Enfermedad hepática grasa no alcohólica en personas no obesas: revisión narrativa de la literatura
DOI:
https://doi.org/10.52784/27112330.129Palabras clave:
enfermedad del hígado graso no alcohólico, esteatosis, síndrome metabólico, diabetes mellitus, polimorfismo.Resumen
La enfermedad hepática grasa no alcohólica (EHGNA) es una condición altamente prevalente y usualmente relacionada con el sobrepeso y la obesidad, pero afecta al 10% de la población no obesa en el mundo, con tendencia al aumento. Mecanismos diferentes a los tradicionalmente relacionados con el exceso de grasa corporal, como algunos polimorfismos genéticos y la exposición a ciertos factores ambientales, se han asociado con el desarrollo de esta entidad. Comparados con individuos sanos, las personas con EHGNA tienen con mayor frecuencia desarreglos metabólicos, como resistencia a la insulina y síndrome metabólico. El curso de la enfermedad hepática pareciera ser más benigno en los individuos no obesos en comparación con las personas obesas, pero el riesgo de desarrollar enfermedades como la diabetes mellitus pareciera ser mayor. En Latinoamérica se ha reportado una de las prevalencias más altas de EHGNA, sin embargo, el fenómeno en personas no obesas se ha estudiado principalmente en Asia y los datos en poblaciones latinas son prácticamente inexistentes. El propósito con esta revisión narrativa es sintetizar la información disponible acerca de la EHGNA en personas no obesas, haciendo énfasis en la población latina.
Descargas
Referencias bibliográficas
Lu FB, Zheng KI, Rios RS, Targher G, Byrne CD, Zheng MH. Global epidemiology of lean non-alcoholic fatty liver disease: A systematic review and meta-analysis. J Gastroenterol Hepatol 2020;35:2041-2050. https://doi.org/10.1111/jgh.15156.
Younes R, Bugianesi E. NASH in lean individuals. Semin Liver Dis 2019;39:86-95. https://doi.org/10.1055/s-0038-1677517.
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. https://doi.org/10.7326/0003-4819-132-2-200001180-00004.
Younossi ZM, Stepanova M, Negro F, Hallaji S, Younossi Y, Lam B, et al. Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine (Baltimore) 2012;91:319-327. https://doi.org/10.1097/MD.0b013e3182779d49.
Das K, Das K, Mukherjee PS, Ghosh A, Ghosh S, Mridha AR, et al. Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease. Hepatology 2010;51:1593-1602. https://doi.org/10.1002/hep.23567.
Nishioji K, Mochizuki N, Kobayashi M, Kamaguchi M, Sumida Y, Nishimura T, et al. The impact of PNPLA3 rs738409 genetic polymorphism and weight gain ≥10 kg after age 20 on non-alcoholic fatty liver disease in non-obese Japanese individuals. PLoS One 2015;10:e0140427. https://doi.org/10.1371/journal.pone.0140427.
Sinn DH, Gwak GY, Park HN, Kim JE, Min YW, Kim KM, et al. Ultrasonographically detected non-alcoholic fatty liver disease is an independent predictor for identifying patients with insulin resistance in non-obese, non-diabetic middle-aged Asian adults. Am J Gastroenterol 2012;107:561-567. https://doi.org/10.1038/ajg.2011.400.
Wei JL, Leung JC, Loong TC, Wong GL, Yeung DK, Chan RS, et al. Prevalence and severity of nonalcoholic fatty liver disease in non-obese patients: A population study using proton-magnetic resonance spectroscopy. Am J Gastroenterol 2015;110:1306-1314. https://doi.org/10.1038/ajg.2015.235.
Xu C, Yu C, Ma H, Xu L, Miao M, Li Y. Prevalence and risk factors for the development of nonalcoholic fatty liver disease in a nonobese Chinese population: the Zhejiang Zhenhai Study. Am J Gastroenterol 2013;108:1299-1304. https://doi.org/10.1038/ajg.2013.104.
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. https://doi.org/10.1046/j.1440-1746.2002.02846.x.
Amarapurkar D, Kamani P, Patel N, Gupte P, Kumar P, Agal S, et al. Prevalence of non-alcoholic fatty liver disease: population based study. Ann Hepatol 2007;6:161-163.
