Metabolic dysfunction-associated steatotic liver disease in Egypt: Epidemiology, risk factors and management challenges

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major contributor to liver-related morbidity and mortality worldwide, with Egypt carrying one of the highest national burdens in the Middle East and North Africa region. This narrative review explores the epidemiological landscape, pathophysiological drivers, diagnostic challenges, and therapeutic gaps of MASLD in Egypt, emphasizing its complex interplay with unique local factors. High rates of obesity, type 2 diabetes, and sedentary lifestyle, combined with dietary transitions, socioeconomic disparities, and residual hepatic injury from prior hepatitis C virus infection, have positioned MASLD as a growing public health concern. Despite this, awareness of the disease remains limited among both the public and healthcare providers. Diagnostic approaches are largely restricted to conventional ultrasound and non-invasive scoring systems, with limited access advanced imaging modalities including elastography in routine practice. While lifestyle modification remains the cornerstone of treatment, adherence is low, and pharmacologic and surgical options are often inaccessible due to cost and systemic limitations. Furthermore, stigmatization and knowledge gaps contribute to delayed care and fragmented management. The absence of national guidelines, screening strategies, and integrated care models continues to impede effective disease control. Addressing MASLD in Egypt requires a coordinated public health response that integrates MASLD into broader non-communicable disease strategies. Future efforts should prioritize the development of national diagnostic and treatment pathways, population-based screening for high-risk individuals, enhanced provider education, and research into genetic and environmental determinants of disease progression. Without targeted intervention, MASLD threatens to become the next silent epidemic in Egypt’s evolving liver disease landscape.

Key Words: Metabolic dysfunction-associated steatotic liver disease; Egypt; Epidemiology; Risk factors; Obesity; Prevalence; Non-invasive diagnostics; Management

Core Tip: Egypt faces one of the highest metabolic dysfunction-associated steatotic liver disease (MASLD) burdens globally, yet disease awareness and access to care remain critically limited. Recognizing MASLD as a national health priority and integrating it into non-communicable disease strategies through population-based screening, lifestyle interventions, and provider education, offers a scalable model for other high-risk, resource-constrained settings.

INTRODUCTION

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), encompasses a spectrum of liver conditions associated with metabolic derangements[1]. The updated nomenclature seeks to improve disease recognition and management by explicitly linking hepatic steatosis to metabolic risk factors. Globally, MASLD represents a leading cause of liver-related morbidity and mortality[2]. Approximately 5% of affected individuals progress to end-stage liver disease, positioning MASLD as a primary driver of cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation[3]. Beyond its clinical impact, MASLD poses substantial economic and health-related quality of life (HRQoL) burdens[4], with a global prevalence estimated at 38%[5]. Beyond its hepatic manifestations, MASLD is increasingly recognized for its extra-hepatic implications, particularly as a cardiovascular risk factor[6], in heart failure[7], atherosclerosis[8], cardiovascular events[9] and even Sudden cardiac death[10]. In the Middle East and North Africa (MENA) region, prevalence is even higher around 46%[11]. Egypt, in particular, bears a disproportionate burden due to high rates of obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome[2]. The disease often remains undiagnosed until late stages due to under-recognition and limited screening practices. Given Egypt’s unique combination of epidemiological, cultural, and socioeconomic factors, tailored approaches to diagnosis and management are essential. This review aims to provide a comprehensive overview of MASLD in Egypt by examining its prevalence, risk factors, diagnostic challenges, and management gaps. It also highlights the urgent need for locally adapted guidelines and proposes directions for future research and public health interventions[12,13].

Global and national prevalence of MASLD

MASLD is projected to affect 55.4% of the global population by 2040, representing a growing public health crisis[14]. The disease’s prevalence varies widely across regions: 31.2% in North America and Australia, 28.0% in Asia Pacific, 25.1% in Western Europe, 33.1% in Southeast Asia, 29.7% in East Asia, 33.8% in South Asia, 44.4% in Latin America, and 36.5% in the MENA region[11]. The MENA region, alongside parts of Asia, is witnessing an accelerated increase in MASLD risk factors, including obesity and sedentary lifestyles[15]. According to the 2019 Global Burden of Disease (GBD) data, the global age-standardized MASLD prevalence was 15.7%, while in Arab countries it averaged 27.2%, ranging from 13.5% to 36.2%[16]. Rapid lifestyle transitions, nutritional shifts, and urbanization are key drivers of this trend[17]. Despite the high regional burden, comprehensive data on MASLD remain limited[18]. Studies evaluating prevalence of steatotic liver disease (SLD) in Egypt are scarce and included only small numbers. Between 2017 and 2020, the prevalence of obesity and MASLD rose together with about 70% of obese adolescents affected by MASLD[19]. Using liver stiffness measurement and controlled attenuation parameter by FibroScan, SLD was diagnosed in 47.5% of 120 young adults[20]. Larger and more detailed population studies are needed to assess the actual prevalence of SLD and MASLD and its impact on liver disease in Egypt.

