Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently recognized as the most common chronic liver disease worldwide, affecting an estimated 38% of the adult population (Stefan et al., 2025; Younossi et al., 2023). This substantial burden has positioned MASLD as a major public health challenge and a leading indication for liver transplantation (Gadiparthi et al., 2020). According to recent data from 204 countries, year 2021 witnessed approximately 1,267.9 million MASLD cases worldwide, resulting in 138.3 thousand deaths and 3,667.3 thousand disability-adjusted life years (DALYs) (Huang et al., 2025). Concurrently, the global age-standardized prevalence reached 15,018.1 per 100,000 population, while mortality and DALYs rates were recorded at 1.6 and 42.4 per 100,000 population, respectively (Huang et al., 2025). These metrics represent significant increases of 24.3% in prevalence and 5.5% in both mortality and DALY rates since 1990, underscoring the accelerating impact of this condition on global health outcomes (Huang et al., 2025). Importantly, this epidemiological trend translates into considerable economic strain, with annual direct medical costs in the United States alone estimated to exceed $100 billion (Miao et al., 2024).

Despite substantial progress in understanding the pathophysiology of MASLD, pharmacological treatment options have remained limited (Puengel and Tacke, 2024). A significant breakthrough has been recently achieved with the conditional FDA approval of resmetirom, a selective thyroid hormone receptor-beta agonist (Keam, 2024). This novel agent induces localized hyperthyroid effects in the liver, effectively reducing lipid accumulation and fibrosis in patients with metabolic dysfunction-associated steatohepatitis (MASH) who have significant or advanced fibrosis (Kaya et al., 2025; Au et al., 2024). However, the clinical use of resmetirom is hindered by several challenges–including restricted distribution to specialty pharmacies, high retail costs, and complex preauthorization requirements from payors, thereby complicating the prescribing process and involving multiple stakeholders (Ravela et al., 2025). In this scenario, non-pharmacological interventions–particularly weight reduction through controlled caloric intake and physical activity–continue to represent the foundation of MASLD management for most affected patients (Rajewski et al., 2025; Ali et al., 2024; Stefano et al., 2023; Ratziu, 2017). Current evidence supports targeted weight reduction of 7%–10% of total body weight for most patients, with the 10% threshold specifically recommended for those with at-risk MASH, as this degree of weight loss consistently correlates with significant improvements in hepatic histology (Diaz et al., 2025). For patients with lean MASLD phenotype, a more modest weight reduction of 3%–5% may also confer measurable hepatic benefits (Diaz et al., 2025). Nutritional interventions with established efficacy include the Mediterranean dietary pattern and carbohydrate-restricted approaches–which emphasize limitation of refined carbohydrates and added sugars, particularly fructose, which has been implicated in hepatic de novo lipogenesis (Simancas-Racines et al., 2025). Specifically, clinical recommendations include minimizing consumption of sugar-sweetened beverages, ultra-processed foods, and products containing high-fructose corn syrup (Parra-Vargas et al., 2020). Notably, the therapeutic efficacy of weight loss can be optimized through the synergistic implementation of both dietary modification and structured physical activity regimens (Chen et al., 2025). Both aerobic exercise modalities (e.g., walking, jogging, cycling, swimming) (Mambrini et al., 2024; Machado, 2021) and resistance training protocols (Medeiros et al., 2025; Askari et al., 2025) have demonstrated efficacy in improving hepatic steatosis and metabolic parameters in patients with MASLD. For adults without cardiovascular or musculoskeletal contraindications, current evidence supports 150–300 min weekly of moderate-intensity aerobic activity, 75–150 min weekly of vigorous-intensity aerobic activity, or an equivalent combination thereof (Diaz et al., 2025). Concurrent resistance training performed ≥2 days weekly can also provide complementary metabolic benefits that improve hepatic and systemic outcomes (Diaz et al., 2025).

Despite robust evidence supporting non-pharmacological interventions for MASLD, their implementation in contemporary clinical settings remains suboptimal due to multiple complex challenges at both societal and individual levels. These hurdles may include–but are not limited to–organizational constraints, limited healthcare provider training, patient adherence difficulties, and insufficient integration into routine clinical workflows (Deshpande et al., 2024; Shibayama et al., 2024; Gu et al., 2023; Heredia et al., 2022; Arora et al., 2021; Stine et al., 2021; Haigh et al., 2019). Building on these premises, we carried out a qualitative evidence synthesis with three primary objectives: 1) to investigate and analyze the societal and individual barriers that may impede the implementation of non-pharmacological interventions for MASLD; 2) to characterize the facilitators that can enhance intervention adherence and effectiveness; and 3) to develop a multidisciplinary framework for integrating lifestyle interventions into MASLD clinical care pathways. Our overarching goals were to inform clinical practice standards, to guide healthcare policy development, and to stimulate targeted research initiatives that may advance the implementation of non-pharmacological management strategies across the MASLD spectrum.