Kwon YM, Oh SW, Hwang SS, Lee C, Kwon H, Chung GE. Association of nonalcoholic fatty liver disease with components of metabolic syndrome according to body mass index in Korean adults. Am J Gastroenterol 2012;107:1852-1858. https://doi.org/10.1038/ajg.2012.314.
Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004;40:1387-1395. https://doi.org/10.1002/hep.20466.
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 2005;42:44-52. https://doi.org/10.1002/hep.20734.
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;64:73-84. https://doi.org/10.1002/hep.28431.
Prieto-Ortiz JE, Sánchez Pardo S, Rojas Díaz L, Huertas Pacheco S. Hígado graso: aspectos clínicos en un centro de tercer nivel en Bogotá-período 2009-2013. Rev Colomb Gastroenterol 2014;29:117-124.
Vanegas CM, Restrepo C, Vargas N, Marín AE, Martínez LM, Yepes CE, et al. Caracterización de pacientes con enfermedad del hígado graso no alcohólica en un hospital de alta complejidad, Colombia 2013. Rev Colomb Gastroenterol 2014;29:342-346.
Ochoa C E, Calambás F. Hígado graso no alcohólico en consulta de gastroenterología. Repert Med Cir 2017;26:225-230. https://doi.org/10.1016/j.reper.2017.10.005.
Ye Q, Zou B, Yeo YH, Li J, Huang DQ, Wu Y, et al. Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2020;5:739-752. https://doi.org/10.1016/s2468-1253(20)30077-7.
Lu F-B, Zheng KI, Rios RS, Targher G, Byrne CD, Zheng M-H. Global epidemiology of lean non-alcoholic fatty liver disease: A systematic review and meta-analysis. J Gastroenterol Hepatol 2020;35:2041-2050. https://doi.org/10.1111/jgh.15156.
Riquelme A, Arrese M, Soza A, Morales A, Baudrand R, Pérez-Ayuso RM, et al. Non-alcoholic fatty liver disease and its association with obesity, insulin resistance and increased serum levels of C-reactive protein in Hispanics. Liver Int 2009;29:82-88. https://doi.org/10.1111/j.1478-3231.2008.01823.x.
Arab JP, Dirchwolf M, Álvares-da-Silva MR, Barrera F, Benítez C, Castellanos-Fernandez M, et al. Latin American Association for the study of the liver (ALEH) practice guidance for the diagnosis and treatment of non-alcoholic fatty liver disease. Ann Hepatol 2020;19:674-690. https://doi.org/10.1016/j.aohep.2020.09.006.
Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008;40:1461-1465. https://doi.org/10.1038/ng.257.
Honda Y, Yoneda M, Kessoku T, Ogawa Y, Tomeno W, Imajo K, et al. Characteristics of non-obese non-alcoholic fatty liver disease: Effect of genetic and environmental factors. Hepatology Res 2016;46:1011-1018. https://doi.org/10.1111/hepr.12648.
Fracanzani AL, Petta S, Lombardi R, Pisano G, Russello M, Consonni D, et al. Liver and cardiovascular damage in patients with lean nonalcoholic fatty liver disease, and association with visceral obesity. Clin Gastroenterol Hepatol 2017;15:1604-1611. https://doi.org/10.1016/j.cgh.2017.04.045.
Arab JP, Riquelme A, Benítez CE, Barrera F, Soza A, Miquel JF, et al. High prevalence of PNPLA3 rs738409 (I148M) polymorphism in Chilean-Latino population and its association to non-alcoholic fatty liver disease risk and histological disease severity. Hepatology 2015;62:1285A.
Unalp-Arida A, Ruhl CE. Patatin-like phospholipase domain-containing protein 3 I148M and liver fat and fibrosis scores predict liver disease mortality in the U.S. population. Hepatology 2020;71:820-834. https://doi.org/10.1002/hep.31032.
Adams LA, Marsh JA, Ayonrinde OT, Olynyk JK, Ang WQ, Beilin LJ, et al. Cholesteryl ester transfer protein gene polymorphisms increase the risk of fatty liver in females independent of adiposity. J Gastroenterol Hepatol 2012;27:1520-1527. https://doi.org/10.1111/j.1440-1746.2012.07120.x.