A recent analysis showed an increase in MENA MASLD prevalence from 35.4% (2008-2016) to 46.2% (2017-2020). Using GBD-2019 data, the region was estimated to have 141.5 million MASLD cases, with Egypt accounting for the highest national burden at 25.7 million cases, followed by Türkiye and Iran[5]. MASLD prevalence exceeded 40% in 10 of 21 countries, with the highest rates reported in Kuwait (45.4%), Egypt (45.0%), Qatar (44.4%), and Jordan (43.3%). This trend underscores MASLD as a major contributor to global liver disease burden[11]. Key contributors to this epidemic include coexisting metabolic conditions such as T2DM and obesity[5,21]. A recent meta-analysis indicated a 38% global prevalence between 2016 and 2019 reflecting a 50% increase compared to 1990-2006 figures[11].

RISK FACTORS FOR MASLD IN EGYPT

Metabolic risk factors

Obesity and central adiposity: MASLD is more prevalent in overweight or obese individuals, with global prevalence reaching 50% in this group and nearly 60% among individuals with T2DM[22]. Obesity is a major driver of MASLD, particularly in Egypt, which ranks fourth globally in overall obesity prevalence and first among women, excluding sparsely populated Pacific Island nations[23]. Very few studies have been published about the burden of diseases in Egypt in general, and the burden of obesity is even more complex as the impact of obesity is a result of its comorbidities[24]. In Egypt, approximately 71.2% of adult men and 79.4% of adult women are overweight, with obesity rates of 26.4% and 48.4%, respectively[20]. While obesity is a well-established MASLD risk factor, a subset of individuals with a normal body mass index (BMI) termed “lean MASLD” also develop the disease. This is particularly relevant in those with BMI < 25 kg/m² (non-Asian) or < 23 kg/m² (Asian)[25]. In these individuals, factors such as visceral adiposity, adipose dysfunction, sarcopenia, and early β-cell failure likely contribute to both MASLD and T2DM development[25].

Type 2 diabetes and insulin resistance: MASLD frequently coexists with T2DM and other cardiometabolic risk factors, reflecting their shared pathophysiological basis in insulin resistance, inflammation, and obesity[26,27]. Patients with MASLD have a 2 5-fold increased risk of developing T2DM, particularly in the presence of advanced fibrosis[28]. Conversely, individuals with T2DM and coexisting MASLD especially with fibrosis demonstrate poorer glycemic control over time, as indicated by higher glycosylated hemoglobin levels[29]. Epidemiological data show that MASLD affects up to 70% of patients with T2DM, and biopsy-based studies report prevalence rates exceeding 90%[30]. As a result, recent clinical guidelines recommend routine MASLD fibrosis screening in all T2DM patients[31,32]. It was predicted that there are 24.96 million cases of MASLD with T2D in the MENA region[5]. However, there is limited data on the extent of MASLD between diabetics in Egypt.

Dyslipidemia and hypertension: Dyslipidemia, commonly underdiagnosed in Egypt, affects up to 37% of the population, including children and adolescents[33]. The dyslipidemic profile in MASLD typically features elevated low-density lipoprotein cholesterol and triglycerides, along with reduced high-density lipoprotein cholesterol levels, observed in 60%-70% of patients[34]. Hypertension, another independent MASLD risk factor, has been strongly associated with hepatic steatosis and fibrosis[35]. Studies have shown that 50% of hypertensive patients have MASLD[36]. Several studies have demonstrated a more pronounced association between hypertension and adverse liver outcomes compared to other metabolic traits[37-39]. However, Egypt-specific data on hypertension prevalence in MASLD cohorts remain limited.

