Clinical workup of fatty liver for the primary care provider

References

• Fabbrini E, Sullivan S, Klein S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology. 2010 Feb;51(2):679–689. PubMed PMID: 20041406; PubMed Central PMCID: PMCPMC3575093.
   PubMed Web of Science ®Google Scholar
• Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005 Jun;41(6):1313–1321. PubMed PMID: 15915461.
   PubMed Web of Science ®Google Scholar
• Pais R, Barritt A, Calmus Y, et al. NAFLD and liver transplantation: current burden and expected challenges. J Hepatol. 2016 Dec;65(6):1245–1257. PubMed PMID: 27486010; PubMed Central PMCID: PMCPMC5326676.
   PubMed Web of Science ®Google Scholar
• Zezos P, Renner EL. Liver transplantation and non-alcoholic fatty liver disease. World J Gastroenterol. 2014 Nov 14;20(42):15532–15538. PubMed PMID: 25400437; PubMed Central PMCID: PMCPMC4229518.
   PubMed Web of Science ®Google Scholar
• Ascha MS, Hanouneh IA, Lopez R, et al. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology. 2010 Jun;51(6):1972–1978. PubMed PMID: 20209604.
   PubMed Web of Science ®Google Scholar
• Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004 Dec;40(6):1387–1395. PubMed PMID: 15565570.
   PubMed Web of Science ®Google Scholar
• Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology. 2003 Jan;124(1):71–79. PubMed PMID: 12512031; eng.
   PubMed Web of Science ®Google Scholar
• 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. 2011 Aug;34(3):274–285. PubMed PMID: 21623852.
   PubMed Web of Science ®Google Scholar
• Ekstedt M, Franzen LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006 Oct;44(4):865–873. PubMed PMID: 17006923.
   PubMed Web of Science ®Google Scholar
• Canbay A, Sowa JP, Syn WK, et al. NASH cirrhosis - the new burden in liver transplantation: how should it be managed? Visc Med. 2016 Aug;32(4):234–238. PubMed PMID: 27722159; PubMed Central PMCID: PMCPMC5040943.
   PubMed Web of Science ®Google Scholar
• Charlton MR, Burns JM, Pedersen RA, et al. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology. 2011 Oct;141(4):1249–1253. PubMed PMID: 21726509.
   PubMed Web of Science ®Google Scholar
• Calzadilla Bertot L, Adams LA. The natural course of non-alcoholic fatty liver disease. Int J Mol Sci. 2016 May 20;17(5). PubMed PMID: 27213358; PubMed Central PMCID: PMCPMC4881593. DOI:10.3390/ijms17050774
   PubMed Web of Science ®Google Scholar
• Islami F, Miller KD, Siegel RL, et al. Disparities in liver cancer occurrence in the United States by race/ethnicity and state. CA Cancer J Clin. 2017 Jul 08;67(4):273–289. PubMed PMID: 28586094.
   PubMed Web of Science ®Google Scholar
• Korenblat KM, Fabbrini E, Mohammed BS, et al. Liver, muscle, and adipose tissue insulin action is directly related to intrahepatic triglyceride content in obese subjects. Gastroenterology. 2008 May;134(5):1369–1375. PubMed PMID: 18355813; PubMed Central PMCID: PMCPMC2629391.
   PubMed Web of Science ®Google Scholar
• Treeprasertsuk S, Leverage S, Adams LA, et al. The Framingham risk score and heart disease in nonalcoholic fatty liver disease. Liver Int. 2012 Jul;32(6):945–950. PubMed PMID: 22299674; PubMed Central PMCID: PMCPMC3348257.
   PubMed Web of Science ®Google Scholar
• Targher G, Bertolini L, Rodella S, et al. Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular events in type 2 diabetic patients. Diabetes Care. 2007 Aug;30(8):2119–2121. PubMed PMID: 17519430.
   PubMed Web of Science ®Google Scholar
• Talim M. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients: response to Targher et al. and Hu et al. Diabetes Care. 2007 Jun;30(6):e55. author reply e56. PubMed PMID: 17526817.
   PubMedGoogle Scholar
• Musso G, Gambino R, Cassader M, et al. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011 Dec;43(8):617–649. PubMed PMID: 21039302.
   PubMed Web of Science ®Google Scholar
• Musso G, Gambino R, Tabibian JH, et al. Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. PLoS Med. 2014 Jul;11(7):e1001680. PubMed PMID: 25050550; PubMed Central PMCID: PMCPMC4106719.
   PubMed Web of Science ®Google Scholar
• Johnson RJ, Stenvinkel P, Martin SL, et al. Redefining metabolic syndrome as a fat storage condition based on studies of comparative physiology. Obesity (Silver Spring). 2013 Apr;21(4):659–664. PubMed PMID: 23401356; PubMed Central PMCID: PMC3660463. eng.
   PubMed Web of Science ®Google Scholar
• Marcos A, Fisher RA, Ham JM, et al. Selection and outcome of living donors for adult to adult right lobe transplantation. Transplantation. 2000 Jun 15;69(11):2410–2415. PubMed PMID: 10868650.
