The prevalence of NAFLD is increasing in line with obesity, with an estimated global prevalence of 25%.
Public HealthNon-alcoholic fatty liver disease – A global public health perspective
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]
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.
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