Lifestyle and dietary factors

Modern lifestyles marked by rapid eating and sedentary habits have significantly contributed to the MASLD epidemic. Several studies have shown that eating at a fast pace is associated with higher caloric intake, insulin resistance, and metabolic dysregulation[40-42]. Frequent fast eaters (≥ 2 times/week) are at 81% increased risk for MASLD, with meta-analyses confirming this association (odds ratio = 1.22; 95% confidence interval: 1.07-1.39)[43]. Ultra-processed foods (UPFs), rich in sugars, fats, and additives but low in fiber and micronutrients, also promote hepatic steatosis by enhancing de novo lipogenesis and worsening insulin resistance[44]. High UPF consumption is linked to obesity, MASLD, and related complications in both pediatric and adult populations[45,46]. The widespread adoption of sedentary lifestyles and nutrient-poor diets, combined with low physical activity levels and rising pediatric obesity, further amplifies the risk and progression of MASLD in Egypt[47]. Egypt like many developing nations is experiencing significant changes in dietary habits characterized by increased calorie-dense food consumption alongside challenges such as food prices and limited access to diverse, nutrient rich foods[48]. These shifts have profound fat consumption patterns and their health implications within the Egyptian context[49].

Genetic and ethnic factors

Ethnic variability in MASLD progression: Ethnic differences significantly affect MASLD susceptibility and outcomes. A meta-analysis of United States data revealed that Hispanic individuals had the highest MASLD prevalence (22.9%) compared to White (14.4%) and Black (13.0%) populations[50]. This disparity correlates with differences in the distribution of genetic risk alleles, including PNPLA3, TM6SF2, HSD17B13, MBOAT7, and GCKR[50,51]. A longitudinal study by Nguyen et al[52] found that while Black patients have a lower MASLD prevalence, they experience worse overall and non-liver-related mortality outcomes once diagnosed. These findings highlight the role of structural inequities, comorbid conditions, and delayed access to care[53].

Genetic predisposition in the Egyptian population: Several genetic variants are implicated in MASLD, including PNPLA3 (rs738409C>G), TM6SF2 (rs58542926C>T), HSD17B13 (rs9992651G>A), and GCKR (rs1260326T>C)[54-58]. Although the prevalence and impact of these polymorphisms in the Egyptian population remain underexplored[59], global genome-wide association studies have validated them as significant risk factors for MASLD[60]. Notably, PNPLA3 (rs738409) shows the strongest correlation with disease severity, as supported by predicted protein-protein interactions in network analyses[61].

Environmental and socioeconomic factors

Urban rural differences: Urbanization in Egypt has contributed significantly to the rising burden of MASLD. Rapid socioeconomic shifts, characterized by smaller household sizes, increased employment rates, and higher disposable income, have resulted in reduced time for home-cooked meals and increased reliance on processed or ready-to-eat foods[62,63]. These transitions, coupled with a sedentary lifestyle and increased consumption of calorie-dense diets, have escalated MASLD-associated metabolic risk factors[64,65]. With respect to men, women of fertile age show a lower susceptibility to develop MASLD, pointing to the relevance of the hepato-ovarian axis and of estrogen signaling in female liver physiopathology[66]. In the female liver, estrogen’s effects are mainly mediated by the estrogen receptor alpha, whose activation contributes to reducing lipid synthesis, uptake, and storage while promotes lipid catabolism and export[67]. Despite this general protection, women’s risk of developing MASLD varies throughout their reproductive lifespan[68]. Moreover, women with MASLD often exhibit different clinical and pathological features compared to men[68].

HEALTHCARE DISPARITIES IN UNDERSERVED AREAS

The regional burden of MASLD is modulated by disparities in food security and healthcare accessibility. In high socio-demographic index (SDI) countries, MASLD is often driven by consumption of ultra-processed, nutrient-poor diets[65]. Conversely, in low-SDI settings, underdiagnosis may explain lower reported MASLD prevalence, despite increasing exposure to risk factors[69]. Food insecurity in these populations contributes indirectly by exacerbating obesity and T2DM, both primary drivers of MASLD[70]. Furthermore, limited healthcare infrastructure and insufficient access to diagnostic tools in rural and underserved regions of Egypt may result in significant underreporting of MASLD cases[65]. Addressing these gaps through targeted health policy reforms is essential.