   PubMed Web of Science ®Google Scholar
• Hilden M, Christoffersen P, Juhl E, et al. Liver histology in a ‘normal’ population–examinations of 503 consecutive fatal traffic casualties. Scand J Gastroenterol. 1977;12(5):593–597. PubMed PMID: 918553.
   PubMed Web of Science ®Google Scholar
• Lee RG. Nonalcoholic steatohepatitis: a study of 49 patients. Hum Pathol. 1989 Jun;20(6):594–598. PubMed PMID: 2656500.
   PubMed Web of Science ®Google Scholar
• Gholam PM, Kotler DP, Flancbaum LJ. Liver pathology in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery. Obes Surg. 2002 Feb;12(1):49–51. PubMed PMID: 11868297.
   PubMed Web of Science ®Google Scholar
• Marchesini G, Moscatiello S, Di Domizio S, et al. Obesity-associated liver disease. J Clin Endocrinol Metab. 2008 Nov;93(11 Suppl 1):S74–S80. PubMed PMID: 18987273.
   PubMed Web of Science ®Google Scholar
• Zhang WJ, Chen LL, Zheng J, et al. Association of adult weight gain and nonalcoholic fatty liver in a cross-sectional study in Wan Song Community, China. Braz J Med Biol Res. 2014 Feb;47(2):151–156. PubMed PMID: 24519131; PubMed Central PMCID: PMCPMC4051179.
   PubMed Web of Science ®Google Scholar
• Fan JG, Zhu J, Li XJ, et al. Prevalence of and risk factors for fatty liver in a general population of Shanghai, China. J Hepatol. 2005 Sep;43(3):508–514. PubMed PMID: 16006003.
   PubMed Web of Science ®Google Scholar
• Lazo M, Hernaez R, Eberhardt MS, et al. Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988–1994. Am J Epidemiol. 2013 Jul 1;178(1):38–45. PubMed PMID: 23703888; PubMed Central PMCID: PMCPMC3698993.
   PubMed Web of Science ®Google Scholar
• Kim HJ, Lim CW, Lee JH, et al. Gender-based differences in the relationship between fatty liver disease and atherosclerosis. Cardiovasc J Afr. 2016 Sep/Oct 23;27(5):281–286. PubMed PMID: 26972662; PubMed Central PMCID: PMCPMC5370319.
   PubMed Web of Science ®Google Scholar
• Eguchi Y, Hyogo H, Ono M, et al. Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: a multicenter large retrospective study. J Gastroenterol. 2012 May;47(5):586–595. PubMed PMID: 22328022.
   PubMed Web of Science ®Google Scholar
• Caballeria L, Pera G, Auladell MA, et al. Prevalence and factors associated with the presence of nonalcoholic fatty liver disease in an adult population in Spain. Eur J Gastroenterol Hepatol. 2010 Jan;22(1):24–32. PubMed PMID: 19730384.
   PubMed Web of Science ®Google Scholar
• Zelber-Sagi S, Nitzan-Kaluski D, Halpern Z, et al. Prevalence of primary non-alcoholic fatty liver disease in a population-based study and its association with biochemical and anthropometric measures. Liver Int. 2006 Sep;26(7):856–863. PubMed PMID: 16911469.
   PubMed Web of Science ®Google Scholar
• Wang Z, Xu M, Hu Z, et al. Prevalence of nonalcoholic fatty liver disease and its metabolic risk factors in women of different ages and body mass index. Menopause. 2015 Jun;22(6):667–673. PubMed PMID: 25513983.
   PubMed Web of Science ®Google Scholar
• Bruno Ade S, Rodrigues MH, Alvares MC, et al. Non-alcoholic fatty liver disease and its associated risk factors in Brazilian postmenopausal women. Climacteric. 2014 Aug;17(4):465–471. PubMed PMID: 24517420.
   PubMed Web of Science ®Google Scholar
• Shen L, Fan JG, Shao Y, et al. Prevalence of nonalcoholic fatty liver among administrative officers in Shanghai: an epidemiological survey. World J Gastroenterol. 2003 May;9(5):1106–1110. PubMed PMID: 12717867; PubMed Central PMCID: PMCPMC4611383.
   PubMed Web of Science ®Google Scholar
• Wang Z, Xu M, Hu Z, et al. Sex-specific prevalence of fatty liver disease and associated metabolic factors in Wuhan, south central China. Eur J Gastroenterol Hepatol. 2014 Sep;26(9):1015–1021. PubMed PMID: 25003744.
   PubMed Web of Science ®Google Scholar
• Hamaguchi M, Kojima T, Ohbora A, et al. Aging is a risk factor of nonalcoholic fatty liver disease in premenopausal women. World J Gastroenterol. 2012 Jan 21;18(3):237–243. PubMed PMID: 22294826; PubMed Central PMCID: PMCPMC3261540.