A qualitative evidence synthesis was conducted through searches of PubMed, Scopus, ScienceDirect, and Google Scholar electronic databases. The literature review encompassed original research articles, reviews, meta-analyses, and systematic reviews published in English-language journals between 1 January 2015, and 15 April 2025. Selection criteria specifically targeted non-pharmacological interventions for the prevention and management of MASLD, with emphasis on dietary modification strategies and physical activity interventions. Excluded were conference abstracts, case reports, editorials, letters, and non-peer-reviewed materials (e.g., preprints). The detailed search strategy and keywords are presented in Table 1, while Table 2 describes the construction of search strings and the application of filters for each database. Following an initial screening of titles and abstracts, full-text articles deemed potentially relevant were assessed. Data extraction prioritized identifying barriers and facilitators influencing the implementation of non-pharmacological interventions. A thematic synthesis approach was used to analyze the extracted data on barriers and facilitators. Relevant excerpts from the included studies were inductively coded to identify recurring patterns and concepts related to the non-pharmacological management of MASLD. Codes were compared across studies and refined through an iterative process to ensure consistency and rigor in theme development. Thematic analysis continued until no new themes emerged, indicating thematic saturation. The identified barriers and facilitators were then systematically reviewed and organized using a dual-level taxonomy that distinguishes between individual-level and societal-level determinants. Finally, the findings were synthesized narratively to inform the design of a multidisciplinary framework for integrating lifestyle interventions into MASLD clinical care pathways.

