MAFLD-Epidemiology, Natural History, Outcomes and Prevention



Abstract Views
788

Downloads
614

Citations

Share

##plugins.themes.bootstrap3.article.sidebar##

Submitted Jun 20, 2021
Published Jul 20, 2021
10.24018/ejmed.2021.3.4.941

Abstract viewed = 788 times

Table of Contents

##plugins.themes.bootstrap3.article.main##

Scientists have recently modified the term Non-Alcoholic Fatty Liver Disease (NAFLD) to Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in an attempt to improve the understanding and overall outcomes of the disease. The leaping prevalence and formidable mortality rate of fatty liver disease throughout the world is quite worrisome. Due to the lack of appropriate knowledge of the natural history of disease, suitable pharmacotherapy could never be devised. Thus, the management solely relies on patients’ earnest co-operation with fierce lifestyle changes such as exercise, weight loss and dietary modifications. In this era, it is essential to come up with strategies to curtail the underlying risk factors in order to prevent the rapid progression of MAFLD. In this review, we will discuss the epidemiology of NAFLD and the newly found evidence on.

Keywords: Epidemiology, MAFLD, NAFLD, Natural history, Prevention

Downloads

Download data is not yet available.

References

  1. Valenti, Gamal Shiha, Claudio Tiribelli, Hannele Yki-Järvinen, Jian-Gao Fan, Henning Grønbæk, Yusuf Yilmaz, Helena Cortez-Pinto et al. "A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement".
     Google Scholar
  2. Wong RJ, Aguilar M, Cheung R, Perumpail RB, Harrison SA, Younossi ZM, Ahmed A. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148(3):547–55.
     Google Scholar
  3. Younossi Z, Stepanova M, Ong JP, Jacobson IM, Bugianesi E, Duseja A, et al.; Global Nonalcoholic Steatohepatitis Council. Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates. Clin Gastroenterol Hepatol. 2019;17(4):748–755.e3. pii: S1542-3565(18)30611-6.
     Google Scholar
  4. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84. https://doi.org/10.1002/hep.28431.
     Google Scholar
  5. Lu, F.-B., Zheng, K. I., Rios, R. S., Targher, G., Byrne, C. D., and Zheng, M.-H. (2020) Global epidemiology of lean non-alcoholic fatty liver disease: A systematic review and meta-analysis. Journal of Gastroenterology and Hepatology, 35: 2041–2050. https://doi.org/10.1111/jgh.15156.
     Google Scholar
  6. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84. https://doi.org/10.1002/hep.28431.
     Google Scholar
  7. Ong JP, Elariny H, Collantes R, Younoszai A, Chandhoke V, Reines HD, et al. Predictors of nonalcoholic steatohepatitis and advanced fibrosis in morbidly obese patients. Obes Surg. 2005;15(3):310–5
     Google Scholar
  8. Wong, Robert J., and Ramsey Cheung. "Trends in the Prevalence of Metabolic Dysfunction–Associated Fatty Liver Disease in the United States, 2011–2018." Clinical Gastroenterology and Hepatology (2021).
     Google Scholar
  9. Chen, Yu-ling, Hao Li, Shu Li, Zhou Xu, Shen Tian, Juan Wu, Xin-yu Liang et al. "Prevalence of and risk factors for metabolic associated fatty liver disease in an urban population in China: a cross-sectional comparative study." BMC gastroenterology 21, no. 1 (2021): 1-12.
     Google Scholar
  10. Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology 2018;67:123-133.
     Google Scholar
  11. Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015;13(4):643–54.e1–9.
     Google Scholar