   PubMed Web of Science ®Google Scholar
• Gutierrez-Grobe Y, Ponciano-Rodriguez G, Ramos MH, et al. Prevalence of non alcoholic fatty liver disease in premenopausal, posmenopausal and polycystic ovary syndrome women. The role of estrogens. Ann Hepatol. 2010 Oct-Dec;9(4):402–409. PubMed PMID: 21057159.
   PubMed Web of Science ®Google Scholar
• Vassilatou E. Nonalcoholic fatty liver disease and polycystic ovary syndrome. World J Gastroenterol. 2014 Jul 14;20(26):8351–8363. PubMed PMID: 25024594; PubMed Central PMCID: PMCPMC4093689.
   PubMed Web of Science ®Google Scholar
• Shen M, Shi H. Sex hormones and their receptors regulate liver energy homeostasis. Int J Endocrinol. 2015;2015:294278. PubMed PMID: 26491440; PubMed Central PMCID: PMCPMC4600502.
   PubMed Web of Science ®Google Scholar
• Zhou YJ, Li YY, Nie YQ, et al. Prevalence of fatty liver disease and its risk factors in the population of South China. World J Gastroenterol. 2007 Dec 21;13(47):6419–6424. PubMed PMID: 18081233; PubMed Central PMCID: PMCPMC4205463.
   PubMed Web of Science ®Google Scholar
• Li H, Wang YJ, Tan K, et al. Prevalence and risk factors of fatty liver disease in Chengdu, Southwest China. Hepatobiliary Pancreat Dis Int. 2009 8;Aug(4):377–382. PubMed PMID: 19666406.
   Google Scholar
• Hu X, Huang Y, Bao Z, et al. Prevalence and factors associated with nonalcoholic fatty liver disease in Shanghai work-units. BMC Gastroenterol. 2012 Sep;14(12):123. PubMed PMID: 22978800; PubMed Central PMCID: PMCPMC3499402.
   PubMed Web of Science ®Google Scholar
• Lonardo A, Bellentani S, Non-alcoholic Fatty Liver Disease Study G, et al.. Epidemiological modifiers of non-alcoholic fatty liver disease: focus on high-risk groups. Dig Liver Dis. 2015 Dec;47(12):997–1006. PubMed PMID: 26454786.
   PubMedGoogle Scholar
• Smits MM, Ioannou GN, Boyko EJ, et al. Non-alcoholic fatty liver disease as an independent manifestation of the metabolic syndrome: results of a US national survey in three ethnic groups. J Gastroenterol Hepatol. 2013 Apr;28(4):664–670. PubMed PMID: 23286209.
   PubMed Web of Science ®Google Scholar
• Schneider AL, Lazo M, Selvin E, et al. Racial differences in nonalcoholic fatty liver disease in the U.S. population. Obesity (Silver Spring). 2014 Jan;22(1):292–299. PubMed PMID: 23512725; PubMed Central PMCID: PMCPMC3690150.
   PubMed Web of Science ®Google Scholar
• Wong RJ, Ahmed A. Obesity and non-alcoholic fatty liver disease: disparate associations among Asian populations. World J Hepatol. 2014 May 27;6(5):263–273. PubMed PMID: 24868320; PubMed Central PMCID: PMCPMC4033284.
   PubMedGoogle Scholar
• Wong VW, Chu WC, Wong GL, et al. Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography. Gut. 2012 Mar;61(3):409–415. PubMed PMID: 21846782.
   PubMed Web of Science ®Google Scholar
• Tabibian JH, Lazo M, Durazo FA, et al. Nonalcoholic fatty liver disease across ethno-racial groups: do Asian-American adults represent a new at-risk population? J Gastroenterol Hepatol. 2011 Mar;26(3):501–509. PubMed PMID: 21332546; PubMed Central PMCID: PMCPMC4937792.
   PubMed Web of Science ®Google Scholar
• Mohanty SR, Troy TN, Huo D, et al. Influence of ethnicity on histological differences in non-alcoholic fatty liver disease. J Hepatol. 2009 Apr;50(4):797–804. PubMed PMID: 19231016.
   PubMed Web of Science ®Google Scholar
• Kallwitz ER, Guzman G, TenCate V, et al. The histologic spectrum of liver disease in African-American, non-hispanic white, and hispanic obesity surgery patients. Am J Gastroenterol. 2009 Jan;104(1):64–69. PubMed PMID: 19098851; eng.
   PubMed Web of Science ®Google Scholar
• Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008 Dec;40(12):1461–1465. PubMed PMID: 18820647; PubMed Central PMCID: PMCPMC2597056.
   PubMed Web of Science ®Google Scholar
• Kotronen A, Johansson LE, Johansson LM, et al. A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans. Diabetologia. 2009 Jun;52(6):1056–1060. PubMed PMID: 19224197.
   PubMed Web of Science ®Google Scholar
• Kozlitina J, Smagris E, Stender S, et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2014 Apr;46(4):352–356. PubMed PMID: 24531328; PubMed Central PMCID: PMCPMC3969786.
