Discussion

NAFLD and its histological subtype, non-alcoholic steatohepatitis (NASH), have emerged as the most common forms of chronic liver disease in most regions worldwide. This study comprehensively describes NAFLD prevalence and temporal trends in NAFLD prevalence over the past three decades at the global, regional and national levels. In general, we found that NAFLD prevalence was heterogeneous across the globe, with almost all countries demonstrating significantly increasing trends between 1990 and 2017. These increases have been consistent across sexes and age groups. The highest prevalence overall was observed in countries located in North Africa and the Middle East. The most significant increases in prevalence were observed in Western European countries.

According to a recent study, the estimated prevalence of overweight status was highest in several countries North African and Middle Eastern countries (including Qatar, Libya and Kuwait) across both sexes.6 The distribution of overweight status lines up significantly with NAFLD prevalence, as demonstrated in this and other studies.12 The greatest increase in NAFLD prevalence was found in Western Europe, which may primarily be ascribed to the rapid increase in overweight status in these countries.6 This striking increase in NAFLD prevalence has prompted investigators to explore the disease’s risk factors. So far, well-established risk factors for NAFLD include obesity, type 2 diabetes, an unhealthy diet (eg, high intake of red meat and processed meat) and physical inactivity.13–17 Of these, an unhealthy lifestyle is deemed to be the most important contributor to NAFLD.18 Key lifestyle parameters include an increased intake of glucose, fructose, and saturated fat, induced hepatic de novo lipogenesis, subclinical inflammation in the adipose tissue and liver, and insulin resistance in adipose tissue, the liver, and skeletal muscle. These parameters are also accompanied by an increased risk of type 2 diabetes.19

Additionally, gut dysbiosis, which is induced in most cases by an unhealthy diet, is believed to be a major contributor to the accumulation of fat in the liver and to the pathogenesis of NASH. There is a set of clinical trials currently underway that focuses on liver-specific and extrahepatic targets, including the microbiome and gut–liver signalling axis, as well as other organs that contribute to metabolic syndrome, especially muscle and adipose tissue.20 Although there is a great deal of activity in terms of drug development targeting NASH—for example, with an farnesoid X receptor (FXR) agonist (obeticholic acid), a peroxisome proliferator-activated receptor (PPAR)α and PPARδ agonist (elafibrinor) and a C-C chemokine receptor (CCR)2 and CCR5 antagonist (cenicriviroc)—it is too early to prioritise these drugs or mechanisms based on which seems most promising. It will take time to translate the findings of all these studies into long-term safety and efficacy.20 For these reasons, the primary preventative steps in terms of the abovementioned risk factors, including adherence to a healthy lifestyle and maintaining a healthy BMI, remain the optimal approach to preventing NAFLD.

Our study found that approximately 0.9 billion people suffered from NAFLD in 2017. What sets NAFLD apart from other common liver diseases is the sheer number of patients worldwide. Unfortunately, we also observed increasing trends in NAFLD prevalence globally. Consequently, the complications and sequelae of NAFLD might also be on the rise. For example, this increasing prevalence of NAFLD is accompanied by increasing prevalence of other non-communicable diseases, including cardiovascular disease, obesity-associated and type 2 diabetes-associated cancer and advanced liver diseases such as hepatic cirrhosis and HCC.21 As the clinical consequences of NAFLD grow, so too will the economic repercussions. One model based on the populations of the USA and four European countries (Germany, France, Italy and the UK) estimated the annual burden associated with all incident and prevalent NAFLD cases at US$103 billion in the USA (or US$1613 per patient) and €35 billion in these four European countries (from €354 to €1163 per patient).22 Unfortunately, as our results show, we found significant increases in both obesity and diabetes prevalence in most countries over the last decade. If the annual rate of increase in NAFLD-related costs parallels annual growth in the prevalence of obesity—and taking into account an ageing population—then the expected 10-year burden for NAFLD could increase to an estimated US$1.005 trillion in the USA and €334 billion in these Europe countries.22 Interestingly, we also found a significant positive correlation between national HDI and increase magnitude in NAFLD prevalence. This result suggests a striking increase in NAFLD risk factors, particularly in developed countries; these factors likely include an ever-growing ageing population, physical inactivity, increases in consumption of red meat and processed meat and other unhealthy lifestyles choices that contribute to NAFLD.16 23 Given the observable increases in obesity and diabetes prevalence, NAFLD prevalence is anticipated to continue to increase in the near future if no effective interventions are introduced.3 Moreover, this persistent increase in NAFLD also indicates an increasing need for medical facilities and improved health systems in these countries, given that more NAFLD patients will continue to be diagnosed.