LIMITED AWARENESS AMONG PHYSICIANS AND THE PUBLIC

Low levels of awareness about MASLD among both healthcare providers and the general population remain a critical barrier. Medical education curricula often allocate minimal time to MASLD, resulting in inadequate physician preparedness[71]. Public knowledge is also limited, with surveys indicating widespread misconceptions, such as the belief that MASLD only occurs in older individuals or runs strictly in families[71-74]. A regional survey identified substantial knowledge gaps in the diagnosis and management of MASLD among healthcare professionals in Egypt, Saudi Arabia, and Türkiye[75]. In response to this global awareness deficit, a 91-country panel of over 200 multidisciplinary experts achieved consensus in 2022 on the urgent need for education, advocacy, and public engagement surrounding MASLD[18]. Figure 1 illustrates the multifactorial risk landscape contributing to MASLD in Egypt.

Figure 1 The multifactorial risk landscape contributing to metabolic dysfunction-associated steatotic liver disease in Egypt. MASLD: Metabolic dysfunction-associated steatotic liver disease; DM: Diabetes mellitus.

PATHOPHYSIOLOGY OF MASLD IN THE EGYPTIAN CONTEXT

Central mechanisms: Insulin resistance, lipotoxicity, and inflammation

The pathogenesis of MASLD is underpinned by a complex interplay of genetic, metabolic, and environmental factors. At its core lies a cycle driven by insulin resistance, hyperinsulinemia, lipotoxicity, and low-grade chronic inflammation[76-78]. These mechanisms result in hepatic fat accumulation and promote cellular injury through oxidative stress and inflammatory cascades. Emerging evidence also implicates the gut-liver axis, particularly gut dysbiosis and increased intestinal permeability, in exacerbating hepatic steatosis and inflammation[79]. In individuals consuming unhealthy diets, the liver becomes overwhelmed by pro-inflammatory molecules and toxic lipid intermediates. This sets off a self-perpetuating cycle of hepatocellular injury, fibrogenesis, and metabolic dysfunction[80].

Unique contributing factors in Egypt

Dietary patterns and nutritional transition: Egypt faces a dual burden of malnutrition, where undernutrition (e.g., micronutrient deficiencies and stunting) coexists with high rates of obesity and overnutrition[63,81]. Over the past decades, dietary patterns have shifted markedly toward increased consumption of refined carbohydrates, sugar, and vegetable oils, largely due to subsidy-driven distortions[82]. Fructose consumption, in particular, has emerged as a key modifiable risk factor. Excessive intake of high-fructose diets has been strongly linked to obesity, insulin resistance, cardiovascular disease, MASLD, and even cancer[83,84]. These dietary imbalances have contributed to Egypt’s alarmingly high obesity rates and rising prevalence of MASLD.

Residual liver injury from chronic hepatitis C virus: Egypt’s longstanding hepatitis C virus (HCV) epidemic has left a significant imprint on the hepatic landscape. Hepatic steatosis has been reported in 30% to 70% of patients with chronic HCV, especially those infected with genotype 3[85]. Although direct-acting antivirals have successfully achieved viral eradication, the evolution of hepatic steatosis post-sustained virologic response remains contentious[86]. Notably, both pre- and post-treatment steatosis have been associated with increased risk of cirrhosis and HCC[87,88]. While some studies report resolution or reduction of steatosis following HCV clearance[89], others describe persistence or even emergence of steatosis, independent of weight changes[90]. Recent data suggest that individuals with a history of HCV infection and concurrent MASLD are at greater risk of significant liver fibrosis than those with HCV or MASLD alone. In one study, fibrosis prevalence reached 58% in the MASLD group, compared to 45% in the HCV-steatosis group and 39% in those without steatosis[91]. This co-existence likely creates a synergistic effect through mechanisms involving oxidative stress, steatosis, and hepatic metabolic dysregulation[91].

Micronutrient deficiencies (vitamin D, E, B12, folic acid): Low serum vitamin D levels have been frequently associated with increased MASLD risk[92]. Although the exact mechanisms remain under investigation, vitamin D appears to exert anti-inflammatory and anti-fibrotic effects on hepatic stellate cells, in addition to modulating insulin sensitivity and lipid metabolism[92]. Egyptian studies confirm that MASLD patients often present with deficient vitamin D levels[93]. Vitamin E, known for its antioxidant properties, has demonstrated beneficial effects in improving aminotransferase levels, hepatic steatosis, and fibrosis in MASLD[94-96]. Egyptian clinical studies corroborate these findings, showing improvement in both biochemical and histological parameters following vitamin E supplementation. Data on vitamin B12 and folate are more limited. While some studies indicate that low levels of these micronutrients may increase all-cause mortality in MASLD patients[97], interventional studies report inconsistent outcomes. For example, one Egyptian trial noted reduced fasting glucose, oxidative stress markers, and liver steatosis following vitamin B12 supplementation; however, the differences did not reach statistical significance compared to placebo[98].

