Managing Nonalcoholic Fatty Liver Disease Through Structured Lifestyle Modification Interventions

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a significant global health burden. It comprises a broad pathological spectrum ranging from simple liver steatosis to steatohepatitis with variable degrees of fibrosis, and liver failure. Patients with NAFLD have an increased risk of liver-related and overall mortality. While the trials to assess the efficacy of the medications are ongoing, lifestyle modification is the first line of therapy recommended. The primary aim of this review paper is to synthesize literature related to current evidence-based lifestyle interventions for preventing and managing NAFLD. The review and synthesis of the literature reveal that personalized nutritional, exercise, and behavior change interventions are effective in managing NAFLD. Evidence suggests that there are several gaps in managing NAFLD. The gaps discussed in this paper include a lack of awareness of the disease, ineffective patient-provider communication, shortage of specialists, under-recognition of the disease, and liver health disparities. This paper highlights the evidence-based opportunities to overcome those gaps, such as utilizing comprehensive models of care, clinical care pathways, and clinical practice guidelines. Primary care physicians and endocrinologists, who are the first point of contact must utilize these opportunities for diagnosing and managing patients with NAFLD.

“The key factor in preventing and treating NAFLD is a holistic lifestyle modification approach, consisting of healthy eating patterns and exercise to prevent disease progression.”

Introduction

Nonalcoholic Fatty Liver Disease (NAFLD), (i.e., Metabolic Dysfunction Associated Steatotic Liver Disease [MASLD]) is a rising epidemic worldwide, affecting 25% of the world’s population.^1-4 NAFLD is a progressive disease with no liver inflammation (hepatic steatosis) to begin with, but leads to steatohepatitis with inflammation and advancement of fibrosis if left untreated.^2,5,6 It is associated with substantial morbidity and mortality due to life-threatening complications such as liver cirrhosis, liver failure, and hepatocellular carcinoma.^2,7,8 NAFLD can increase the risk of type 2 diabetes mellitus, chronic kidney disease, and cardiac/cardiovascular diseases.^5,7,9,10 Despite its increasing prevalence, disease burden, and financial burden on patients as well as on the healthcare system, there exist many challenges to preventing or managing NAFLD effectively.^11-13 The pharmacotherapies for NAFLD are limited and evolving. Therefore, the current treatment options focus on lifestyle modification and the use of medications to treat metabolic comorbidities.^14-18

The primary aim of this review paper is to pool and condense literature on evidence-based management approaches with special emphasis on lifestyle modification strategies for the prevention and management of NAFLD. This review paper will also discuss the current understanding of Nonalcoholic Fatty Liver Disease (NAFLD), its stages, pathophysiology, preventative measures, pharmacological/non-pharmacological management approaches, and gaps and opportunities to effectively manage NAFLD.

Methods

A systematic search was conducted using PubMed, Scopus, and the Cochrane databases. The search terms using the MeSH were “Nonalcoholic fatty liver disease,” “Metabolic Dysfunction Associated Steatotic Liver Disease,” “steatohepatitis,” “lifestyle interventions” (“exercise” & “nutrition “or “diet,” “personalized interventions,” “clinical care pathways,” “models of care,” “evidence-based clinical practice guidelines,” “challenges,” and “gaps and opportunities.” We limited our search to peer-reviewed articles published in English. The article types included in the review were quantitative and qualitative research, systematic review and meta-analysis, integrative review, evidence-based clinical practice guidelines, clinical care pathways, and state-of-the-science articles. We excluded case reports, dissertations, conference abstracts, non-full-text articles, and articles focused on alcoholic fatty liver disease.

The initial search resulted in 122 articles from PubMed and 32 articles from Scopus, 11 Randomized Clinical Trials (RCT), and 6 systematic review and meta-analysis articles from Cochrane databases. Only articles that focused on the review aims were included in the narrative review. Based on these criteria, 72 articles were reviewed. Out of 72 articles, 3 were RCTs, 5 were systematic reviews and meta-analysis articles, 5 were clinical practice guideline-based articles, 2 were clinical care pathway articles, 1 was a qualitative review article, and the remaining 56 articles focused on disease, management, challenges, models of care, and gaps and opportunities to effectively manage NAFLD. The articles selected for review were synthesized, and a narrative review was reported.

Results

Prevalence and Incidence

Nonalcoholic Fatty Liver Disease affects approximately 37% of US adults. ² It remains a global healthcare burden since it can cause a cluster of clinical features of metabolic syndrome.^5,13,19,20 In the United States, NAFLD has evolved into the second leading cause of liver transplantation in the last 2 decades, and it is a leading cause of liver transplantation in developing countries. Non-alcoholic Steatohepatitis (NASH) [Currently renamed as metabolic-associated steatohepatitis (MASH)] is the fastest-increasing indication for liver transplantation.^8,21,22 It is predicted to become the most frequent indication for liver transplantation by 2030.^7,9 The estimated annual direct medical costs exceed $100 billion in the United States alone. NAFLD is, therefore, a very costly disease for the healthcare system due to comorbidities and devastating complications.^1,23-25

The incidence is rising in children and adolescents with obesity. ²⁶ Studies have demonstrated the true burden of pediatric NAFLD and its progression to advanced fibrosis, cirrhosis, and end-stage liver disease in adulthood.^2,26,27 Although options are expanding, there is no effective pharmacotherapy to treat NAFLD in the pediatric population.^26-28

Definition of NAFLD

In 2020, an international multi-society Delphi consensus renamed NAFLD as metabolic (dysfunction) associated steatotic liver disease/steatotic liver disease (MASLD/SLD) to reflect the pathogenesis of NAFLD more accurately. The new definition includes at least 1 of 5 cardiometabolic risk factors.^19,20,29,30 The name change comes with a simple set of criteria for diagnosing the condition at the bedside for the general medical community, including primary care physicians (PCPs). The use of the term MASLD over the traditional NAFLD benefited the practitioners in identifying high-risk individuals, understanding the disease associations, and appreciating the risk of liver and extrahepatic mortality.^20,30 NAFLD is defined by at least 5% fat infiltration in the liver without hepatocellular injury and in the absence of other etiologic factors such as alcohol, drugs, and other chronic liver diseases.^10,31,32

Types, Stages, and Pathophysiology

NAFLD is a multisystem disease involving excessive lipid deposition in the liver.^7,29 The pathological changes in lipid and carbohydrate metabolism lead to excess lipid accumulation and oxidative stress, which create a lipotoxic environment in hepatocytes leading to liver injury, death, and accumulation of inflammatory cells and fibrosis.^29,34 It is estimated that liver fibrosis progresses by 1 stage per decade, but the rate of progression or regression varies by individual characteristics and environmental factors.^24,33