   PubMed Web of Science ®Google Scholar
• Pan JJ, Fallon MB. Gender and racial differences in nonalcoholic fatty liver disease. World J Hepatol. 2014 May 27;6(5):274–283. PubMed PMID: 24868321; PubMed Central PMCID: PMCPMC4033285.
   PubMedGoogle Scholar
• Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2017 Sep 20;15:11–20. PubMed PMID: 28930295.
   PubMed Web of Science ®Google Scholar
• Trepo E, Romeo S, Zucman-Rossi J, et al. PNPLA3 gene in liver diseases. J Hepatol. 2016 Aug;65(2):399–412. PubMed PMID: 27038645.
   PubMed Web of Science ®Google Scholar
• Petta S, Miele L, Bugianesi E, et al. Glucokinase regulatory protein gene polymorphism affects liver fibrosis in non-alcoholic fatty liver disease. PLoS One. 2014;9(2):e87523. PubMed PMID: 24498332; PubMed Central PMCID: PMCPMC3911959.
   PubMed Web of Science ®Google Scholar
• Speliotes EK, Yerges-Armstrong LM, Wu J, et al. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet. 2011 Mar;7(3):e1001324. PubMed PMID: 21423719; PubMed Central PMCID: PMCPMC3053321.
   PubMed Web of Science ®Google Scholar
• Burke JE, Dennis EA. Phospholipase A2 structure/function, mechanism, and signaling. J Lipid Res. 2009 Apr;50 Suppl:S237–S242. PubMed PMID: 19011112; PubMed Central PMCID: PMCPMC2674709.
   PubMed Web of Science ®Google Scholar
• Hernaez R, McLean J, Lazo M, et al. Association between variants in or near PNPLA3, GCKR, and PPP1R3B with ultrasound-defined steatosis based on data from the third National Health and Nutrition Examination Survey. Clin Gastroenterol Hepatol. 2013 Sep;11(9):1183–1190 e2. PubMed PMID: 23416328; PubMed Central PMCID: PMCPMC4197011.
   PubMed Web of Science ®Google Scholar
• Mehta MB, Shewale SV, Sequeira RN, et al. Hepatic protein phosphatase 1 regulatory subunit 3B (Ppp1r3b) promotes hepatic glycogen synthesis and thereby regulates fasting energy homeostasis. J Biol Chem. 2017 Jun 23;292(25):10444–10454. PubMed PMID: 28473467; PubMed Central PMCID: PMCPMC5481556.
   PubMed Web of Science ®Google Scholar
• Leite NC, Salles GF, Araujo AL, et al. Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver Int. 2009 Jan;29(1):113–119. PubMed PMID: 18384521.
   PubMed Web of Science ®Google Scholar
• Portillo Sanchez P, Bril F, Maximos M, et al. High prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus and normal plasma aminotransferase levEls. J Clin Endocrinol Metab. 2014 Oct 10:jc.2014–jc.2739. PubMed PMID: 25303488. DOI:10.1210/jc.2014-2739
   PubMed Web of Science ®Google Scholar
• Hamaguchi M, Kojima T, Takeda N, et al. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med. 2005 Nov 15;143(10):722–728. PubMed PMID: 16287793.
   PubMed Web of Science ®Google Scholar
• Donati G, Stagni B, Piscaglia F, et al. Increased prevalence of fatty liver in arterial hypertensive patients with normal liver enzymes: role of insulin resistance. Gut. 2004 Jul;53(7):1020–1023. PubMed PMID: 15194655; PubMed Central PMCID: PMCPMC1774102.
   PubMed Web of Science ®Google Scholar
• Jensen T, Abdelmalek MF, Sullivan S, et al. Fructose and sugar: a major mediator of non-alcoholic fatty liver disease. J Hepatol. 2018 May;68(5):1063–1075. PubMed PMID: 29408694; PubMed Central PMCID: PMCPMC5893377.
   PubMed Web of Science ®Google Scholar
• Mosca A, Nobili V, De Vito R, et al. Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents. J Hepatol. 2017 May;66(5):1031–1036. PubMed PMID: 28214020.
   PubMed Web of Science ®Google Scholar
• Zhou Z, Song K, Qiu J, et al. Associations between serum uric acid and the remission of non-alcoholic fatty liver disease in Chinese males. PLoS One. 2016;11(11):e0166072. PubMed PMID: 27835657; PubMed Central PMCID: PMCPMC5106003.
   PubMed Web of Science ®Google Scholar
• Mirmiran P, Amirhamidi Z, Ejtahed HS, et al. Relationship between diet and non-alcoholic fatty liver disease: a review article. Iran J Public Health. 2017 Aug;46(8):1007–1017. PubMed PMID: 28894701; PubMed Central PMCID: PMCPMC5575379.
   PubMed Web of Science ®Google Scholar
• Oddy WH, Herbison CE, Jacoby P, et al. The Western dietary pattern is prospectively associated with nonalcoholic fatty liver disease in adolescence. Am J Gastroenterol. 2013 May;108(5):778–785. PubMed PMID: 23545714.