CLINICAL PRESENTATION AND DIAGNOSIS OF MASLD

Clinical presentation

Diagnosing MASLD and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), presents substantial challenges. These include low disease awareness among clinicians, limited consensus on optimal diagnostic tools, and non-availability of approved pharmacological agent like resmetirom[99-101]. Consequently, MASLD is often discovered incidentally during routine blood tests or imaging performed for unrelated reasons[102]. Traditionally described as asymptomatic, MASLD is increasingly recognized to impact patients’ HRQoL even at early stages. Some patients report subtle symptoms such as fatigue and vague abdominal discomfort, including pain localized to the right upper quadrant[103,104]. These non-specific manifestations, combined with under-recognition, contribute to delayed diagnosis and care.

MASLD-associated HCC

Although the annual incidence of MASLD-related HCC is lower than that observed in chronic viral hepatitis (ranging from 0.7% to 2.6% in cirrhotic patients and 0.1 to 1.3 per 1000 patient-years in non-cirrhotic MASLD), the sheer size of the MASLD population suggests a rising future burden[2,105,106]. The pathogenesis of MASLD-related HCC is multifactorial, involving chronic inflammation, lipotoxicity, endoplasmic reticulum stress, organelle dysfunction, and genetic instability[106]. Unlike viral hepatitis, MASLD-related HCC often occurs in non-cirrhotic livers, making early detection more challenging. Moreover, MASLD-HCC is frequently diagnosed at advanced stages due to the absence of routine surveillance in non-cirrhotic individuals[107]. Recent transplant registry data (2013-2022) reveal a striking trend: While MASLD accounted for 19% of liver transplant candidates without HCC in 2013, this proportion rose to 27% by 2022. Among candidates with HCC, MASLD-related cases increased from 10% to 31% during the same period underscoring its growing contribution to the HCC burden[3].

Patient-reported outcomes

Chronic liver disease significantly impairs HRQoL and patient-reported outcomes (PROs). A multicenter study in Saudi Arabia, Türkiye, and Egypt revealed that younger age, female sex, advanced fibrosis, comorbidities, and lack of physical activity were independently associated with worse PROs among MASLD patients[108]. MASLD patients frequently experience fatigue, emotional distress, and reduced productivity, particularly in the presence of advanced fibrosis or extrahepatic comorbidities[109]. These impairments are not always captured by traditional clinical assessments, underscoring the importance of integrating PROs into both clinical trials and real-world care settings.

DIAGNOSTIC CHALLENGES OF MASLD

Limited access to advanced diagnostic tools

While advances in non-invasive diagnostic modalities have improved the evaluation of liver fibrosis, their accessibility remains limited in many parts of Egypt. Tools such as the enhanced liver fibrosis test and FIBROSpect II go beyond routine biochemical markers and can more accurately assess fibrotic progression. However, their integration into clinical practice is constrained by cost and availability[32]. Imaging modalities including vibration-controlled transient elastography (FibroScan), magnetic resonance elastography, and magnetic resonance imaging (MRI)-derived proton density fat fraction are useful in quantifying steatosis and fibrosis, but are often confined to tertiary centers. In most healthcare settings, diagnosis still relies heavily on conventional ultrasound, despite its limitations in detecting mild steatosis and advanced fibrosis[32,110,111].

Reliance on non-invasive scores (fibrosis-4, NAFLD fibrosis score)

Several non-invasive scoring systems have been developed to stratify fibrosis risk in MASLD patients and reduce dependence on liver biopsy[112]. Among the most widely used are: Fibrosis-4 index: This score incorporates age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. A value < 1.3 suggests low risk for advanced fibrosis, while a value > 2.67 is predictive of advanced disease[113,114]. However, reliance on age may result in overestimation in elderly patients due to age-related elevations[113] which led to modification of the low cutoff point in those over 65 years old to be 2 instead of 1.6. NAFLD fibrosis score (NFS): Based on age, BMI, fasting glucose, platelet count, albumin, and AST/ALT ratio, this score distinguishes between low and high-risk patients. Scores ≤ -0.640 rule out significant fibrosis, while those > -0.640 indicate higher risk[115,116]. NFS correlates with cardiovascular morbidity and mortality but performs poorly in assessing hepatic steatosis[117]. Both fibrosis-4 and NFS are endorsed by the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) as initial triage tools in primary care to identify patients who may require hepatology referral[32,118].

