Journal of Clinical Medicine Review What Do We Know about Inequalities in NAFLD Distribution and Outcomes? A Scoping Review Mar Talens 1 , Natalia Tumas 1,2,3 , Jeffrey V. Lazarus 4 , Joan Benach 1,2,5 and Juan M. Pericàs 1,2,6,7, * 1 Research Group on Health Inequalities, Environment, and Employment Conditions, Department of Social and Political Science, Pompeu Fabra University, 08005 Barcelona, Spain; mar.talens01@estudiant.upf.edu (M.T.); natalia.tumas@upf.edu (N.T.); joan.benach@upf.edu (J.B.) 2 Public Policy Center (UPF-BSM), Johns Hopkins University-Pompeu Fabra University, 08005 Barcelona, Spain 3 Centro de Investigaciones y Estudios sobre Cultura y Sociedad, Consejo Nacional de Investigaciones Científicas y Técnicas y Universidad Nacional de Córdoba, Córdoba 5016, Argentina 4 Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain; jeffrey.lazarus@isglobal.org 5 Transdisciplinary Research Group on Socioecological Transitions (GinTrans2), Universidad Autónoma de Madrid, 28049 Madrid, Spain 6 Liver Unit, Internal Medicine Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute for Research, 08035 Barcelona, Spain 7 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain * Correspondence: jpericas@vhebron.net Abstract: With prevalence high and rising given the close relationship with obesity and diabetes mellitus, non-alcoholic fatty liver disease (NAFLD) is progressively becoming the most common  chronic liver condition worldwide. However, little is known about the health inequalities in NAFLD  distribution and outcomes. This review aims to analyze health inequalities in NAFLD distribution Citation: Talens, M.; Tumas, N.; globally and to assess the health disparities in NAFLD-related outcomes. We conducted a scoping Lazarus, J.V.; Benach, J.; Pericàs, J.M. review of global health inequalities in NAFLD distribution and outcomes according to gender/sex, What Do We Know about Inequalities ethnicity/race, and socioeconomic position from PubMed’s inception to May 2021. Ultimately, in NAFLD Distribution and 20 articles were included in the review, most (75%) of them carried out in the United States. Males Outcomes? A Scoping Review. J. Clin. Med. 2021, 10, 5019. https://doi.org/ were found to have a higher NAFLD prevalence (three articles), while available evidence suggests 10.3390/jcm10215019 that women have an overall higher burden of advanced liver disease and complications (four articles), whereas they are less likely to be liver-transplanted once cirrhosis develops (one article). In Academic Editor: Francesco Azzaroli the US, the Hispanic population had the highest NAFLD prevalence and poorer outcomes (seven articles), whereas Whites had fewer complications than other ethnicities (two articles). Patients Received: 27 September 2021 with low socioeconomic status had higher NAFLD prevalence (four articles) and a higher likelihood Accepted: 25 October 2021 of progression and complications (five articles). In conclusion, globally there is a lack of studies Published: 28 October 2021 analyzing NAFLD prevalence and outcomes according to various axes of inequality through joint intersectional appraisals, and most studies included in our review were based on the US population. Publisher’s Note: MDPI stays neutral Available evidence suggests that NAFLD distribution and outcomes show large inequalities by social with regard to jurisdictional claims in group. Further research on this issue is warranted. published maps and institutional affil- iations. Keywords: non-alcoholic fatty liver disease; health inequalities; social determinants of health Copyright: © 2021 by the authors. 1. Introduction Licensee MDPI, Basel, Switzerland. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases This article is an open access article distributed under the terms and ranging from simple hepatic steatosis (fatty liver) to steatohepatitis (NASH) to cirrhosis and conditions of the Creative Commons hepatocellular carcinoma (HCC) [1]. NAFLD is currently considered the liver manifestation Attribution (CC BY) license (https:// of metabolic syndrome (which also encompasses obesity, type 2 diabetes mellitus (T2DM), creativecommons.org/licenses/by/ insulin resistance, and dyslipidemia) [2]. A significant part of the scientific community 4.0/). J. Clin. Med. 2021, 10, 5019. https://doi.org/10.3390/jcm10215019 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021, 10, 5019 2 of 22 advocates for a change in terminology by which NAFLD is progressively replaced by metabolic-associated fatty liver disease (MAFLD) [3]. The increasing burden of disease owing to NAFLD and associated disorders has led to a massive scientific effort to better depict its epidemiology, natural history, and potential treatments. NAFLD has an estimated global prevalence of 25% of the general population, whereas the global prevalence of NASH has reached nearly 5% [4]. Therefore, NAFLD has become the most common cause of chronic liver diseases in many parts of the world [5], and NASH is one of the leading underlying causes of liver transplantation [6]. However, most countries, including Western countries, are not prepared to address NAFLD, lacking adequate policies and civil society awareness and engagement, guidelines, epidemiology, and care management [7]. Structural changes and new models of care are needed in order to improve NAFLD management and public health policies [7,8]. Besides the complex mechanisms underlying its pathogenesis [9], NAFLD is caused by interactions between many social, environmental, and genetic factors [10]. Among such factors, several social and economic conditions seem essential to understanding the current picture of NAFLD globally, as well as its differences between social groups. Although it is well known that social determinants of health (SDH) have a great impact on the non- communicable disease (NCDs) burden [11], there is an important gap in the literature of how they may be related to health inequalities in NAFLD global distribution and outcomes. Preliminary evidence from scattered studies suggests that Hispanic ethnicity [12] and male sex [13] are associated with a higher likelihood of having NAFLD in the United States. However, most studies have approached such disparities with a biomedical focus rather than a social lens, i.e., attributing them to the frequency of a polymorphism in the PNPLA3 gene in the Hispanic population [14], or to estrogen protection in premenopausal females [15]. This review aims to analyze the health inequalities on NAFLD distribution globally, including prevalence and incidence, and to assess the health disparities in NAFLD-related outcomes, including advanced liver disease and complications. 2. Materials and Methods 2.1. Selection of the Review Approach A scoping review approach was chosen because this topic has not been extensively reviewed to date and has a complex and heterogeneous nature [16]. The methodologic pro- posal of Arksey and O’Malley was followed [17]. PRISMA guidelines were followed [18]. 