Petta S, Valenti L, Tuttolomondo A, Dongiovanni P, Pipitone RM, Cammà C, et al. Interferon lambda 4 rs368234815 TT>δG variant is associated with liver damage in patients with nonalcoholic fatty liver disease. Hepatology 2017;66:1885-1893. https://doi.org/10.1002/hep.29395.
Nakatsuka A, Matsuyama M, Yamaguchi S, Katayama A, Eguchi J, Murakami K, et al. Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis. Sci Rep 2016;6:21721. https://doi.org/10.1038/srep21721.
Kumar R, Prakash S, Chhabra S, Singla V, Madan K, Gupta SD, et al. Association of pro-inflammatory cytokines, adipokines & oxidative stress with insulin resistance & non-alcoholic fatty liver disease. Indian J Med Res 2012;136:229-236.
Stojsavljević S, Gomerčić Palčić M, Virović Jukić L, Smirčić Duvnjak L, Duvnjak M. Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol 2014;20:18070-18091. https://doi.org/10.3748/wjg.v20.i48.18070.
Ruderman NB, Schneider SH, Berchtold P. The "metabolically-obese," normal-weight individual. Am J Clin Nutr 1981;34:1617-1621. https://doi.org/10.1093/ajcn/34.8.1617.
Stefan N, Schick F, Häring HU. Causes, characteristics, and consequences of metabolically unhealthy normal weight in humans. Cell Metab 2017;26:292-300. https://doi.org/10.1016/j.cmet.2017.07.008.
Sookoian S, Puri P, Castaño GO, Scian R, Mirshahi F, Sanyal AJ, et al. Nonalcoholic steatohepatitis is associated with a state of betaine-insufficiency. Liver Int 2017;37:611-619. https://doi.org/10.1111/liv.13249.
Feng R, Luo C, Li C, Du S, Okekunle AP, Li Y, et al. Free fatty acids profile among lean, overweight and obese non-alcoholic fatty liver disease patients: a case - control study. Lipids Health Dis 2017;16:165. https://doi.org/10.1186/s12944-017-0551-1.
Assy N, Nasser G, Kamayse I, Nseir W, Beniashvili Z, Djibre A, et al. Soft drink consumption linked with fatty liver in the absence of traditional risk factors. Can J Gastroenterol 2008;22:811-816. https://doi.org/10.1155/2008/810961.
Abid A, Taha O, Nseir W, Farah R, Grosovski M, Assy N. Soft drink consumption is associated with fatty liver disease independent of metabolic syndrome. J Hepatol 2009;51:918-924. https://doi.org/10.1016/j.jhep.2009.05.033.
Toshimitsu K, Matsuura B, Ohkubo I, Niiya T, Furukawa S, Hiasa Y, et al. Dietary habits and nutrient intake in non-alcoholic steatohepatitis. Nutrition 2007;23:46-52. https://doi.org/10.1016/j.nut.2006.09.004.
Yasutake K, Nakamuta M, Shima Y, Ohyama A, Masuda K, Haruta N, et al. Nutritional investigation of non-obese patients with non-alcoholic fatty liver disease: the significance of dietary cholesterol. Scand J Gastroenterol 2009;44:471-477. https://doi.org/10.1080/00365520802588133.
Albhaisi S, Chowdhury A, Sanyal AJ. Non-alcoholic fatty liver disease in lean individuals. JHEP rep 2019;1:329-341. https://doi.org/10.1016/j.jhepr.2019.08.002.
Ampuero J, Aller R, Gallego-Durán R, Banales JM, Crespo J, García-Monzón C, et al. The effects of metabolic status on non-alcoholic fatty liver disease-related outcomes, beyond the presence of obesity. Aliment Pharmacol Ther 2018;48:1260-1270. https://doi.org/10.1111/apt.15015.
Hagström H, Nasr P, Ekstedt M, Hammar U, Stål P, Hultcrantz R, et al. Risk for development of severe liver disease in lean patients with nonalcoholic fatty liver disease: A long-term follow-up study. Hepatol Commun 2017;2:48-57. https://doi.org/10.1002/hep4.1124.
