MENU
WGO
Back to Top
World Gastroenterology Organisation
World Gastroenterology Organisation
Follow
WGO: Facebook WGO: Twitter
Share

From Obesity to Fatty Liver/NASH: Two Parallel Epidemics

Sofia Carvalhana, MD

Sofia Carvalhana, MD
Departamento de Gastrenterologia, Hospital Santa Maria, CHLN
Lisbon, Portugal

   
Helena Cortez-Pinto, MD, PhD

Helena Cortez-Pinto, MD, PhD
Unidade de Nutrição e Metabolismo, Faculdade de Medicina de
Lisboa, IMM
Lisbon, Portugal

Abstract

Nonalcoholic fatty liver disease (NAFLD) is believed to be the most common form of chronic liver disease in Western countries. The clinicopathologic spectrum of NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). NAFLD is commonly associated with the components of the metabolic syndrome, including obesity. The prevalence of adult obesity and the metabolic syndrome, estimated at
34% in the United States, has reached epidemic proportions. NAFLD affects approximately 30% of general Western population and has obesity
as an independent risk factor. There is however evidence that the epidemic of obesity may be stabilizing, so it is possible that also NAFLD/NASH and its complications may halt its progressive incidence in the near future.

This article reviews the epidemiology of obesity and NAFLD, including non-alcoholic steatohepatitis (NASH).

Introduction

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disease in western countries and it is the leading cause
of abnormal functional liver tests in the primary care setting 1. The clinic-pathologic spectrum of NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Whereas simple steatosis seems to have a relatively benign clinical course, patients with NASH can develop fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) 2.

NAFLD is closely associated with the components of metabolic syndrome (MS), including obesity and Type 2 diabetes. Approximately 90% of NAFLD patients have more than one component of the MS and one-third has the MS. In addition, the risk of having NAFLD increases exponentially with the addition of each of the MS components 3. The alarming epidemic of obesity has fueled an increasing prevalence of NAFLD, making NASH potentially the most common cause of advanced liver disease in coming decades 4. At present, the real prevalence of NAFLD is still underestimated.

Epidemiology of Obesity

Obesity is becoming one of the most serious public health problems worldwide and its prevalence has dramatically increased in the last few decades, reaching epidemic levels. According to the National Health and Nutrition Examination Survey (NHANES) data, prevalence of obesity in the U.S. was relatively low and stable between 1960 and 1980, but more than doubled among adults (from 15% to 32.9%) and tripled among children (from 5.5% to 17.1%) between 1980 and 2004. In 2003–2004, 66.2% of U.S. adults were either overweight or obese 5. Furthermore, one in every 20 Americans had either morbid obesity (defined as a body mass index [BMI] > 35 kg/m2 together with obesity-associated diseases or a BMI > 40 with or without obesity-associated diseases) 6. In Europe, the prevalence of obesity is increasing too, and predictably will continue to increase 7. However, in 2009-2010, the prevalence of obesity in the U.S. was 35.5% among adult men and 35.8% among adult women, with no significant change compared with 2003-2008, thus suggesting that the epidemic may be slowing or leveling off 8. Also, recent studies suggest a leveling off of the epidemic in children and adolescents from Australia, Europe, Japan and the USA, with
heterogeneity according to socioeconomic status 9.

Nonetheless, the World Health Organization (WHO) projects that by 2015, approximately 2.3 billion adults will be overweight and more than 700 million will be obese.

Epidemiology of NAFLD

Prevalence

The prevalence of NAFLD has not been well established. It varies with the study population and the modality used to establish the diagnosis (eg, liver enzymes, imaging, liver biopsy). In the USA, a study performed in an ambulatory clinic cohort, found the prevalence of ultrasonographic NAFLD to be 46%, with a high prevalence of diabetes and obesity (45%); when performing liver biopsy in ultrasound positive patients, it was found that 30% of patients with NAFLD (12% of the total cohort) had NASH 10. Also, Younossi et al, when comparing three cycles of NHANES, from 1988 to 2008, found that NAFLD had been continuously increasing and was now the more frequent chronic liver disease in the USA, accounting for 75.1% of chronic liver diseases (CLD) in the 2005-2008 period. Importantly, obesity was an independent predictor of NAFLD in all periods 11.