Role of ultrasound as the primary diagnostic modality

Ultrasound remains the frontline imaging technique for diagnosing hepatic steatosis and for HCC surveillance. In moderate to severe steatosis, ultrasound offers high sensitivity (approximately 90%) and specificity (approximately 95%), but sensitivity drops to 50%-62% in mild cases[110,119]. Diagnostic accuracy is also limited by operator dependency and reduced performance in patients with obesity or low-grade steatosis. For HCC surveillance, both AASLD and EASL recommend biannual abdominal ultrasound, with or without serum alpha-fetoprotein[120]. However, ultrasound alone may miss early-stage HCC, especially in patients with non-cirrhotic MASLD. In cases of inconclusive ultrasound, MRI or computed tomography should be considered[121]. Interestingly, recent studies suggest that patients with MASLD-related cirrhosis exhibit slower tumor growth compared to those with viral etiologies, raising concerns about appropriate surveillance intervals and diagnostic sensitivity[121].

MANAGEMENT OF MASLD IN EGYPT

Effective management of MASLD requires a multidisciplinary approach that encompasses prevention, early diagnosis, lifestyle modification, pharmacological treatment, comorbidity control, and public health engagement. Given Egypt’s unique socioeconomic context, tailored interventions that are locally adaptable and scalable are essential[122].

Lifestyle interventions

Lifestyle modification remains the foundational intervention for MASLD. The increasing prevalence of the disease is closely associated with sedentary behavior, caloric excess, and poor dietary quality[123,124]. Hypocaloric diets, which reduce overall caloric intake, have demonstrated benefit in hepatic steatosis reduction[125]. The Mediterranean diet rich in unsaturated fats, fiber, and antioxidants has shown superior outcomes in reducing hepatic fat and improving metabolic profiles[126]. Intermittent fasting, including 5:2 protocols and time-restricted eating, has also shown potential benefits for hepatic and glycemic parameters[127]. Although no single diet has been universally established as superior, all effective nutritional strategies share the aim of promoting weight loss and improving hepatic and systemic inflammation[31]. Physical activity contributes significantly to these improvements by enhancing insulin sensitivity and reducing intrahepatic lipid accumulation[128]. Nonetheless, the literature remains inconclusive on the optimal frequency, intensity, and type of exercise for MASLD, requiring personalization[129]. Although evidence suggests that a weight loss of ≥ 5% improves steatosis, ≥ 7% is needed to resolve steatohepatitis, and ≥ 10% can lead to fibrosis regression or stabilization[130], unfortunately, adherence is low; over 80% of MASLD patients fail to sustain lifestyle modifications long-term[131], highlighting the need for culturally adapted behavioral counseling and patient support programs.

Pharmacological therapies

While lifestyle change is essential, pharmacologic interventions are needed in patients with more advanced disease or insufficient response. Despite the failure of several drug candidates in clinical trials[132], recent progress has been made. Resmetirom, a selective thyroid hormone receptor-β agonist, was recently approved by the United States Food and Drug Administration as the first pharmacotherapy for MASH, demonstrating efficacy in reducing hepatic fat and improving fibrosis[133,134]. Some anti-diabetic medications have shown benefits in reducing liver disease progression and non-hepatic causes of morbidity and mortality, especially cardiovascular disease[135]. Pioglitazone, a peroxisome proliferator-activated receptor γ agonist, has been shown to improve steatosis, hepatocellular ballooning, and inflammation, though its effects on fibrosis are less consistent[31,136]. Its clinical use is tempered by adverse effects such as bone loss and increased fracture risk, particularly in postmenopausal women[137]. Vitamin E has also demonstrated benefit in MASLD. Meta-analyses confirm improvements in ALT, AST, steatosis, and fibrosis when administered at ≥ 600 IU/day or over ≥ 12 months[138]. In Egypt, studies have shown that vitamin E, alone or in combination with other agents, leads to favorable biochemical and histological improvements in both adult and pediatric populations[96,139].

