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Lean NASH: distinctiveness and clinical implication

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Abstract

Introduction

Non-alcoholic fatty liver (NAFL) in the absence of overweight and/or obesity, defined by the anthropometric parameter, body mass index (BMI), has been designated as ‘lean NASH.’ While maintaining a close pathophysiological link with metabolic syndrome (MS) and insulin resistance (IR), the presence of subtle alterations in measures of total body and regional adiposity not exceeding the designed cut-offs, are hallmarks of ‘lean NASH.’

Material and methods

Available literature related to non-alcoholic steatohepatitis (NASH) in lean or non-obese individuals and its pathogenesis in general published in English language journals till the time of manuscript preparation were reviewed and critically analysed.

Analysis

Being a closely related but variant phenotype of NASH, its features metabolically resemble the well-characterized entity ‘metabolically obese normal weight (MONW)’ individuals. Apart from total body adiposity, distribution of fat in different body compartments has assumed greater pathophysiologic relevance in characterizing ‘lean NASH’. Detection of NASH in stringently defined non-obese individuals, by both BMI and waist circumference indices, indicates existence of a subset of NASH in which fat compartmentalization at ectopic sites is not picked up by the anthropometric yardsticks used. Volume [Quantity] and biological behavior of the visceral and deep subcutaneous adipose tissues contribute to this variant of NASH in non-obese subjects. Genetic predisposition to IR and MS along with the environmental influences like childhood nutritional status, dietary composition and gut microbiome possibly play pathogenetic role.

Conclusion

The most important concern is in the principles of nomenclature within syndromes where clinical dissimilarities exist despite biological similarities. Till a uniformly acceptable pathophysiological and/or etiology-based classification emerges, the term “lean NASH” would continue to provide us an opportunity to ponder over and refine this subset of fatty liver in non-obese people and potentially significant liver disease.

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References

  1. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003;37(4):917–923

    Article  PubMed  Google Scholar 

  2. Kim LJ, Nalls MA, Eiriksdottir G, Sigurdsson S, Launer LJ, Koster A, et al. AGES-Reykjavik Study Investigators. 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):1265–1271

    Article  Google Scholar 

  3. Misra A, Vikram NK. Insulin resistance syndrome (metabolic syndrome) and obesity in Asian Indians: evidence and implications. Nutrition 2004;20(5):482–491

    Article  CAS  PubMed  Google Scholar 

  4. Chen CH, Huang MH, Yang JC, Nien CK, Yang CC, Yeh YH, et al. Prevalence and risk factors of nonalcoholic fatty liver disease in an adult population of Taiwan: metabolic significance of nonalcoholic fatty liver disease in nonobese adults. J Clin Gastroenterol 2006;40(8):745–752

    Article  CAS  PubMed  Google Scholar 

  5. 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):2169–2175

    Article  PubMed  Google Scholar 

  6. 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):319–327

    Article  Google Scholar 

  7. Margariti E, Deutsch M, Manolakopoulos S, Papatheodoridis GV. Non-alcoholic fatty liver disease may develop in individuals with normal body mass index. Ann Gastroenterology 2012;25(1):45–51

    Google Scholar 

  8. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380(9859):2224–2260

    Article  PubMed  Google Scholar 

  9. Ruderman NB, Schneider SH, Berchtold P. The “metabolically-obese,” normal-weight individual. Am J Clin Nutr 1981;34(8):1617–21

    CAS  PubMed  Google Scholar 

  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

    Article  PubMed Central  PubMed  Google Scholar 

  11. 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 USA 2006;103(48):18273–18277

    Article  CAS  PubMed  Google Scholar 

  12. 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;51:1593–1602

    Article  CAS  PubMed  Google Scholar 

  13. Phan-Hug F, Beckmann JS, Jacquemont S. Genetic testing in patients with obesity. Best Pract Res Clin Endocrinol Metab 2012;26(2):133–143

    Article  CAS  PubMed  Google Scholar 

  14. Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006;444(7121):860–867

    Article  CAS  PubMed  Google Scholar 

  15. Troiano RP, Frongillo EA Jr, Sobal J, Levitsky DA. The relationship between body weight and mortality: a quantitative analysis of combined information from existing studies. Int J Obes Relat Metab Disord 1996;20(1):63–75

    CAS  PubMed  Google Scholar 

  16. Fracanzani AL, Valenti L, Bugianesi E, Vanni E, Grieco A, Miele L, et al. Risk of nonalcoholic steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease and low visceral adiposity. J Hepatol 2011;54(6):1244–1249