2.2. Literature Search Strategy A PubMed search was conducted using the following keywords and expressions: [“NAFLD” OR “NASH” OR “fatty liver” OR “MAFLD”) AND/OR (“prevalence” AND/OR “distribution” AND/OR “incidence”, AND/OR “epidemiology”) AND/OR [“cirrhosis” AND/OR “hepatocellular carcinoma” OR “liver cancer”, AND/OR “advanced fibrosis” AND/OR “cardiovascular events” AND/OR “hepatic events”, AND/OR “mortality”] AND (“gender” AND/OR “sex” AND/OR “ethnicity” AND/OR “race” AND/OR “uni- versal health coverage” AND/OR “socioeconomic position” AND/OR “socioeconomic status” AND/OR “education” AND/OR “housing”, AND/OR “income”) AND/OR [“dis- parities” OR “inequities” OR “equity” OR “inequalities”] from PubMed inception to 31 May 2021. Furthermore, a manual search of secondary references from screened articles was performed. 2.3. Eligibility Criteria Articles were included if all the following inclusion criteria were met: (i) articles written in English; (ii) original articles; (iii) studies of at least one element of each of the two following pairs: NAFLD or MAFLD, distribution or outcomes (see definitions below); and (iv) studies analyzing at least one axis of inequality (e.g., articles including SDH J. Clin. Med. 2021, 10, 5019 3 of 22 as subvariables for analysis without specific analysis of how they impact disparities in NAFLD distribution or outcomes were not included). Articles were excluded if they: (i) mostly analyzed other causes of hepatic steatosis such as chronic viral hepatitis (C and/or B hepatitis viruses), drugs, or alcohol-related liver disease; (ii) did not exclude patients with elevated alcohol consumption (over 20 g/day in females and over 30 g/day in males), even if the most likely diagnosis was NAFLD; (iii) focused on pediatric population (<18 years); (iv) the study sample was smaller than 150 individuals; and (v) were reviews, meta-analyses, editorials, or commentaries. 2.4. Study Selection and Data Extraction Articles were first screened based on the search keywords with title and abstract. Subsequently, a screening applying the inclusion/exclusion criteria was conducted, and ultimately a full-text reading was performed. Extracted data included: (i) first author name, (ii) publication year, (iii) period of study, (iv) country of study, (v) study design and population, (vi) method of diagnosis, (vii) distribution index/analyzed outcomes, (viii) axes of inequality, (ix) results, (x) con- clusions, and (xi) limitations of the study. Finally, data were summarized in two tables depending on whether the study analyzed NAFLD distribution (Table 1) or analyzed other outcomes such as advanced liver disease or complications (Table 2). 2.5. Definitions The definitions that we used are as follows: Advanced fibrosis: Liver fibrosis in stages 3 and 4 [5]. Advanced liver disease: NAFLD/NASH with advanced fibrosis or cirrhosis. Axes of inequality: social determinants, such as social class, socioeconomic position, gender/sex, and ethnicity/race among, others that determine the opportunities for good health and reveal the existence of health inequalities due to hierarchies of power, prestige, or access to resources [19]. Cirrhosis: histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury, which leads to portal hypertension and end-stage liver disease [20]. Complications of NAFLD: unfavorable results of the disease, comprising liver de- compensation, liver cancer, liver transplant, cardiovascular events, hospitalization, and mortality. Distribution of NAFLD: frequency and pattern of health events in the population, comprising prevalence and incidence. Ethnicity/Race: historical social groups that share specific social, cultural, and some biological attributes [21]. Gender: a social construct regarding culture-bound conventions, roles, and behaviors for, as well as relationships between and among women and men and boys and girls, as opposed to sex, which is determined by the genetic background and secondary sexual characteristics [21]. Health inequalities: differences in health status or in the distribution of health re- sources between different population groups, which are not only unnecessary and avoid- able, but in addition, are considered unfair and unjust [22]. Lean NAFLD/NASH: individuals with <25 BMI with clear evidence of NAFLD or NASH presence [23]. Liver decompensation: acute deterioration in liver function in a patient with cirrhosis and is characterized by jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome, or variceal hemorrhage [24]. Outcomes of NAFLD: NAFLD-related consequences comprising NAFLD progression to advanced liver disease and NAFLD-related complications. Social determinants of health: conditions in which people are born, grow, work, live, and age, and the wider set of forces and systems shaping the conditions of daily life. These J. Clin. Med. 2021, 10, 5019 4 of 22 forces and systems include economic policies and systems, development agendas, social norms, social policies, and political systems [25]. Social groups: sets of people whose ways of living have been historically determined by one or various social determinants of health such as gender, ethnicity, migration status, or socioeconomic position [25]. Social inequalities: in the context of health, health disparities, within and between countries, that are judged to be unfair, unjust, avoidable, and unnecessary (meaning: are neither inevitable nor irremediable) and that systematically burden populations ren- dered vulnerable by underlying social structures and political, economic, and legal institu- tions [21]. Socioeconomic position/status: an aggregate concept that includes both resource- based and prestige-based measures, as linked to both childhood and adult social class position. Resource-based measures refer to material and social resources and assets, includ- ing income, wealth, and educational credentials [21]. 3. Results 3.1. Literature Search Of 603 articles retrieved from the initial search, 481 (79.8%) were excluded by title, and 122 (20.2%) articles were selected for abstract screening. Of 122 articles, 81 (66.4%) were excluded applying the inclusion/exclusion criteria, and 41 (33.6%) were selected for full-text reading. At this point, 26 studies were added from reference lists of other selected articles. After the full-text reading, 47 did not meet the inclusion/exclusion criteria. Therefore, a total of 20 articles were selected to perform the review (Figure 1). Figure 1. Flowchart of studies disposition throughout the search and article selection process according to PRISMA guidelines for scoping reviews [18]. The studies were classified into two different groups—NAFLD distribution and NAFLD outcomes—although some of them were clustered in both groups (n = 4). The first group (Table 1) includes those articles addressing NAFLD distribution, i.e., analyzing the prevalence or incidence of NAFLD according to different axes of inequality (n = 17, 85%). The second group (Table 2) includes those articles that analyze NAFLD-related outcomes (n = 12, 60%), such as progression to advanced liver disease (n = 5, 25%) or complications (n = 8, 40%). Articles on advanced liver disease comprised advanced fibrosis (n = 2, 10%) and cirrhosis (n = 3, 15%), and complications included liver cancer (n = 3, 15%), hospitalization events (n = 1, 5%), liver transplants (n = 4, 20%), and mortality (n = 4, 20%). Yet, no study was found that analyzed health inequalities in cardiovascular events related to NAFLD or liver decompensation. J. Clin. Med. 2021, 10, 5019 5 of 22 Table 1. Summary of included studies assessing NAFLD distribution. Period, Design and Diagnostic Distribution Axes of Author Results Conclusions Limitations Country Population Methods Index Inequality Lean NAFLD is Lean individuals with Cross-sectional independently associated NAFLD have a study DB: with younger age, female sex, different clinical Does not perform Younossi, 2012 1988–1994 NHANES III Ultrasound Prevalence Sex and a decreased likelihood of profile than an intersectional [23] US n = 11,613 having IR and overweight-obese analysis. Age ≥ 20 hypercholesterolemia individuals with (p < 0.05) NAFLD. NAFLD prevalence: Prospective Hispanics (58.3%) > NAFLD prevalence is Brooke Army Caucasians (44.4%) > African higher than the Medical Center Ultrasound and Americans (35.1%) estimate. Hispanics Does not perform Williams, 2011 2007–2010 Ethnicity n = 328 (156 optional liver Prevalence Males (58.9%) > Females and patients with an intersectional [26] US Sex positive biopsy (41.1%) diabetes are at the analysis. ultrasound) A 74% of the diabetic greatest risk for Age 28–70 population was diagnosed NAFLD. with NAFLD. NAFLD prevalence: 26.5% of men > 20.1% women. NAFLD prevalence was highest in younger men and older women. Younger men NAFLD is common in aged ≤45 years have a higher a gentrifying Chinese prevalence than older men population, Abdominal Cross-sectional aged >45 years (30.1% vs. particularly in The studied region computed Zhou, 2019 2012–2013 study Sex 24.2%, p = 0.021), whereas younger men of high may not be tomography Prevalence [27] China n = 4002 SES younger women aged ≤45 socioeconomic status representative of (Liver-spleen Age 25–75 years have a lower prevalence and older women all of China. ratio ≤ 1.1) of NAFLD compared to older with sedentary women aged >45 years behavior who eat red (15.2% vs. 22.8%, p < 0.001). meat. A higher proportion of men with NAFLD had an annual household income ≥ 75000CNY. J. Clin. Med. 2021, 10, 5019 6 of 22 Table 1. Cont. Period, Design and Diagnostic Distribution Axes of Author Results Conclusions Limitations Country Population Methods Index Inequality NAFLD prevalence: Latinos (56% M vs. 47% W) > The results suggest Japanese Americans (38% M strong evidence for vs. 46% W) > Native Cross-sectional disproportionately Hawaiians (35%M vs. 42%W) study. greater susceptibility > Whites (23% M vs. 21% W) DB: Multiethnic to intra-abdominal 2013–2016 Abdominal MRI Ethnicity > African Americans (21%M Purely biological Lim, 2019 [28] cohort study Prevalence adiposity among US scan Sex vs. 18% W). approach n = 1794 Japanese compared to Compared with African Age 58–74 (PMP other ethnic/racial Americans, Japanese women) groups and greater Americans had a greater prevalence of NAFLD mean visceral fat area (45%M in Latinos. vs. 73%W), and mean liver fat (61%M vs. 122%W) The prevalence of NAFLD was similar for both women NAFLD is related to and men; highest among the presence of AAC Retrospective Hispanics (40.1%) and lowest on Blacks and women. study among Blacks (11.1%) and Remigio- These suggest Does not perform 2002–2005 DB: MESA Computed Ethnicity Chinese (11.6%). Baker, 2017 Prevalence disparities in the an intersectional US n = 326 tomography Sex Among Blacks, NAFLD was [29] pathophysiologic analysis. Age 45–84 (PMP associated with a greater pathways in which women) AAC prevalence (41%), and atherosclerosis among women, NAFLD was develops. associated with a 13% greater prevalence of AAC. J. Clin. Med. 2021, 10, 5019 7 of 22 Table 1. Cont. Period, Design and Diagnostic Distribution Axes of Author Results Conclusions Limitations Country Population Methods Index Inequality NAFLD prevalence: Mexican-Americans (21.2%) > non-Hispanic Whites (12.5%) > African American (11.6%). Mexican-Americans Mexican-Americans were had a significantly Cross-sectional more likely to have NAFLD higher prevalence of study (OR 1.67, 95% CI 1.26–2.22). Does not perform Schneider, 1988–1994 Ultrasound and Ethnicity NAFLD. DB: NHANES III Prevalence African Americans were an intersectional 2014 [30] US elevated AST Sex Racial differences are n = 9675 significantly less likely to analysis. not fully explained by Age 20–74 have NAFLD with elevated lifestyle, adiposity, aminotransferases (OR 0.51, and metabolic factors. 95% CI 0.27–0.97). Racial differences were attenuated among those with normal BMI. Among people with NAFLD, the majority were nonwhite: Hispanics (28%), Asians These racial and (18%), African Americans gender variations may Cross-sectional (3%), and other race(s) (6%). reflect differences in study African Americans with genetic susceptibility DB: Chronic Liver NAFLD were significantly Radiology and an to visceral adiposity, Weston, 2005 1998–2000 Disease Sex older than other racial or Purely biological optional liver Prevalence including hepatic [31] US Surveillance Study Ethnicity ethnic groups (p < 0.001), and approach biopsy involvement, and may n = 742 (333 with in Asians, NAFLD was 3.5 have implications for NAFLD) times more common in males the evaluation of Age 20–74 than in females (p = 0.016). persons with Hispanics with NAFLD were metabolic syndrome. over-represented (28–10%) and whites were under-represented (45–59%). J. Clin. Med. 2021, 10, 5019 8 of 22 Table 1. Cont. Period, Design and Diagnostic Distribution Axes of Author Results Conclusions Limitations Country Population Methods Index Inequality Larger rate of increase in Hospitalizations with NAFLD hospitalization NAFLD are rapidly among males vs. females increasing in the US, Retrospective ICD-9 The diagnostic (83/100,000 vs. 75/100,000), with a cross-sectional NIS does not modality is Sex Hispanics vs. Whites vs. disproportionately Adejumo, 2019 2007–2014 study contain Incidence unknown. Ethnicity Blacks (107/100,000 >. higher burden among [32] US DB: HCUP-NIS information on Prevalence Does not perform SES 80/100,000 > 48/100,000), certain demographic n = 210,660 how NAFLD was an intersectional and government-insured or groups: males, Age ≥18 diagnosed. analysis. uninsured patients vs. Hispanics, and privately insured (94/100,000 non-privately-insured vs. 74/100,000). population. 