  12. Patel YA, Gifford EJ, Glass LM, McNeil R, Turner MJ, Han B, et al. Risk factors for biopsy-proven advanced non-alcoholic fatty liver disease in the Veterans Health Administration. Aliment Pharmacol Ther. 2018;47(2):268–78. https://doi.org/10.1111/apt.14411.
     Google Scholar
  13. Sanyal, A.J.; Banas, C.; Sargeant, C.; Luketic, V.A.; Sterling, R.K.; Stravitz, R.T.; Shiffman, M.L.; Heuman, D.; Coterrell, A.; Fisher, R.A.; et al. Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C. Hepatology 2006, 43, 682–689.
     Google Scholar
  14. McPherson S, Hardy T, Henderson E, Burt AD, Day CP, Anstee QM. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. J Hepatol. 2015;62(5):1148–55.
     Google Scholar
  15. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84. https://doi.org/10.1002/hep.28431.
     Google Scholar
  16. Pelusi S, Petta S, Rosso C, Borroni V, Fracanzani AL, Dongiovanni P, et al. Renin-angiotensin system inhibitors, type 2 diabetes and fibrosis progression: an observational study in patients with nonalcoholic fatty liver disease. PLoS One. 2016;11(9):e0163069.
     Google Scholar
  17. Porro, S.; Genchi, V.A.; Cignarelli, A.; Natalicchio, A.; Laviola, L.; Giorgino, F.; Perrini, S. Dysmetabolic adipose tissue in obesity: Morphological and functional characteristics of adipose stem cells and mature adipocytes in healthy and unhealthy obese subjects. J. Endocrinol. Investig. 2020, 1–21.
     Google Scholar
  18. Cimini, F.A.; Barchetta, I.; Ciccarelli, G.; Leonetti, F.; Silecchia, G.; Chiappetta, C.; Di Cristofano, C.; Capoccia, D.; Bertoccini, L.; Ceccarelli, V.; et al. Adipose tissue remodelling in obese subjects is a determinant of presence and severity of fatty liver disease. Diabetes Metab. Res. Rev. 2021, 37, e3358.
     Google Scholar
  19. Kim D, Kim WR. Nonobese fatty liver disease. Clin Gastroenterol Hepatol 2017;15:474-485.
     Google Scholar
  20. Liu, Jiaye, Ibrahim Ayada, Xiaofang Zhang, Ling Wang, Yang Li, Tianfu Wen, Zhongren Ma et al. "Estimating global prevalence of metabolic dysfunction-associated fatty liver disease in overweight or obese adults." Clinical Gastroenterology and Hepatology (2021).
     Google Scholar
  21. Kim D, Kim W, Joo SK, et al. Association between body sizemetabolic phenotype and nonalcoholic steatohepatitis and significant fibrosis. J Gastroenterol 2020;55:330-341.
     Google Scholar
  22. Davila, J.A. Diabetes and hepatocellular carcinoma: What role does diabetes have in the presence of other known risk factors? Am. J. Gastroenterol. 2010, 105, 632–634.
     Google Scholar
  23. Blond, E.; Disse, E.; Cuerq, C.; Drai, J.; Valette, P.-J.; Laville, M.; Thivolet, C.; Simon, C.; Caussy, C. EASL–EASD–EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease in severely obese people: Do they lead to over-referral? Diabetologia 2017, 60, 1218–1222.
     Google Scholar
  24. Lazo M, Hernaez R, Eberhardt MS, et al. Prevalence of nonalcoholic fatty liver disease in the United States: The Third National Health and Nutrition Examination Survey, 1988-1994. Am J Epidemiol 2013;178:38-45.
     Google Scholar
  25. Guerrero R, Vega GL, Grundy SM, Browning JD. Ethnic differences in hepatic steatosis: an insulin resistance paradox? Hepatology. 2009;49(3):791–801.
     Google Scholar
  26. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461–5.
     Google Scholar
  27. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461–5.
     Google Scholar
  28. Mandorfer M, Scheiner B, Stattermayer AF, Schwabl P, Paternostro R, Bauer D, et al. Impact of patatin-like phospholipase domain containing 3 rs738409 G/G genotype on hepatic decompensation and mortality in patients with portal hypertension. Aliment Pharmacol Ther. 2018;48:451.
