Metabolic Steatotic Liver Disease: Current Knowledge, Therapeutic Treatments, and Future Directions

Metabolic Fatty Liver Disease: Current Knowledge, Therapeutic Treatments, and Future Directions provides the most updated research findings and defines the current data gaps on metabolic fatty liver disease. The book extensively covers key areas in metabolic fatty liver disease research, including epidemiology (adults and children), economic burden, patient-reported outcome burden, natural history, current treatments, current diagnostic methods, controversies (NAFLD/MAFLD), current guidelines, fatty liver disease in the presence of other liver diseases as well as guidance on future research.

This book will provide translational researchers with a current and comprehensive resource dedicated to all aspects of research in metabolic fatty liver disease, identify current gaps in research and make future research recommendations. It also offers clinicians a look at important background information in metabolic fatty liver disease and thoroughly reviews the latest research in this area to inform treatment outcomes.

• Compiles the latest, up-to-date science from key experts in the field on metabolic fatty liver disease
• Reviews best practices and current guidelines for a comprehensive overview
• Identifies recommendations for future research endeavors

• Language: English
• Publisher: Academic Press
• Release date: Jun 21, 2024
• ISBN: 9780323996501

Book preview

Preface

It is a pleasure to present to you, the reader, the current state of knowledge about fatty liver disease associated with metabolic conditions. As this book goes to print, a new nomenclature has been adopted to better describe this fatty liver disease which until now has been known as nonalcoholic fatty liver disease (NAFLD) and its progressive disease state, nonalcoholic steatohepatitis (NASH) [1].

The undertaking to rename this liver disease has been ongoing for the past 3 years and was driven by trying to determine a terminology that better describes what the disease is rather than what it is not. Also, many perceived that the current nomenclature caused feelings of stigma among individuals with NAFLD and perceived discomfort among health care providers to discuss NAFLD with patients. Together, these factors were thought to contribute to a lack of awareness of NAFLD despite its rapid global growth. Additionally, in countries where the use of alcohol is prohibited, NAFLD was not used to name the disease. The use of alcohol in the terminology was also not deemed to be an appropriate term for use among children with fatty liver and metabolic abnormalities [2–7].

As such, steatotic liver disease (SLD) has been chosen as the overarching term to encompass the various etiologies of steatosis and to retain the term steatohepatitis. Metabolic dysfunction–associated steatotic liver disease (MASLD) has been chosen to replace NAFLD. MASLD is the presence of liver steatosis alongside at least one of five cardiometabolic risk factors (body mass index, fasting glucose, low density triglycerides, high density triglycerides, and blood pressure). Those with no metabolic parameters and no known cause of steatosis are deemed to have cryptogenic SLD. A new category termed, MetALD, has been added to describe those with MASLD who consume greater amounts of alcohol per week but do not reach the limits of alcohol consumption denoted as alcohol-related liver disease (ALD). In this context, alcohol consumption in MASLD is based on a gradient where MASLD is used for those who consume 20/30 g/day (female/male), while Met ALD is for those who consume >30 g day but less than 50 g day for females and 40 g a day but less than 60 g day for males. ALD is considered when alcohol consumption is greater than 50 g/day for females and 60 g/week for males regardless of metabolic comorbidities present. It is important to note that the use of this gradient of alcohol consumption allows for a greater amount of alcohol consumption for MASLD than was allowed for NAFLD where the allowed alcohol consumption was less than 10 g a day for females and 20 g a day for males [1,8].

Given these differences, work is now underway to determine if the MASLD definition and NAFLD definition will capture the same patients so that all work done for those with NAFLD is still applicable to those with MASLD. At this time, preliminary findings indicate that the concordance between MASLD and NAFLD is excellent at almost 98% [9]. The patients not captured under NAFLD but under MASLD is mostly due to the difference in alcohol consumption allowed per definition. [9]

As such, the information contained within these pages will provide anyone interested in fatty liver disease associated with metabolic abnormalities with the current state of knowledge provided by experts in the field. We thank each author for sharing their time and vast knowledge with us to make this book possible. We hope each reader will gain new wisdom after reading.