The analysis identified 67 barriers (Table 3) and 64 facilitators (Table 4) relevant to the implementation of non-pharmacological interventions for MASLD. For descriptive clarity, these factors were classified as either societal or individual. Importantly, the relationship between societal and individual factors was characterized by substantial interconnectedness, with numerous elements demonstrating bidirectional influences. In this context, addressing individual-level barriers may contribute to alleviating broader societal challenges, while interventions at the societal level have the potential to diminish individual obstacles. For instance, healthcare system barriers such as “limited reimbursement for lifestyle interventions” (Gobble et al., 2022; Freeman et al., 2021) at the societal level directly impact individual-level treatment accessibility, while psychological factors like “low motivation for sustained lifestyle change” (Tincopa et al., 2021; Hardcastle et al., 2015) at the individual level can undermine the effectiveness of even well-designed societal interventions. Notably, the implementation of non-pharmacological interventions for MASLD revealed a complex interplay where factors frequently function as both barriers and facilitators depending on context, implementation strategy, and specific circumstances. This duality creates a dynamic intervention landscape requiring nuanced understanding for effective clinical practice. The digital environment presents a notable example of this dual role phenomenon. In this regard, digital technologies appear in both tables–as potential barriers when characterized by “limited access to evidence-based digital health tools” (Giebel et al., 2023) and “poor integration of lifestyle tracking apps with healthcare systems” (Magrabi et al., 2019), yet simultaneously as facilitators through “mobile apps for tracking dietary intake and physical activity” (Kamel Boulos and Yang, 2021; Coughlin et al., 2015) and “telehealth platforms connecting patients with multidisciplinary teams” (Belber et al., 2023). This duality highlights how technological solutions can either hinder or enhance MASLD management depending on implementation, accessibility, and digital literacy levels. Cultural factors similarly operate at this intersection, functioning as barriers when “cultural dietary patterns high in refined carbohydrates and saturated fats” (Zhang et al., 2024; Clemente-Suárez et al., 2023) and “social gatherings centered around unhealthy eating” (Buksh et al., 2022; Levy et al., 2021) prevail. However, when cultural elements are integrated into intervention design through “cultural adaptation of lifestyle interventions” (Sevilla-González et al., 2025; Siddiqui et al., 2018) and “partnerships with community organizations,” (Jones et al., 2023; Lazarus et al., 2023) they become powerful facilitators for sustainable behavior change. Health problems themselves demonstrate this complex relationship. While conditions like “fatigue and reduced exercise capacity associated with MASLD” (Younossi et al., 2024) and “comorbidities limiting exercise options” (Deshpande et al., 2024) represent significant barriers, they simultaneously create opportunities for targeted interventions when addressed through “personalized exercise prescriptions based on fitness level and liver health” (Akuta et al., 2024; Glass et al., 2022) and “adapted exercise protocols for patients with comorbidities” (Farrugia et al., 2023). With respect to intervention design and implementation, physical activity programs for MASLD require well-designed approaches that acknowledge both barriers and facilitators. Within this framework, effective exercise programs must transcend the universal barriers of “increasing sedentary lifestyle” (Kim et al., 2020; Hallsworth and Adams, 2019) and “limited time for physical activity” (Patel et al., 2024) through tailored solutions that include “combined aerobic and resistance training programs” (Hashida et al., 2017) and “strategies for integrating physical activity into daily routines” (Arlinghaus and Johnston, 2018). Conversely, the emphasis on “supervised exercise sessions with progressive intensity increases” (Keating et al., 2023) reflects the need to address psychological barriers including “low motivation for sustained lifestyle change” (Livia et al., 2016) and “poor self-efficacy for exercise” (Frith et al., 2010). Nutritional interventions demonstrate similar complexity. Against barriers like “food industry influence promoting ultra-processed foods” (Grinshpan et al., 2023) and “disparities in access to healthy foods” (Kardashian et al., 2022), effective facilitators include adoption of the “Mediterranean dietary pattern emphasizing plant foods and healthy fats” (Zelber-Sagi et al., 2017) and “evidence-based nutritional advice” (Hydes et al., 2020). These approaches must be complemented by “techniques for navigating social eating situations” (Buksh et al., 2022) to overcome the barrier of “social gatherings centered around unhealthy eating” (Levy et al., 2021). The healthcare system itself encompasses significant barriers, including the “paucity of specialized MASLD clinics offering multidisciplinary care” (McPherson et al., 2022). These systemic challenges are compounded by healthcare professional practice barriers such as “inadequate training of physicians in nutrition science” (Mogre et al., 2018) and “focus on pharmacological rather than non-pharmacological interventions” (Hossain et al., 2016). Addressing these challenges requires facilitators that include “implementation of multidisciplinary MASLD care models” (Zoncapè et al., 2022) and “expanded reimbursement for evidence-based lifestyle interventions” (Patel, 2025). Professional education facilitators like “enhanced nutrition and exercise science education in medical curricula” (Khiri and Howells, 2025; Mealy et al., 2019) and “training in motivational interviewing and health behavior change techniques” (Bischof et al., 2021) directly target the identified barriers in clinical practice. Our results also revealed that current digital technologies present paradoxical implications in MASLD management, simultaneously offering therapeutic potential while introducing implementation challenges and possible adverse consequences. Accordingly, while barriers like “low digital health literacy” (Arias López et al., 2023) and “information overload from unverified online sources” (Figueroa et al., 2024) exist, thoughtfully designed technological facilitators can transform patient care through “wearable devices monitoring metabolic health parameters” (Keshet et al., 2023) and “virtual coaching for personalized exercise and nutrition guidance” (Buzcu et al., 2024; Albers et al., 2023) Behavioral support emerges as another critical domain addressing psychological barriers. Against challenges like “emotional eating patterns” (Ley et al., 2021) and “immediate reward preferences over long-term health benefits” (Michaelsen and Esch, 2023) effective facilitators include “motivational interviewing to address ambivalence about lifestyle change” (Almansour et al., 2023) and “cognitive behavioral strategies for managing emotional eating” (Smith et al., 2023). At the broader societal level, factors like “limited public health measures addressing metabolic health” (Díaz et al., 2022) and “socioeconomic barriers to gym memberships and exercise facilities” (Salmi et al., 2023) create substantial impediments to effective MASLD management. These challenges necessitate policy-level facilitators including “development of policies promoting healthy lifestyles” (Lobczowska et al., 2022) and “food policy initiatives targeting ultra-processed food reduction” (Popkin et al., 2021). Social inequalities represent particularly persistent barriers, with “higher prevalence of MASLD in marginalized populations with fewer resources” (Lorek et al., 2025) and “unequal access to healthcare professionals with MASLD expertise” (Miller et al., 2025). Addressing these disparities requires concerted efforts through facilitators like “community-based metabolic health education programs” (Okube et al., 2022) and “expanded funding for lifestyle intervention research” (Pagoto, 2011). The multidimensional nature of MASLD barriers and facilitators suggests that integrated approaches are essential for effective management. The implementation of “4P medicine (preventive, participatory, personalized, predictive)” (Lonardo et al., 2021) as a facilitator directly addresses multiple barriers across both societal and individual levels. Similarly, “personalized meal plans addressing individual metabolic profiles” (Marin-Alejandre et al., 2021) counters barriers related to conflicting nutritional messaging and cultural resistance to dietary modifications. The facilitator of “expanded preventive medicine approaches focusing on metabolic health” (Schattenberg et al., 2023) directly counteracts the barrier of “insufficient screening protocols for early MASLD detection” (Ilagan-Ying et al., 2023). Based on the available evidence, it is imperative to prioritize preventive approaches rather than focusing exclusively on treating patients with MASLD. However, expanding access to preventive care requires addressing fundamental societal barriers including “socioeconomic barriers” (Nasr et al., 2024) and “disparities in access to healthy foods” (Drisdelle et al., 2020). Importantly, the complexity of MASLD management necessitates coordinated efforts across multiple sectors and levels. While individual-level interventions like “self-monitoring tools for tracking progress” (Carpenter et al., 2022) are essential, they must be complemented by societal-level facilitators such as “public education campaigns on MASLD risk factors” (Balakrishnan and Rehm, 2024) and “workplace wellness initiatives addressing nutrition and physical activity” (Peñalvo et al., 2021). The adoption of such an integrated, multidisciplinary framework represents a critical prerequisite for addressing the multifaceted barriers that have historically hindered the real-world translation of evidence-based non-pharmacological strategies in MASLD management.

