. Diabetes Metab Res Rev 17:374-379, 2001.
109. El-Serag HB, Hampel H, Javadi F. The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol 4:369-380, 2006.
110. Regimbeau JM, Colombat M, Mognol P, Durand F, Abdalla E, Degott C, Degos F et al. Obesity and diabetes as a risk factor for hepatocellular carcinoma. Liver Transpl 10(2 Suppl1):S69-73, 2004.
111. Calle EE, Teras LR, Thun MJ. Obesity and mortality. New Engl J Med 353:2197-2199, 2005.
112. Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ. Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol 159:1160-1167, 2004.
113. Ratziu V, Bonyhay L, Di Martino V, Charlotte F, Cavallaro L, Sayegh-Tainturier MH, Giral P et al. Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrosis. Hepatology 35:1485-1493, 2002.
114. Bugianesi E. Review article: steatosis, the metabolic syndrome and cancer. Aliment Pharmacol Ther 22(Suppl 2):40-43, 2005.
115. Nair S, Mason A, Eason J, Loss G, Perrillo RP. Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis? Hepatology 3:150-155, 2002.


 
 
 
 
 
 
 
 
 
 
 
 
Está expresamente prohibida la redistribución y la redifusión de todo o parte de los contenidos de la Sociedad Iberoamericana de Información Científica (SIIC) S.A. sin previo y expreso consentimiento de SIIC.
ua31618