   PubMed Web of Science ®Google Scholar
• Green AK, Jacques PF, Rogers G, et al. Sugar-sweetened beverages and prevalence of the metabolically abnormal phenotype in the Framingham Heart Study. Obesity (Silver Spring). 2014 May;22(5):E157–E163. PubMed PMID: 24550031; PubMed Central PMCID: PMCPMC4139414.
   PubMed Web of Science ®Google Scholar
• Vos MB, Colvin R, Belt P, et al. Correlation of vitamin E, uric acid, and diet composition with histologic features of pediatric NAFLD. J Pediatr Gastroenterol Nutr. 2012 Jan;54(1):90–96. PubMed PMID: 22197855; PubMed Central PMCID: PMCPMC3208079.
   PubMed Web of Science ®Google Scholar
• Lim JS, Mietus-Snyder M, Valente A, et al. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nat Rev Gastroenterol Hepatol. 2010 May;7(5):251–264. PubMed PMID: 20368739.
   PubMed Web of Science ®Google Scholar
• Stanhope KL, Schwarz JM, Keim NL, et al. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest. 2009 May;119(5):1322–1334. PubMed PMID: 19381015; PubMed Central PMCID: PMCPMC2673878.
   PubMed Web of Science ®Google Scholar
• Abdelmalek MF, Suzuki A, Guy C, et al. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology. 2010 Jun;51(6):1961–1971. PubMed PMID: 20301112; PubMed Central PMCID: PMCPMC2922495.
   PubMed Web of Science ®Google Scholar
• Yu J, Marsh S, Hu J, et al. The pathogenesis of nonalcoholic fatty liver disease: interplay between diet, gut microbiota, and genetic background. Gastroenterol Res Pract. 2016;2016:2862173. PubMed PMID: 27247565; PubMed Central PMCID: PMCPMC4876215.
   PubMed Web of Science ®Google Scholar
• Maersk M, Belza A, Stodkilde-Jorgensen H, et al. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Am J Clin Nutr. 2012 Feb;95(2):283–289. PubMed PMID: 22205311.
   PubMed Web of Science ®Google Scholar
• Bruckdorfer KR, Khan IH, Yudkin J. Dietary carbohydrate and fatty acid synthetase activity in rat liver and adipose tissue. Biochem J. 1971 Jun;123(2):7P. PubMed PMID: 5127347; PubMed Central PMCID: PMC1176949. eng.
   PubMed Web of Science ®Google Scholar
• Ackerman Z, Oron-Herman M, Grozovski M, et al. Fructose-induced fatty liver disease: hepatic effects of blood pressure and plasma triglyceride reduction. Hypertension. 2005 May;45(5):1012–1018. PubMed PMID: 15824194.
   PubMed Web of Science ®Google Scholar
• Collison KS, Maqbool ZM, Inglis AL, et al. Effect of dietary monosodium glutamate on HFCS-induced hepatic steatosis: expression profiles in the liver and visceral fat. Obesity (Silver Spring). 2010 Jun;18(6): 1122–1134.
   PubMed Web of Science ®Google Scholar
• Sanchez-Lozada LG, Mu W, Roncal C, et al. Comparison of free fructose and glucose to sucrose in the ability to cause fatty liver. Eur J Nutr. 2010 Feb;49(1):1–9. PubMed PMID: 19626358; PubMed Central PMCID: PMC2805058. eng.
   PubMed Web of Science ®Google Scholar
• Ferolla SM, Ferrari TC, Lima ML, et al. Dietary patterns in Brazilian patients with nonalcoholic fatty liver disease: a cross-sectional study. Clinics (Sao Paulo). 2013 Jan;68(1):11–17. PubMed PMID: 23420151; PubMed Central PMCID: PMCPMC3552450.
   PubMed Web of Science ®Google Scholar
• Rosqvist F, Iggman D, Kullberg J, et al. Overfeeding polyunsaturated and saturated fat causes distinct effects on liver and visceral fat accumulation in humans. Diabetes. 2014 Jul;63(7):2356–2368. PubMed PMID: 24550191.
   PubMed Web of Science ®Google Scholar
• Bjermo H, Iggman D, Kullberg J, et al. Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. Am J Clin Nutr. 2012 May;95(5):1003–1012. PubMed PMID: 22492369.
   PubMed Web of Science ®Google Scholar
• Lanaspa MA, Ishimoto T, Li N, et al. Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome. Nat Commun. 2013 Sep 11;4:2434. PubMed PMID: 24022321; eng.
   PubMed Web of Science ®Google Scholar
• Choi Y, Lee JE, Chang Y, et al. Dietary sodium and potassium intake in relation to non-alcoholic fatty liver disease. Br J Nutr. 2016 Oct;116(8):1447–1456. PubMed PMID: 27725000.
   PubMed Web of Science ®Google Scholar
• Lanaspa MA, Kuwabara M, Andres-Hernando A, et al. High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism. Proc Natl Acad Sci USA. 2018 Mar 20;115(12):3138–3143. PubMed PMID: 29507217; PubMed Central PMCID: PMCPMC5866545.