29% (95% CI 26–32%) were food-insecure. NAFLD prevalence Cross-sectional Food insecurity may food-insecure 34% vs. analysis be independently NAFLD prevalence Does not perform Golovaty, 2020 2005–2014 DB: NHANES SES (Food associated with USFLI Prevalence food-secure 31% (p = 0.21) an intersectional [33] US n = 2627 of insecurity) NAFLD among Multivariable model: analysis. low-income adults low-income adults in food-insecure adults are more Age ≥ 20 the US. likely to have NAFLD (adjusted OR 1.38, 95% CI 1.08-1.77) FI 56.8% in cases, with NAFLD and 26.1% in controls without NAFLD (p < 0.001). The likelihood of NAFLD The prevalence of Case-control study was higher in the food insecurity in Does not perform Tutunchi, 2021 2019 n = 210 (95 case vs. Ultrasonography Prevalence SES (FI) food-insecure (OR 2.2, 95% patients with NAFLD an intersectional [34] Iran 115 controls) CI: 1.12–3.43), depressed (OR is significantly higher analysis. Age 20–60 1.9, 95% CI 1.02–3.62), compared to controls. overweight (OR 2.6, 95% CI 1.81–3.92), and obese (OR 2.9, 95% CI 2.02–5.34) subjects. J. Clin. Med. 2021, 10, 5019 9 of 22 Table 1. Cont. Period, Design and Diagnostic Distribution Axes of Author Results Conclusions Limitations Country Population Methods Index Inequality In retired people, NAFLD Cross-sectional The prevalence of Only studies the prevalence: females (81.2%) > study Ultrasonic NAFLD is related to retired population males (75%). 2015 Diabetes quantitative SES the socioeconomic and does not Hu, 2020 [35] Prevalence As income increased, NAFLD China prevention determination of Sex level and female perform an prevalence of NAFLD program fat content gender (among intersectional increased progressively n = 930Age 40–76 retirees) analysis. (p < 0.05). Individuals with low SES (OR 1.70, 95% CI 1.42–2.04, p < 0.001) or low HGS (OR Both low SES and low 12.16, 95% CI 9.55–15.49, HGS are p < 0.001) had a significantly Cross-sectional independently and higher risk of NAFLD. Low study synergistically Does not perform 2014–2018 SES combined with a low Cho, 2021 [36] DB: KNHANES HSI and CNS Prevalence SES associated with an an intersectional South Korea HGS increased the risk of n = 5272 increased risk of analysis. NAFLD when adjusted for all Age < 50 and ≥ 65 NAFLD in the covariates (OR 2.48, 95% middle-aged Korean CI 1.35–4.55, p = 0.003), adults. compared with individuals with a high SES and a high HGS (OR 1). Footnote: AAC (abdominal aortic calcification), ALT (alanine aminotransferase), AOR (adjusted odds ratio), AST (aspartate aminotransferase), BMI (body mass index), CI (confidence interval), CNS (comprehensive NAFLD score), DB (database), FI (food insecurity), HCUP (Healthcare Cost and Utilization Project), HGS (handgrip strength), HSI (hepatic steatosis index), ICD-9 (international classification of disease), KNHANES (Korean national health and nutrition examination survey), M (men), MESA (multi-ethnic study of atherosclerosis), NAFLD (non-alcoholic fatty liver disease), NIS (national inpatient survey), NHANES (national health and nutrition examination survey), OR (odds ratio), PMP (postmenopausal), RF (risk factor), SES (socioeconomic status/position), USFLI (ultrasound fatty liver index), W (women). J. Clin. Med. 2021, 10, 5019 10 of 22 The most frequently addressed axes of inequalities were gender/sex (n = 16, 80%), ethnicity (n = 10, 50%), and socioeconomic position (n = 7, 35%). Although 12 studies ana- lyzed more than one axis of inequality (60%), only 4 articles (20%) analyzed the intersection between them. 3.2. NAFLD Distribution 3.2.1. Gender/Sex In the general population, NAFLD is more prevalent among men than women [26–28]. Specifically, in China, there is an NAFLD prevalence of 26.5% in men and 20.1% in women [27], and among US citizens, men comprise 58% of the total population with NAFLD [26]. However, this prevalence disparity is not conserved when models are ad- justed for body mass index and age. Among lean or non-overweight populations, women seem to have a higher prevalence than men [23], while when only postmenopausal women are taken into account, NAFLD prevalence seems to be the same between males and females [28,29]. Additionally, men tend to have an NAFLD onset sooner than women. Younger men (≤45 years) have a higher prevalence than older men (30% vs. 24%) [27]. Conversely, women have a higher prevalence at an older age. In the Chinese population, women aged less than 45 years have a lower prevalence of NAFLD compared to women aged more than 45 years (15% vs. 22.8%) [27], and in the US population, elderly females are more likely to have NAFLD than younger females (28–14%) [37]. Further, it has also been described that increased age is associated with a decreased risk of having NAFLD in men (OR 0.87) and increased risk in women (OR 1.22) [27]. Therefore, although NAFLD seems to affect more males than females, age and menopausal status play an important role in sex inequalities in NAFLD prevalence. More- over, even though several studies refer to this SDH as gender, the analyses are based on biological sex (male vs. female) only. 3.2.2. Ethnicity/Race The exact prevalence of ethnicity differs according to the methodology employed and the population investigated. Overall, the prevalence of NAFLD appears to be higher among Hispanics, followed by non-Hispanic Whites and Asians, and lastly, African Americans in the US population [26,29–31]. Furthermore, this ethnic disparity has also been observed in hospitalized patients [32] and lean-NAFLD patients [23]. In the US population, NAFLD prevalence is higher in Mexican-Americans (21.2%) followed by non-Hispanic Whites (12.5%), and lower in African Americans (11.6%) [30]. Even so, a recent prospective study suggests that NAFLD prevalence among the Hispanic population might be much higher (40%) [28,29]. Additionally, Hispanic ethnicity is a risk factor to develop NAFLD [23,33], whereas African Americans have lower odds to develop fatty liver disease (OR 2.03 vs. 0.42) [33]. In addition, there are substantial differences in the mean age of NAFLD onset by race. Although it seems that Mexican Americans have an earlier NAFLD onset (36.7 years) [30], it is not clear whether African Americans or non-Hispanic Whites have the latest onset. Schneider et al. observed that the mean age for Non-Hispanic Whites is 43.1 years, while the mean age for African Americans is 39.5 years [30]. Another study suggested that African Americans with NAFLD were significantly older than other racial or ethnic groups [31]. Although Hispanic ethnicity has the highest NAFLD prevalence, Japanese Ameri- cans have a greater susceptibility to intra-abdominal adiposity, which is a risk factor for NAFLD [28]. Even though Hispanics have a higher visceral fat mass, once the total mass is accounted for, their visceral fat mass proportion is similar to that of Whites [28]. There are also differences in liver enzymes such as aspartate and alanine transaminases levels, which are used as NAFLD biomarkers. Although AST and ALT levels are the highest among Hispanics, African Americans have significantly higher mean AST levels compared to non-Hispanic Whites [30]. Hence, although the adiposity body distribution and AST/ALT levels differ between ethnicities, they do not follow the same prevalence pattern as NAFLD. J. Clin. Med. 2021, 10, 5019 11 of 22 Hispanics appeared to have a higher NAFLD prevalence, a sooner onset, and a worse metabolic profile than other ethnicities. Of note, all the studies that analyze ethnic disparities were performed among the US population. 