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Current Hepatology Reports

, Volume 15, Issue 2, pp 134–139 | Cite as

Lean NAFLD: an Underrecognized Outlier

  • Julia Wattacheril
  • Arun J. SanyalEmail author
Fatty Liver Disease (SA Harrison and J George, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is commonly diagnosed in obese or overweight individuals. However, lean individuals with NAFLD are not rare but represent one significant end of the phenotypic spectrum of NAFLD. Although initial observations between obese and lean NAFLD reveal some metabolic parallels, these associations vary widely given differences in study populations and metabolic parameters assessed. The role of body composition in risk assessment is significant and incompletely assessed during most clinical encounters. Recent multinational investigation reveals an increased mortality in lean individuals with nonalcoholic steatohepatitis (NASH). Many aspects of lean NAFLD need further exploration including epidemiology, clinical risk assessment, histologic changes unique to lean NAFLD, genetic and pathophysiologic mechanisms predisposing at risk individuals, natural history, and treatment strategies in this underrecognized population.

Keywords

Lean Nonobese Normal weight Nonalcoholic fatty liver disease (NAFLD) Nonalcoholic steatohepatitis (NASH) 

Notes

Compliance with Ethical Standards

Conflict of Interest

JW and AJS declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Consultation WHOE. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363(9403):157–63.CrossRefGoogle Scholar
  2. 2.
    Bhat G, Baba CS, Pandey A, Kumari N, Choudhuri G. Insulin resistance and metabolic syndrome in nonobese Indian patients with non-alcoholic fatty liver disease. Trop Gastroenterol. 2013;34(1):18–24.CrossRefPubMedGoogle Scholar
  3. 3.
    Nishioji K, Sumida Y, Kamaguchi M, Mochizuki N, Kobayashi M, Nishimura T, et al. Prevalence of and risk factors for non-alcoholic fatty liver disease in a non-obese Japanese population, 2011–2012. J Gastroenterol. 2015;50(1):95–108.CrossRefPubMedGoogle Scholar
  4. 4.
    Feng RN, Du SS, Wang C, Li YC, Liu LY, Guo FC, et al. Lean-non-alcoholic fatty liver disease increases risk for metabolic disorders in a normal weight Chinese population. World J Gastroenterol. 2014;20(47):17932–40.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Margariti E, Deutsch M, Manolakopoulos S, Papatheodoridis GV. Non-alcoholic fatty liver disease may develop in individuals with normal body mass index. Ann Gastroenterol. 2012;25(1):45–51.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Kim HJ, Kim HJ, Lee KE, Kim DJ, Kim SK, Ahn CW, et al. Metabolic significance of nonalcoholic fatty liver disease in nonobese, nondiabetic adults. Arch Intern Med. 2004;164(19):2169–75.CrossRefPubMedGoogle Scholar
  7. 7.
    Kim LJ, Nalls MA, Eiriksdottir G, Sigurdsson S, Launer LJ, Koster A, et al. Associations of visceral and liver fat with the metabolic syndrome across the spectrum of obesity: the AGES-Reykjavik study. Obesity (Silver Spring). 2011;19(6):1265–71.CrossRefGoogle Scholar
  8. 8.
    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(6):319–27.CrossRefGoogle Scholar
  9. 9.
    Petersen KF, Dufour S, Feng J, Befroy D, Dziura J, Dalla Man C, et al. Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men. Proc Natl Acad Sci U S A. 2006;103(48):18273–7.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Chandalia M, Lin P, Seenivasan T, Livingston EH, Snell PG, Grundy SM, et al. Insulin resistance and body fat distribution in South Asian men compared to Caucasian men. PLoS One. 2007;2(8):e812.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.•
    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(5):1593–602. This study is one of the early prospective, biopsy-proven studies that described lean NAFLD in a nonclassical phenotype. The implications for the developed and developing world are not insignificant in terms of disease burden.CrossRefPubMedGoogle Scholar
  12. 12.••
    Dela Cruz AC, Bugianesi E, George J, Day CP, Liaquat H, Charatcharoenwitthaya P, et al. Characteristics and long-term prognosis of lean patients with nonalcoholic fatty liver disease. In: Digestive Disease Week; May 3-6, 2014; Chicago, Illinois. Abstract 3490. This large, multinational study with histologically proven NAFLD in lean individuals demonstrated increased mortality in this population compared with non-lean NAFLD. Although limited to an abstract, these outcomes highlight significant areas for future investigation.Google Scholar
  13. 13.
    Vos B, Moreno C, Nagy N, Fery F, Cnop M, Vereerstraeten P, et al. Lean non-alcoholic fatty liver disease (Lean-NAFLD): a major cause of cryptogenic liver disease. Acta Gastroenterol Belg. 2011;74(3):389–94.PubMedGoogle Scholar
  14. 14.
    Kim JY, van de Wall E, Laplante M, Azzara A, Trujillo ME, Hofmann SM, et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J Clin Invest. 2007;117(9):2621–37.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Grundy SM. Adipose tissue and metabolic syndrome: too much, too little or neither. Eur J Clin Invest. 2015;45(11):1209–17.CrossRefPubMedGoogle Scholar
  16. 16.
    Musso G, Gambino R, Durazzo M, Biroli G, Carello M, Faga E, et al. Adipokines in NASH: postprandial lipid metabolism as a link between adiponectin and liver disease. Hepatology. 2005;42(5):1175–83.CrossRefPubMedGoogle Scholar
  17. 17.
    Roust LR, Jensen MD. Postprandial free fatty acid kinetics are abnormal in upper body obesity. Diabetes. 1993;42(11):1567–73.CrossRefPubMedGoogle Scholar
  18. 18.
    Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD. Splanchnic lipolysis in human obesity. J Clin Invest. 2004;113(11):1582–8.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Guo Z, Hensrud DD, Johnson CM, Jensen MD. Regional postprandial fatty acid metabolism in different obesity phenotypes. Diabetes. 1999;48(8):1586–92.CrossRefPubMedGoogle Scholar
  20. 20.
    Guerrero R, Vega GL, Grundy SM, Browning JD. Ethnic differences in hepatic steatosis: an insulin resistance paradox? Hepatology. 2009;49(3):791–801.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Vega GL, Chandalia M, Szczepaniak LS, Grundy SM. Metabolic correlates of nonalcoholic fatty liver in women and men. Hepatology. 2007;46(3):716–22.CrossRefPubMedGoogle Scholar
  22. 22.•
    Karpe F, Pinnick KE. Biology of upper-body and lower-body adipose tissue—link to whole-body phenotypes. Nat Rev Endocrinol. 2015;11(2):90–100. The role of adiposity and body composition has clear implications in the development of lean NAFLD. This review elaborates on the connections between adipose tissue and the metabolic syndrome that are important for hepatologists to know.CrossRefPubMedGoogle Scholar
  23. 23.
    Das K, Chowdhury A. Lean NASH: distinctiveness and clinical implication. Hepatol Int. 2013;7 Suppl 2:806–13.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Center for Liver Disease and Transplantation, Columbia University Medical CenterNew York Presbyterian HospitalNew YorkUSA
  2. 2.VCU Medical CenterVirginia Commonwealth UniversityRichmondUSA

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