NASH involves at least 5% steatosis and inflammation with hepatocyte injury (ballooning), with or without fibrosis.^10,31,32 Advanced fibrosis is the major predictor of morbidity and liver-related mortality in patients with NFLD. Studies show that both all-cause and liver-specific mortality increase once stage 2 fibrosis has developed. The risk of death from liver disease increases by a factor of 50 to 80 for patients with nonalcoholic steatohepatitis who have stage 3 and 4 fibrosis.^10,24,31,33 Cardiometabolic disorders, including central obesity, atherogenic dyslipidemia, hypertension, insulin resistance, and hyperglycemia accompany NAFLD. These can cause heart attacks and stroke—the most common causes of mortality in patients with NAFLD.^5,7,29,31,35

Primary and Secondary Prevention

Risk Factors Identification

Modifiable Risk Factors

Sedentary behaviors and poor dietary habits are associated with NAFLD risk.^3,5,24,33,36 Over-nutrition, dietary composition, physical inactivity, and the central obesity that results from these behaviors are the modifiable risk factors that can cause NAFLD.^6,36,37 NASH is strongly associated with visceral adiposity and metabolic syndrome. ³³ The dietary composition of the human diet has changed over the years. It is well understood that consumption of a diet rich in processed meat, red meat, saturated fat, added sugars, and sweetened beverages is associated with NFLD disease progression. High consumption of a diet enriched in saturated and trans-fat, omega-6 fatty acids, carbohydrates, high-energy nutrients, fructose, and corn syrup will again worsen the NAFLD risk.^14,38 It has been found that changing the dietary composition of increased intake of polyunsaturated fatty acids, fiber, micronutrients, fruits, vegetables, proteins, and omega-3 fatty acids plays a critical role in reversing the NAFLD progression.^36-38

Nonmodifiable Risk Factors

The nonmodifiable risk factors include age, ethnicity, gender, heredity (genetic/epigenetics), and lean body status. As age advances, there is an increased risk of NAFLD and NAFLD-related fibrosis, hepatocellular carcinoma, and type 2 diabetes.^6,33,39,40 Racial and ethnic disparities and gender disparities are noted in the NFLD and other liver diseases. It can be linked to various social determinants of health.^19,41,42 The highest prevalence of NAFLD is observed in Hispanics, followed by non-Hispanic White individuals. There is a rising trend in White, Asian American Pacific Islanders (AAPI), and American Indian and Alaska Natives (AI/AN), although African American (AA) individuals showed a nonsignificant change.^33,41

NAFLD prevalence in women is increasing worldwide.^37,40 Studies indicate greater NAFLD risk, severe hepatic fibrosis, and high mortality in postmenopausal women compared to premenopausal women and men. ⁴³ However, women of reproductive age have lower rates of NAFLD compared to men.^37,40-42

Genetic markers specific to people from multiple races and ethnicities have been identified as markers causing hepatic steatosis and NASH.^8,16,42 One of the genetic markers, the rs738409 G allele, has been associated with severe steatosis, NASH, and liver fibrosis in adults.^24,33 The role of intestinal microbiota, its by-products as risk factors for causing NAFLD, and its pathophysiology have been documented in the literature.^5,44 Evidence suggests that heritable factors account for about half of the inter-individual differences in the prevalence of nonalcoholic steatohepatitis with cirrhosis.^7,24 Epigenetic alterations can influence metabolic pathways controlling adiposity, insulin sensitivity, and tissue generation or regeneration. It has been investigated that epigenetic mechanisms can cause cellular and metabolic alterations among families with adult-onset diabetes.^7,24 It will lead to increasing susceptibility to nonalcoholic steatohepatitis, disease progression, and disease severity.^{17,24,33,42,45}

NAFLD can occur in lean individuals whose BMI is lower compared to obese or overweight individuals. People with lean NAFLD will have an abnormal metabolism compared to people who are obese.^33,46 Recent data suggest that people with lean NAFLD have higher fibrosis scores, rates of cardiovascular morbidity, and all-cause mortality in advanced stages.^17,46

Assessing the Symptoms

Many people with NAFLD often experience no symptoms in the initial stages. NASH can be asymptomatic in many patients until they present with severe scarring, cirrhosis of the liver, and end-stage liver disease. ³⁵ When symptoms occur, patients may complain of fatigue, dull pain in the right abdomen, hepatomegaly due to the liver’s fatty infiltration, acanthosis nigricans, and lipomatosis.^1,7,35 The symptoms associated with cirrhosis and severe scarring include weakness, jaundice, itching, fluid build-up and ascites, peripheral edema, mental confusion, enlarged spleen, shortness of breath, red palms, and spider-like blood vessels beneath the skin’s surface.^1,7,35

Screening for NAFLD

NAFLD can be associated with advanced fibrosis and significant complications such as cardiometabolic risk and hepatocellular carcinoma. Therefore, accurate diagnosis and early recognition of NASH and NAFLD progression is mandatory.^2,24,31,33 The American Gastroenterological Association (AGA) has proposed screening algorithms for NAFLD. ³¹ Patients who are in high-risk groups that present with prediabetes, type 2 diabetes, obesity, and/or ≥ 2 cardiometabolic risks, steatosis on imaging, and elevated aminotransferase (>30 IU/L) must be screened for NFLD in primary care clinics.^31,33

Measures and Indices for Screening

Non-invasive Screening Tools

One or more Non-Invasive Tools (NITs) can be used to detect the presence of NASH and the progression of fibrosis.^4,31 The standard tests include the Fibrosis-4 index (FIB 4-Score), the Steatosis Associated Fibrosis Estimate (SAFE) score, the NFS (NAFLD Fibrosis Score), the Metabolic Dysfunction Associated Fibrosis-5 (MAF-5) score, and the Aspartate Aminotransferase values to Platelet Ratio (APRI) index.^2,31,47,48 The non-invasive measures and indices for screening NAFLD are presented in Table 1.

Table 1.

Screening for Nonalcoholic Fatty Liver Disease (NAFLD).