References

1. Rinella M.E, Lazarus J.V, Ratziu V, Francque S.M, Sanyal A.J, Kanwal F, NAFLD Nomenclature Consensus Group, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023 Dec 1;78(6):1966–1986.

2. Matteoni C, Younossi Z, Gramlich T, Boparai N, Liu Y, Mccullough A. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116:1413–1419.

3. Eslam M, Sanyal A.J, George J, Sanyal A, Neuschwander-Tetri B, Tiribelli C, et al. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology. 2020;158:1999–2014.

4. Eslam M, Newsome P.N, Sarin S.K, Anstee Q.M, Targher G, Romero-Gomez M, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020;73:202–209.

5. Eslam M, Sarin S.K, Wong V.W.S, Fan J.G, Kawaguchi T, Ahn S.H, et al. The Asian pacific association for the study of the liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease. Hepatol Int. 2020;14:889–919.

6. Younossi Z.M, Rinella M.E, Sanyal A.J, Harrison S.A, Brunt E.M, Goodman Z, et al. From NAFLD to MAFLD: implications of a premature change in terminology. Hepatology. 2021;73:1194–1198.

7. Ratziu V, Rinella M, Beuers U, Loomba R, Anstee Q.M, Harrison S, et al. The times they are a-changin’ (for NAFLD as well). J Hepatol. 2020;73:1307–1309.

8. Ludwig J, Viggiano T.R, McGill D.B, Oh B.J. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980 Jul;55(7):434–438.

9. Ciardullo S, Carbone M, Invernizzi P, Perseghin G. Exploring the landscape of steatotic liver disease in the general United States population. Liver Int. 2023;43:2425–2433. doi: 10.1111/liv.15695.

Chapter 1: Global epidemiology of NAFLD

Margaret L.P. Teng¹, Cheng Han Ng², Mark Muthiah¹,², Mindie H. Nguyen³,⁴, and Daniel Q. Huang¹,²     ¹Division of Gastroenterology and Hepatology, National University Hospital, Singapore, Singapore     ²Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore     ³Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, United States     ⁴Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, United States

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a common cause of liver disease with an estimated global prevalence of 30%. The prevalence of NAFLD is projected to increase further with time, fueled by the ongoing epidemics of obesity and type 2 diabetes mellitus. There is substantial variation in NAFLD prevalence between regions due to genetic, environmental, and social factors. Despite the rising prevalence of NAFLD, disease awareness is poor. There is an urgent need to improve knowledge and understanding of the condition among patients and physicians.

Keywords

Awareness; Disease burden; Epidemiology; Global; Non-alcoholic fatty liver; Non-alcoholic steatohepatitis; Prevalence; Regional

Epidemiology of NAFLD

Global

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide [1]. It presents a spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), which can progress to liver fibrosis and cirrhosis [2]. As of 2019, the estimated global prevalence of NAFLD among adults was 29.8% (Fig. 1.1) [3]. The estimated global incidence of NAFLD ranges from 28.01 per 1000 person-years to 52.34 per 1000 person-years [4]. NASH has risen to become one of the most common etiologies of chronic liver disease for liver transplantation in the United States (US) [5], and it is also the second most common etiology of hepatocellular carcinoma requiring liver transplantation [6].

Regional

The prevalence of NAFLD was highest in South America and North America at 35.7% and 35.3%, respectively; similar in Europe and Asia at 30.9% and 30.5%, respectively; and lowest in Africa at 28.2%, based on a recent systematic review and meta-analysis by Le et al. [3]. The increase in prevalence with time was the most in South America at 2.7% annually, followed by Europe, Asia, and North America at 1.1%, 0.9%, and 0.8% per year [3].

In North America, the prevalence of NAFLD varies with ethnicity. It appears that there is a higher prevalence of NAFLD in Hispanics and a lower proportion of NAFLD in blacks [7–10]. This could be attributed to genetic factors such as the palatin-like phospholipase domain-containing protein 3 (PNPLA3) mutation, which confers an increased risk for NAFLD and is more common in Hispanics [11–13]. A more recent study utilizing data from the National Health and Nutrition Examination Survey (NHANES) found that NAFLD prevalence was 28.4% among nonHispanic whites and 18.3% among Asian Americans [14]. Another study utilizing the NHANES cohort found that NAFLD was present in almost half (48.4%) of Mexican Americans, and NAFLD prevalence was lowest at 18% among nonHispanic blacks as well as 18.1% in nonHispanic Asians [15], confirming the relatively low prevalence of NAFLD in Asian Americans.