The conceptual foundation of a multidisciplinary framework for non-pharmacological MASLD management is predicated upon several interdependent core principles–including the strategic integration of diverse professional expertise with clear role delineation; patient-centered interventions that address both societal and individual barriers while leveraging facilitators; early preventive measures to halt disease progression prior to the development of significant fibrosis; tailored approaches responsive to disease severity and comorbidities; optimized monitoring protocols with specific thresholds for intervention adjustment; and judicious incorporation of digital health technologies, accounting for variability in digital literacy (Lara-Romero and Romero-Gómez, 2024). The subsequent analysis examines these fundamental aspects in detail.

This qualitative synthesis of the available evidence has provided a comprehensive elucidation of barriers and facilitators influencing the real-world implementation of non-pharmacological strategies for MASLD management. Our findings suggest that, to optimize effectiveness in real-world settings, nutritional and physical activity interventions require coordinated, multilevel strategies that concurrently address both societal and individual barriers, while strategically harnessing facilitating factors. In response, the multidisciplinary framework presented herein outlines a systematic implementation approach encompassing the full spectrum from primary prevention to the management of advanced hepatic pathology. This framework emphasizes the critical need for therapeutic customization based on disease severity, individual patient contexts, and sociocultural determinants. Moreover, it highlights the essential shift from fragmented care models toward integrated, patient-centered paradigms, wherein hepatologists, primary care providers, nutritionists, exercise physiologists, and behavioral health specialists operate collaboratively with harmonized objectives and well-defined communication pathways.

Several critical insights emerge from the reviewed evidence. Foremost among these is the recognition that early intervention is of paramount importance. Although growing evidence indicates that even cirrhosis may be reversible under certain conditions (Jung and Yim, 2017; Sohrabpour et al., 2012), initiating dietary and physical activity interventions prior to the development of significant fibrosis in patients with MASLD represents a more rational and effective strategy than attempting to reverse advanced liver pathology. Early intervention may also benefit from a lower burden of MASLD-associated comorbidities, such as fatigue and sarcopenia, which are known to impede successful lifestyle modifications. However, barriers to implementation extend beyond the individual patient level, permeating healthcare systems, professional education curricula, and broader societal structures. These observations underscore the necessity for coordinated, multi-tiered interventions. In this context, digital health technologies can offer both opportunities and challenges, presenting a complex landscape that demands meticulous implementation strategies. It is also noteworthy that cultural determinants and psychological factors might exert a profound influence on adherence to lifestyle modifications. This highlights the need for personalized, culturally sensitive approaches, rather than reliance on standardized recommendations, to enhance the effectiveness and sustainability of interventions.

The operational agenda delineated herein addresses critical knowledge gaps, particularly concerning personalized intervention strategies and implementation methodologies across diverse healthcare environments. Future research should prioritize the development and rigorous validation of cost-effective, scalable delivery models for evidence-based lifestyle interventions that can be systematically integrated into routine clinical practice within heterogeneous healthcare systems. Health policymakers and healthcare leadership should recognize that meaningful advancements in MASLD management require substantial investment in preventive strategies and lifestyle intervention infrastructure. This includes expanding reimbursement frameworks for evidence-based lifestyle programs, systematically incorporating nutrition specialists and exercise physiologists into hepatology care teams, enhancing professional education in nutritional science and physical activity prescription, and implementing public health initiatives that improve food environment quality and opportunities for physical activity. For clinicians, the current evidence synthesis offers pragmatic guidance for the implementation of multidisciplinary care models and for systematically overcoming common barriers to sustainable lifestyle modification. The proposed framework underscores that, although weight reduction remains a key therapeutic objective, an exclusive focus on anthropometric outcomes may be counterproductive. Instead, prioritizing improvements in metabolic health through sustainable dietary patterns and structured physical activity regimens represents a more constructive and patient-centered approach for many individuals with MASLD.