Screening for NAFLD	Uses/Variables	Measurement Indices
Fibrosis-4 (Fib-4) index31,47,52	○ Most validated tool	High risk: Fib 4 score > 2.67(High risk for advanced fibrosis)
	○ Able to predict changes in hepatic fibrosis
	○ Used to estimate the risk of advanced fibrosis, liver scarring, liver cirrhosis, and need for liver biopsy	Intermediate risk: Fib 4 score between 1.3 and 2.67 (Moderate risk for advanced fibrosis)
	○ it is calculated by computing age, AST, ALT, and platelet count	Low risk: Fib 4 score <1.3 (Low risk for advanced fibrosis)
SAFE (Steatosis associated fibrosis estimate) Score 49	○ Used in the primary care settings to evaluate fibrosis in populations with low risk of fibrosis	High-risk (≥100): High risk for advanced fibrosis
	○ Used for F2 and higher grades of fibrosis	Intermediate risk (0-100): Intermediate risk for advanced fibrosis
	○ Uses readily available variables (aminotransferase levels, globulin level, platelet count, age, BMI, presence of diabetes	Low risk (below 0): Low risk for advanced fibrosis
NFS (NAFLD fibrosis Score)10,31,32	○ Used to estimate the severity of liver fibrosis or advanced by using six variables (AST/ALT ratio, albumin, platelet count, age, BMI, presence of diabetes)	Grade F3-F4 (>0.67): Significant fibrosis/NASH
	○ Used in hepatology clinics, must be avoided in primary and endocrinology clinics due to overestimation of fibrosis	Undetermined: 1.455-0.67-Liver biopsy is recommended
		Grade F0-F2 (<-1.455): Indicates no significant fibrosis
Metabolic dysfunction-associated Fibrosis-5 (MAF-5) Score10,48	○ Used in primary care populations with metabolic dysfunction	High-risk (≥1): High risk for fibrosis
	○ Helps to identify high-risk patients for fibrosis and all-cause mortality	Low risk (below 0): Low risk for fibrosis
	○ Uses age-independent variables (BMI, liver enzymes, waist circumference)
Aspartate aminotransferase values to the platelet ratio (APRI) index2,10,31,47	○ Used to estimate liver fibrosis and cirrhosis	≥1.5: High APRI (Higher likelihood of significant fibrosis or cirrhosis), >0.5-<1.5: Mid-range APRI (presence or absence of fibrosis and cirrhosis), ≤0.5: Low APRI (Low likelihood of liver fibrosis and cirrhosis)
	○ Lower platelet count and increased liver enzymes are associated with liver fibrosis
Laboratory tests2,10,31	○ To screen for changes in the liver enzymes	Elevated values indicate risk for NAFLD
Liver function tests (AST, ALT, tests for viral hepatitis), CBC, lipid profile, and hemoglobin A1c	○ To screen for co-morbid conditions such as hyperlipidemia and type 2 diabetes
Laboratory test: Enhanced Liver fibrosis (ELF) test31,51,52	○ Measures 3 extracellular molecules involved in the liver matrix metabolism	ELF score <9.80: Low risk of disease progression from advanced fibrosis to cirrhosis or liver-related events >9.80 - ≤ 11.30: Moderate risk >11.30: Higher risk
	○ This can help identify patients with advanced fibrosis and cirrhosis

NITs such as the Fibrosis-4 index (FIB-4 Score) can be used to identify patients at risk for fibrosis.^2,4,31,47 This tool uses age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. Individuals with FIB-4 scores between 1.3 and 2.67 are in the intermediate-risk category, and those with > 2.67 are placed in the high-risk category. Those in the intermediate-risk category are referred for liver stiffness measurement (LSM), and those in the high-risk category will be referred to hepatologists. Fibrosis is defined when the liver stiffness measurement is > 8.0 kPa. Those in the low-risk category with a FIB-4 score < 1.2 must repeat NIT after 2 years or earlier.^2,4,15,32 Despite its benefits to screening for risk stratification, the FIB-4 index can have high negative predictive values in excluding advanced liver fibrosis and future liver-related events. Moreover, the FIB-4 index lacks diagnostic performance in patients below 40 years. Therefore, the FIB-4 score is recommended in primary care for initial evaluation, with follow-up for abnormal results by subsequent workups or specialist referrals.^4,31,49

The SAFE score is recommended for an initial assessment to detect low-risk NFLD in primary care settings.^48,49 This risk stratification tool uses widely available variables such as age, body mass index, platelet count, aspartate and alanine aminotransferase, and globulins (total serum protein minus albumin). It has good diagnostic accuracy in detecting fibrosis and is particularly useful for referral decisions in patients with NAFLD.^48,49

The NAFLD fibrosis score (NFS) estimates the amount of scarring in the liver. It is commonly used in hepatology clinics due to the overestimation of advanced fibrosis in people with obesity in primary care settings. ³¹ The scoring system includes hyperglycemia, Aspartate aminotransferase and Alanine aminotransferase ratio (AST/ALT ratio), albumin, platelet count, age, and BMI to estimate the severity of liver fibrosis. ³¹

A new NIT, the Metabolic Dysfunction-Associated Fibrosis- 5 (MAF-5) score, uses waist circumference, body mass index, aspartate aminotransferase, platelet count, and diagnosis of diabetes to assess fibrosis risk.^31,49 It is an age-dependent, anthropometric-based score to assess fibrosis risk among the general population. To predict liver fibrosis in MASLD patients, MAF-5 scored excellent in detecting liver stiffness measurement ≥ 12 kPa. Additionally, the MAF-5 score outperformed the FIB-4 Score in identifying patients at elevated risk for liver fibrosis and increased risk of all-cause mortality in the primary care population, by using simple variables.^31,49

The use of Aspartate Aminotransferase values to the Platelet Ratio (APRI) index is another tool recommended for the mass screening of populations at high risk of NAFLD complications. ⁴⁷ It is reported to be accurate in identifying patients at low risk for progression of NAFLD and a good predictor for advanced fibrosis in NAFLD patients. The APRI index can also be used in ruling out significant fibrosis in patients with NAFLD and living in resource-limited rural settings.^47,50

Laboratory Tests

Blood tests such as liver function tests, CBC, lipid profile, and Hemoglobin A1c must be performed during the initial patient visit to diagnose NAFLD and co-morbid conditions. ³² The Enhanced Liver Fibrosis (ELF) test is another specialized blood test that measures 3 molecules involved in the liver matrix metabolism to give a score reflecting the severity of liver fibrosis. This test facilitates the early recognition of fibrosis.^31,51,52

