Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The global NAFLD epidemic

Abstract

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: The prevalence of NAFLD plotted as a function of the prevalence of obesity in various countries around the world.

References

  1. 1

    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).

    Article  PubMed  Google Scholar 

  2. 2

    Adams, L. A. et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 129, 113–121 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3

    Matteoni, C. A. et al. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 116, 1413–1419 (1999).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4

    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).

    CAS  Article  Google Scholar 

  5. 5

    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).

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6

    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).

    CAS  Article  PubMed  Google Scholar 

  7. 7

    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).

    Article  Google Scholar 

  8. 8

    Loomba, R. et al. Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis. Hepatology 56, 943–951 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9

    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).

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10

    Centers for Disease Control and Prevention Overweight and Obesity [online], (2012).

  11. 11

    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).

    Article  PubMed  Google Scholar 

  12. 12

    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).

    CAS  Article  PubMed  Google Scholar 

  13. 13

    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).

    Article  Google Scholar 

  14. 14

    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).

    Article  PubMed  PubMed Central  Google Scholar 

  15. 15

    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).

    Article  PubMed  Google Scholar 

  16. 16

    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).

    CAS  Article  PubMed  Google Scholar 

  17. 17

    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).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. 18

    Amarapurkar, D. et al. Prevalence of non-alcoholic fatty liver disease: population based study. Ann. Hepatol. 6, 161–163 (2007).

    PubMed  Google Scholar 

  19. 19

    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).

    PubMed  Google Scholar 

  20. 20

    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).

    Article  PubMed  Google Scholar 

  21. 21

    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).

    PubMed  Google Scholar 

  22. 22

    Mendez-Sanchez, N. Non alcoholic fatty liver disease. Ann. Hepatol. 8 (Suppl. 1), S3 (2009).

    PubMed  Google Scholar 

  23. 23

    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).

    Article  PubMed  Google Scholar 

  24. 24

    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).

    Article  PubMed  Google Scholar 

  25. 25

    Larrain, S. & Rinella, M. E. A myriad of pathways to NASH. Clin. Liver Dis. 16, 525–548 (2012).

    Article  PubMed  Google Scholar 

  26. 26

    Pratt, D. S., Knox, T. A. & Erban, J. Tamoxifen-induced steatohepatitis. Ann. Intern. Med. 123, 236 (1995).

    CAS  Article  PubMed  Google Scholar 

  27. 27

    McLaren, D. S., Bitar, J. G. & Nassar, V. H. Protein–calorie malnutrition and the liver. Prog. Liver Dis. 4, 527–536 (1972).

    CAS  PubMed  Google Scholar 

  28. 28

    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).

    CAS  PubMed  Google Scholar 

  29. 29

    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).

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30

    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).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31

    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).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32

    Fan, J. G. et al. Effects of nonalcoholic fatty liver disease on the development of metabolic disorders. J. Gastroenterol. Hepatol. 22, 1086–1091 (2007).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33

    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).

    CAS  PubMed  Google Scholar 

  34. 34

    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).

    PubMed  Google Scholar 

  35. 35

    Romeo, S. et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet. 40, 1461–1465 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36

    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).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37

    Chalasani, N. et al. Genome-wide association study identifies variants associated with histologic features of nonalcoholic fatty liver disease. Gastroenterology 139, 1567–1576 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38

    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).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39

    Miele, L. et al. The Kruppel-like factor 6 genotype is associated with fibrosis in nonalcoholic fatty liver disease. Gastroenterology 135, 282–291 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40

    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).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. 41

    Anstee, Q. M. & Day, C. P. The genetics of NAFLD. Nat. Rev. Gastroenterol. Hepatol. http://dx.doi.org/10.1038/nrgastro.2013.183.

  42. 42

    Petersen, K. F. et al. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N. Engl. J. Med. 362, 1082–1089 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43

    Ekstedt, M. et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 44, 865–873 (2006).

    CAS  Article  Google Scholar 

  44. 44

    Rafiq, N. et al. Long-term follow-up of patients with nonalcoholic fatty liver. Clin. Gastroenterol. Hepatol. 7, 234–238 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  45. 45

    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.

  46. 46

    Sanyal, A. J. et al. Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C. Hepatology 43, 682–689 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  47. 47

    Ascha, M. S. et al. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 51, 1972–1978 (2010).

    Article  Google Scholar 

  48. 48

    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).

    Article  PubMed  PubMed Central  Google Scholar 

  49. 49

    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).

    CAS  Article  PubMed  Google Scholar 

  50. 50

    Charlton, M. R. et al. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology 141, 1249–1253 (2011).

    Article  PubMed  Google Scholar 

  51. 51

    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).

    Article  PubMed  PubMed Central  Google Scholar 

  52. 52

    WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363, 157–163 (2004).

Download references

Acknowledgements

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.

Author information

Affiliations

Authors

Contributions

The authors contributed equally to researching data for this article, writing the article and discussion of content. A. J. Sanyal reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Arun J. Sanyal.

Ethics declarations

Competing interests

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.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Loomba, R., Sanyal, A. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol 10, 686–690 (2013). https://doi.org/10.1038/nrgastro.2013.171

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing