Dr. Meagan Gray explains nonalcoholic fatty liver disease (NAFLD) in humans

Prepared by Dr. Meagan Gray, a gastroenterologist with specialties in gastroenterology, hepatology , and liver transplantation

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of disorders ranging from simple steatosis to steatohepatitis and cirrhosis. NAFLD is the most common cause of chronic liver disease worldwide, affecting approximately 25% of the adult population globally (1) and 31% of adults in the United States (2). It is currently the second most common indication for liver transplantation (3), and the second most common cause of hepatocellular carcinoma (HCC) in patients awaiting liver transplantation in the US (4). The diagnosis of NAFLD requires >5% hepatic steatosis with lack of secondary causes for hepatic fat accumulation. Approximately 25% of patients with NAFLD will have nonalcoholic steatohepatitis (NASH), which is associated with a 20% risk of progression to cirrhosis (1, 5). Projections estimate that prevalent NAFLD and NASH cases will increase to 100.9 and 27 million by 2030, and incidence of decompensated cirrhosis, HCC, and liver-related deaths due to NAFLD will increase to 105,430, 12,240, and 78,300, respectively (6). Patients at highest risk for developing NAFLD are those with obesity and features of the metabolic syndrome. It is estimated that between 40–70% of patients with diabetes mellitus (DM) have NAFLD (1, 7, 8), as well as up to 67% of adults with a body mass index (BMI) between 25–30 kg/m2 and up to 91% of adults with a BMI >30 kg/m2 (9–13). Due to lack of approved pharmacologic treatment, current treatment recommendations are for weight loss of >10% total body weight, which is associated with NASH resolution and fibrosis regression (14). Weight loss of even 5% can stabilize or improve fibrosis in 94% of cases. Specific dietary recommendations are to reduce or eliminate processed foods, high fructose corn syrup, concentrated sugars, and saturated fat from the diet (15, 16, 17).

  1. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Alimentary pharmacology & therapeutics. 2011;34(3):274-285.

  2. Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40(6):1387-1395.

  3. Charlton MR, Burns JM, Pedersen RA, Watt KD, Heimbach JK, Dierkhising RA. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology. 2011;141(4):1249-1253.

  4. Younossi Z, Stepanova M, Ong JP, et al. Nonalcoholic Steatohepatitis Is the Fastest Growing Cause of Hepatocellular Carcinoma in Liver Transplant Candidates. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2019;17(4):748-755 e743.

  5. Adams LA, Lymp JF, St Sauver J, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129(1):113-121.

  6. 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(1):123-133.

  7. Leite NC, Salles GF, Araujo AL, Villela-Nogueira CA, Cardoso CR. Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver international : official journal of the International Association for the Study of the Liver. 2009;29(1):113-119.

  8. Prashanth M, Ganesh HK, Vima MV, et al. Prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. The Journal of the Association of Physicians of India. 2009;57:205-210.

  9. Boza C, Riquelme A, Ibanez L, et al. Predictors of nonalcoholic steatohepatitis (NASH) in obese patients undergoing gastric bypass. Obesity surgery. 2005;15(8):1148-1153.

  10. Haentjens P, Massaad D, Reynaert H, et al. Identifying non-alcoholic fatty liver disease among asymptomatic overweight and obese individuals by clinical and biochemical characteristics. Acta Clin Belg. 2009;64(6):483-493.

  11. Machado M, Marques-Vidal P, Cortez-Pinto H. Hepatic histology in obese patients undergoing bariatric surgery. Journal of hepatology. 2006;45(4):600-606.

  12. Colicchio P, Tarantino G, del Genio F, et al. Non-alcoholic fatty liver disease in young adult severely obese non-diabetic patients in South Italy. Annals of nutrition & metabolism. 2005;49(5):289-295.

  13. Beymer C, Kowdley KV, Larson A, Edmonson P, Dellinger EP, Flum DR. Prevalence and predictors of asymptomatic liver disease in patients undergoing gastric bypass surgery. Arch Surg. 2003;138(11):1240-1244.

  14. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis. Gastroenterology. 2015;149(2):367-378 e365; quiz e314-365.

  15. 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(1):328-357.

  16. European Association for the Study of the L, European Association for the Study of D, European Association for the Study of O. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Diabetologia. 2016;59(6):1121-1140.

  17. Kani AH, Alavian SM, Esmaillzadeh A, Adibi P, Azadbakht L. Effects of a novel therapeutic diet on liver enzymes and coagulating factors in patients with non-alcoholic fatty liver disease: A parallel randomized trial. Nutrition. 2014;30(7-8):814-821.