Diagnosis of NAFLD/NASH

Imaging Tests and Liver Biopsy

Abdominal ultrasonography is the most commonly used method to diagnose fatty liver. ⁴ Various non-invasive imaging and scanning techniques are used to diagnose and stratify risk in patients with NFLD. These include Vibration-Controlled Transient Elastography (VCTE), Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF), Magnetic Resonance Elastography (MRE), CT scan, and Acoustic Radiation Force Impulse (ARFI). These diagnostic tests are used to measure liver stiffness and determine the presence and severity of fibrosis.^{20,31,32,35,53} Histological evaluation with liver biopsy remains the gold standard for diagnosing NASH. Liver biopsy helps to identify hepatic steatosis, ballooning, and lobular inflammation with or without fibrosis. ⁵³

Treatment Approaches

Medical Management

Once the diagnosis of NAFLD is made, the focus should shift to treatment and monitoring for disease progression and associated complications.^6,8

Pharmacological

In the past 5 years, significant advances have been achieved in the pharmacotherapies of NAFLD and NASH, and the trials remain ongoing.^15,17,18,54 Current pharmacotherapies focus on pathogenic factors, key links of pathogenesis, and related metabolic disorders as targets. The goal is to attenuate metabolic dysregulation and cell injury or directly target the ensuing inflammation and fibrosis.^15,17,18,29 The pharmacotherapy for NAFLD and its targets are presented in Table 2.

Table 2.

Pharmacotherapy for Nonalcoholic Fatty Liver Disease.

Medications	Targets /Action
(Thiazolidinediones) pioglitazone31,54,56	• To manage type 2 diabetes, obesity, and cardiovascular issues
	• It improves insulin sensitivity, glucose, and lipid metabolism
	• Contributes to reversing steatohepatitis
Glucon like peptides-1 (GLP-1) receptor agonists (Liraglutide and semaglutide) & dual agonists (tirzipatide)31,54,56	• Useful for treating type 2 diabetes, obesity
	• Useful for glycemic and weight control
	• Reduces hepatic lipogenesis, very low-density lipoproteins, and triglycerides; reduces CVD risks
Sodium-glucose co-transporter-2 (SGLP2) inhibitors) (Empagliflozin and dapagliflozin)31,54,56	• Empagliflozin and dapagliflozin reduce steatosis in patients with type 2 diabetes (improves glucose control, lipid level, and blood pressure; induce weight loss and help cardio-renal protection)
	• Dapagliflozin reduces liver fibrosis, improves/resolves steatohepatitis, and improves cardiometabolic benefits
Farnesoid X receptor axis inhibitors (obeticholic acid) 55	• Improves liver histology
	• Improves weight loss
Metformin31,54,56	• Help to manage type 2 diabetes
Statin and fibrates18,54,56	• Improves lipid metabolism and cardiovascular risks
Fibroblast growth factor 21 (FGF21) analog (pegozafermin) 55	• Reduces hepatic fat content, and NASH resolution and/or fibrosis regression
Thyroid hormone receptor-β (THRβ) agonist (resmetriom)	• Reduces hepatic fat content, and NASH resolution and/or fibrosis regression
Nuclear receptor agonists (resmetirom, lanifibranor, obeticholic acid)54,55	• Reduce the activation of inflammatory cascades
	• NASH resolution without worsening symptoms
	• Improve glucose and lipid metabolism with significant reduction in the intra-hepatic triglycerides
Modulators of lipotoxicity (aramchol, acetyl-CoA carboxylase inhibitors)55,56	• Improves NAFLD/NASH pathogenesis (steatosis, inflammation, and fibrosis)
Modification of genetic variants (PNPLA3 gene silencing) 55	• PNPLA3 helps to mobilize polyunsaturated fatty acids
	• Enhances hepatic secretion of large-sized low-density lipoproteins
Lipase inhibitor (Orlistat)55,56	• To treat pediatric and adult obesity
Naltrexone/bupropion55,56	• To treat adult obesity, help to maintain weight loss
Norepinephrine reuptake inhibitor (phentermine combined with topiramate)55,56	• To treat adult and pediatric obesity (among older adolescents)
VitaminE 31	• Improves NASH resolution and/or fibrosis regression in type 2 diabetes patients

Patients with NAFLD should be evaluated for coexisting metabolic comorbidities such as obesity, diabetes mellitus, hypertension, dyslipidemia, and cardiovascular disease. These conditions should be managed with medications and lifestyle modifications.^{8,16-18,31,55} To manage comorbidities, medications that may have a positive effect on reducing fibrosis, such as thiazolidinediones (pioglitazone), GLP-1 receptor agonists (liraglutide and semaglutide) and dual agonists (Tirzipatide), sodium-glucose co-transporter-2 inhibitors (empagliflozin and dapagliflozin), Farnesoid X receptor axis inhibitors (obeticholic acid), metformin, and statins and fibrates are recommended.^{8,16,17,29,31} Early results indicate that empagliflozin and dapagliflozin reduce steatosis in patients with type 2 diabetes, and dapagliflozin may reduce liver fibrosis and improve steatohepatitis and cardiovascular outcomes.^4,6,31,55

Research studies focusing on the effects of the fibroblast growth factor 21 (FGF21) analog (pegozafermin) and the thyroid hormone receptor-β (THRβ) agonist (resmetriom) on hepatic fat content, and NASH resolution and/or fibrosis regression, are ongoing with promising results.^18,19,29 The targets for reducing the activation of inflammatory cascades include nuclear receptor agonists (e.g., resmetirom, lanifibranor, obeticholic acid), modulators of lipotoxicity (e.g., aramchol, acetyl-CoA carboxylase inhibitors), and modification of genetic variants with PNPLA3 (e.g., PNPLA3 gene silencing).^16,29

Orlistat, a lipase inhibitor, and Naltrexone/bupropion are recommended to manage obesity in adult and pediatric populations. ⁵⁶ For weight reduction management (4% BMI reduction), Phentermine, a norepinephrine reuptake inhibitor, is recommended for short-term use in adults and older adolescents. The FDA has approved phentermine, combined with Topiramate, to treat obesity in children between 12-16 years.^55,56

Non-pharmacological

The roles of dietary supplements such as Vitamin E, polyunsaturated fatty acids (PUFAs), ginger, and probiotics have also been investigated. ²⁷ Evidence suggests that vitamin supplementation, mainly vitamin E, has been shown to improve the histology and steatosis score for patients with NAFLD.^8,27,57 In patients without diabetes, 800 IU of vitamin E daily has been shown to improve NASH but does not affect fibrosis.^27,31,35 When pediatric patients were treated with 800 IU of vitamin E, significant resolution of NASH was noticed at 96 weeks. ⁵⁶ A recent meta-analysis of 11 epidemiological studies showed that regular coffee consumption can prevent the progression of NAFLD. ⁵⁷ A range of natural products has been reported as regulators of NAFLD with therapeutic effects to manage NAFLD. ⁵⁸