Management of comorbidities

The close relationship between MASLD and metabolic comorbidities necessitates a comprehensive treatment strategy. Statins are pivotal for managing dyslipidemia in MASLD patients and are safe even in those with elevated liver enzymes. Beyond lipid-lowering, they exhibit anti-inflammatory and anti-fibrotic properties[140-142]. Hypertension, a common comorbidity, should be treated aggressively. Blockade of the renin-angiotensin system improves adipokine profiles and inflammatory responses, potentially reducing hepatic fibrosis in MASLD[143]. In diabetic patients, glucagon-like peptide-1 receptor agonists, including liraglutide, semaglutide, and dulaglutide, are gaining prominence due to their dual benefits in glycemic control and hepatic fat reduction. These agents also provide cardiovascular protection and have been endorsed in MASLD-related guidelines for high-risk patients[144-147]. Sodium-glucose co-transporter 2 inhibitors, by improving insulin sensitivity and reducing hepatic steatosis, represent another promising option under ongoing investigation[148].

Bariatric surgery

Bariatric surgery is a highly effective intervention for obese patients with advanced MASLD or MASH. It leads to substantial and sustained weight loss, reduces hepatic steatosis, improves insulin resistance, and has been associated with histological improvements. Studies report that 80% of patients experience resolution of MASH within one-year post-surgery, and 30%-40% show regression in liver fibrosis[149,150]. Sustained weight loss of up to 30% can be achieved through surgical intervention, far exceeding outcomes of lifestyle therapy alone[151]. Despite these benefits, long-term data on the safety and efficacy of different bariatric procedures in MASLD are limited, particularly in patients with advanced fibrosis or cirrhosis. Therefore, surgery should be considered following a thorough benefit-risk evaluation by a multidisciplinary team, ideally involving hepatologists, bariatric surgeons, and endocrinologists[32]. Figure 2 shows suggested public health framework for MASLD prevention in Egypt.

Figure 2 Suggested public health framework for metabolic dysfunction-associated steatotic liver disease prevention in Egypt. MASLD: Metabolic dysfunction-associated steatotic liver disease.

Barriers to MASLD care in Egypt

A recent global survey highlighted that the stigma associated with MASLD is largely rooted in its link to obesity, with 38% of healthcare providers perceiving the disease as stigmatizing compared to only 8% of patients[152]. The perception of MASLD-related stigma varies across patient groups, medical specialties, and geographic regions, further complicating its recognition and management[152]. Another factor contributing to limited awareness was the absence of approved pharmacological therapies for MASLD, which diminishes both urgency and attention to the disease[153]. Compounding these issues is a persistent knowledge gap in the identification, diagnosis, and management of MASLD, as observed in several high-burden countries including Egypt, Saudi Arabia, and Türkiye[75]. In Egypt, these challenges are exacerbated by the lack of a national screening program and the absence of locally adapted clinical guidelines. Diagnostic and therapeutic options remain limited, particularly outside urban tertiary centers, resulting in delayed diagnosis and fragmented care. In addition, lack of clinical trials assessing the current situation in Egypt is still a barrier for well-defined data analysis and outcomes.

Future perspectives for MASLD in Egypt

Future directions should prioritize the integration of MASLD into Egypt’s national non-communicable disease agenda. A comprehensive national strategy is urgently needed one that incorporates population-level screening for high-risk groups, standardized non-invasive diagnostic pathways, and evidence-based, locally adapted clinical guidelines. Efforts must also be directed toward strengthening provider education, expanding public health campaigns to reduce stigma and promote lifestyle change, and investing in accessible diagnostic and therapeutic infrastructure beyond tertiary care settings.

Research priorities should include longitudinal cohort studies to better characterize MASLD progression in the Egyptian population, genome-wide studies to elucidate ethnic and genetic determinants, and implementation science to evaluate the effectiveness of policy interventions. Egypt’s successful model of HCV elimination demonstrates that with political will, multisectoral collaboration, and a clear roadmap, scalable and impactful liver health strategies are achievable. MASLD now demands similar attention, before its silent epidemic translates into a national crisis of liver failure, HCC, and increasing healthcare costs.

CONCLUSION

MASLD represents an urgent yet underrecognized public health challenge in Egypt. With one of the highest national burdens in the MENA region, Egypt faces a convergence of risk factors including obesity, diabetes, sedentary lifestyles, and nutritional transitions that have amplified the prevalence and clinical impact of MASLD. The legacy of chronic HCV, widespread micronutrient deficiencies, and socioeconomic disparities further complicate the pathophysiological landscape. Despite increasing global attention, awareness of MASLD among both healthcare providers and the public remains limited, and diagnostic and treatment strategies are often fragmented, inaccessible, or inconsistently applied.