     Google Scholar
  29. Liu YL, Patman GL, Leathart JB, Piguet AC, Burt AD, Dufour JF, et al. Carriage of the PNPLA3 rs738409 C>G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol. 2013;61(1):75–81.
     Google Scholar
  30. Sookoian, S.; Castaño, G.O.; Scian, R.; Mallardi, P.; Fernandez Gianotti, T.; Burgueño, A.L.; San Martino, J.; Pirola, C.J. Genetic variation in transmembrane 6 superfamily member 2 and the risk of nonalcoholic fatty liver disease and histological disease severity. Hepatology 2015, 61, 515–525.
     Google Scholar
  31. Mancina RM, Dongiovanni P, Petta S, Pingitore P, Meroni M, Rametta R, et al. The MBOAT7-TMC4 variant rs641738 increases risk of nonalcoholic fatty liver disease in individuals of European descent. Gastroenterology. 2016;150(5):1219–30.e6.
     Google Scholar
  32. Santoro N, Zhang CK, Zhao H, Pakstis AJ, Kim G, Kursawe R, et al. Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents. Hepatology. 2011;55:781–9.
     Google Scholar
  33. Pericleous M, Kelly C, Wang T, Livingstone C, Ala A. Wolman’s disease and cholesteryl ester storage disorder: the phenotypic spectrum of lysosomal acid lipase deficiency. Lancet Gastroenterol Hepatol. 2017;2(9):670–9.
     Google Scholar
  34. Ma, Y.; Belyaeva, O.V.; Brown, P.M.; Fujita, K.; Valles, K.; Karki, S.; De Boer, Y.S.; Koh, C.; Chen, Y.; Du, X.; et al. 17-beta hydroxysteroid dehydrogenase 13 is a hepatic retinol dehydrogenase associated with histological features of nonalcoholic fatty liver disease. Hepatology 2019, 69, 1504–1519.
     Google Scholar
  35. Dongiovanni P, Meroni M, Mancina RM, Baselli G, Rametta R, Pelusi S, et al. Protein phosphatase 1 regulatory subunit 3B gene variation protects against hepatic fat accumulation and fibrosis in individuals at high risk of nonalcoholic fatty liver disease. Hepatol Commun. 2018;2(6):666–75.
     Google Scholar
  36. Liu, Zhenqiu, Chen Suo, Oumin Shi, Chunqing Lin, Renjia Zhao, Huangbo Yuan, Li Jin, Tiejun Zhang, and Xingdong Chen. "The health impact of MAFLD, a novel disease cluster of NAFLD, is amplified by the integrated effect of fatty liver disease related genetic variants." Clinical Gastroenterology and Hepatology (2020).
     Google Scholar
  37. Caussy C, Soni M, Cui J, Bettencourt R, Schork N, Chen CH, et al. Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis. J Clin Invest. 2017;127(7):2697–704.
     Google Scholar
  38. Breij LM, Kerkhof GF, Hokken-Koelega AC. Accelerated infant weight gain and risk for nonalcoholic fatty liver disease in early adulthood. J Clin Endocrinol Metab. 2014;99(4):1189–95.
     Google Scholar
  39. Valenti L, Romeo S. Destined to develop NAFLD? The predictors of fatty liver from birth to adulthood. J Hepatol. 2016;65(4):668–70.
     Google Scholar
  40. Gerhard GS, DiStefano JK. Micro RNAs in the development of non-alcoholic fatty liver disease. World J Hepatol. 2015;7(2):226–34.
     Google Scholar
  41. Kirpich IA, Marsano LS, McClain CJ. Gut-liver axis, nutrition, and non-alcoholic fatty liver disease. Clin Biochem 2015;48:923e930.
     Google Scholar
  42. Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149:389–397.e10. doi: 10.1053/j.gastro.2015.04.043.
     Google Scholar
  43. Dulai PS, Singh S, Patel J, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology. 2017; 65: 1557- 1565.
     Google Scholar
