Elsevier

Journal of Hepatology

Volume 70, Issue 3, March 2019, Pages 531-544
Journal of Hepatology

Public Health
Non-alcoholic fatty liver disease – A global public health perspective

https://doi.org/10.1016/j.jhep.2018.10.033Get rights and content

Summary

As the epidemics of obesity and type 2 diabetes mellitus increase worldwide, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing proportionately. The subtype of NAFLD which can be characterised as non-alcoholic steatohepatitis (NASH) is a potentially progressive liver disease that can lead to cirrhosis, hepatocellular carcinoma, liver transplantation, and death. NAFLD is also associated with extrahepatic manifestations such as chronic kidney disease, cardiovascular disease and sleep apnoea. NAFLD and NASH carry a large economic burden and create poor health-related quality of life. Despite this important burden, we are only beginning to understand its mechanisms of pathogenesis and the contribution of environmental and genetic factors to the risk of developing a progressive course of disease. Research is underway to identify appropriate non-invasive diagnostic methods and effective treatments. Although the risk of liver-related mortality is increased in patients with NAFLD and liver fibrosis stages F3 or F4, the leading cause of death is cardiovascular disease. Given the rapidly growing global burden of NAFLD and NASH, efforts must continue to find accurate non-invasive diagnostic and prognostic biomarkers, to develop effective treatments for individuals with advanced NASH and prevention methods for individuals at high risk of NAFLD and progressive liver disease.

Introduction

Chronic liver disease (CLD) is a major cause of mortality, morbidity, and health care resource utilisation worldwide.1 From 1980 through 2010, mortality related to CLD increased by 46% worldwide.2 This increase was mostly observed in low- and low-middle-income countries of Asia and Africa.3 The factors that contribute to increases in mortality vary in different parts of the world. In a recent study from the United States (US), the increase in liver mortality was associated with the increased prevalence of non-alcoholic fatty liver disease (NAFLD).4 These trends are also observed in other parts of the world, where the burdens of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection could be positively impacted with effective HBV vaccination and potent antiviral regimens for both HBV and HCV.1

Section snippets

NAFLD

NAFLD is a liver disease associated with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), hypertension, hyperlipidaemia, and metabolic syndrome. The subtype of NAFLD that is histologically categorised as non-alcoholic steatohepatitis (NASH) has a potentially progressive course leading to liver fibrosis, cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation. All of these complications of NASH can pose significant health, economic, and patient-experience burdens to the

Risk factors for NAFLD

Obesity increases the risk of NAFLD.[6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16] Overweight has been defined by the World Health Organization (WHO) as a body mass index (BMI) greater than or equal to 25 and obesity is defined as a BMI greater than or equal to 30. BMI has been the most useful population-level measure to define overweight and obesity, because the measurement applies to both sexes and adults of all ages. Nevertheless, because of diverse populations in Asia, the WHO

T2DM

Parallel to the high prevalence of obesity, T2DM is also on the rise worldwide. T2DM is another important risk factor for NAFLD and NASH. The International Diabetes Federation reports that more than 400 million people were living with diabetes as of 2015.9 The WHO estimates that 90% of people who have diabetes worldwide have T2DM.10 In 2012, diabetes caused an estimated 1.5 million deaths – more than 80% of these were in low- and middle-income countries. In developing nations, more than half of

Prevalence and incidence of NAFLD

The prevalence of NAFLD is increasing at approximately the same rate as obesity.[12], [13] In fact, the global prevalence of NAFLD in the general population has been estimated to be 25% whereas the global prevalence of NASH has been estimated to range from 3% to 5%.[15], [16], [19]

The prevalence of NAFLD is increasing in line with obesity, with an estimated global prevalence of 25%.

It is important to note that the prevalence of NAFLD varies across the globe.[12], [13], [14], [15], [16], [17],

Lean NAFLD

Some patients with NAFLD are neither overweight nor obese and are considered to have lean NAFLD, which encompasses a heterogeneous spectrum of disease and is thought to be linked to worse outcomes.