   PubMed Web of Science ®Google Scholar
• Roychowdhury S, Selvakumar PC, Cresci GAM. The role of the gut microbiome in nonalcoholic fatty liver disease. Med Sci (Basel). 2018 Jun 5;6(2). PubMed PMID: 29874807; PubMed Central PMCID: PMCPMC6024579. DOI:10.3390/medsci6020047
   PubMedGoogle Scholar
• Saltzman ET, Palacios T, Thomsen M, et al. Intestinal microbiome shifts, dysbiosis, inflammation, and non-alcoholic fatty liver disease. Front Microbiol. 2018;9:61. PubMed PMID: 29441049; PubMed Central PMCID: PMCPMC5797576.
   PubMed Web of Science ®Google Scholar
• Adorini L, Pruzanski M, Shapiro D. Farnesoid X receptor targeting to treat nonalcoholic steatohepatitis. Drug Discov Today. 2012 Sep;17(17–18):988–997. PubMed PMID: 22652341.
   PubMed Web of Science ®Google Scholar
• Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the study of liver diseases. Hepatology. 2017 Jul 17. PubMed PMID: 28714183. DOI:10.1002/hep.29367
   Google Scholar
• European Association for the Study of the L, European Association for the Study of D, European Association for the Study of O. EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016 Jun;64(6):1388–1402. PubMed PMID: 27062661.
   PubMed Web of Science ®Google Scholar
• Corey KE, Klebanoff MJ, Tramontano AC, et al. Screening for nonalcoholic steatohepatitis in individuals with type 2 diabetes: a cost-effectiveness analysis. Dig Dis Sci. 2016 Jul;61(7):2108–2117. PubMed PMID: 26825843; PubMed Central PMCID: PMCPMC4920690.
   PubMed Web of Science ®Google Scholar
• Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002 Sep;123(3):745–750. PubMed PMID: 12198701.
   PubMed Web of Science ®Google Scholar
• Uslusoy HS, Nak SG, Gulten M, et al. Non-alcoholic steatohepatitis with normal aminotransferase values. World J Gastroenterol. 2009 Apr 21;15(15):1863–1868. PubMed PMID: 19370784; PubMed Central PMCID: PMCPMC2670414.
   PubMed Web of Science ®Google Scholar
• Bedogni G, Bellentani S, Miglioli L, et al. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006;6:33. Published 2006 Nov 2. DOI:10.1186/1471-230X-6-33
   Google Scholar
• Poynard T, Ratziu V, Naveau S, et al. The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis. Comp Hepatol. 2005 Dec;23(4):10. PubMed PMID: 16375767; PubMed Central PMCID: PMCPMC1327680.
   PubMedGoogle Scholar
• Kotronen A, Peltonen M, Hakkarainen A, et al. Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors. Gastroenterology. 2009 Sep;137(3):865–872. PubMed PMID: 19524579.
   PubMed Web of Science ®Google Scholar
• Lee SS, Park SH. Radiologic evaluation of nonalcoholic fatty liver disease. World J Gastroenterol. 2014 Jun 21;20(23):7392–7402. PubMed PMID: 24966609; PubMed Central PMCID: PMCPMC4064084.
   PubMed Web of Science ®Google Scholar
• van Werven JR, Marsman HA, Nederveen AJ, et al. Assessment of hepatic steatosis in patients undergoing liver resection: comparison of US, CT, T1-weighted dual-echo MR imaging, and point-resolved 1H MR spectroscopy. Radiology. 2010 Jul;256(1):159–168. PubMed PMID: 20574093.
   PubMed Web of Science ®Google Scholar
• de Moura Almeida A, Cotrim HP, Barbosa DB, et al. Fatty liver disease in severe obese patients: diagnostic value of abdominal ultrasound. World J Gastroenterol. 2008 Mar 07;14(9):1415–1418. PubMed PMID: 18322958; PubMed Central PMCID: PMCPMC2693692.
   PubMed Web of Science ®Google Scholar
• Park SH, Kim PN, Kim KW, et al. Macrovesicular hepatic steatosis in living liver donors: use of CT for quantitative and qualitative assessment. Radiology. 2006 Apr;239(1):105–112. PubMed PMID: 16484355.
   PubMed Web of Science ®Google Scholar
• Hagstrom H, Nasr P, Ekstedt M, et al. Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD. J Hepatol. 2017 Aug 10. PubMed PMID: 28803953. DOI:10.1016/j.jhep.2017.07.027
   PubMed Web of Science ®Google Scholar
• Buzzetti E, Lombardi R, De Luca L, et al. Noninvasive assessment of fibrosis in patients with nonalcoholic fatty liver disease. Int J Endocrinol. 2015;2015:343828. PubMed PMID: 26064107; PubMed Central PMCID: PMCPMC4430647.