Leung JC, Loong TC, Wei JL, Wong GL, Chan AW, Choi PC, et al. Histological severity and clinical outcomes of nonalcoholic fatty liver disease in nonobese patients. Hepatology 2017;65:54-64. https://doi.org/10.1002/hep.28697.
Dela Cruz A, Bugianesi E, George J, Day C, Liaquat H, Charatcharoenwitthaya P, et al. Characteristics and long-term prognosis of lean patients with nonalcoholic fatty liver disease (379). Gastroenterology 2014;146:S909.
Sinn DH, Kang D, Cho SJ, Paik SW, Guallar E, Cho J, et al. Lean non-alcoholic fatty liver disease and development of diabetes: a cohort study. Eur J Endocrinol 2019;181:185-192. https://doi.org/10.1530/eje-19-0143.
Sung KC, Seo DC, Lee SJ, Lee MY, Wild SH, Byrne CD. Non alcoholic fatty liver disease and risk of incident diabetes in subjects who are not obese. Nutr Metab Cardiovasc Dis 2019;29:489-495. https://doi.org/10.1016/j.numecd.2019.01.016.
Kim SS, Cho HJ, Kim HJ, Kang DR, Berry JR, Kim JH, et al. Nonalcoholic fatty liver disease as a sentinel marker for the development of diabetes mellitus in non-obese subjects. Dig Liver Dis 2018;50:370-377. https://doi.org/10.1016/j.dld.2017.12.018.
Lazar MV, Eapen M, Nair HR, Siyad I, Gopalakrishna R. Correlation between insulin resistance and liver histology in patients with nonalcoholic steatohepatitis with and without obesity. Indian J Gastroenterol 2020;39:42-49. https://doi.org/10.1007/s12664-020-01024-z.
Promrat K, Kleiner DE, Niemeier HM, Jackvony E, Kearns M, Wands JR, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010;51:121-129. https://doi.org/10.1002/hep.23276.
Wong VW, Wong GL, Chan RS, Shu SS, Cheung BH, Li LS, et al. Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease. J Hepatol 2018;69:1349-1356. https://doi.org/10.1016/j.jhep.2018.08.011.
Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres-Gonzalez A, Gra-Oramas B, Gonzalez-Fabian L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology 2015;149:367-378. https://doi.org/10.1053/j.gastro.2015.04.005.
Zhuang X, Sun F, Li L, Jiang D, Li X, Sun A, et al. Therapeutic effect of metformin on chemerin in non-obese patients with non-alcoholic fatty liver disease (NAFLD). Clin Lab 2015;61:1409-1414. https://doi.org/10.7754/clin.lab.2015.150211.
Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. Jama 2011;305:1659-1668.
Lu FB, Zheng KI, Rios RS, Targher G, Byrne CD, Zheng MH. Global epidemiology of lean non-alcoholic fatty liver disease: A systematic review and meta-analysis. J Gastroenterol Hepatol 2020;35:2041-2050. https://doi.org/10.1111/jgh.15156.
Younes R, Bugianesi E. NASH in lean individuals. Semin Liver Dis 2019;39:86-95. https://doi.org/10.1055/s-0038-1677517.
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. https://doi.org/10.7326/0003-4819-132-2-200001180-00004.
Younossi ZM, Stepanova M, Negro F, Hallaji S, Younossi Y, Lam B, et al. Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine (Baltimore) 2012;91:319-327. https://doi.org/10.1097/MD.0b013e3182779d49.
Das K, Das K, Mukherjee PS, Ghosh A, Ghosh S, Mridha AR, et al. Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease. Hepatology 2010;51:1593-1602. https://doi.org/10.1002/hep.23567.
Nishioji K, Mochizuki N, Kobayashi M, Kamaguchi M, Sumida Y, Nishimura T, et al. The impact of PNPLA3 rs738409 genetic polymorphism and weight gain ≥10 kg after age 20 on non-alcoholic fatty liver disease in non-obese Japanese individuals. PLoS One 2015;10:e0140427. https://doi.org/10.1371/journal.pone.0140427.
Sinn DH, Gwak GY, Park HN, Kim JE, Min YW, Kim KM, et al. Ultrasonographically detected non-alcoholic fatty liver disease is an independent predictor for identifying patients with insulin resistance in non-obese, non-diabetic middle-aged Asian adults. Am J Gastroenterol 2012;107:561-567. https://doi.org/10.1038/ajg.2011.400.