Although most patients with NAFLD are overweight or obese, some may have a BMI that is considered lean. Although patients with lean NAFLD are not obese, they may be metabolically abnormal compared to people who are not obese and do not have NAFLD.[44], [45], [46], [47], [48], [49], [50], [51], [52],

Disease progression

Before an individual can be diagnosed with NAFLD, other liver diseases, such as alcoholic liver disease, must be ruled out. Alcohol-related liver disease can be contemplated in men who consume more than 30 g alcohol/day and women who consume more than 20 g alcohol/day.54

Although hepatic steatosis can occur when there is more than 5% fat in hepatocytes, progression can ensue if these fatty hepatocytes are exposed to insults or stress, which can then cause cell death, apoptosis, inflammation, and

Mortality, HCC and liver transplantation in NAFLD

The presence of metabolic syndrome, especially obesity and insulin resistance, can increase the rate of liver fibrosis progression, leading to cirrhosis, HCC, and/or death. In fact, the more components of metabolic syndrome, the higher the risk of mortality.[62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87]

Liver-specific mortality among patients with NAFLD was reported to be 0.77 per 1,000

Changing profile of CLD

An analysis of the US NHANES (1988–2008 data) found that that the prevalence rates for CLD increased from 11.78% in 1988–1994 to 14.78% in 2005–2008. The prevalence rates of HBV-related, HCV-related, and alcohol-related liver disease remained generally stable, but the prevalence rate of NAFLD doubled; obesity was an independent predictor of NAFLD.88 However, it is important to keep in mind that aetiologies of CLD vary worldwide. Prevalence values are affected by external factors such as

Future projections

Modelling suggests that the global burden of NAFLD will continue to increase, with the largest increase in prevalence expected in China.

The global epidemic of NAFLD appears to be increasing at the same rate as epidemics of obesity and diabetes, so researchers used mathematical modelling analyses to estimate the future disease burden associated with NAFLD in the US. Their results indicate increases in cases of advanced liver disease and liver-related mortality in the coming years.44 More

Economic burden

The huge clinical burden of NAFLD is associated with a large economic burden.[95], [96], [97], [98], [99], [100], [101] In an analysis of data from the US Medical Expenditure Panel Survey (2004–2013) conducted to determine the effects of CLD (including NAFLD) on worker productivity, researchers found that, compared to people without CLD, patients with CLD were significantly less likely to be employed, due to illness/disability.92 People with CLD had more health care use, generating higher

Patient-reported outcomes

Patient-reported outcomes (PROs) are defined as “any report of the status of a patient's health condition that comes directly from the patient, without interpretation of the patient's response by a clinician or anyone else”.102 Therefore, the tools used to measure PROs attempt to provide patients a platform to explain what they are able to do and how they feel doing what they are doing through a series of questions that assess patients’ perception of their physical and mental health as well as

Impact of NAFLD on patients with other liver diseases

There are concerns about the effects of NAFLD on the outcomes of other liver diseases. NAFLD and HCV infection are each associated with development of T2DM. The combined effects of NAFLD and HCV on T2DM could create a cycle of poor health that eventually increases all-cause mortality and liver-related and cardiovascular complications. Conversely, reducing fatty liver and eradicating HCV with direct-acting antiviral agents might reduce risk of T2DM and improve patient outcomes. Further studies

Strategies to decrease NAFLD prevalence

Despite our increasing knowledge of NAFLD, many questions remain about progression, staging, diagnosis, and management. As we move forward, research should focus on identification of biomarkers that can be measured noninvasively, clarification of pathogenic pathways, development of screening guidelines, and determination of clinical endpoints, which are necessary to effectively assess the safety of new therapeutic agents.[118], [119] Until then, we must push forward the global initiative to

Conclusions

Due to the increasing prevalence of obesity and T2DM in children and adults, along with the world’s aging population, the prevalence of NAFLD is increasing. The rate of NAFLD-related HCC is also increasing, along with demand for livers for transplantation, of which there are not enough. NAFLD decreases patients’ HRQoL and causes a significant economic burden. Although agents are being tested in clinical trials for their ability to reverse the effects of fatty liver, the only proven treatments

Conflict of interest

The author declares no conflicts of interest that pertain to this work.

Please refer to the accompanying ICMJE disclosure forms for further details.

Acknowledgement

The author thanks Linda Henry PhD for medical writing and editorial assistance.

References (123)

  • S. McPherson

    Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management

    J Hepatol

    (2015)
  • R. Pais et al.

    A systematic review of follow-up biopsies reveals disease progression in patients with non-alcoholic fatty liver

    J Hepatol

    (2013)
  • G. Baffy et al.

    Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace

    J Hepatol

    (2012)
  • P. Bertuccio et al.

    Global trends and predictions in hepatocellular carcinoma mortality

    J Hepatol

    (2017)
  • H. Hagström et al.

    Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD

    J Hepatol

    (2017)
  • A. Spahillari et al.

    The association of lean and fat mass with all-cause mortality in older adults: The Cardiovascular Health Study

    Nutr Metab Cardiovasc Dis

    (2016)
  • M. Stepanova et al.

    Independent association between nonalcoholic fatty liver disease and cardiovascular disease in the US population

    CGH

    (2012)
  • E. Bugianesi et al.

    Hepatic and cardiac steatosis: are they coupled?

    Heart Fail Clin

    (2012 Oct)
  • A.P. Desai et al.

    Geographic variability in liver disease-related mortality rates in the United States

    Am J Med

    (2018)
  • L. Pimpin et al.

    Burden of liver disease in Europe: epidemiology and analysis of risk factors to identify prevention policies

    J Hepatol

    (2018)
  • Z.M. Younossi et al.

    Clinical and economic burden of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

    Clin Liver Dis

    (2018)
  • P. Marcellin et al.

    Liver diseases: a major, neglected global public health problem requiring urgent actions and large-scale screening

    Liver Int

    (2018)
  • A.A. Mokdad et al.

    Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis

    BMC Med

    (2014)
  • M. Stepanova et al.

    Direct and indirect economic burden of chronic liver disease in the United States

    Clin Gastroenterol Hepatol

    (2017)
  • D. Kim et al.

    Changing trends in etiology-based annual mortality from chronic liver disease, from 2007 through 2016

    Gastroenterology

    (2018)
  • Z. Younossi et al.

    Global perspectives on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

    Hepatology

    (2018)
  • WHO Expert Consultation

    Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies

    Lancet

    (2004)
  • Tenfold increase in childhood and adolescent obesity in four decades: new study by Imperial College London and WHO 11...
  • World Obesity Facts. Obtained from the world wide web at:...
  • Type 2 Diabetes Mellitus-International Diabetes Federation. IDF diabetes atlas. 8th ed. 2017 obtained from the world...
  • WHO Diabetes Fact Sheets. Obtained from the world wide web at:...
  • Centers for Disease Control. Rates of new diagnosed cases of type 1 and type 2 diabetes on the rise among children,...
  • World Health Organization (WHO). Obesity and overweight. Obtained from the world wide web at:...
  • World Health Assembly. Action plan to reduce global obesity. Obtained from the world wide web at:...
  • G. Vernon et al.

    Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults

    Aliment Pharmacol Ther

    (2011)
  • Z. Younossi et al.

    Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention

    Nat Rev Gastroenterol Hepatol

    (2018)
  • S.M. Camhi et al.

    The relationship of waist circumference and BMI to visceral, subcutaneous, and total body fat: sex and race differences

    Obesity

    (2011)
  • M. Mongraw-Chaffin et al.

    The sex and race specific relationship between anthropometry and body fat composition determined from computed tomography: evidence from the multi-ethnic study of atherosclerosis

    PLoS One

    (2015)
  • Z.M. Younossi et al.

    Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes

    Hepatology

    (2016 Jul)
  • H.P. Cotrim et al.

    Nonalcoholic Fatty Liver Disease Brazilian Society of Hepatology consensus

    Arq Gastroenterol

    (2016 Apr-Jun;)
  • G.C. Andrade et al.

    Non-alcoholic fatty liver disease (NAFLD) in different populations: a clinical and epidemiological study – sample of São José do Rio Preto

    Rev Assoc Med Bras (1992)

    (2016)
  • J.G. Fan

    Epidemiology of alcoholic and nonalcoholic fatty liver disease in China

    J Gastroenterol Hepatol

    (2013)
  • Y. Eguchi et al.

    Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: a multicenter large retrospective study

    J Gastroenterol

    (2012)
  • C.D. Zois et al.

    Steatosis and steatohepatitis in postmortem material from Northwestern Greece

    World J Gastroenterol

    (2010)
  • L. Caballería 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)
  • K. Das et al.

    Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease

    Hepatology

    (2010)
  • A.S. Dassanayake et al.

    Prevalence and risk factors for non-alcoholic fatty liver disease among adults in an urban Sri Lankan population

    J Gastroenterol Hepatol

    (2009)
  • The economic cost and health burden of liver diseases in Australia

    (2012)
  • National Health Survey: First Results, 2014–15....
  • K.J. Coppell et al.

    Obesity and the extent of liver damage among adult New Zealanders: findings from a national survey

    Obes Sci Pract

    (2015)
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