    Article  CAS  PubMed  Google Scholar 

  17. Wang ZM, Pierson RN Jr, Heymsfield SB. The five-level model: a new approach to organizing body-composition research. Am J Clin Nutr 1992;56(1):19–28

    CAS  PubMed  Google Scholar 

  18. WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363(9403):157–163

    Article  Google Scholar 

  19. Kohli S, Sniderman AD, Tchernof A, Lear SA. Ethnic-specific differences in abdominal subcutaneous adipose tissue compartments. Obesity (Silver Spring) 2010;18(11):2177–2183

    Article  Google Scholar 

  20. Chang Y, Ryu S, Sung E, Woo HY, Cho SI, Yoo SH, et al. Weight gain within the normal weight range predicts ultrasonographically detected fatty liver in healthy Korean men. Gut 2009;58(10):1419–1425

    Article  CAS  PubMed  Google Scholar 

  21. Tanaka S, Honda M, Wu B, Kazumi T. Clinical features of normal weight Japanese patients with type 2 diabetes who had formerly been obese. J Atheroscler Thromb 2011;18(2):115–121

    Article  PubMed  Google Scholar 

  22. Stevens J, McClain JE, Truesdale KP. Selection of measures in epidemiologic studies of the consequences of obesity. Int J Obes (Lond) 2008;32(Suppl 3):S60–S66

    Article  Google Scholar 

  23. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, et al. Dynamics of fat cell turnover in humans. Nature 2008;453(7196):783–787

    Article  CAS  PubMed  Google Scholar 

  24. Jernås M, Palming J, Sjöholm K, Jennische E, Svensson PA, Gabrielsson BG, et al. Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression. FASEB J 2006;20(9):1540–1542

    Article  PubMed  Google Scholar 

  25. Flegal KM, Troiano RP. Changes in the distribution of body mass index of adults and children in the US population. Int J Obes Relat Metab Disord 2000;24(7):807–818

    Article  CAS  PubMed  Google Scholar 

  26. Kozlitina J, Boerwinkle E, Cohen JC, Hobbs HH. Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance. Hepatology 2011;53(2):467–474

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Petersen KF, Dufour S, Hariri A, Nelson-Williams C, Foo JN, Zhang XM, et al. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N Engl J Med 2010;362(12):1082–1089

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Perry JR, Voight BF, Yengo L, Amin N, Dupuis J, Ganser M. Stratifying type 2 diabetes cases by BMI identifies genetic risk variants in LAMA1 and enrichment for risk variants in lean compared to obese cases. PLoS Genet 2012;8(5):e1002741

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Yasutake K, Nakamuta M, Shima Y, Ohyama A, Masuda K, Haruta N, et al. Nutritional investigation of non-obese patients with non-alcoholic fatty liver disease: the significance of dietary cholesterol. Scand J Gastroenterol 2009;44(4):471–477

    Article  CAS  PubMed  Google Scholar 

  30. Shanahan F. The gut microbiota-a clinical perspective on lessons learned. Nat Rev Gastroenterol Hepatol 2012;9(10):609–614

    Article  CAS  PubMed  Google Scholar 

  31. Machado MV, Cortez-Pinto H. Non-invasive diagnosis of non-alcoholic fatty liver disease. A critical appraisal. J Hepatol 2013;58(5):1007–1019

    Article  PubMed  Google Scholar 

  32. Torres DM, Harrison SA. Diagnosis and therapy of nonalcoholic steatohepatitis. Gastroenterology 2008;134(6):1682–1698

    Article  CAS  PubMed  Google Scholar 

  33. Wieckowska A, Feldstein AE. Diagnosis of nonalcoholic fatty liver disease: invasive versus noninvasive. Semin Liver Dis 2008;28(4):386–395

    Article  CAS  PubMed  Google Scholar 

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Conflict of interest

Abhijit Chowdhury and Kausik Das declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects.

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Authors and Affiliations

  1. Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, 244 A.J.C. Bose Road, Kolkata, 700020, India

    Kausik Das & Abhijit Chowdhury

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  1. Kausik Das
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  2. Abhijit Chowdhury
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Correspondence to Abhijit Chowdhury.

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Das, K., Chowdhury, A. Lean NASH: distinctiveness and clinical implication. Hepatol Int 7 (Suppl 2), 806–813 (2013). https://doi.org/10.1007/s12072-013-9477-5

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