Wei JL, Leung JC, Loong TC, Wong GL, Yeung DK, Chan RS, et al. Prevalence and severity of nonalcoholic fatty liver disease in non-obese patients: A population study using proton-magnetic resonance spectroscopy. Am J Gastroenterol 2015;110:1306-1314. https://doi.org/10.1038/ajg.2015.235.
Xu C, Yu C, Ma H, Xu L, Miao M, Li Y. Prevalence and risk factors for the development of nonalcoholic fatty liver disease in a nonobese Chinese population: the Zhejiang Zhenhai Study. Am J Gastroenterol 2013;108:1299-1304. https://doi.org/10.1038/ajg.2013.104.
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. https://doi.org/10.1046/j.1440-1746.2002.02846.x.
Amarapurkar D, Kamani P, Patel N, Gupte P, Kumar P, Agal S, et al. Prevalence of non-alcoholic fatty liver disease: population based study. Ann Hepatol 2007;6:161-163.
Kwon YM, Oh SW, Hwang SS, Lee C, Kwon H, Chung GE. Association of nonalcoholic fatty liver disease with components of metabolic syndrome according to body mass index in Korean adults. Am J Gastroenterol 2012;107:1852-1858. https://doi.org/10.1038/ajg.2012.314.
Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004;40:1387-1395. https://doi.org/10.1002/hep.20466.
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 2005;42:44-52. https://doi.org/10.1002/hep.20734.
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;64:73-84. https://doi.org/10.1002/hep.28431.
Prieto-Ortiz JE, Sánchez Pardo S, Rojas Díaz L, Huertas Pacheco S. Hígado graso: aspectos clínicos en un centro de tercer nivel en Bogotá-período 2009-2013. Rev Colomb Gastroenterol 2014;29:117-124.
Vanegas CM, Restrepo C, Vargas N, Marín AE, Martínez LM, Yepes CE, et al. Caracterización de pacientes con enfermedad del hígado graso no alcohólica en un hospital de alta complejidad, Colombia 2013. Rev Colomb Gastroenterol 2014;29:342-346.
Ochoa C E, Calambás F. Hígado graso no alcohólico en consulta de gastroenterología. Repert Med Cir 2017;26:225-230. https://doi.org/10.1016/j.reper.2017.10.005.
Ye Q, Zou B, Yeo YH, Li J, Huang DQ, Wu Y, et al. Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2020;5:739-752. https://doi.org/10.1016/s2468-1253(20)30077-7.
Lu F-B, Zheng KI, Rios RS, Targher G, Byrne CD, Zheng M-H. Global epidemiology of lean non-alcoholic fatty liver disease: A systematic review and meta-analysis. J Gastroenterol Hepatol 2020;35:2041-2050. https://doi.org/10.1111/jgh.15156.
Riquelme A, Arrese M, Soza A, Morales A, Baudrand R, Pérez-Ayuso RM, et al. Non-alcoholic fatty liver disease and its association with obesity, insulin resistance and increased serum levels of C-reactive protein in Hispanics. Liver Int 2009;29:82-88. https://doi.org/10.1111/j.1478-3231.2008.01823.x.
Arab JP, Dirchwolf M, Álvares-da-Silva MR, Barrera F, Benítez C, Castellanos-Fernandez M, et al. Latin American Association for the study of the liver (ALEH) practice guidance for the diagnosis and treatment of non-alcoholic fatty liver disease. Ann Hepatol 2020;19:674-690. https://doi.org/10.1016/j.aohep.2020.09.006.
Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008;40:1461-1465. https://doi.org/10.1038/ng.257.
Honda Y, Yoneda M, Kessoku T, Ogawa Y, Tomeno W, Imajo K, et al. Characteristics of non-obese non-alcoholic fatty liver disease: Effect of genetic and environmental factors. Hepatology Res 2016;46:1011-1018. https://doi.org/10.1111/hepr.12648.
Fracanzani AL, Petta S, Lombardi R, Pisano G, Russello M, Consonni D, et al. Liver and cardiovascular damage in patients with lean nonalcoholic fatty liver disease, and association with visceral obesity. Clin Gastroenterol Hepatol 2017;15:1604-1611. https://doi.org/10.1016/j.cgh.2017.04.045.