   PubMed Web of Science ®Google Scholar
• Kowdley KV, Belt P, Wilson LA, et al. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease. Hepatology. 2012 Jan;55(1):77–85. PubMed PMID: 21953442; PubMed Central PMCID: PMCPMC3245347.
   PubMed Web of Science ®Google Scholar
• Tapper EB, Krajewski K, Lai M, et al. Simple non-invasive biomarkers of advanced fibrosis in the evaluation of non-alcoholic fatty liver disease. Gastroenterol Rep (Oxf). 2014 Nov;2(4):276–280. PubMed PMID: 25002154; PubMed Central PMCID: PMCPMC4219143.
   PubMedGoogle Scholar
• Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007 Apr;45(4):846–854. PubMed PMID: 17393509.
   PubMed Web of Science ®Google Scholar
• Sumida Y, Yoneda M, Hyogo H, et al. Validation of the FIB4 index in a Japanese nonalcoholic fatty liver disease population. BMC Gastroenterol. 2012 Jan;05(12):2. PubMed PMID: 22221544; PubMed Central PMCID: PMCPMC3266187.
   PubMed Web of Science ®Google Scholar
• Shah AG, Lydecker A, Murray K, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009 Oct;7(10):1104–1112. PubMed PMID: 19523535; PubMed Central PMCID: PMCPMC3079239.
   PubMed Web of Science ®Google Scholar
• Wong VW, Vergniol J, Wong GL, et al. Liver stiffness measurement using XL probe in patients with nonalcoholic fatty liver disease. Am J Gastroenterol. 2012 Dec;107(12):1862–1871. PubMed PMID: 23032979.
   PubMed Web of Science ®Google Scholar
• Sirli R, Sporea I, Deleanu A, et al. Comparison between the M and XL probes for liver fibrosis assessment by transient elastography. Med Ultrason. 2014 Jun;16(2):119–122. PubMed PMID: 24791843.
   PubMed Web of Science ®Google Scholar
• Kim D, Kim WR, Talwalkar JA, et al. Advanced fibrosis in nonalcoholic fatty liver disease: noninvasive assessment with MR elastography. Radiology. 2013 Aug;268(2):411–419. PubMed PMID: 23564711; PubMed Central PMCID: PMCPMC3721049.
   PubMed Web of Science ®Google Scholar
• Sumida Y, Nakajima A, Itoh Y. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2014 Jan 14;20(2):475–485. PubMed PMID: 24574716; PubMed Central PMCID: PMCPMC3923022.
   PubMed Web of Science ®Google Scholar
• Hannah WN Jr., Harrison SA. Noninvasive imaging methods to determine severity of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology. 2016 Dec;64(6):2234–2243. PubMed PMID: 27338123.
   PubMed Web of Science ®Google Scholar
• Venkatesh SK, Yin M, Ehman RL. Magnetic resonance elastography of liver: technique, analysis, and clinical applications. J Magn Reson Imaging. 2013 Mar;37(3):544–555. PubMed PMID: 23423795; PubMed Central PMCID: PMCPMC3579218.
   PubMed Web of Science ®Google Scholar
• Siddiqui MS, Vuppalanchi R, Van Natta ML, et al. Vibration-controlled transient elastography to assess fibrosis and steatosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2018 Apr 26. PubMed PMID: 29705261. DOI:10.1016/j.cgh.2018.04.043
   Web of Science ®Google Scholar
• Romero-Gomez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol. 2017 Oct;67(4):829–846. PubMed PMID: 28545937.
   PubMed Web of Science ®Google Scholar
• Ryan MC, Itsiopoulos C, Thodis T, et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol. 2013 Jul;59(1):138–143. PubMed PMID: 23485520.
   PubMed Web of Science ®Google Scholar
• Aguilar-Olivos NE, Almeda-Valdes P, Aguilar-Salinas CA, et al. The role of bariatric surgery in the management of nonalcoholic fatty liver disease and metabolic syndrome. Metabolism. 2016 Aug;65(8):1196–1207. PubMed PMID: 26435078.
   PubMed Web of Science ®Google Scholar
• Nostedt JJ, Switzer NJ, Gill RS, et al. The effect of bariatric surgery on the spectrum of fatty liver disease. Can J Gastroenterol Hepatol. 2016;2016:2059245. PubMed PMID: 27777925; PubMed Central PMCID: PMCPMC5061986.
   PubMedGoogle Scholar
• Mummadi RR, Kasturi KS, Chennareddygari S, et al. Effect of bariatric surgery on nonalcoholic fatty liver disease: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2008 Dec;6(12):1396–1402. PubMed PMID: 18986848.
   PubMed Web of Science ®Google Scholar
• Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010 May 6;362(18):1675–1685. PubMed PMID: 20427778; PubMed Central PMCID: PMCPMC2928471.