Figure 1.1  Global prevalence of nonalcoholic fatty liver disease (NAFLD), and contributing factors.

The prevalence of NAFLD in South America may be even higher than that reported by Le et al. A meta-analysis published in 2022 by Rojas found that the estimated overall NAFLD prevalence in Latin America was 59%, and the prevalence among general and captive populations was 24% [16]. The high prevalence of NAFLD in South America may be related to the prevalence of metabolic risk factors on a background of increased genetic susceptibility [17]. Data from South America shows a high prevalence of PNPLA3 genetic polymorphism in the general population, especially in those with Native American ancestry [18–20]. South Americans are also more likely to have metabolic risk factors such as obesity and type 2 diabetes mellitus (DM). South America is the region with the largest number of obese or overweight people globally. Additionally, a cross-sectional study across four geographical regions found that South America had the largest proportion of study participants with abdominal adiposity [21]. The meta-analysis by Le also showed that South American NAFLD individuals had a higher percentage of DM and higher mean cholesterol compared to other regions [3]. In addition, South Americans tend to lead more sedentary lifestyles. Latin America is one of the top-ranked regions in the world for inadequate physical activity, with a prevalence of insufficient physical activity of 32% [22].

Within Asia, the prevalence of NAFLD is highly variable, as the region is large and heterogeneous and contains countries with a range of ethnicities and socio-economic statuses. The estimated prevalence of NAFLD was 42.04% in Southeast Asia, 37.09% in West Asia, 30.17% in South Asia, and 28.94% in East Asia [23,24]. The estimated incidence rate of NAFLD was 50.9 per 1000 person-years [24]. In this study, NAFLD diagnosed by ultrasound was most prevalent in Indonesia (51.04%) and least prevalent in Japan (22.28%). Focusing on East Asia, a meta-analysis by Wu et al. found that the NAFLD prevalence was 29.88% and the incidence rate was 56.7 per 1000 person-years in China [25], and another meta-analysis reported an NAFLD prevalence of 29.2% in China [26]. A more recent meta-analysis published in 2021 by Ito et al. confirmed that NAFLD prevalence in Japan was relatively lower at 25.5% and the incidence of NAFLD was 23.5 per 1000 person-years [27]. This could be related to the lower prevalence of obesity [28] and diabetes [29] in Japan compared to other countries. Last but not least, a meta-analysis by Im et al. revealed that NAFLD prevalence was 30.3% in South Korea [30]. The estimated prevalence of NAFLD was 31.79% in the Middle East [31]. Additionally, an unpublished population-based survey of 113,239 apparently healthy individuals found that NAFLD prevalence reached 48.3% in Turkey [4].

The NAFLD epidemic in Asia differs from the West, as more individuals may be classified as having lean NAFLD (body mass index (BMI) < 23) or nonobese NAFLD (BMI < 25) [32]. The meta-analysis by Le showed that Asian NAFLD individuals had a lower mean BMI compared to those from other regions [3]. Among Asians with BMI < 25, around 8%–19% have NAFLD [33]. The phenomenon of nonobese NAFLD in Asians may be due to a few reasons. Asians have a higher percentage of visceral fat compared to those of other ethnicities [34]. Visceral adiposity plays an important role in the pathogenesis of insulin resistance [35] and is hence linked with the development of metabolic syndrome and NAFLD [36]. As such, body fat distribution rather than total body fat may contribute to the development of nonobese or lean NAFLD [37–40]. Asians also tend to develop DM at a younger age and lower BMI levels [41–43], resulting in a longer duration of disease and an increased likelihood of complications. In addition, other risk factors, such as genetic polymorphisms, of which the most well-known is PNPLA3, may increase the risk of developing NAFLD independent of metabolic disease [44].