3.2.3. Socioeconomic Position/Status Overall, NAFLD prevalence seems to be higher among individuals with lower so- cioeconomic position in Western countries [33,34]. However, data coming from Eastern countries is not so consistent [35,36]. A study conducted in South Korea found that people with a low socioeconomic status have a significantly higher risk of developing NAFLD (OR 1.7) [36]. A Chinese study also found that people with a higher median income had a 1.96 higher risk of developing NAFLD than the low-income population [35]. However, this study had a notable selection bias that limits external validity [35]. In the field of NAFLD, the socioeconomic position has been particularly studied by addressing how it relates to food insecurity and the limited or uncertain access to nutritionally adequate and safe foods [33,34]. Approximately 29% of US adults in low- income households with NAFLD live in food-insecure households [33]. Subjects who live under food insecurity have higher odds of developing NAFLD (OR 1.38) [33]. Similarly, in the Iranian population, the prevalence of food insecurity is much higher among the NAFLD population (56.8%) than among individuals without NAFLD (26.1%) [34]. 3.3. NAFLD Outcomes 3.3.1. Advanced Liver Disease in NAFLD Gender/Sex Although a global population study concluded that among the population below 70 years, males had a higher prevalence of cirrhosis and several DALYs (Disability-Adjusted Life Years) because of liver disease [38]. In the US, women seem to have a higher prevalence of NASH-related cirrhosis than males, both compensated and decompensated [32,39]. Little has been studied about gender/sex differences in NAFLD progression to advanced fibrosis; however, it seems that the prevalence of advanced fibrosis is similar (OR 1.6 vs. 1.4) when only postmenopausal women are analyzed [40]. Furthermore, among females, the elderly have higher rates of advanced fibrosis at NAFLD onset (OR 1.8) [40]. Ethnicity/Race No studies analyzing the impact of ethnicity/race as a risk factor of either advanced liver fibrosis or cirrhosis nor the comparative risks or burdens in NAFLD patients were found. Socioeconomic Position/Status Advanced liver disease is more prevalent in individuals with lower socioeconomic status [33,36,38]. In geographic regions with an overall lower socioeconomic position, there is higher cirrhosis prevalence [38]. Furthermore, among low-income households, food insecurity is associated with higher odds of advanced fibrosis (OR 2.20) [33]. J. Clin. Med. 2021, 10, 5019 12 of 22 Table 2. Summary of included studies assessing NAFLD outcomes. Period Design and Diagnosis Axes of Author, Year Outcomes Results Conclusions Limitations Country population method Inequality NASH was the leading cause NASH is the second of LT for women and the 2nd leading cause for LT Study cohort leading cause for men waitlist logistic (following alcoholic liver COMP (LT) registration/LT and in Noureddin, 2004–2016 Regression Sex disease). NASH increased as Includes other Not specified and AdLD females, the leading 2018 [6] US DB: UNOS/OPTN Ethnicity the cause in all ethnic liver diseases. (NASH) cause. NASH will rise n = 127,164 subgroups and was the to become the leading Age ≥ 18 leading cause in 2016 among indication for LT in Asian, Hispanic, and males non-Hispanic white females. NASH is independently Cross-sectional Patients with NASH associated with being study are commonly Does not perform Younossi, 2012 1988–1994 Hispanic (OR 1.72; 95% CI DB: NHANES III Ultrasound AdLD (NASH) Ethnicity Hispanic and less an intersectional [23] US 1.28–2.33) and less associated n = 11,613 likely to be African analysis. with being African American Age ≥ 20 American. (OR 0.52, 95% CI 0.34–0.78). NASH prevalence: Hispanics Prospective 19.4% > Caucasians 9.8% NASH prevalence is Brooke army (p = 0.03) higher than estimated. Ultrasound and Does not perform Williams, 2011 2007–2010 medical center Ethnicity NASH has a prevalence of Hispanics and optional liver AdLD (NASH) an intersectional [26] US n = 328 (156 Sex 22.2% in the diabetic patients with diabetes biopsy analysis. positive US) population. are at the greatest risk Age 28–70 NASH patients are for NASH. predominantly male (65%). Females develop HCC at a significantly older age (66 Older females with Retrospective Histologically Includes other years vs. 61.6 years, p < 0.001). HCC have more analysis (biopsy at liver diseases. 1993–2017 Elderly females (≥65 years) NAFLD/NASH and Wu, 2018 [37] Medical records. surgery), imaging COMP (HCC) Sex Does not perform US are more likely than elderly may be overlooked by n = 1206 (CT and MRI) and an intersectional males to have current surveillance Age ≥ 18 AFP analysis. NAFLD/NASH-related HCC guidelines. (28.0% vs. 14.8%, p = 0.0006). J. Clin. Med. 2021, 10, 5019 13 of 22 Table 2. Cont. Period Design and Diagnosis Axes of Author, Year Outcomes Results Conclusions Limitations Country population method Inequality Females had a 5% shorter LOS than males (4.35 [95% CI, 4.26–4.45] vs. 4.18 [95% CI 4.08–4.27]; p < 0.0001) and 10% lower odds of mortality (AOR 0.91, 95% CI 0.83–0.99; p = 0.03). African American had a 7% longer LOS than Whites (4.48 [95% CI 4.34–4.62] Males, Hispanics, Retrospective ICD-9 vs. 4.20 [95% CI 4.11–4.29] individuals with COMP (hospi- cross-sectional NIS does not days; p < 0.0001); and 14% non-private health talization and Sex Does not perform Adejumo, 2019 2007–2014 study contain greater odds of unfavorable insurance are mortality) Ethnicity an intersectional [32] US DB: HCUP-NIS information on discharge compared with disproportionately AdLD SES analysis. n = 210,660 how NAFLD was Whites (AOR 1.14, 95% CI affected, with higher (cirrhosis) Age diagnosed 1.06–1.22; p < 0.0001). NAFLD Non-private insured patients complications. had 14% higher mortality than those with private insurance (AOR 1.14, 95% CI 1.09–1.67; p = 0.002). Females had a higher frequency of compensated (2.39% vs. 1.93%) and decompensated (2.80% vs. 2.31%) cirrhosis. A total of 29% (95% CI: 26%, Food insecurity may Cross-sectional 32%) were food-insecure. be independently analysis NAFLD fibrosis AdLD Multivariable model: associated with Does not perform Golovaty, 