   PubMed Web of Science ®Google Scholar
• El Hadi H, Vettor R, Rossato M. Vitamin E as a treatment for nonalcoholic fatty liver disease: reality or myth? Antioxidants (Basel). 2018 Jan 16;7(1). PubMed PMID: 29337849; PubMed Central PMCID: PMCPMC5789322. DOI:10.3390/antiox7010012
   PubMedGoogle Scholar
• Cusi K, Orsak B, Bril F, et al. Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial. Ann Intern Med. 2016 Sep 6;165(5):305–315. PubMed PMID: 27322798.
   PubMed Web of Science ®Google Scholar
• Hossain N, Kanwar P, Mohanty SR. A comprehensive updated review of pharmaceutical and nonpharmaceutical treatment for NAFLD. Gastroenterol Res Pract. 2016;2016:7109270. PubMed PMID: 27006654; PubMed Central PMCID: PMCPMC4781972.
   PubMed Web of Science ®Google Scholar
• Armstrong MJ, Houlihan DD, Rowe IA, et al. Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta-analysis of the LEAD program. Aliment Pharmacol Ther. 2013 Jan;37(2):234–242. PubMed PMID: 23163663.
   PubMed Web of Science ®Google Scholar
• Kuchay MSKS, Mishra SK, Mithal A Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT trial). Endocrine Society Annual Meeting; Chicago; 2018.
   Google Scholar
• Pastori D, Polimeni L, Baratta F, et al. The efficacy and safety of statins for the treatment of non-alcoholic fatty liver disease. Dig Liver Dis. 2015 Jan;47(1):4–11. PubMed PMID: 25224698.
   PubMedGoogle Scholar
• Scorletti E, Byrne CD. Omega-3 fatty acids and non-alcoholic fatty liver disease: evidence of efficacy and mechanism of action. Mol Aspects Med. 2018 Mar 22;64:135–146. PubMed PMID: 29544992.
   PubMed Web of Science ®Google Scholar
• Neuschwander-Tetri BA, Loomba R, Sanyal AJ, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015 Mar 14;385(9972):956–965. PubMed PMID: 25468160; PubMed Central PMCID: PMCPMC4447192.
   PubMed Web of Science ®Google Scholar
• Ratziu V, Harrison SA, Francque S, et al. Elafibranor, an agonist of the peroxisome proliferator-activated receptor-alpha and -delta, induces resolution of nonalcoholic steatohepatitis without fibrosis worsening. Gastroenterology. 2016 May;150(5):1147–1159 e5. PubMed PMID: 26874076.
   PubMed Web of Science ®Google Scholar
• Loomba R, Lawitz E, Mantry PS, et al. The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: a randomized, phase 2 trial. Hepatology. 2017 Sep 11. PubMed PMID: 28892558; PubMed Central PMCID: PMCPMC5814892. DOI:10.1002/hep.29514
   Google Scholar
• American Diabetes A. 6. Glycemic targets: standards of medical care in diabetes-2018. Diabetes Care. 2018 Jan;41(Suppl 1):S55–S64. PubMed PMID: 29222377.
   PubMedGoogle Scholar
• Portillo-Sanchez P, Cusi K. Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) in patients with type 2 diabetes mellitus. Clin Diabetes Endocrinol. 2016;2:9. PubMed PMID: 28702244; PubMed Central PMCID: PMCPMC5471954.
   PubMedGoogle Scholar
• Targher G, Lonardo A, Byrne CD. Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus. Nat Rev Endocrinol. 2018 Feb;14(2):99–114. PubMed PMID: 29286050.
   PubMed Web of Science ®Google Scholar
• Paneni F, Luscher TF. Cardiovascular protection in the treatment of type 2 diabetes: a review of clinical trial results across drug classes. Am J Cardiol. 2017 Jul 1;120(1S):S17–S27. PubMed PMID: 28606340.
   PubMedGoogle Scholar
• Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S1–S45. PubMed PMID: 24222016.
   PubMed Web of Science ®Google Scholar
• Gitto S, Vitale G, Villa E, et al. Treatment of nonalcoholic steatohepatitis in adults: present and future. Gastroenterol Res Pract. 2015;2015:732870. PubMed PMID: 25866507; PubMed Central PMCID: PMCPMC4381725.
   PubMedGoogle Scholar
• Aron-Wisnewsky J, Clement K, Pepin JL. Nonalcoholic fatty liver disease and obstructive sleep apnea. Metabolism. 2016 Aug;65(8):1124–1135. PubMed PMID: 27324067.
   PubMed Web of Science ®Google Scholar
• Sundaram SS, Halbower A, Pan Z, et al. Nocturnal hypoxia-induced oxidative stress promotes progression of pediatric non-alcoholic fatty liver disease. J Hepatol. 2016 Sep;65(3):560–569. PubMed PMID: 27501738; PubMed Central PMCID: PMCPMC4992457.
   PubMed Web of Science ®Google Scholar
• Sundaram SS, Halbower AC, Klawitter J, et al. Treating obstructive sleep apnea and chronic intermittent hypoxia improves the severity of nonalcoholic fatty liver disease in children. J Pediatr. 2018 May 8;198:67–75.e1. PubMed PMID: 29752170.
   PubMed Web of Science ®Google Scholar