  44. Nguyen, Vy H., Michael H. Le, Ramsey C. Cheung, and Mindie H. Nguyen. "Differential clinical characteristics and mortality outcomes in persons with NAFLD and/or MAFLD." Clinical Gastroenterology and Hepatology (2021).
     Google Scholar
  45. Stepanova M, Rafiq N, Makhlouf H, Agrawal R, Kaur I, Younoszai Z, McCullough A, Goodman Z, Younossi ZM. Predictors of all-cause mortality and liver-related mortality in patients with non-alcoholic fatty liver disease (NAFLD). Dig Dis Sci. 2013;58(10):3017–23.
     Google Scholar
  46. Mantovani, Alessandro, Graziana Petracca, Giorgia Beatrice, Alessandro Csermely, Amedeo Lonardo, Jörn M. Schattenberg, Herbert Tilg, Christopher D. Byrne, and Giovanni Targher. "Non-alcoholic fatty liver disease and risk of incident chronic kidney disease: an updated meta-analysis." Gut (2020).
     Google Scholar
  47. Lee, Hokyou, Yong-ho Lee, Seung Up Kim, and Hyeon Chang Kim. "Metabolic Dysfunction-Associated Fatty Liver Disease and Incident Cardiovascular Disease Risk: A Nationwide Cohort Study." Clinical Gastroenterology and Hepatology (2020).
     Google Scholar
  48. Deng, Yunlei, Qianwen Zhao, and Rong Gong. "Association Between Metabolic Associated Fatty Liver Disease and Chronic Kidney Disease: A Cross-Sectional Study from NHANES 2017–2018." Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 14 (2021): 1751.
     Google Scholar
  49. Sun, Dan-Qin, Yan Jin, Ting-Yao Wang, Kenneth I. Zheng, Rafael S. Rios, Hao-Yang Zhang, Giovanni Targher, Christopher D. Byrne, Wei-Jie Yuan, and Ming-Hua Zheng. "MAFLD and risk of CKD." Metabolism 115 (2021): 154433.
     Google Scholar
  50. Kim D, Li AA, Perumpail BJ, et al. Changing trends in etiology-based and ethnicity-based annual mortality rates of cirrhosis and hepatocellular carcinoma in the United States. Hepatology 2019;69:1064-1074.
     Google Scholar
  51. Vilar-Gomez E, Calzadilla-Bertot L, Wai-Sun Wong V, Castellanos M, Aller-de la Fuente R, Metwally M, et al. Fibrosis severity as a determinant of cause-specific mortality in patients with advanced nonalcoholic fatty liver disease: a multi-national cohort study. Gastroenterology. 2018;155(2):443–457.e17.
     Google Scholar
  52. Cholankeril G, Wong RJ, Hu M, Perumpail RB, Yoo ER, Puri P, et al. Liver transplantation for nonalcoholic steatohepatitis in the US: temporal trends and outcomes. Dig Dis Sci. 2017;62(10):2915–22.
     Google Scholar
  53. Wong RJ, Aguilar M, Cheung R, Perumpail RB, Harrison SA, Younossi ZM, Ahmed A. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148(3):547–55.
     Google Scholar
  54. Nyberg, L.M., Cheetham, T.C., Patton, H.M., Yang, S.-J., Chiang, K.M., Caparosa, S.L., Stern, J.A. and Nyberg, A.H. (2021), The Natural History of NAFLD, a Community-Based Study at a Large Health Care Delivery System in the United States. Hepatol. Commun., 5: 83-96. https://doi.org/10.1002/hep4.1625.
     Google Scholar
  55. Myers, Shuna, Isabelle Neyroud-Caspar, Laurent Spahr, Konstantinos Gkouvatsos, Evelyne Fournier, Emiliano Giostra, Giulia Magini et al. "NAFLD and MAFLD as emerging causes of HCC: A populational study." JHEP Reports 3, no. 2 (2021): 100231.
     Google Scholar
  56. Kim D, Li AA, Perumpail BJ, et al. Changing trends in etiology-based and ethnicity-based annual mortality rates of cirrhosis and hepatocellular carcinoma in the United States. Hepatology 2019;69:1064-1074.
     Google Scholar
  57. Jafri, W., and M. Kamran. "NAFLD: The Enemy Within." Austin Hepatol 1.1 (2016): 1003.
     Google Scholar
