NAFLD, an epidemic and a health disparity

In association with the blanket term “metabolic syndrome” (which can be defined by increased insulin resistance, diabetes, obesity, increased blood pressure, high blood sugar, abnormal cholesterol or triglyceride levels, etc.) is non-alcoholic fatty liver disease (NAFLD), a burgeoning chronic hepatic disorder affecting ~25% of the world’s population (20-30% of the North American population and up to one third of the general US population) with an ever-increasing, rapid worldwide incidence [1-5]. While NAFLD is relatively benign in some individuals, ~25% of patients with this disease will go on to develop non-alcoholic steatohepatitis (NASH), a more serious disease characterized by liver inflammation [4, 6]. Further, patients with NASH can go on to develop additional complications, i.e., 2% of patients will die of NAFLD liver-related mortality due to portal hypertension, liver failure, and/or hepatocellular cancer [4].

Three decades ago, the NAFLD spectrum of disorders was considered a disease of adults. However, the medical community has witnessed the prevalence of NAFLD rise with the growing epidemic of overweight and obese individuals in all age groups, ethnicities, and races. However, the trend that is most concerning, due to its future disease burden, is the enormous increase in obesity and NAFLD in the US pediatric population, which has positioned NAFLD as the most common liver disease in US children and adolescents. Data derived from the National Health and Nutrition Examination Survey (NHANES) demonstrate that 17% of US children between 2 and 19 years of age are obese, with NAFLD prevalence having doubled among US adolescents in the last three decades [7]. This represents approximately two million additional adolescents who already have or are at increased risk of developing liver failure, cardiovascular disease, and liver cancer in adulthood. In addition, most NAFLD population-based studies indicate that the US Hispanic population is most at risk, having the highest prevalence of NAFLD and being most severely affected by the disease [8].

References:

[1] W. Dunn, J.B. Schwimmer, The obesity epidemic and nonalcoholic fatty liver disease in children, Current gastroenterology reports, 10 (2008) 67-72.

[2] M.W. Fleischman, M. Budoff, I. Zeb, D. Li, T. Foster, NAFLD prevalence differs among hispanic subgroups: the Multi-Ethnic Study of Atherosclerosis, World journal of gastroenterology, 20 (2014) 4987-4993.

[3] S. O’Neill, L. O’Driscoll, Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies, Obesity reviews : an official journal of the International Association for the Study of Obesity, 16 (2015) 1-12.

[4] Z.M. Younossi, A.B. Koenig, D. Abdelatif, Y. Fazel, L. Henry, M. Wymer, Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes, Hepatology, 64 (2016) 73-84.

[5] N.L. Gluchowski, M. Becuwe, T.C. Walther, R.V. Farese, Jr., Lipid droplets and liver disease: from basic biology to clinical implications, Nature reviews. Gastroenterology & hepatology, (2017).

[6] C.A. Matteoni, Z.M. Younossi, T. Gramlich, N. Boparai, Y.C. Liu, A.J. McCullough, Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity, Gastroenterology, 116 (1999) 1413-1419.

[7] R. Loomba, C.B. Sirlin, J.B. Schwimmer, J.E. Lavine, Advances in pediatric nonalcoholic fatty liver disease, Hepatology, 50 (2009) 1282-1293.

[8] J.N. Davis, K.A. Le, R.W. Walker, S. Vikman, D. Spruijt-Metz, M.J. Weigensberg, H. Allayee, M.I. Goran, Increased hepatic fat in overweight Hispanic youth influenced by interaction between genetic variation in PNPLA3 and high dietary carbohydrate and sugar consumption, Am J Clin Nutr, 92 (2010) 1522-1527.