NAFLD prevalence has also persistently increased in developing regions, including the sub-Saharan Africa, a region where NAFLD had previously been a less frequent diagnosis. This increase might be ascribed to the increasing availability of healthcare and the concomitant rise in accurate NAFLD diagnosis, as well as to transitions in lifestyle. Increased awareness and urgent action is needed if we want to control the NAFLD pandemic worldwide. Specifically, (1) our governments should play a strong leadership role in reinforcing the importance of addressing obesity and establishing more effective prevention strategies; (2) funds should be allocated specifically to create a culture that promotes healthy eating and an active lifestyle, especially for children and adolescents; (3) we must create multifaceted interventions aimed at motivating behavioural changes, including setting-based health promotion and education programmes (eg, in preschools, schools, workplaces, religious settings and hospitals), mass media campaigns, social marketing to share knowledge and skills within our communities and routine primary healthcare and counselling appointments to facilitate obesity prevention and management.24

Our study has several limitations that should be noted. First, the data we used were derived from mathematical models rather than surveillance. Differences in data processing approaches between the GBD study and previous studies might also contribute to disparities in the NAFLD prevalence rates proposed in our study when compared with those from the previous meta-analyses.4 25 For example, Younossi et al reported that the global prevalence of NAFLD derived from a meta-analysis was 25.24%, which is significantly higher than the estimates in our study.4 We assume that this difference can be explained as follows: (1) Most studies included in the meta-analysis were conducted in Europe, Asia and North America, where NAFLD prevalence is relatively high. In Africa and Australia, where NAFLD is not a major public health concern, studies on NAFLD are rare. However, in the GBD study, NAFLD prevalence was estimated from country to country using mathematical models; (2) The GBD study included a wider study population, ranging in age from 0 to ≥85 years. Children, adolescents and young adults are relatively less afflicted by NAFLD than middle-aged people and elderly people26 and (3) To ensure the robustness of its estimates, NAFLD prevalence rates that were significantly higher than the regional, superregional, or global rates were excluded from the GBD study.

Second, NAFLD is a complex and heterogeneous disease. The scarcity of histological and stage data in the GBD database made it difficult to describe the NAFLD disease burden in detail. This type of descriptive study also lacks information at the individual level. For example, the GBD study did not include information on hepatic fibrosis evaluations, which are a key determinant of NAFLD outcomes. Future studies assessing the NAFLD disease burden should also take these histological and pathological data into account. Third, NAFLD prevalence was estimated using a mathematical model that included patients who were diagnosed only by USS or another imaging diagnostic tool. Since there are few effective diagnostic methods available in daily clinical practice—and because we excluded NAFLD diagnosed using other methods (eg, non-invasive scores)—our data may underestimate the NAFLD disease burden.

In summary, NAFLD prevalence is increasing worldwide and the disease is being diagnosed in all parts of the world. The highest prevalence was observed in North Africa and the Middle East, while the greatest increase was detected in Western Europe and North America. This dramatic and significant increase in NAFLD prevalence is alarming and suggests that NAFLD has emerged as a new public health concern worldwide. More efficient prevention strategies are urgently needed.