Endoscopic Interventions and Surgical Approaches

In patients with severe obesity and NAFLD, endoscopic bariatric interventions and bariatric surgery are recommended as treatment options.^4,6,10,29,31 Multiple bariatric endoscopic procedures are available for adult patients to achieve weight loss goals. ⁵⁹ Bariatric surgery is effective for weight loss and reducing liver fat in people with severe obesity.^6,10,31 NAFLD is the most common cause of liver transplantation in young adults.^56,60 Liver transplantation is the only life-saving modality for patients with complications of cirrhosis, T2 hepatocellular carcinoma, and end-stage liver disease.^40,60

Lifestyle Modification Interventions

Given that research trials for the pharmaceutical treatment of NAFLD are ongoing and the outcome of curing the disease remains uncertain, efforts must focus on mitigating risk factors, lifestyle modifications, and dietary interventions leading to weight loss.^2-4,14,17,59 Excess liver fat is an independent risk factor for developing NAFLD and disease progression. Reducing liver fat and its mediators through lifestyle modification is beneficial for delaying or preventing the onset of these life-threatening conditions. ⁶¹ Evidence suggests that intensive lifestyle modification interventions with dietary recommendations, exercise, weight loss, and treatment of metabolic syndrome are recommended for NAFLD after the diagnosis is made.^{3,5,6,8,12,14,16,17,31,32,35,36,54,62-65}

It has been found that weight loss of >10 % can induce a near-universal nonalcoholic steatohepatitis resolution and fibrosis improvement by at least one stage. Modest weight loss of >5% can also produce histologic and cardiometabolic benefits.^31,36,59,64 Weight loss will also decrease the cardiovascular and diabetes risk in patients with NAFLD. ³⁶ In patients with nonalcoholic steatohepatitis, weight loss of 5% of total body weight can decrease hepatic steatosis, weight loss of 7% of total body weight can lead to nonalcoholic steatohepatitis resolution, and weight loss of 10% of total body weight can result in fibrosis regression or stability. ⁸ However, patients with lean NAFLD (body mass index 26 kg/m2 non-Asian or body mass index 24 kg/m2 Asian)—a lower target weight loss threshold of 3%–5%—will experience similar histologic benefits for steatosis and nonalcoholic steatohepatitis compared to obese/overweight patients. ⁸

Weight loss management through lifestyle modification approaches comprising hypocaloric diet, changes in dietary composition, and exercise remain the cornerstones of NAFLD management. ¹⁴ Therefore, the primary care provider must focus on instructing the patients about the importance of lifestyle modification comprising calorie restriction and increased physical activity, after the NAFLD is diagnosed.^8,14

Nutrition

Evidence suggests that patients with NAFLD must change their dietary patterns and follow a low carbohydrate and hypocaloric diet targeting at least 30% calorie reduction or 1200-1500 kcal/d or a reduction of 500-1000 kcal/d from baseline to achieve weight loss.^8,25,31,65 Choosing the right dietary composition is critical in the management of NAFLD. Studies report that patients with NFLD must restrict sugars, carbohydrates, starch, saturated fats, and trans fatty acids such as red and processed meat, triglycerides, ultra-processed food, and alcohol. Adhering to these dietary regimens will slow disease progression and cardiovascular complications.^8,14,25,31 Increased intake of polyunsaturated fatty acids, monounsaturated fatty acids, and antioxidants, and balanced intake of micronutrients and macronutrients, are helpful for weight loss and NAFLD disease progression. Food items and supplements such as fish, olive oil, fruits and vegetables, whole grains, vitamins, and polyphenols are beneficial for metabolic disorders.^3,14,25

The Mediterranean Diet (MD) is the most common diet recommended for achieving liver-related outcomes in NAFLD.^{3,14,25,31,36,38,63-65} The MD consists of a low carbohydrate intake, especially low sugars, and refined carbohydrates (40% of the calories vs 50%–60% in a typical low-fat diet), and increased monounsaturated and omega-3 fatty acid intake (40% of the calories as fat vs up-to 30% in a typical low-fat diet). ³⁶ MD will reduce the risk of cardiovascular diseases and metabolic syndrome as this diet constitutes polyunsaturated fats, protein, omega-3 to omega-6 fatty balance, polyphenols, antioxidants, vitamins, and carotenoids with their anti-inflammatory and antioxidant effects.^36,66

Dietary patterns such as a plant-based diet, Dietary Approaches to Stop Hypertension (DASH) diet, and vegetarian/vegan diets are also reported to be beneficial in patients with NAFLD.^3,38,63 Patients who follow meal replacement protocols, time-restricted diet, intermittent fasting, and alternate-day fasting receive increased benefits from disease progression.^8,14,67 Based on the evidence from 2 randomized controlled trials, researchers recommend the alternate-day fasting (ADF) schedule for effectively reducing liver steatosis score, circulating levels of alanine aminotransferase (ALT), and reducing body weight in patients with NFLD. It was evident that patients who followed an intermittent fasting plus exercise protocol for 3 months showed a significant reduction in hepatic steatosis by 5.5% vs controls. ⁶⁷

Personalized and culturally/economically tailored nutritional interventions based on the patient’s preferences are the novel therapeutic approaches that primary care providers must recommend in NAFLD management for quality outcomes.^{3,5,31,59,66,68} Nutritional genomics is another evolving branch of science investigating the interaction of dietary habits and exposure with the human genome. ⁵ The genome-informed nutrient and food-based dietary practices are recommended for genetically diverse populations to prevent diseases and minimize adverse outcomes in nutrient-related diseases like NAFLD. ⁵

Physical Activity

Physical activity decreases pro-inflammatory and oxidative stress markers, liver enzyme profiles, intra-hepatic fat and triglycerides, and liver histology. It will also improve hepatic and peripheral insulin sensitivity and glucose metabolism, thus slowing down the progression of NAFLD and associated complications.^31,62

Aerobic and resistance exercises, which are more structured and deliberate, constitute a powerful lifestyle therapy to improve several parameters of NAFLD.^{3,17,36,54,62,64,65} Data from a systematic review of 24 exercise-only trials showed that structured exercise (moderate to vigorous intensity, 3-5 days per week) produced a 20%–30% relative reduction in hepatic steatosis in patients with NAFLD.^62,65 The recent evidence-based practice guidelines recommend a target of 150-300 minutes of moderate-intensity or 75-150 minutes of vigorous-intensity aerobic exercise per week. ⁸