Data on the epidemiology of NAFLD in Africa is scarce [4,45,46]. In comparison to the meta-analysis by Le et al., which reported a prevalence of NAFLD of 28.2%, an earlier meta-analysis from 2016 reported a prevalence of 13.48%, ranging from 8.67% in Nigeria to 20% in Sudan [31]. Based on data from the global burden of disease study, it was estimated that age-standardized NAFLD prevalence in sub-Saharan Africa ranged from 5%–7.5% to 10.1%–12.5%. This study found that in Western sub-Saharan Africa NAFLD individuals increased from 8.4 per million in 1990 to 23.2 per million in 2017, with age-standardized prevalence increasing from 6.5% to 8%; in central sub-Saharan Africa NAFLD individuals increased from 2.3 per million in 1990 to 6.2 per million in 2017, with age-standardized prevalence increasing from 6.5% to 7.5%; in Southern sub-Saharan Africa NAFLD individuals increased from 3.7 per million in 1990 to 8.1 per million in 2017, with age-standardized prevalence increasing from 9.3% to 11.4%; in Eastern sub-Saharan Africa NAFLD individuals increased from 7.1 per million in 1990 to 18 per million in 2017, with age-standardized prevalence increasing from 6% to 7% [47]. The greater prevalence of NAFLD in southern sub-Saharan Africa may be related to the fact that the obesity rate in Southern sub-Saharan Africa is highest in the region [46]. Furthermore, southern sub-Saharan Africa is the region with the highest prevalence of human immunodeficiency virus (HIV) infection worldwide, and the metabolic consequences of HIV infection and its treatment with antiretroviral medications may play an additive role in raising NAFLD prevalence [48].

Likewise, there is also a paucity of data on the epidemiology of NAFLD in Oceania. Data regarding the prevalence of NAFLD in Australia are limited, with a lack of population-based studies on the prevalence of NAFLD using ultrasound [49]. There is a need for more studies on the incidence and prevalence of NAFLD in Africa and Oceania, as well as studies on risk factors for its occurrence and progression, in order to better understand the burden of disease in these regions.

Projections for the burden of NAFLD

The prevalence of NAFLD is likely to increase substantially with time. A modeling study based on data from the US forecasted that by 2030, NAFLD individuals could increase by 21% from 83.1 million in 2015 to 100.9 million, and NAFLD prevalence was predicted at 33.5% [50]. Another modeling study involving eight countries found that the number of individuals with NAFLD is projected to increase from 13.98 million to 16.05 million between 2016 and 2030 in France; 18.45 million to 20.95 million between 2016 and 2030 in Germany; 15.22 million to 17.42 million between 2016 and 2030 in Italy; 10.53 million to 12.65 million between 2016 and 2030 in Spain; and 14.08 million to 16.92 million between 2016 and 2030 in the United Kingdom (UK). By 2030, the estimated prevalence of NAFLD was projected to be highest in Italy (29.5%), followed by Spain (27.6%), Germany (26.4%), the UK (24.7%), and France (23.6%) [51].

Within Asia, China was projected to have the greatest overall and relative increase in the estimated prevalence of NAFLD, with the NAFLD population potentially growing from 243.67 million in 2016 to 314.58 million in 2030, with an expected prevalence of 22.2% in 2030. Japan was predicted to have the smallest increment in the NAFLD population from 22.67 million in 2016 to 22.74 million in 2030, with an expected prevalence of 18.8% in 2030 [51]. A similar study involving four other Asian countries projected that between 2019 and 2030, NAFLD prevalence would have the largest relative increase of 20% in Singapore and the lowest relative increase of 6% in South Korea. By 2030, the estimated prevalence of NAFLD was projected to be highest in Singapore (28.7%), followed by Taiwan (23.2%), South Korea (22.8%), and Hong Kong (22.5%) [52]. These models were based on obesity prevalence data, with the assumption that changes in NAFLD prevalence occur in tandem with changes in obesity prevalence. However, another study using Bayesian modeling based on NAFLD prevalence data projected that the prevalence of NAFLD in Japan would reach 39.3% in 2030 and 44.8% in 2040 [27].

A separate study in Australia forecasted NAFLD individuals to increase by 25% from 5.56 million in 2019 to 7.03 million in 2030, and NAFLD prevalence was predicted to rise from 22% to 23.6% by 2030 [53].