However, our findings need to be interpreted in the context of several limitations. First, we recognize that socioeconomic determinants may play a fundamental role in shaping adherence to non-pharmacological interventions for MASLD, as they influence access to resources, health literacy, and the ability to sustain lifestyle changes. Factors such as income disparities, limited access to healthy foods, and financial barriers to exercise facilities can exacerbate disease progression, particularly in marginalized populations. To enhance adherence, our proposed framework integrates targeted strategies like including social workers in multidisciplinary teams to address these determinants directly, alongside community partnerships and policy advocacy for equitable resource distribution. While we acknowledge that stratifying barriers and facilitators by specific socioeconomic factors would provide further insight into intervention tailoring, this level of granularity was not feasible within the scope of our current synthesis. Future research should prioritize detailed stratification to better understand how socioeconomic subgroups experience distinct challenges and to develop even more targeted approaches. Second, the effectiveness of any management framework depends on its adaptation to specific regional and cultural contexts. As each community presents a unique combination of barriers and facilitators, a one-size-fits-all approach to non-pharmacological interventions cannot be considered satisfactory. In the future, it will be essential to conduct regional studies and culturally adapt research to address the distinct socioeconomic conditions, healthcare access, and social determinants of health that characterize different populations. Third, when implementing nutritional interventions–particularly those based on the Mediterranean dietary pattern–it is crucial to emphasize to both patients and healthcare providers that the primary goal is to select foods with comparable nutritional profiles, rather than sourcing items exclusively from Mediterranean countries. This includes an emphasis on plant-based foods and minimally processed ingredients. To enhance feasibility, sustainability, and adherence, the dietary approaches should be adapted to local food availability and culinary traditions. Furthermore, recommendations to increase fruit intake should be accompanied by careful guidance. Although fruits are excellent sources of vitamins, fiber, and beneficial phytochemicals, some varieties are also high in fructose, which–when consumed in excess–may contribute to hepatic fat accumulation and disease progression. Clinical advice should therefore emphasize moderation, encourage the selection of whole, fiber-rich fruits over fruit juices or sweetened fruit products, and be individualized to consider each patient’s metabolic and clinical profile. An additional limitation of this synthesis is that the barriers and facilitators identified were not stratified according to disease duration. It is likely that patients with longstanding MASLD/MASH may experience distinct challenges–such as intervention fatigue, cumulative comorbidities, or adaptive behaviors–compared to those who are recently diagnosed, whose primary barriers may relate more to health literacy or initial motivation. Future research should specifically address how barriers and facilitators to non-pharmacological management change over the disease trajectory, to inform the design of stage-specific interventions that support sustained adherence. We also acknowledge that the evidence base synthesized in this review is derived from studies exhibiting substantial heterogeneity in design, population characteristics, intervention modalities, and outcome measures. This variability may constrain the direct comparability of findings and limit the strength of our synthesized conclusions. As with all qualitative syntheses, the potential for selection and interpretation bias during coding, theme development, and synthesis remains an inherent limitation. Furthermore, the transferability of these results to health systems and countries with different MASLD burdens may be restricted. Future research should aim to validate these identified barriers, facilitators, and proposed frameworks in diverse international contexts, especially in regions facing a high or increasing prevalence of MASLD.

In conclusion, while non-pharmacological strategies are widely acknowledged as foundational in MASLD management, their full therapeutic potential remains unrealized without systematic operationalization that addresses implementation barriers and leverages facilitators. This necessitates progressing beyond broad conceptual acceptance toward the adoption of evidence-based frameworks that afford lifestyle interventions methodological rigor comparable to pharmacotherapies–including standardized protocols, longitudinal outcome monitoring, and integration into clinical care pathways. Future efforts should concentrate on bridging persistent implementation gaps through precision nutrition strategies, culturally adapted exercise prescriptions, and digital health solutions that enhance scalability. Concurrently, advancing biomarker-driven monitoring frameworks and interdisciplinary training programs will strengthen the evidence-based application of these interventions. Collectively, these measures will enable the hepatology community to transition from viewing lifestyle interventions as theoretically foundational to delivering them as practically transformative, thereby substantially reducing the global burden of MASLD-related morbidity.