2020 2005–2014 DB: NHANES score (NFS) for SES (Food (advanced food-insecure adults are more NAFLD and an intersectional [33] US n = 2627 of advanced liver Insecurity) fibrosis) likely to have advanced advanced fibrosis analysis. low-income adults fibrosis (adjusted OR 2.20; 95% CI: among low-income Age ≥ 20 1.27–3.82). adults in the US. J. Clin. Med. 2021, 10, 5019 14 of 22 Table 2. Cont. Period Design and Diagnosis Axes of Author, Year Outcomes Results Conclusions Limitations Country population method Inequality The global DALYs numbers of liver cancer due to NASH were negatively associated with SDI levels (r = −0.409, p < 0.001). The global burden of The accuracy of The global prevalence NASH-associated the GBD estimates Retrospective AdLD (NASH, number of liver cancer due to liver cancer has was limited by the Zhang, 2021 1990–2017 analysis cirrho- Sex NASH peaked at 60–64 years Not specified increased significantly quality and [38] Global DB: GBD study, sis)COMP SES in males and 65–69 years in since 1990, with age, availability of 2017 (liver cancer) females. Globally, the burden sex, and geographic original hospital was heavier in males disparity. and claims data. compared with females. In groups > 70 years, the DALYs in females for cirrhosis started to be higher than in males. Females had higher rates of NASH (29.8% vs. 21.2%, p < 0.001) than males. Although lower rates of listing (7.5% vs. 9.8%; In patients with p < 0.001) and LT (3.5% vs. Retrospective cirrhosis, women were COMP 5.2%; p < 0.001) among analysis not at an increased Does not perform Mazumder, 2006–2012 (mortality, LT) women, no significant DB: OPTN Not specified Sex risk of liver-related an intersectional 2020 [39] US AdLD (NASH, difference was noted for n = 20,045 death despite lower analysis. cirrhosis) either all-cause mortality Age ≥ 18 rates of listing and (sHR 1.09; 95% CI 0.88–1.35) transplantation. or liver-related death (sHR 1.12; 95% CI 0.87–1.43). Females had higher rates of NASH-related cirrhosis (29.8% vs. 21.2% p < 0.001) J. Clin. Med. 2021, 10, 5019 15 of 22 Table 2. Cont. Period Design and Diagnosis Axes of Author, Year Outcomes Results Conclusions Limitations Country population method Inequality The likelihood for greater fibrosis severity was ACOR: 1.4 (95% CI 0.9–2.1, p = 0.17) for PMP women and ACOR 1.6 for men (95% CI 1.0–2.5, p = 0.03), with premenopausal women as a Men are at a higher reference. risk of having more Cross-sectional Before age 50, men had a severe fibrosis study Does not perform higher risk of having greater compared to women DB: DUHS AdLD an intersectional 2007–2010 Sex severity of fibrosis than before menopause, Yang, 2014 [40] NAFLD Clinical Liver biopsy (advanced analysis. US Ethnicity women ACOR 1.8 (95% CI, while postmenopausal DB fibrosis) Purely biological 1.1–2.9, p = 0.02). After age 50, women have a similar n = 203 approach. the protective effect observed severity of liver Age ≥ 18 in women appeared to be fibrosis compared to eliminated (ACOR 1.2, 95% men. CI 0.7–2.1, p = 0.59). Age ≥ 50 was associated with an increased risk of having more advanced fibrosis only among women (ACOR 1.8, 95% CI 1.2–2.7, p < 0.01) Multicenter Among patients with HCC, The frequency of They do not retrospective NAFLD was the underlying underlying NAFLD classify women as Phipps, 2020 2000–2014 study Imaging or biopsy COMP (HCC) Sex etiology of liver disease in was significantly pre/PMP. [41] US Hospital centers 23.3% of cases compared with higher in women than Includes other n = 5327Age ≥ 18 12.4% of men. men. liver diseases. J. Clin. Med. 2021, 10, 5019 16 of 22 Table 2. Cont. Period Design and Diagnosis Axes of Author, Year Outcomes Results Conclusions Limitations Country population method Inequality NASH is a more frequent indication for LT listing in women than men. LT is lower among women than men with NASH (52.4% Women with NASH Retrospective vs. 64.3%), and women are cirrhosis had a higher study with an Does not perform 2005–2012 COMP (LT and more likely to experience risk of death on the LT Loy, 2018 [42] 8-year follow-up Not specified Sex an intersectional US mortality) death on the WL (17.1% vs. waiting list and were DB UNOS/STAR analysis. 11.4%). In multivariable less likely to receive n = 76,149 analysis adjusting for LT compared to men. covariates, the rate of LT remained lower for women with NASH (aHR 0.81 95% CI 0.75–0.88). Non-Hispanic whites are Hispanics have more commonly transplanted similar or better Retrospective for NASH than Hispanics. long-term post-LT Only analyzes analysis Ochoa, 2020 2002–2013 COMP Hispanics had a decreased outcomes compared Hispanics and DB: UNOS/OPTN Not specified Ethnicity [43] US (mortality, LT) risk of death when to non-Hispanic non-Hispanic n = 45,767 transplanted for NASH (HR whites despite a Whites. Age ≥ 18 0.84, 95% CI 0.71–0.99; worse pretransplant p = 0.04). risk factor profile. Footnote: ACOR (adjusted cumulative odds ratio), AFP (alpha-fetoprotein), aHR (adjusted hazard ratio), AdLD (advanced liver disease), AOR (adjusted odds ratio), CI (confidence interval), COMP (complications), CT (computed tomography), DALYs (disability-adjusted life years), DB (database), DUHS (Duke University Health System), GBD (global burden of disease), HCC (hepatocellular carcinoma), HCUP (Healthcare Cost and Utilization Project), HR (hazard ratio), ICD-9 (international classification of disease), LOS (length of stay), LT (liver transplant), M (men), MRI (magnetic resonance imaging), NAFLD (non-alcoholic fatty liver disease), NASH (non-alcoholic steatohepatitis), NIS (national inpatient survey), NHANES (national health and nutrition examination survey), OPTN (Organ Procurement and Transplantation Network), OR (odds ratio), PMP (postmenopausal), RF (risk factor), SDI (sociodemographic index), SES (socioeconomic status/position), sHR (subdistribution hazard ratio), STAR (Standard Transplant Analysis and Research), UNOS (United Network for Organ Sharing), W (women), WL (waitlist). J. Clin. Med. 2021, 10, 5019 17 of 22 3.3.2. NAFLD-Related Complications Gender/Sex Regarding liver cancer, in a Chinese cohort of 1206 patients with HCC, Wu et al. found that just 25% were women, who were more likely to undergo HCC surveillance, had smaller tumor size at diagnosis, and less vascular involvement [30]. However, 21.5% of females had NAFLD as underlying liver disease, whereas only 7.2% of males did. Moreover, males who met the Milan criteria for liver transplantation were more likely to undergo liver transplant than women who met the criteria [30]. In an American cohort including 5327 patients with HCC, 22.6% were women, who had a significantly higher frequency of NAFLD (23% vs. 12%) and lower frequency of alcoholic liver disease (5% vs. 15%). The proportion of noncirrhotic HCC was higher among women (17% vs. 10%). Women had less-advanced HCC at presentation by tumor, node, metastasis