A decrease in hepatic steatosis with exercise is observed even without significant weight loss.^31,55 Therefore, focusing on the intensity of exercise is more important than the type of exercise when NAFLD is diagnosed. Despite the challenges in adopting long-term exercise programs, patients with NAFLD must adhere to structured exercise training programs.^8,31

Weight Loss Challenges and Opportunities

Maintenance of weight loss is a major challenge in patients with NAFLD due to noncompliance.^32,62 Some patients gain back weight. Maintaining a stable weight requires addressing barriers to behavior changes. Self-monitoring or monitoring using technology can influence adherence and induce greater weight loss. Self-monitoring increases a person’s awareness of targeted behaviors and the circumstances surrounding those behaviors. ⁶² The personalized lifestyle coaching intervention trial using a mobile app has been very effective in both physiological and psychological outcomes. ⁶⁹ Therefore, interventions focusing on behavioral modification strategies and using technology to self-monitor the lifestyle interventions will improve adherence and weight loss maintenance in patients with NAFLD.^32,62,71

There are more benefits to lifestyle intervention programs if multidisciplinary team members participate in offering personalized nutrition, exercise, and psychological counseling. This strategy will maximize compliance and long-term engagement to achieve quality outcomes.^31,32,61,69

Lifestyle Modification Interventions in Pediatric Populations

Although options are expanding, there is no effective pharmacotherapy to treat NAFLD in the pediatric population.^26-28 Personalized dietary and exercise interventions combined with psychological counseling and behavior modification remain the effective treatment approaches for pediatric patients with NAFLD.^26,56,70 Changes in family lifestyle and individual or group counseling have also been recommended as strategies to change lifestyles and improve self-efficacy among children and adolescents.^26-28,70

The dietary changes recommended in the pediatric population aim to create an energy deficit—reduction in simple sugar consumption, sweetened drinks, trans-fat, and junk food as the nutritional modification in conjunction with increased physical activity to optimize BMI and the progression of NAFLD in the pediatric population.^26,31,70 Main interventions include adhering to diets low in carbohydrates, free sugars, fructose, and lipids and possible nutritional interventions with n-3 polyunsaturated fatty acids (EPA and DHA), high protein diets, amino acids (cysteine, L-carnitine), cysteamine, vitamin E supplements, antioxidant supplementation, Mediterranean diet, Dietary Approach to Stop Hypertension (DASH) diet, ginger, and single strain or multi-strain probiotics.^26,27,31

Physical activity, mostly aerobic exercises that are structured and systematic, has been reported to be effective in children and adolescents with NAFLD.^28,70 Some of the activities—such as swimming, cycling, gymnastics, track and field, and basketball that are carried out for at least 60 minutes /6 times a week—have shown significant improvement in children with NAFLD. ⁷⁰

Discussion

Based on the review of recent literature, it is evident that NAFLD presents a broad spectrum of hepatic injuries, ranging from simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma.^5,8 If left untreated, there is a high chance of developing liver-related complications and metabolism-related comorbidities. Therefore, NAFLD poses a significant public health concern due to its increasing prevalence and its potential for progression into Nonalcoholic Steatohepatitis, liver failure, and increased mortality.^11-13 The pharmacotherapies for managing NAFLD are evolving. Medications that reduce liver inflammation, insulin resistance, and hepatic fat content are initiated when NAFLD is diagnosed.^{14-16,29,31,55} The key factor in preventing and treating NAFLD is a holistic lifestyle modification approach, consisting of healthy eating patterns and exercise to prevent disease progression.^18,65 Evidence indicates that there are gaps in managing NAFLD. ²³ Despite these challenges, multiple strategies exist to prevent and manage NAFLD.^23,31 The gaps in managing NAFLD and the opportunities to address these gaps are presented in Figure 1.

Figure 1.

Gaps and opportunities in managing nonalcoholic fatty liver disease JPEG.

Gaps in Managing NAFLD

At the Individual, Health Care Provider / Health Care Settings Level

One of the main challenges is that there is a severe lack of awareness of NAFLD by the general population. ¹¹ There is a substantial knowledge gap among individuals related to NAFLD as a multisystem disease and its prevention and management compared to other preventable noncommunicable diseases such as type 2 diabetes, hypertension, dyslipidemia, and heart attack.^11,31,32,68 Due to a lack of awareness about the disease and its complex nature of the disease, there can be delays in diagnosing and treating the disease. Patients usually do not seek care for NAFLD until signs and symptoms of advanced liver disease are present. ³² This time gap may further exacerbate the pathological issues causing variable degrees of fibrosis and liver cirrhosis in patients with NAFLD.^12,32,68,70

In the United States, most NAFLD patients are seen by primary care physicians (PCPs) or endocrinologists in primary care settings. A survey of over 2200 physicians revealed a knowledge gap regarding NAFLD among providers, especially primary care physicians (PCPs) and endocrinologists. ³¹ NASH and advanced fibrosis often remain undiagnosed in primary care settings and endocrinology clinics.^2,11,68,71 Primary care is the ideal setting to institute multidisciplinary care, especially specialist consults, dietary and physical activity counseling, and initiating the discussion of bariatric surgery in patients with severe obesity.^4,12,32,68 Ineffective communication about the disease between primary care physicians, patients, and the multidisciplinary team is also reported. ⁷¹ Therefore, to prevent the development of cirrhosis and other comorbidities, PCPs, and endocrinologists play a vital role in identifying patients with NAFLD, recognizing at-risk patients, screening fibrosis using non-invasive techniques, and making timely referrals.^2,4,31,32

Evidence suggests that PCPs and hospital specialists, excluding gastroenterologists, underrecognize NAFLD patients.^4,11,31,32 In a survey of 751 clinicians in the United States, including PCPs, endocrinologists, gastroenterologists, and hepatologists, it was found that the clinicians underestimated the prevalence of NAFLD in high-risk groups. More than half of the PCPs considered the prevalence of NAFLD in the general population to be ≤ 10%, and 85% of PCPs do not use transient elastography, fibrosis biomarkers, and NAFLD management algorithms.^11,32 Due to the knowledge gap and under-recognition of the disease, underutilization of medications with proven efficacy in patients with NASH have been reported.^11,31,32

