NAFLD is a clinical syndrome characterized by predominant macrovesicular steatosis of the liver. The clinical and histological phenotypes of NAFLD extend from a nonalcoholic fatty liver to NASH. Although the prevalence of NAFLD is increasing globally, and it is set to become the predominant cause of chronic liver disease in many parts of the world, the epidemiology and demographic characteristics of NAFLD vary worldwide. Indeed, the condition is associated with obesity and insulin resistance in most cases in the Western world, but the disease manifests at a lower BMI in Asian countries and many patients do not seem to have insulin resistance as determined using conventional methods. The similarities and differences in the epidemiology of NAFLD in different regions of the world are discussed and the potential role of genetics and insulin resistance in disease progression is also presented.
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Chalasani, N. et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 55, 2005–2023 (2012).
Adams, L. A. et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 129, 113–121 (2005).
Matteoni, C. A. et al. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 116, 1413–1419 (1999).
Clark, J. M., Brancati, F. L. & Diehl, A. M. The prevalence and etiology of elevated aminotransferase levels in the United States. Am. J. Gastroenterol. 98, 960–967 (2003).
Welsh, J. A., Karpen, S. & Vos, M. B. Increasing prevalence of nonalcoholic fatty liver disease among United States adolescents, 1988–1994 to 2007–2010. J. Pediatr. 162, 496–500 (2013).
Eguchi, Y. 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. 47, 586–595 (2012).
Williams, C. D. et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology 140, 124–131 (2011).
Loomba, R. et al. Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis. Hepatology 56, 943–951 (2012).
Browning, J. D. et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40, 1387–1395 (2004).
Centers for Disease Control and Prevention Overweight and Obesity [online], (2012).
Babusik, P., Bilal, M. & Duris, I. Nonalcoholic fatty liver disease of two ethnic groups in Kuwait: comparison of prevalence and risk factors. Med. Princ. Pract. 21, 56–62 (2012).
Caballeria, L. 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).
Bedogni, G. et al. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 42, 44–52 (2005).
Ratziu, V., Bellentani, S., Cortez-Pinto, H., Day, C. & Marchesini, G. A position statement on NAFLD/NASH based on the EASL 2009 special conference. J. Hepatol. 53, 372–384 (2010).
Fan, J. G. et al. Guidelines for the diagnosis and management of nonalcoholic fatty liver disease: update 2010: (published in Chinese on Chinese Journal of Hepatology 2010; 18, 163–166). J. Dig. Dis. 12, 38–44 (2011).
Farrell, G. C., Wong, V. W. & Chitturi, S. NAFLD in Asia—as common and important as in the West. Nat. Rev. Gastroenterol. Hepatol. 10, 307–318 (2013).
Das, K. et al. Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease. Hepatology 51, 1593–1602 (2010).
Amarapurkar, D. et al. Prevalence of non-alcoholic fatty liver disease: population based study. Ann. Hepatol. 6, 161–163 (2007).
Singh, S. P. et al. Prevalence of nonalcoholic fatty liver disease in coastal eastern India: a preliminary ultrasonographic survey. Trop. Gastroenterol. 25, 76–79 (2004).
Amarapurkar, D. N. et al. How common is non-alcoholic fatty liver disease in the Asia–Pacific region and are there local differences? J. Gastroenterol. Hepatol. 22, 788–793 (2007).
Onyekwere, C. A., Ogbera, A. O. & Balogun, B. O. Non-alcoholic fatty liver disease and the metabolic syndrome in an urban hospital serving an African community. Ann. Hepatol. 10, 119–124 (2011).
Mendez-Sanchez, N. Non alcoholic fatty liver disease. Ann. Hepatol. 8 (Suppl. 1), S3 (2009).
Chitturi, S. et al. Non-alcoholic fatty liver disease in the Asia–Pacific region: definitions and overview of proposed guidelines. J. Gastroenterol. Hepatol. 22, 778–787 (2007).
Farrell, G. C., Chitturi, S., Lau, G. K., Sollano, J. D. & Asia–Pacific Working Party on NAFLD. Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia–Pacific region: executive summary. J. Gastroenterol. Hepatol. 22, 775–777 (2007).
Larrain, S. & Rinella, M. E. A myriad of pathways to NASH. Clin. Liver Dis. 16, 525–548 (2012).
Pratt, D. S., Knox, T. A. & Erban, J. Tamoxifen-induced steatohepatitis. Ann. Intern. Med. 123, 236 (1995).
McLaren, D. S., Bitar, J. G. & Nassar, V. H. Protein–calorie malnutrition and the liver. Prog. Liver Dis. 4, 527–536 (1972).
Misra, A. et al. Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. J. Assoc. Physicians India 57, 163–170 (2009).
Doycheva, I., Patel, N., Peterson, M. & Loomba, R. Prognostic implication of liver histology in patients with nonalcoholic fatty liver disease in diabetes. J. Diabetes Complications 27, 293–300 (2013).