staging, a higher proportion within Milan criteria (39% vs. 35%), and a greater overall survival (2.5 ± 2.9 years vs. 2.2 ± 2.7 years) [41]. NAFLD-related mortality according to sex differs across studies. Adejumo and col- leagues found that in the US from 2007 to 2014 women had a significantly lower in-hospital mortality [32]. However, this study was based on ICD-9 diagnosis code, whose ability to capture NAFLD-related diagnosis and complications is severely limited. Meanwhile, in a population of 76,149 patients listed for liver transplant between 2005 and 2012 of whom 7.2% were listed for NASH, Loy et al. found that women with NASH cirrhosis had a higher risk of death on the liver transplant waiting list [42]. NASH is the main cause of liver transplant among females and the second one in males, right after alcoholic liver disease [6,42], yet the US women with NASH are 19% less likely to receive a liver transplant compared to men [42]. Ethnicity/Race NASH has increased as a cause of liver transplant in all ethnic subgroups. Ethnic inequalities have been observed in NAFLD-related complications such as liver transplant and hospitalization events. In 2016, NASH was the leading liver transplant cause among Asian, Hispanic, and non-Hispanic White females [6]. According to the lowest NASH prevalence, African American population had a lower increase in the rate of waitlist registration for NASH compared to the other ethnic groups [6]. Additionally, although the highest NASH prevalence has been seen among the Hispanic population [23,26], non-Hispanic White patients are more commonly transplanted for NASH compared to Hispanics in the US [43]. Although seemingly the lowest NASH prevalence is found among the African American population [23,26], these have a 14% greater odds of unfavorable discharge compared with whites [32]. Socioeconomic Position/Status Patients with low socioeconomic status have higher liver cancer rates [31]. The odds of dying on the waitlist increase by 14% in NASH patients without health insurance or self-paid [32]. 4. Discussion NAFLD distribution and outcomes show large inequalities by social group. Males have higher NAFLD prevalence, while available evidence suggests that women have an overall higher risk of progression to advanced liver disease and more complications, whereas they are less likely to undergo transplantation once cirrhosis develops. In the US, the Hispanic population has the highest NAFLD prevalence and poorer outcomes, whereas Whites have fewer complications than other ethnicities. Patients with low socioeconomic status have higher NAFLD prevalence and higher likelihood of progression and compli- cations. Globally, there is a lack of studies analyzing NAFLD prevalence and outcomes according to various axes of inequality through joint intersectional appraisals, and most studies included in our review are based on the US population. J. Clin. Med. 2021, 10, 5019 18 of 22 Although in the general population males have a higher prevalence, if only post- menopausal women are taken into account, the prevalence is similar between male and female individuals. In addition, females have a greater risk of progression to advanced liver disease. In a systematic review, Balakrishnan et al. found that although they have a lower risk of NAFLD than men, once NAFLD is established, women have a higher risk of advanced fibrosis, especially after age 50 [13]. Although estrogens have been shown to play an important role as a protective factor against steatosis and therefore may at least par- tially account for an earlier NAFLD onset among men [15], little research has been carried out to elucidate such sex differences in NAFLD prevalence. Because females have lower healthcare access [44], they might be underdiagnosed or may receive a later diagnosis that can lead to further progression of the disease. Moreover, the fact that males tend to have a higher alcohol consumption than females [31] might predispose healthcare providers to rule out liver disease in men rather than women. Thus, aspects such as access to healthcare, living and working conditions, and gender roles should be included in further research exploring gender disparities in NAFLD. Ethnicity/race is the axis of inequality that has been more largely documented (50% of analyzed studies addressed it), and it has been shown to have a greater influence on health inequalities in NAFLD prevalence and outcomes. In particular, the Hispanic population has a higher NAFLD prevalence and burden of advanced liver disease and complications. Yet, ethnic disparities in NAFLD distribution have mostly been studied among the US population [23,26,29–31], and further studies should be conducted to determine if these inequalities are conserved in other countries. Ethnic disparities are not fully explained by the metabolic profile and the cardiometabolic comorbidities of the individuals, such as obesity, T2DM, or hypertension. For instance, although African Americans have the lowest prevalence, they have a worse cardiovascular profile [29] and similar diabetes and obesity prevalence as for other ethnicities [45,46]. Most studies suggest that ethnic disparities might be better explained by PNPLA3 polymorphisms, which are more frequent in the Hispanic population and promote fat accumulation on the liver [14]. Although genetic polymor- phisms and metabolic profiles may play an important role in ethnic disparities, living and working conditions have a major impact on health inequalities beyond individual factors. The higher NAFLD prevalence among Hispanic ethnicity could be also explained by the fact that they have the worst health care access [47,48] and health insurance coverage [49]. Hence, further research is needed to understand the gene–environment interactions and epigenetic mechanisms including environmental and social factors determining NAFLD onset and progression. Socioeconomic status is tightly associated with the risk of developing NAFLD. Our findings are consistent with previous studies that demonstrate that NCDs are more preva- lent among the population with lower socioeconomic status [50]. Additionally, food insecurity seems to play an important role in NAFLD onset, as food-insecure households have been described as having a greater burden of cardiometabolic diseases, such as di- abetes, obesity, and hypertension [51,52]. Food insecurity is characterized by difficult access to healthy food, which can lead to an early obesity onset in young ages that ends up with a metabolic syndrome. Therefore, since NAFLD is a metabolic disease, the increased NAFLD prevalence in the food-insecure population can be related to a higher prevalence of metabolic syndrome among this population [33]. In addition, low socioeconomic position is also associated with other individual outcomes such as depression and anxiety, or com- munity conditions such as poor healthcare