Abstract

Nonalcoholic fatty liver disease (NAFLD) is quickly becoming one of the most prominent causes of liver disease worldwide. The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it. Current efforts to elucidate the mechanism and causes of the disease have answered some questions, but much remains unknown about NAFLD. The aim of this article is to discuss the current knowledge regarding the athogenesis of the disease, as well as the current and future diagnostic, preventative, and therapeutic options available to clinicians for the management of NAFLD.

• 1.   Younossi Z.M., Stepanova M., Afendy M., Fang Y., Younossi Y., Mir H., Srishord M. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol. 2011
• 2.   Strauss R.S., Barlow S.E., Dietz WH. Prevalence of abnormal serum aminotransferase values in overweight and obese adolescents. J Pediatr. 2000; 136: 727–733.
• 3.   Suzuki A., Angulo P., Lymp J., St Sauver J., Muto A., Okada T., Lindor K. Chronological development of elevated aminotransferases in a nonalcoholic population. Hepatology. 2005; 41: 64–71. doi: 10.1002/hep.20543.
• 4.   Hamaguchi M., Kojima T., Takeda N., Nakagawa T., Taniguchi H., Fujii K., Omatsu T., Nakajima T., Sarui H., Shimazaki M., et al. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med. 2005; 143: 722–728.
• 5.   Whalley S., Puvanachandra P., Desai A., Kennedy H. Hepatology outpatient service provision in secondary care: A study of liver disease incidence and resource costs. Clin Med. 2007; 7: 119–124.
• 6.   Sozio M.S., Liangpunsakul S., Crabb D. The role of lipid metabolism in the pathogenesis of alcoholic and nonalcoholic hepatic steatosis. Semin Liver Dis. 2010; 30: 378–390.
• 7.   Ludwig J., Viggiano T.R., McGill D.B., Oh B.J. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease.
• 8.   Cohen J.C., Horton J.D., Hobbs H.H. Human fatty liver disease: old questions and new insights. Science. 2011; 332: 1519–1523.
• 9.   World Gastroenterology Organisation Global Guidelines. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis 2012.
• 10.   Neuschwander-Tetri B.A. Nonalcoholic steatohepatitis and the metabolic syndrome. Am J Med Sci. 2005; 330: 326–335.
• 11.   Argo C.K., Caldwell S.H. Epidemiology and natural history of non-alcoholic steatohepatitis. Clin Liver Dis. 2009.
• 12.   Brown M.S., Goldstein J.L. The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription43 IJMHS / Volume 13, Number 1 / January – June 2026 factor. Cell. 1997.
• 13.   Yamashita H., Takenoshita M., Sakurai M., Bruick R.K., Henzel W.J., Shillinglaw W., Arnot D., Uyeda K. A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver. Proc Natl Acad Sci USA. 2001; 98: 9116.
• 14.   Ma L., Robinson L.N., Towle H.C. ChREBP*Mlx is the principal mediator of glucose-induced gene expression in the liver. J Biol Chem. 2006;
• 15.   Willy P.J., Umesono K., Ong E.S., Evans RM, Heyman R.A., Mangelsdorf D.J. LXR, a nuclear receptor that defines a distinct retinoid response pathway.
• 16.   Huang Y., He S., Li J.Z., Seo Y.K., Osborne T.F., Cohen J.C., Hobbs H.H. A feed-forward loop amplifies nutritional regulation of PNPLA3. Proc Natl Acad Sci USA. 2010; 107: 7892–7897.
• 17.   Cha J.Y., Repa J.J. The liver X receptor (LXR) and hepatic lipogenesis. The carbohydrateresponse element-binding protein is a target gene of LXR. J Biol Chem. 2007; 282: 743–751. doi: 10.1074/jbc.M605023200.
• 18.   Langin D. Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome. Pharmacol Res. 2006; 53: 482–491. doi: 10.1016/j.phrs.2006.03.009.
• 19.   Hooper A.J., Adams L.A., Burnett J.R. Genetic determinants of hepatic steatosis in man. J Lipid Res. 2011; 52: 593–617. doi: 10.1194/jlr. R008896.
• 20.   Bandsma R.H., Prinsen B.H., van Der Velden Mde S., Rake J.P., Boer T., Smit G.P., Reijngoud D.J., Kuipers F. Increased de novo lipogenesis and delayed conversion of large VLDL into intermediate density lipoprotein particles contribute to hyperlipidemia in glycogen storage disease type 1a. Pediatr Res.
• 21.   Schwimmer J.B., Celedon M.A., Lavine J.E., Salem R., Campbell N., Schork N.J., Shiehmorteza M., Yokoo T., Chavez A., Middleton M.S., et al. Heritability of nonalcoholic fatty liver disease. Gastroenterology.
• 22.   Hesham A. Kader H. Nonalcoholic fatty liver disease in children living in the obeseogenic society. World J Pediatr. 2009; 5: 245–254.
• 23.   Browning J.D., Szczepaniak L.S., Dobbins R., Nuremberg P., Horton J.D., Cohen J.C., Grundy S.M., Hobbs H.H. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology.
• 24.   Bambha K., Belt P., Abraham M., Wilson L.A., Pabst M., Ferrell L., Unalp-Arida A., Bass N. Ethnicity and nonalcoholic fatty liver disease. Hepatology.
• 25.   Speliotes E.K., Butler J.L., Palmer C.D., Voight B.F., Hirschhorn J.N. PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease.
• 26.   Romeo S., Kozlitina J., Xing C., Pertsemlidis A., Cox D., Pennacchio L.A., Boerwinkle E., Cohen J.C., Hobbs H.H. Gene.tic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease.

Data Sharing Statement

Funding