Arab JP, Riquelme A, Benítez CE, Barrera F, Soza A, Miquel JF, et al. High prevalence of PNPLA3 rs738409 (I148M) polymorphism in Chilean-Latino population and its association to non-alcoholic fatty liver disease risk and histological disease severity. Hepatology 2015;62:1285A.
Unalp-Arida A, Ruhl CE. Patatin-like phospholipase domain-containing protein 3 I148M and liver fat and fibrosis scores predict liver disease mortality in the U.S. population. Hepatology 2020;71:820-834. https://doi.org/10.1002/hep.31032.
Adams LA, Marsh JA, Ayonrinde OT, Olynyk JK, Ang WQ, Beilin LJ, et al. Cholesteryl ester transfer protein gene polymorphisms increase the risk of fatty liver in females independent of adiposity. J Gastroenterol Hepatol 2012;27:1520-1527. https://doi.org/10.1111/j.1440-1746.2012.07120.x.
Petta S, Valenti L, Tuttolomondo A, Dongiovanni P, Pipitone RM, Cammà C, et al. Interferon lambda 4 rs368234815 TT>δG variant is associated with liver damage in patients with nonalcoholic fatty liver disease. Hepatology 2017;66:1885-1893. https://doi.org/10.1002/hep.29395.
Nakatsuka A, Matsuyama M, Yamaguchi S, Katayama A, Eguchi J, Murakami K, et al. Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis. Sci Rep 2016;6:21721. https://doi.org/10.1038/srep21721.
Kumar R, Prakash S, Chhabra S, Singla V, Madan K, Gupta SD, et al. Association of pro-inflammatory cytokines, adipokines & oxidative stress with insulin resistance & non-alcoholic fatty liver disease. Indian J Med Res 2012;136:229-236.
Stojsavljević S, Gomerčić Palčić M, Virović Jukić L, Smirčić Duvnjak L, Duvnjak M. Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol 2014;20:18070-18091. https://doi.org/10.3748/wjg.v20.i48.18070.
Ruderman NB, Schneider SH, Berchtold P. The "metabolically-obese," normal-weight individual. Am J Clin Nutr 1981;34:1617-1621. https://doi.org/10.1093/ajcn/34.8.1617.
Stefan N, Schick F, Häring HU. Causes, characteristics, and consequences of metabolically unhealthy normal weight in humans. Cell Metab 2017;26:292-300. https://doi.org/10.1016/j.cmet.2017.07.008.
Sookoian S, Puri P, Castaño GO, Scian R, Mirshahi F, Sanyal AJ, et al. Nonalcoholic steatohepatitis is associated with a state of betaine-insufficiency. Liver Int 2017;37:611-619. https://doi.org/10.1111/liv.13249.
Feng R, Luo C, Li C, Du S, Okekunle AP, Li Y, et al. Free fatty acids profile among lean, overweight and obese non-alcoholic fatty liver disease patients: a case - control study. Lipids Health Dis 2017;16:165. https://doi.org/10.1186/s12944-017-0551-1.
Assy N, Nasser G, Kamayse I, Nseir W, Beniashvili Z, Djibre A, et al. Soft drink consumption linked with fatty liver in the absence of traditional risk factors. Can J Gastroenterol 2008;22:811-816. https://doi.org/10.1155/2008/810961.
Abid A, Taha O, Nseir W, Farah R, Grosovski M, Assy N. Soft drink consumption is associated with fatty liver disease independent of metabolic syndrome. J Hepatol 2009;51:918-924. https://doi.org/10.1016/j.jhep.2009.05.033.
Toshimitsu K, Matsuura B, Ohkubo I, Niiya T, Furukawa S, Hiasa Y, et al. Dietary habits and nutrient intake in non-alcoholic steatohepatitis. Nutrition 2007;23:46-52. https://doi.org/10.1016/j.nut.2006.09.004.
Yasutake K, Nakamuta M, Shima Y, Ohyama A, Masuda K, Haruta N, et al. Nutritional investigation of non-obese patients with non-alcoholic fatty liver disease: the significance of dietary cholesterol. Scand J Gastroenterol 2009;44:471-477. https://doi.org/10.1080/00365520802588133.