access or absence of safe spaces to exercise [51] that could also participate in inequalities in NAFLD distribution and outcomes. NAFLD, like all non-communicable diseases, is a multifactorial disease that is in- fluenced by both individual factors, such as behavior or genetics, and contextual factors such as culture, demographics, income inequality, environment, or health policies [51,53]. Nevertheless, most studies are only focused on the individual level, emphasizing self- responsibility through a “victim-blaming” approach and ignoring the deeper social, eco- nomic, and environmental determinants of living and working conditions that can lead to J. Clin. Med. 2021, 10, 5019 19 of 22 NAFLD onset [54]. Even though genetic and metabolic factors have a paramount impact on NAFLD prevalence and progression, they do not explain all the observed inequalities. In the field of hepatology, social conditions are closely linked to liver disease prevalence and outcomes, as chronic liver disease disproportionately impacts racial and ethnic minorities, low socioeconomic position communities, and immigrants [55]. Therefore, NAFLD should be understood as context-sensitive and analyzed by taking into account the jointly influence of individual factors, such as genetics or behaviors, social factors such as culture, race, income, and education; environmental factors, such as availability and access to healthy foods, energy-dense foods or the proximity of safe walking spaces; and macro-level factors such as the influence of media and advertising, access to health care or governmental policies [51]. Hence, it is urgent to study NAFLD, as well as all NCDs, through approaches embedding multilevel analysis that allows examining simultaneously both community- level and individual-level SDH that can influence NAFLD onset and progression [56]. It should be noted that besides the scarcity of studies paying attention to SDH and inequalities in the field of NAFLD, there are two other relevant barriers that hinder an accurate epidemiological approach. Although the definition of NAFLD relies on the presence of steatosis in at least 5% of hepatocytes, in reality, the approach to NAFLD diagnosis widely varies across studies, which largely impacts the reports of NAFLD prevalence. Moreover, whereas the concept of MAFLD has been proposed by some experts to facilitate the clinical approach to fatty liver disease in patients with relevant metabolic disorders [57], it is a potential source of heterogeneity both in clinical and epidemiological studies. By neither excluding patients with alcohol consumption over the dose traditionally considered for risk for liver injury nor those with concomitant liver disease, MAFLD widely differs from NAFLD. Hence, data from studies reporting on MAFLD distribution and outcomes should be carefully analyzed, and direct extrapolation between MAFLD and NAFLD should be avoided. This study has several limitations. First, this is the first review on a vast topic and it only explored the PubMed database, and only articles written in English were included, so some articles may have been missed. Yet, scoping reviews are a rigorous, transparent, and replicable method that provide a robust assessment of the potential size and scope of available research literature and allow for identifying knowledge gaps when there is not enough evidence in the field to raise a specific question that can be studied through a systematic review [16]. Second, most studies addressing advanced liver disease in NAFLD also include other causes of liver disease, such as viral hepatitis or alcoholic liver disease. Thus, it is difficult to extract data that include only NAFLD/NASH as a cause of liver disease. Third, we have not analyzed some axes of inequalities that can have an important influence on health disparities, such as migration status or other axes. Fourth, most of the included studies do not specify how gender has been described and may be referring to biological sex as gender. However, we acknowledge that part of the differences between men and women on NAFLD are related to gendered social roles and not to biological features. Additionally, although gender is a spectrum of many genders, we have only analyzed male and female identities, as they are the most studied ones. Fifth, most studies included in our review concern the US population, therefore limiting the external validity; e.g., some geographical settings such as South America and some Asian countries appear to have higher burdens of NAFLD [4], but data are lacking on its distribution according to SDH. Fifth, we decided to include only original articles and therefore excluded both meta- analyses and reviews from our study, which might have led to the omission of relevant studies addressing at least one of the axes of inequality in the distribution and outcomes of NAFLD [58]. Finally, the included studies do not specifically analyze the impact of social determinants of health on the onset of health inequalities, and most of them do not assess the intersection of more than one axis of inequality. Hence, more research should be conducted to understand how the interaction between different social determinants of health (e.g., employment and neighborhood environment) leads to social health inequalities in NAFLD. J. Clin. Med. 2021, 10, 5019 20 of 22 5. Conclusions Hispanics, males, and people with low socioeconomic position present higher rates of NAFLD, whereas females present relatively poorer outcomes. Overall, little has been studied on the relationship between SDH and NAFLD. Moreover, most research has been carried out in the US; hence, evidence to provide an accurate assessment of the relation- ship between SDH and NAFLD in many regions is lacking. In addition, intersectional approaches encompassing several SDH and axes of inequality that provide an integrated account of both the biomedical and social determinants of NAFLD are needed. Further research is warranted to shed light on the impact of SDH on NAFLD distribution and outcomes both at the national and global levels. Author Contributions: Conceptualization, J.B. and J.M.P.; methodology, J.B. and J.M.P.; validation, J.V.L., J.B. and J.M.P.; investigation, M.T. and J.M.P.; resources, J.M.P.; data curation, M.T. and J.M.P.; writing—original draft preparation, M.T. and J.M.P.; writing—review and editing, N.T., J.V.L. and J.B.; visualization, N.T., J.V.L., J.B. and J.M.P.; supervision, J.B. and J.M.P.; project administration, J.B. and J.M.P.; funding acquisition, J.M.P. All authors have read and agreed to the published version of the manuscript. Funding: This work has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement N◦ 89102 (Natalia Tumas was supported by this grant). Joan Benach gratefully acknowledges the financial support by ICREA under the ICREA Academia program. 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