  58. Srivastava, A.; Gailer, R.; Tanwar, S.; Trembling, P.; Parkes, J.; Rodger, A.; Suri, D.; Thorburn, D.; Sennett, K.; Morgan, S.; et al. Prospective evaluation of a primary care referral pathway for patients with non-alcoholic fatty liver disease. J. Hepatol. 2019, 71, 371–378.
     Google Scholar
  59. de Freitas Junior, J. R., V. M. T. Sagae, G. H. P. de Oliveira, G. M. V. de Souza, T. F. de Souza, C. P. M. S. de Oliveira, D. T. H. de Moura et al. "Intragastric Balloon as a New Approach for Metabolic Dysfunction-Associated Fatty Liver Disease (Mafld): A Systematic Review and Meta-Analysis." Endoscopy 53, no. S 01 (2021): OP42.
     Google Scholar
  60. Vilar-Gomez, E.; Martinez-Perez, Y.; Calzadilla-Bertot, L.; Torres-Gonzalez, A.; Gra-Oramas, B.; Gonzalez-Fabian, L.; Friedman, S.L.; Diago, M.; Romero-Gomez, M. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology 2015, 149, 367–378.e5.
     Google Scholar
  61. Wong VW, Wong GL, Choi PC, et al. Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut. 2010; 59: 969- 974.
     Google Scholar
  62. T. Andersen, C. Gluud, M.-B. Franzmann, and P. Christoffersen, “Hepatic effects of dietary weight loss in morbidly obese subjects,” Journal of Hepatology, vol. 12, no. 2, pp. 224–229, 1991.
     Google Scholar
  63. Hamurcu Varol P, Kaya E, et al. Role of intensive dietary and lifestyle interventions in the treatment of lean nonalcoholic fatty liver disease patients. Eur J Gastroenterol Hepatol, 2020.
     Google Scholar
  64. M Zachut, A Arieli, H Lehrer, L Livshitz, S Yakoby, U Moallem: Effects of increased supplementation of n-3 fatty acids to transition dairy cows on performance and fatty acid profile in plasma, adipose tissue, and milk fat. J Dairy Sci 93, 5877-5889 (2010).
     Google Scholar
  65. H Yki-Järvinen: Nutritional modulation of nonalcoholic fatty liver disease and insulin resistance: human data. Curr Opin Clin Nutr Metab Care (2010).
     Google Scholar
  66. Ryan MC, Itsiopoulos C, Thodis T, et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol 2013;59:138-43. 10.1016/j.jhep.2013.02.012.
     Google Scholar
  67. J Frith, CP Day, L Robinson, C Elliott, DE Jones, JL Newton: Potential strategies to improve uptake of exercise interventions in non-alcoholic fatty liver disease. J Hepatol 52, :112-116 (2010).
     Google Scholar
  68. O’Gorman, Philip, Sara Naimimohasses, Ann Monaghan, Megan Kennedy, Ashanty M. Melo, Deirdre Ní Fhloinn, Derek G. Doherty et al. "Improvement in histological endpoints of MAFLD following a 12‐week aerobic exercise intervention." Alimentary Pharmacology & Therapeutics 52, no. 8 (2020): 1387-1398.
     Google Scholar
  69. KD Kistler, EM Brunt, JM Clark, AM Diehl, JF Sallis, JB Schwimmer: Physical activity recommendations, exercise intensity, and histological severity of nonalcoholic Fatty liver disease. Am J Gastroenterol 106, 460-468 (2011).
     Google Scholar
  70. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology 2018;67:328e357.
     Google Scholar
  71. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016;64:1388e1402.
     Google Scholar
  72. Venetsanaki V, Karabouta Z, Polyzos SA. Farnesoid X nuclear receptor agonists for the treatment of nonalcoholic steatohepatitis. Eur J Pharmacol 2019;863:172661.
     Google Scholar
  73. Niriella MA, Ediriweera DS, Kasturiratne A, De Silva ST, Dassanayaka AS, De Silva AP, Kato N, Pathmeswaran A, Wickramasinghe AR, de Silva HJ. Outcomes of NAFLD and MAFLD: Results from a community-based, prospective cohort study. PLoS One. 2021 Feb 3;16(2):e0245762. doi: 10.1371/journal.pone.0245762.
     Google Scholar