Loomba, R. et al. Genetic covariance between γ-glutamyl transpeptidase and fatty liver risk factors: role of β2-adrenergic receptor genetic variation in twins. Gastroenterology 139, 836–845 (2010).
Petersen, K. F. et al. Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men. Proc. Natl Acad. Sci. USA 103, 18273–18277 (2006).
Fan, J. G. et al. Effects of nonalcoholic fatty liver disease on the development of metabolic disorders. J. Gastroenterol. Hepatol. 22, 1086–1091 (2007).
Prashanth, M. et al. Prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. J. Assoc. Physicians India 57, 205–210 (2009).
Fan, J. G. & Peng, Y. D. Metabolic syndrome and non-alcoholic fatty liver disease: Asian definitions and Asian studies. Hepatobiliary Pancreat. Dis. Int. 6, 572–578 (2007).
Romeo, S. et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet. 40, 1461–1465 (2008).
Rotman, Y. et al. The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease. Hepatology 52, 894–903 (2010).
Chalasani, N. et al. Genome-wide association study identifies variants associated with histologic features of nonalcoholic fatty liver disease. Gastroenterology 139, 1567–1576 (2010).
Speliotes, E. K. et al. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet. 7, e1001324 (2011).
Miele, L. et al. The Kruppel-like factor 6 genotype is associated with fibrosis in nonalcoholic fatty liver disease. Gastroenterology 135, 282–291 (2008).
Bechmann, L. P. et al. Glucokinase links Kruppel-like factor 6 to the regulation of hepatic insulin sensitivity in nonalcoholic fatty liver disease. Hepatology 55, 1083–1093 (2012).
Anstee, Q. M. & Day, C. P. The genetics of NAFLD. Nat. Rev. Gastroenterol. Hepatol. http://dx.doi.org/10.1038/nrgastro.2013.183.
Petersen, K. F. et al. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N. Engl. J. Med. 362, 1082–1089 (2010).
Ekstedt, M. et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 44, 865–873 (2006).
Rafiq, N. et al. Long-term follow-up of patients with nonalcoholic fatty liver. Clin. Gastroenterol. Hepatol. 7, 234–238 (2009).
Noureddin, M. et al. Clinical and histological determinants of nonalcoholic steatohepatitis and advanced fibrosis in elderly patients. Hepatology http://dx.doi.org/10.1002/hep.26465.
Sanyal, A. J. et al. Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C. Hepatology 43, 682–689 (2006).
Ascha, M. S. et al. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 51, 1972–1978 (2010).
White, D. L., Kanwal, F. & El-Serag, H. B. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin. Gastroenterol. Hepatol. 10, 1342–1359 (2012).
Sanyal, A., Poklepovic, A., Moyneur, E. & Barghout, V. Population-based risk factors and resource utilization for HCC: US perspective. Curr. Med. Res. Opin. 26, 2183–2191 (2010).
Charlton, M. R. et al. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology 141, 1249–1253 (2011).
Finucane, M. M. et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 377, 557–567 (2011).
WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363, 157–163 (2004).
Role of Funding Agencies: This work is supported in part by a grant from the NIH DKRO1081410 to A. J. Sanyal, which provided protected time for data collection, analysis and writing of the Perspectives. There is no conflict of interest with funding agencies. The authors have received funding support from the American Gastroenterological Association (AGA) Foundation Sucampo ASP Designated Research Award in Geriatric Gastroenterology and by a T. Franklin Williams Scholarship Award. Funding was also provided by: Atlantic Philanthropies, Inc., the John A. Hartford Foundation, the Association of Specialty Professors and the AGA and K23 DK090303 to R. Loomba. The authors' research work was also funded in part with the support of the UCSD Digestive Diseases Research Development Center, U. S. PHS grant #DK080506.
R. Loomba has received research grant funding from the American Gastroenterology Association, Daiichi Sankyo Inc. and Merck Inc. He has also served as a consultant or on the medical advisory board of Corgenix, Gilead, Merck Inc. and Siemens Inc. A. J. Sanyal serves as a consulting advisor for Amylin, Astellas, Bayer-Onyx (where he is on an analysis of data on health-care burden of liver cancer), Exhalenz, Gilead, Ikaria, Pfizer, Salix, Sanofi-Aventis and Takeda. He provided advice on the design of Clinical Research Forms for Gideon trial; however, he is not involved with Virginia Commonwealth University participation in Gideon. He is a member of the data safety monitoring board for Vertex, and has signed a contract to participate on the advisory board for Norgine, which has not materialized and no remuneration has been received. He receives research grants from Gilead, Intercept, Roche, Salix and Sanofi-Aventis, and conducts nonfunded research with CSL Behring, Ferring Lipomics and Regulus. He receives royalty income from UpToDate.
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Loomba, R., Sanyal, A. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol 10, 686–690 (2013). https://doi.org/10.1038/nrgastro.2013.171
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