Factors contributing to the increasing burden of NAFLD

The global epidemics of obesity and DM drive the prevalence of NAFLD [54,55]. NAFLD is associated with metabolic comorbidities such as obesity, type 2 DM, insulin resistance, dyslipidemia, and hypertension [23,56,57]. Obesity increases the risk of NAFLD [58]. Additionally, type 2 DM has a complex bidirectional relationship with NAFLD [59,60]. These observations were affirmed by a meta-analysis, which found that 51% of NAFLD individuals and 82% of NASH patients were obese, and 23% of NAFLD individuals and 47% of NASH patients had DM [31].

Changing dietary patterns can also lead to an increase in the presence of metabolic risk factors and the prevalence of NAFLD. The consumption of soft drinks, which can contain added sugar in the form of fructose, has been increasing globally [61]. Sugar-sweetened beverages have been reported to be associated with obesity and type 2 DM [61,62], and they are also associated with an elevated risk of NAFLD [63]. A cross-sectional study based on the Israeli National Health and Nutrition Survey found that after adjusting for age, gender, BMI, and total caloric intake, intake of soft drinks and meat was significantly associated with an increased risk of NAFLD [64]. Furthermore, there has been increasing consumption of processed and ultra-processed food in the US and Europe [65,66]. Another cross-sectional study from Israel found that high consumption of ultra-processed food was associated with higher odds of metabolic syndrome and its components, and among NAFLD individuals, it was also linked with an increased risk of NASH [67]. A prospective cohort study conducted in Tianjin, China, indicated that high consumption of ultra-processed food was associated with a higher risk of NAFLD [68]. These studies add to growing evidence that increasing consumption of ultra-processed food may have adverse outcomes with regard to metabolic disease and NAFLD in particular.

Poor disease awareness

There is a lack of awareness of NAFLD among patients, physicians, and policymakers.

A study based on data from the NHANES cohort in the US found very low but increasing awareness of NAFLD of 2.1% in 2009–2012 and 3.3% in 2013–16 [69]. Even among high-metabolic-risk individuals and NAFLD individuals, there was poor recognition of the condition. In a survey of 302 outpatients visiting an endocrinology subspecialty clinic, 18% were aware of NAFLD, and 67% of those who were unaware had metabolic risk factors [70]. In another cross-sectional analysis of middle-aged adults within a longitudinal population-based cohort study, 3.5% of participants with metabolic syndrome were aware of NAFLD, and 2.4% of participants with imaging-defined NAFLD were aware of the diagnosis of NAFLD [71]. Only 4% of NAFLD individuals in the NHANES cohort knew that they had a liver condition. In this study, awareness was associated with older age, diabetes, advanced fibrosis, and a higher number of healthcare visits [72].

There is limited awareness of NAFLD in Asia as well. A population-based telephone survey conducted in Hong Kong found that only 17% were aware of NAFLD, with misconceptions about the diagnosis of NAFLD. Among participants who were familiar with NAFLD, 81% perceived their knowledge to be inadequate [73]. A survey of participants who attended a forum on digestive diseases in Singapore reported that 71.2% were aware of NAFLD; however, 75.6% of individuals with one or more metabolic risk factors did not think they were at risk of NAFLD [74]. Another survey of adult outpatients and their family members at a university hospital ultrasound clinic and staff from government offices in Beijing stated that 30.2% had heard of NAFLD [75].

NAFLD is also underrecognized by physicians—both primary care providers and specialists alike. A study based in a primary care setting found that, despite the presence of metabolic risk factors, NAFLD was not evaluated for or recognized in the majority of NAFLD patients [76]. Physicians, especially primary care providers and nongastroenterology specialists, within a predominantly urban setting in the US had a low rate of recognition of NAFLD as a clinically important condition [77].

The lack of awareness of a diagnosis of NAFLD is multifactorial, contributed by the asymptomatic nature of NAFLD early in the course of the disease, inconsistencies in guidelines for screening for NAFLD, low knowledge of NAFLD in the general population, and inadequate understanding of NAFLD among physicians [71,72].

