Special Report

Health and Economic Burden of Nonalcoholic Fatty Liver Disease in the United States and Its Impact on Veterans

NAFLD is a leading cause of chronic liver disease and cirrhosis in the US and is associated with metabolic syndrome, type 2 diabetes, cardiovascular disease, and all-cause mortality.

Fed Pract. 2019 January;36(1):14-19

Author(s):

References

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2. Targher G, Bertolini L, Rodella S, et al. Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients. Diabetologia. 2008;51(3):444-450.

3. Adams LA, Harmsen S, St Sauver JL, et al. Nonalcoholic fatty liver disease increases risk of death among patients with diabetes: a community-based cohort study. Am J Gastroenterol. 2010. 105(7):1567-1573.

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5. 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.

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9. Ahmed O, Liu L, Gayed A, et al. The changing face of hepatocellular carcinoma: forecasting prevalence of nonalcoholic steatohepatitis and hepatitis C cirrhosis. J Clin Exp Hepatol. 2018. In press.

10. Kanwal F, Kramer JR, Duan Z, Yu X, White D, El-Serag HB. Trends in the burden of nonalcoholic fatty liver disease in a United States cohort of veterans. Clin Gastroenterol Hepatol. 2016;14(2):301-308.

11. Kabbany MN, Conjeevaram Selvakumar PK, Watt K, et al. Prevalence of nonalcoholic steatohepatitis-associated cirrhosis in the United States: an analysis of national health and nutrition examination survey data. Am J Gastroenterol. 2017;112(4):581-587.

12. Goldberg D, Ditah IC, Saeian K, et al. Changes in the prevalence of hepatitis C virus infection, nonalcoholic steatohepatitis, and alcoholic liver disease among patients with cirrhosis or liver failure on the waitlist for liver transplantation. Gastroenterology. 2017;152(5):1090-1099.

13. Beste LA, Leipertz SL, Green PK, Dominitz JA, Ross D, Ioannou GN. Trends in burden of cirrhosis and hepatocellular carcinoma by underlying liver disease in US veterans, 2001-2013. Gastroenterology. 2015;149(6):1471-1482.

14. Wong RJ, Aguilar M, Cheung R, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148(3):547-555.

15. Belli LS, Perricone G, Adam R, et al; all the contributing centers (www.eltr.org) and the European Liver and Intestine Transplant Association (ELITA). Impact of DAAs on liver transplantation: major effects on the evolution of indications and results. An ELITA study based on the ELTR registry. J Hepatol. 2018;69(4):810-817.

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19. Sayiner M, Otgonsuren M, Cable R. Variables associated with inpatient and outpatient resource utilization among medicare beneficiaries with nonalcoholic fatty liver disease with or without cirrhosis. J Clin Gastroenterol. 2017;51(3):254-260.

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Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD also is an independent risk factor for cardiovascular disease, type 2 diabetes mellitus (T2DM), chronic kidney disease, cirrhosis, liver cancer, and all-cause mortality.^1-3 As the leading cause of liver disease in the US and globally, NAFLD is strongly associated with obesity and metabolic syndrome, with the rising prevalence of NAFLD closely mirroring the epidemic of obesity and T2DM.^4,5 The unrelenting increase of NAFLD prevalence has led to a significant rise in associated health care and economic burdens, compounded by the boom in childhood obesity and an aging population. In this review, we will discuss the epidemiology and economic burden of NAFLD in the US and how it affects veteran health.

NAFLD Definition

NAFLD is defined as the presence of > 5% of hepatic steatosis in the absence of excessive alcohol use, steatosis-inducing medication, or other concurrent chronic liver diseases.

The disease encompasses a spectrum of histopathologic findings (Figure 1) that can be divided into (1) simple liver steatosis (fat), also called nonalcoholic fatty liver (NAFL); and (2) inflammation with liver cell (hepatocyte) injury or death, also known as nonalcoholic steatohepatitis (NASH).

Compared with patients with NAFL, patients with NASH are at a much higher risk of developing fibrosis (scarring of the liver) and cirrhosis (significant scarring with distorted liver architecture). Patients with either NAFL or NASH, with or without advanced fibrosis, also can develop hepatocellular carcinoma (HCC). Severity of liver fibrosis (ie, fibrosis stage) is the most important predictor of liver-associated mortality and all-cause mortality; those with significant fibrosis (≥ F2 stage of fibrosis) are more likely to die of liver disease or to undergo a liver transplant compared with those with earlier stages of disease (ie, stages 0 to F1). Those with advanced scarring or cirrhosis (≥ F3 stage of fibrosis) exhibit an even higher risk of death or liver transplantation.⁶

NAFLD is a slow and often progressive disease. Time to progression between each stage of fibrosis is about 7 years; however, there has been a documented subset of patients with rapid progression to advanced fibrosis.⁷ The risk factors associated with this increased risk of fibrosis progression remain poorly understood.

Prevalence

The prevalence of NAFLD in the US is about 24% to 26%—about 85 million Americans. Up to 20% to 30% of these cases (about 17-25 million Americans) are thought to have NASH (Figure 2).

Future projections estimate an 18.3% rise in the prevalence of NAFLD by 2030, affecting up to 100 million Americans, and an exponential rise in NASH is expected by 2025, to affect close to 43 million Americans.^5,8,9 These estimates of prevalence vary between studies and specifically differ based on how NAFLD was diagnosed in each study.

Although liver biopsy remains the current gold standard for diagnosis and histopathologic staging of NAFLD, alternatives to liver biopsy include elastography techniques (ie, transient elastography using Fibroscan[Paris, France], shear wave elastography using Supersonic Image Aixplorer [Weston, FL], and magnetic resonance elastography), magnetic resonance spectroscopy, liver enzymes, and noninvasive simple and complex (serologic) scoring systems such as the Fatty Liver Index. Among these, liver enzymes and serologic scores are most likely to underestimate NAFLD disease burden. Transient elastographyis widely used because the test is easy to perform, noninvasive, and reliably estimates the degree of liver fibrosis in patients with NAFLD by measuring the speed of a mechanically induced shear wave using pulse-echo ultrasonic acquisitions in a much larger portion of the tissue (about 100 times more than a liver biopsy core). Transient elastography also can objectively quantify the amount of liver fat by measuring a 3.5 MHz ultrasound coefficient of attenuation or controlled attenuation parameter (CAP). This correlates with the degree of liver fat, and a higher CAP level reflects a greater degree of steatosis.

The largest study of US veterans utilized abnormal (ie, elevated) liver enzymes as the diagnostic criteria and reviewed nearly 10 million veterans who were followed between 2003 and 2011. Investigators reported a NAFLD prevalence of 13.6% in this population and noted an overall increase in NAFLD prevalence from 6.3% in 2003 to 17.6% in 2011, which highlights the continued growth in NAFLD clinical burden.¹⁰ This study, however, is likely to have underestimated the prevalence of NAFLD among veterans because liver enzymes are often normal among those with NAFLD (ie, low sensitivity), and the prevalence of obesity and T2DM are significantly higher in the veteran population vs the general population.