The clinical trials on the efficacy of pharmacotherapy to treat NAFLD are still evolving. As there are no medications available yet to cure the disease, lifestyle modifications, including diet and physical exercise, targeting the weight loss of 5%-10% remain the first line of therapy to manage NAFLD and prevent disease progression.^{8,15,16,59,64} More personalized and sustainable lifestyle modification interventions can maximize adherence and outcomes. However, this would need resource utilization from a multidisciplinary team, which would further increase out-of-pocket costs depending on the type of insurance.^53,59 Racial and ethnic health disparities, as well as social determinants of health, will further impact weight loss goals in some patients and cause delays in seeking care.^{3,5,11,19,40,42,53,59,68}

The out-of-pocket cost that the patients have to bear for multiple diagnostic procedures, and referrals to specialists for diagnosis and treatment can cause delays in seeking care.^4,11,31,53 Eric Rose, the Vice President of HCA Physician Services, reported that with the specialist shortages and the delay in treatment and management of complications, the cost patients bear is increasing, and patients with no good insurance are going to be affected worse in the US. ²³

One major challenge patients face is the delay in getting gastroenterologist and hepatologist appointments. According to Dr. Joseph J. Vicari, a gastroenterologist at Rockford Gastroenterology Associates, “timely access,” especially when waiting a few months, can lead to devastating consequences. ²³ Dr. Daniel J Pampiano, the managing partner of Gastrohealth, reported that the shortage of gastroenterologists and hepatologists, combined with an increased population needing care from advanced care providers, can cause delays in screening and an increase in GI-related cancer as well as noncancer mortality, especially among underserved areas and populations. ²³ According to the US Department of Health and Human Services, the physician shortage is a significant concern affecting specialist access. ²³ It is therefore recommended that PCPs and endocrinologists, as frontline physicians, be trained to identify those at risk for NASH and advanced fibrosis by using risk stratification algorithms, managing patients with low risk in the primary care setting, and making referrals for those diagnosed with intermediate and high-risk groups to liver specialists and multidisciplinary teams.^{11,12,23,31,32}

At the Public Health Level

NAFLD is a preventable chronic liver disease.^4,11 It has become a world public health issue. Despite its increasing prevalence and global health burden, NAFLD has not received adequate attention from public health perspectives. Public health policies for the prevention of NAFLD are insufficient.^11,31 Public awareness about the disease and recognition of NAFLD as a chronic disease is also lacking. Inadequate strategies to create awareness, under-recognition of the disease by the public, lack of population screening, and poor disease surveillance lead to insufficient measures to prevent the disease. It also leads to delayed diagnosis in patients with NAFLD until the disease progresses to advanced stages.^11,12,31 On the NAFLD preparedness index parameter, a third of countries scored zero, and no countries had a comprehensive public health response for NAFLD. ¹² The scarcity of global as well as national strategies, lack of prioritization by the general health providers, and fragmented public health strategies are the significant issues in addressing the NAFLD epidemic.^11-13,31

Evidence indicates that there are health disparities in chronic liver diseases. These liver health disparities will intensify the burden of NAFLD.^19,23,40-42 One of the barriers to recommending evidence-based intervention for chronic liver disease is insufficient federal funding for health disparities research. It is closely tied to the under-recognition of liver-related diseases at the public level.^41,42 There is a pronounced rise in mortality rates from 2003 to 2022, with a rising trend noticed in Asian American Pacific Islanders (AAPI), American Indian and Alaska Natives (AI/AN), and the White population. ⁴¹ In addition to disparities in disease burden, there are marked racial, ethnic, gender, and geography-based disparities related to access to treatments, and liver transplantation.^41,42

Opportunities to Address Gaps in Managing NAFLD

Utilize Effective Models of Care, Care Pathways, and Evidence-Based Guidelines

There are models of care, clinical care pathways, and clinical practice guidelines available to diagnose and manage NAFLD in primary care settings, endocrinology clinics, obesity medicine clinics, and gastroenterology practices in preventing and managing NAFLD/ NASH.^12,31,32 These are excellent tools to improve healthcare practitioners’ awareness of NAFLD/NASH and guide them in assessing and managing the disease in their clinical practices.^12,31,32

Models of Care and Clinical Care Pathways

The evidence-based models of care help address the increasing need for providing best-practice care for patients within various healthcare settings. These models of care are proposed for clinicians and researchers to provide structured care from diagnosis to treatment of NAFLD and NASH.^12,14,32,72 The multidisciplinary clinical care model led by the primary care healthcare provider has been reported to be very effective for screening, diagnosing, and treating patients during each phase of care. ¹⁴ In this care model, the primary care provider will consult with endocrinologists, hepatologists, gastroenterologists, cardiologists, dieticians, exercise therapists, general practitioners, and psychologists. This will facilitate integrated holistic care and personalized attention to diagnose and manage NAFLD patients.^14,32 Close collaboration with the primary care providers will provide opportunities for reinforcement and adherence to medications, nutrition, and exercise. ¹⁴

Lazarus et al (2021) synthesized findings from seven comprehensive models of care for managing patients with NAFLD. They outlined eight recommendations under four categories for healthcare providers and policymakers seeking to design and implement effective care. These recommendations outlined how patients with NAFLD must be managed along the care cascade from diagnosis to management. (1) What services do NAFLD patients require? (2) Where should these services be provided? (3) Who provides the services? (4) How are these services integrated and coordinated within the healthcare system? ¹² This model of care highlights the importance of care pathways and early diagnosis as the first step in preventing the progression of NAFLD. The pathway underscores primary care physicians’ role in delivering preventive care, diagnosing early fibrosis, preventing disease progression and metabolic comorbidities, and linking them to specialists and multidisciplinary teams. This model also describes the importance of effective communication and care coordination within different healthcare systems for achieving the best possible outcomes. ¹² A road map to comprehensive care for NAFLD and NASH from diagnosis to management with 8 recommendations is presented in Table 3.

Table 3.

Comprehensive and Effective Models of Care for Nonalcoholic Fatty Liver Diseases.