General population

Non-invasive radiological modalities applicable to large scale screening studies of NAFLD include ultrasonography, magnetic resonance
imaging (MRI) and magnetic resonance spectroscopy (MRS). The DIONYSOS nutrition and liver study based on ultrasonography demonstrated that the prevalence of NAFLD in two communities of Northern of Italy, with and without suspected liver disease was 25% and 20%, respectively 12. Another study based on ultrasonography, in a cohort of 35,519 Japanese individuals presenting for a health check-up over 10 to 12 years, identified an increased prevalence of NAFLD from 13% to 30% 13; in this study there were no clear exclusions of other liver diseases. Also, Caballeria et al. found in a Spanish cohort of 766 individuals, a prevalence of NAFLD of 25.8%, 33.4% men and 20.3% women 14. A study from Dallas, Texas in 2004, using proton nuclear MRS, identified NAFLD in 31% of a multi-ethnic, population-based
sample 15. Hispanics had the highest prevalence of hepatic steatosis (45%), followed by Caucasians (33%) and African Americans (24%). Lastly, a study from Hong Kong, using proton nuclear MRS and transient elastography (TE), in 922 subjects from the general Chinese population, showed NAFLD in 27.3% of subjects and advanced fibrosis in 4% of NAFLD patients 16.

Selected populations

In a series from obese, undergoing bariatric surgery, prevalence of NAFLD ranges from 74-98%, while that of NASH can be as high as 37% 17-19. The proportion of advanced fibrosis in NAFLD patients ranges from 2-9%. In morbidly obese patients, elevated AST, male gender and type 2 diabetes were found to be predictive of NASH 18. In living liver donors, supposedly healthy, the prevalence of NAFLD ranges from
3% to 51% 20-22 and that of NASH from 1% to 15% 20, 23. In a Korean study in which liver biopsies were performed on 589 consecutive
potential liver transplant donors, reported NAFLD prevalence was 51% 21. In the United States, liver biopsies performed on potential liver
donors revealed that 20% of donors were ineligible for organ donation based on the degree of the steatosis (>30%).

Incidence

Data on the incidence of NAFLD in the general population are quite limited. However, the incidence seems to be rising as the obesity epidemic
continues. In one Japanese study, the annual incidence of NAFLD was estimated to be about 10% 3. Another Japanese study revealed an  overall incidence of non-alcoholic hypertransaminasemia of 31 cases per 1,000 person-year 25. In the 8.5-year follow-up of the DIONYSOS study, the incidence and remission of fatty liver detected by ultrasonography was 18.5 and 55 per 1,000 person-years 26. A recent study of an outpatient hepatology clinic in England reported a referral incidence rate of 29 cases per 100,000 person-years 27. Taking into account the discrepancy among these rates, further studies are needed to determine the true incidence of NAFLD.

Conclusion

Given the parallel increase in prevalence of obesity and NAFLD, it is intuitive to correlate the two epidemics. Also, the fact that obesity is
usually an independent risk factor for NAFLD supports this assumption. Furthermore, as shown in Figure 1, in each area of the world, there is a very strong correlation between the prevalence of NAFLD and obesity 28.

 

Figure 1: Correlation between prevalence of obesity and prevalence of NAFLD around the world Lazo M and Clark JM. “The Epidemiology of Nonalcoholic Fatty Liver Disease: A Global Perspective.” Seminars in Liver Disease. 2008; 28(4). www.thieme.com (reprinted with permission).

 

The recent evidence that obesity epidemics seems to be lowering or at least leveling off is good news. It is possible that the increasing self-consciousness of the risks of obesity, including fatty liver, may lead to improved lifestyle behavior, thus halting the continuous rising incidence of NAFLD/NASH and its complications, such as cirrhosis or hepatocellular carcinoma.