Albhaisi S, Chowdhury A, Sanyal AJ. Non-alcoholic fatty liver disease in lean individuals. JHEP rep 2019;1:329-341. https://doi.org/10.1016/j.jhepr.2019.08.002.
Ampuero J, Aller R, Gallego-Durán R, Banales JM, Crespo J, García-Monzón C, et al. The effects of metabolic status on non-alcoholic fatty liver disease-related outcomes, beyond the presence of obesity. Aliment Pharmacol Ther 2018;48:1260-1270. https://doi.org/10.1111/apt.15015.
Hagström H, Nasr P, Ekstedt M, Hammar U, Stål P, Hultcrantz R, et al. Risk for development of severe liver disease in lean patients with nonalcoholic fatty liver disease: A long-term follow-up study. Hepatol Commun 2017;2:48-57. https://doi.org/10.1002/hep4.1124.
Leung JC, Loong TC, Wei JL, Wong GL, Chan AW, Choi PC, et al. Histological severity and clinical outcomes of nonalcoholic fatty liver disease in nonobese patients. Hepatology 2017;65:54-64. https://doi.org/10.1002/hep.28697.
Dela Cruz A, Bugianesi E, George J, Day C, Liaquat H, Charatcharoenwitthaya P, et al. Characteristics and long-term prognosis of lean patients with nonalcoholic fatty liver disease (379). Gastroenterology 2014;146:S909.
Sinn DH, Kang D, Cho SJ, Paik SW, Guallar E, Cho J, et al. Lean non-alcoholic fatty liver disease and development of diabetes: a cohort study. Eur J Endocrinol 2019;181:185-192. https://doi.org/10.1530/eje-19-0143.
Sung KC, Seo DC, Lee SJ, Lee MY, Wild SH, Byrne CD. Non alcoholic fatty liver disease and risk of incident diabetes in subjects who are not obese. Nutr Metab Cardiovasc Dis 2019;29:489-495. https://doi.org/10.1016/j.numecd.2019.01.016.
Kim SS, Cho HJ, Kim HJ, Kang DR, Berry JR, Kim JH, et al. Nonalcoholic fatty liver disease as a sentinel marker for the development of diabetes mellitus in non-obese subjects. Dig Liver Dis 2018;50:370-377. https://doi.org/10.1016/j.dld.2017.12.018.
Lazar MV, Eapen M, Nair HR, Siyad I, Gopalakrishna R. Correlation between insulin resistance and liver histology in patients with nonalcoholic steatohepatitis with and without obesity. Indian J Gastroenterol 2020;39:42-49. https://doi.org/10.1007/s12664-020-01024-z.
Promrat K, Kleiner DE, Niemeier HM, Jackvony E, Kearns M, Wands JR, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010;51:121-129. https://doi.org/10.1002/hep.23276.
Wong VW, Wong GL, Chan RS, Shu SS, Cheung BH, Li LS, et al. Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease. J Hepatol 2018;69:1349-1356. https://doi.org/10.1016/j.jhep.2018.08.011.
Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres-Gonzalez A, Gra-Oramas B, Gonzalez-Fabian L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology 2015;149:367-378. https://doi.org/10.1053/j.gastro.2015.04.005.
Zhuang X, Sun F, Li L, Jiang D, Li X, Sun A, et al. Therapeutic effect of metformin on chemerin in non-obese patients with non-alcoholic fatty liver disease (NAFLD). Clin Lab 2015;61:1409-1414. https://doi.org/10.7754/clin.lab.2015.150211.
Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. Jama 2011;305:1659-1668.
Anushiravani A, Haddadi N, Pourfarmanbar M, Mohammadkarimi V. Treatment options for nonalcoholic fatty liver disease: a double-blinded randomized placebo-controlled trial. Eur J Gastroenterol Hepatol 2019;31:613-617.
Descargas
Publicado
Cómo citar
Número
Sección
Licencia
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-SinDerivadas 4.0.
La política de reconocimiento de autoría de Hepatología se basa en los criterios indicados por el ICMJE para conferir crédito de un trabajo a una persona, a la vez que se le atribuye responsabilidad por la publicación del mismo.