What	Where	Who	How
Establish patient-centered pathways tailored to the patient’s disease stage	Articulate the roles of and interactions between primary, secondary, and tertiary care providers	Define the composition of the multidisciplinary team responsible for managing NAFLD patients (hepatologist, gastroenterologist, specialist in metabolic medicine, dietician, endocrinologist, cardiovascular expert, exercise physiotherapist, NASH nurse-led care models	Establish systems for coordinating and integrating care across the healthcare system
Develop guidance on screening and testing patients with non-invasive tests	Establish where the colocation of services for the treatment of NAFLD and common comorbidities is feasible and is tailored to the patient’s needs		- Coordination at various levels (primary, secondary, and tertiary) at different specialties (general practitioners, hepatology, endocrinology, cardiology, and dietetics)
Develop guidance on treatment strategies related to the patient’s stage	For example, diabetic clinic, endocrinology clinic, multidisciplinary metabolic hepatology clinic, teleconferencing for dietary and lifestyle modification interventions		-Offer services (one-stop-shop) at multidisciplinary facility
Outline prevention actions in primary care and community settings to prevent disease progression

Adapted from the article: Lazarus JV, Anstee QM, Hagström H, et al. Defining comprehensive models of care for NAFLD. Nat Rev Gastroenterol Hepatol. 2021;18(10): 717-729.doi:10.1038/s41575-021-00477-7.

The American Gastroenterology Association, comprising a multidisciplinary panel of experts, also developed clinical care pathways for primary care providers to screen, diagnose, stage fibrosis risk and referral, and manage NAFLD.^32,73 This clinical care pathway is a great resource recommended for use among healthcare providers.^31,32,73

Clinical Practice Guidelines

The American Association of Clinical Endocrinology (AACE) and the American Association for the Study of Liver Disease (AASLD) have developed clinical practice guidelines for diagnosing and managing NAFLD patients in primary care settings and endocrinology clinics. ³¹ This guideline described 34 easy-to-use evidence-based recommendations to diagnose and manage persons with NAFLD and/or NASH. As NAFLD is linked to obesity and type 2 diabetes, it was reinforced in the guideline that primary care physicians and endocrinologists must play a crucial role in identifying persons at risk and preventing the development of liver cirrhosis and comorbidities. ³¹

Training for Healthcare Professionals

Training for healthcare professionals is crucial to mitigate risk and reverse fibrosis progression. ³¹ The development and implementation of continuing medical education programs and attending conferences will update primary care providers with clinical best practices and updated evidence.^11,31,68 The training will support the primary care providers in initiating the discussions with patients early enough on the benefits of adhering to lifestyle modification and preventing NAFLD progression.^11,31,68

Improve Patient-Provider Communication

Many patients with NAFLD have significantly poor knowledge about the disease, its progression, and its complications. Therefore, promoting patient educational programs about the disease will ensure quality outcomes.^11,12,31,68 Improving patient-provider communication about the liver fibrosis stage, its associated risks, and how to mitigate the risk through telehealth or in person is one of the effective steps in managing NAFLD.^12,68,71

Early Screening, Diagnosis, and Treatment of NAFLD

Simple, cost-effective, and accurate diagnostic tools are available for early screening and diagnosing people at risk for NAFLD and other comorbidities.^2,53 It is crucial that healthcare providers screen and detect the disease, identify those at the highest risk of cirrhosis and other metabolic complications, and refer patients to hepatology or metabolic specialists.^12,31,68 Frontline PCPs or endocrinologists must utilize the implementation of these tools because most of the patients with NASH and stages F2-F4 of liver fibrosis concentrate in primary care clinics and endocrinology.^2,12,31,53 Depending on individualized risk assessments, clinicians must recommend that patients participate in structured weight loss programs.^{2,4,10,14,31,32,49,64}

Studies have examined the effects of metabolic syndrome (MetS) on racial and ethnic disparities in patients with NAFLD.^19,40 Mets severity score analysis, a validated sex-race-ethnicity specific severity score, compared to MetS clinical features alone (atherogenic hyperglycemia, dyslipidemia, hypertriglyceridemia, hypertension, central obesity) is reported to be a clinically relevant tool in identifying NAFLD among racially and ethnically diverse individuals. Mets severity score analysis is recommended in patients with racial and ethnic disparities for preventing and managing NAFLD. ¹⁹

Personalized Weight Loss Management Approach

The relevance of a personalized management approach to NAFLD based on patients’ preferences and needs has been cited as a successful approach for managing NAFLD. These interventions include individualized nutrition, physical activity, and personalized counseling for behavior modification.^3,5,68 As primary care physicians are not adequately trained to provide lifestyle counseling, it is recommended to consider reimbursements for registered dieticians, exercise professionals, and behavior modification specialists when counseling patients with NAFLD. ³²

Need for Public Health Attention and Prioritization

Managing the complications of NAFLD is becoming a growing challenge for public health. With the increasing prevalence and burden that NAFLD places on the healthcare system, the design and implementation of effective models of care and standardized care pathways are recommended for quality outcomes.^12,31,35 However, a rigorous public health response to NAFLD is currently lacking. Therefore, the improvement in national strategies and prioritization by the healthcare systems is needed to manage the NAFLD burden.^11-13

The racial, ethnic, gender, and geographical disparities in liver health diseases present a significant challenge at the public health level. ⁴⁰ To address liver health disparities, intentionally targeted interventions must be implemented at the individual, interpersonal, institutional, community, and societal/governmental levels. The achievable solutions also must be set in short-term (<3 years), intermediate-term (1-3 years), and long-term (>3 years) at each level to improve the NAFLD-related care for vulnerable populations.^40-42 The root causes that drive the inequity of liver disease, such as the social determinants of health, must be understood to achieve health equity. It will require deeper analysis and collective action by professional societies. ⁴⁰ Community-based clinical trials focusing on underserved populations and collaborations with experts in health equity and implementation science will improve health equity in chronic liver diseases. ⁴⁰

Conclusion

The prevalence of nonalcoholic fatty liver disease is rising both globally and in the United States. NAFLD poses a significant challenge to patients, healthcare providers, and public health. Healthcare providers must discuss the impact of sustainable lifestyle modification strategies for preventing NAFLD progression and complications. The liver health disparities must be addressed at the provider and governmental levels to bridge the disease gap and the associated morbidity and mortality. The costs borne by the patients are unmanageably high due to delays in diagnosis and nonconfirmatory diagnosis. Evidence-based tools and resources recommended by experts and professional societies must be utilized in screening, diagnosing, and managing NAFLD. Primary care physicians and endocrinologists must use multidisciplinary models of care, clinical pathways, and evidence-based clinical practice guidelines in all clinical settings. In summary, addressing NAFLD requires deliberate actions at the individual, provider, community, and policy levels.

Ethical Statement

Ethical Approval

This manuscript is an analytic review type. Therefore, approval from the Institutional Review Board was not necessary.

Informed Consent

This manuscript is an analytic review type. Therefore, informed consent from participants was not necessary.

ORCID iD

Andrew Thomas https://orcid.org/0000-0001-5494-9623