References

  1. Armstrong MJ, Houlihan DD, Bentham L, Shaw JC, Cramb R, Olliff S, Gill PS, Neuberger JM, Lilford RJ, Newsome PN. Presence and severity of non-alcoholic fatty liver disease in a large prospective primary care cohort. Journal of Hepatology 2012;56(1):234-240.
  2. Farrell G, Larter C. Nonalcoholic fatty liver disease: From steatosis to cirrhosis. Hepatology 2006;43(2 Suppl 1):S99-S112.
  3. Hamaguchi M, Kojima T, Takeda N, Nakagawa T, Taniguchi H, Fujii K, Omatsu T, Nakajima T, Sarui H, Shimazaki M, Kato T, Okuda J, Ida K. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Annals of Internal Medicine 2005;143(10):722-728.
  4. Agopian VG, Kaldas FM, Hong JC, Whittaker M, Holt C, Rana A, Zarrinpar A, Petrowsky H, Farmer D, Yersiz H, Xia V, Hiatt JR, Busuttil RW. Liver transplantation for nonalcoholic steatohepatitis: The new epidemic. Annals of Surgery 2012;256(4):624-633.
  5. Ogden CL, Yanovski SZ, Carroll MD, Flegal KM- The epidemiology of obesity. Gastroenterology 2007;132(6):2087-2102.
  6. Brzezinski S. Morbid obesity: Issues and challenges in home health. Home Healthc Nurse 2008;26(5):290-297.
  7. Schneider H, Dietrich ES, Venetz WP. Trends and stabilization up to 2022 in overweight and obesity in Switzerland, comparison to France, UK, US and Australia. International Journal of Environmental Research and Public Health 2010;7(2):460-472.
  8. Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA 2012;307(5):491-497.
  9. Rokholm B, Baker JL, Sørensen TIA. The levelling off of the obesity epidemic since the year 1999 – a review of evidence and perspectives. Obesity Reviews 2010;11(12):835-846.
  10. Williams CD, Stengel J, Asike MI, Torres DM, Shaw J, Contreras M, Landt CL, Harrison SA. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasoundand liver biopsy: A prospective study. Gastroenterology 2011;140(1):124-131.
  11. Younossi ZM, Stepanova M, Afendy M, Fang Y, Younossi Y, Mir H, Srishord M. Changes in the prevalence of the most common causes of  chronic liver diseases in the United States from 1988 to 2008. Clinical Gastroenterology and Hepatology 2011;9(6):524-530.
  12. Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S. Prevalence of and risk factors for nonalcoholic fatty liver disease: The Dionysos nutrition and liver study. Hepatology 2005;42(1):44-52.
  13. Kojima S-i, Watanabe N, Numata M, Ogawa T, Matsuzaki S. Increase in the prevalence of fatty liver in japan over the past 12 years: Analysis of clinical background. J Gastroenterol 2003;38(10):954-961.
  14. Caballería L, Pera G, Auladell MA, Torán P, Muñoz L, Miranda D, Alumà A, Casas JD, Sánchez C, Gil D, Aubà J et al. Prevalence and factors associated with the presence of nonalcoholic fatty liver disease in an adult population in Spain. Eur J Gastroenterol Hepatol 2010;22(1):24-32.
  15. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH. Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity. Hepatology 2004;40(6):1387-1395.
  16. Wong VW, Chu WC, Wong GL, Chan RS, Chim AM, Ong A, Yeung DK, Yiu KK, Chu SH, Woo J, Chan FK, Chan HL. Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: A population study using proton-magnetic resonance spectroscopy and transient elastography. Gut 2012;61(3):409-415.
  17. Machado M, Marques-Vidal P, Cortez-Pinto H: Hepatic histology in obese patients undergoing bariatric surgery. Journal of Hepatology 2006;45(4):600-606.
  18. Ong J, Elariny H, Collantes R, Younoszai A, Chandhoke V, Reines H, Goodman Z, Younossi Z. Predictors of nonalcoholic steatohepatitis and advanced fibrosis in morbidly obese patients. Obes Surg 2005;15(3):310-315.
  19. Abrams GA, Kunde SS, Lazenby AJ, Clements RH. Portal fibrosis and hepatic steatosis in morbidly obese subjects: A spectrum of  nonalcoholic fatty liver disease. Hepatology 2004;40(2):475-483.
  20. Minervini MI, Ruppert K, Fontes P, Volpes R, Vizzini G, de Vera ME, Gruttadauria S, Miraglia R, Pipitone L, Marsh JW, Marcos A, Gridelli B, Demetris AJ. Liver biopsy findings from healthy potential living liver donors: Reasons for disqualification, silent diseases and correlation with liver injury tests. Journal of Hepatology 2009;50(3):501-510.
  21. Lee JY, Kim KM, Lee SG, Yu E, Lim YS, Lee HC, Chung YH, Lee YS, Suh DJ. Prevalence and risk factors of non-alcoholic fatty liver disease in potential living liver donors in Korea: A review of 589 consecutive liver biopsies in a single center. Journal of Hepatology 2007;47(2):239–244.
  22. Tran TT, Changsri C, Shackleton CR, Poordad FF, Nissen NN, Colquhoun S, Geller SA, Vierling JM, Martin P. Living donor liver transplantation: Histological abnormalities found on liver biopsies of apparently healthy potential donors. J Gastroenterol Hepatol 2006;21(2):381-383.
  23. Yamamoto K, Takada Y, Fujimoto Y, Haga H, Oike F, Kobayashi N, Tanaka K. Nonalcoholic steatohepatitis in donors for living donor liver transplantation. Transplantation 2007;83(3):257-262.
  24. Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepatitis) and obesity: An autopsy study with analysis of risk factors. Hepatology 1990;12(5):1106-1110.
  25. Suzuki A, Angulo P, Lymp J, St. Sauver J, Muto A, Okada T, Lindor K. Chronological development of elevated aminotransferases in a nonalcoholic population. Hepatology 2005;41(1):64-71.
  26. Bedogni G, Miglioli L, Masutti F, Castiglione A, Croce L, Tiribelli C, Bellentani S. Incidence and natural course of fatty liver in the general population: The Dionysos study. Hepatology 2007;46(5)1387-1391.
  27. Whalley S, Puvanachandra P, Desai A, Kennedy H. Hepatology outpatient service provision in secondary care: A study of liver disease incidence and resource costs. Clin Med 2007;7(2):119-124.
  28. Lazo M, Clark JM. The epidemiology of nonalcoholic fatty liver disease: A global perspective. Semin Liver Dis 2008;28(4):339-350.