Enhancing awareness of NAFLD facilitates efforts at disease prevention. Education on the risks and implications of the diagnosis of NAFLD could be included in the counseling of high-metabolic-risk individuals. Engagement and education of these individuals may encourage lifestyle interventions and modification of risk factors, which can influence the course of the condition. Additionally, improving awareness of NAFLD facilitates early identification and risk stratification of NAFLD patients, which enables the early initiation of targeted interventions to reduce cardiovascular and metabolic risks.

Lack of awareness among care providers

Healthcare practitioners may underestimate the prevalence of NAFLD and have uncertainty about the diagnosis and management of NAFLD. Although a large majority of primary care physicians agreed that NAFLD was an important health issue, 84% underestimated its prevalence in the general population [78]. In another cross-sectional survey of primary care providers, 51% estimated NAFLD prevalence to be ≤ 10% [79]. Nongastroenterology specialists also underestimate NAFLD prevalence—in a survey of nongastroenterology specialists, 75% estimated NAFLD prevalence to be ≤ 10% [80]. The lack of knowledge of NAFLD prevalence indicates deficient knowledge of NAFLD.

A global survey comprising questions on epidemiology, pathogenesis, diagnosis, and management of NAFLD involving 2202 physicians found that hepatologists and endocrinologists had higher knowledge scores compared to gastroenterologists and primary care physicians, respectively [81] Another survey found that 65% of physicians expressed confidence in attaining a diagnosis of NAFLD, and 47% were confident in their management of NAFLD [77]. In this survey, 83% of physicians reported a lack of understanding of NAFLD, and only 35% had access to NAFLD-specific patient-related material. Taken together, this suggests that healthcare providers have limited knowledge of NAFLD, and this varies across specialties.

Healthcare practitioners are also not adequately counseling or educating their patients on the condition. In a population-based survey of 5000 Brooklyn residents, 98% reported that their physicians had never discussed or mentioned NAFLD [82].

Low awareness and inadequate knowledge of NAFLD among physicians may lead to delays in the diagnosis of NAFLD and suboptimal care of NAFLD patients. This may also lead to an underestimation of disease prevalence, which would affect the allocation of resources for public health. Education programs on NAFLD should be offered to primary care providers and nongastroenterology specialists to increase awareness of the condition and provide information on diagnostic modalities, risk stratification, and management principles for NAFLD [76,77,81]. This is essential, as poor knowledge of the condition and its management was cited as a major barrier to the treatment of NAFLD [78]. Primary care providers should be empowered to identify NAFLD patients, especially those at risk of advanced liver disease, who might benefit from referral to a specialist for further evaluation.

Gaps in linkage to care

Clinical care pathways often involve risk stratification of NAFLD patients with noninvasive tests for assessment of fibrosis and subsequent referral of patients at high risk of NASH or advanced fibrosis for further evaluation. As NAFLD is closely related to metabolic comorbidities, primary care physicians and nongastroenterology specialists (cardiologists and endocrinologists) are often the first point of medical contact with individuals at high metabolic risk and hence likely to see a broad cohort of NAFLD individuals. It has been previously reported that only 27%–33% of physicians referred possible NAFLD patients to hepatologists [77,78,80]. However, with increasing awareness of NAFLD over time, an increasing proportion of up to 80% of physicians referred suspected NAFLD patients to hepatologists [81]. A study from Australia that characterized and assessed the appropriateness of such referrals found that after evaluation, two-thirds were discharged back to primary care for continued management. This might be due to primary care providers failing to evaluate disease severity prior to referring, as just 11.5% of referrals contained details regarding disease severity [83].

Looking ahead, care and referral pathways using a two-step approach to detect the presence of advanced liver disease may improve the identification of patients with advanced fibrosis and reduce unnecessary referrals to hepatologists [84,85]. Collaboration between primary care physicians and hepatologists is key; hepatologists should support education efforts for primary care providers and explore and implement such referral pathways to develop strong partnerships with primary care and enhance linkages to care.

Conclusion

One in three adults has NAFLD. The burden of NAFLD is projected to increase substantially over the next decade unless urgent measures are undertaken to combat the metabolic risk factors for NAFLD. There are substantial gaps in care for patients with NAFLD, including a dire lack of disease awareness, a lack of consensus for screening, and limited therapeutic options. We call for greater efforts toward prevention and early detection of NAFLD to reduce the burden of this growing disease.

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