The understanding of liver steatosis, including metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as nonalcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD), has undergone significant evolution in recent years. This shift in terminology reflects a growing recognition of the systemic nature of the disease, particularly among children affected by obesity and metabolic dysfunction. Initially, NAFLD was defined by the presence of hepatic steatosis in the absence of alcohol consumption or other liver diseases, such as viral hepatitis or autoimmune liver disorders [1,2]. However, this definition often excluded children with metabolic risk factors who did not meet the strict criteria for NAFLD, leading to an underestimation of the true prevalence of liver steatosis in pediatric populations, especially among those without overt metabolic syndrome [3,4]. In response to these limitations, the term MAFLD was introduced in 2020, emphasizing the role of metabolic dysfunction as a central driver of the disease [1]. The implementation of this reclassification resulted in an expanded diagnostic scope, encompassing additional risk factors, including obesity, insulin resistance, and dyslipidemia, which have been documented to be prevalent among specific demographic groups of children and adolescents. Subsequently, in 2023, the American Association for the Study of Liver Diseases (AASLD) adopted the term MASLD, further refining the classification to align with updated diagnostic criteria and emphasizing the steatotic nature of the condition [2]. MASLD is inherently more inclusive than its predecessors, requiring fewer metabolic risk factors for diagnosis, which has led to higher detection rates. For instance, studies have reported a 13–15% increase in the identification of liver steatosis cases among children with metabolic risk factors when using MASLD criteria compared to NAFLD [4].
In addition to MASLD, nonalcoholic steatohepatitis (NASH), a more severe form of liver steatosis characterized by liver inflammation and fibrosis, has also undergone a terminological shift. NASH is increasingly referred to as metabolic dysfunction-associated steatohepatitis (MASH), aligning with the MASLD framework and emphasizing the metabolic dysfunction driving the disease [2]. This terminological evolution has been critical for ensuring future consistency in research and clinical practice, as it reflects the underlying pathophysiology of the disease and facilitates the identification of at-risk populations.
Despite the high concordance between MAFLD and MASLD definitions, estimated at over 97% discrepancies in diagnostic methodologies persist [5,6]. These differences are often attributable to the scope and inclusion criteria of each definition. NAFLD primarily focused on hepatic steatosis while excluding other liver diseases, whereas MAFLD and MASLD adopt broader approaches by incorporating metabolic dysfunction. The inconsistent use of diagnostic criteria and methods for liver steatosis impacts research, as reliance on NAFLD criteria may underestimate prevalence, particularly in populations with high obesity and metabolic syndrome rates, hindering reliable prevalence estimates. Imaging techniques such as ultrasound, while widely accessible and cost-effective, often underreport disease prevalence compared to advanced methods like transient elastography, MRI, or controlled attenuation parameter (CAP) scores [5,6].
The lack of uniform diagnostic criteria also presents challenges for tracking liver steatosis progression from childhood into adulthood. Longitudinal studies have shown that liver steatosis frequently advances without noticeable symptoms and is often identified incidentally during routine evaluations [7,8]. While the high concordance between MAFLD and MASLD definitions suggests that the transition to MASLD has not drastically altered the population of diagnosed cases, the variability in prevalence estimates across studies highlights the importance of addressing methodological inconsistencies.
This review employs the AASLD-endorsed MASLD terminology with the objective of maintaining uniformity with prevailing guidelines and aligning with the most recent understanding of the disease. The terms "NAFLD" and "MAFLD" are retained when specifically referencing studies that utilized these nomenclatures in prevalence reports or descriptive tables. Conversely, the terms "MASLD" and "MASH" are employed to reflect the most current understanding of the disease.
The variability in prevalence estimates across studies presents a challenge that can obscure the overall conclusions of this review. Although there are challenges, the findings of this study hold significant importance and provide valuable insights into the evolving understanding of pediatric MASLD. By including longitudinal studies that utilized NAFLD, MAFLD, and possible MASLD criteria, this review provides an integral analysis of the disease’s prevalence and progression across diverse populations and diagnostic methodologies. While differences in prevalence estimates may arise due to variations in diagnostic criteria, the review’s longitudinal focus offers valuable insights into the persistence and systemic impact of MASLD from childhood into adulthood.
1.2Global prevalence and long-term implicationsThe prevalence of liver steatosis is a significant concern, with estimates for MAFLD ranging from 45% in specialized clinics focused on childhood obesity to 34% in the general population of overweight or obese children and adolescents aged 1 to 19 years, regardless of the diagnostic technique used [5]. Globally, the prevalence of MASLD ranges from 8% in children to 36.1% among obese adolescents [9]. These statistics are concerning indicating the high relevance to address the systemic barriers that hinder early diagnosis and effective management. In the United States, the prevalence of MASLD among adults is projected to rise from 33.7% in 2020 to 41.4% by 2050. The number of individuals affected by advanced stages of the disease, such as MASH and fibrosis stage F2 or higher, is expected to increase by 75% during the same period. Furthermore, hepatocellular carcinoma cases are predicted to double, liver transplants to quadruple, and liver-related mortality to rise from 30,500 deaths in 2020 to 95,300 deaths by 2050 [10–15].
Central to the impact of MASLD is its silent progress which leads to severe complications such as liver cirrhosis, cardiovascular disease, and liver-related mortality [16–20]. As a multisystem disorder, it is closely linked to metabolic, renal, and cardiovascular health, contributing to long-term risks such as type 2 diabetes, dyslipidemia, and hypertension [21–24]. Pediatric patients are particularly vulnerable, as metabolic abnormalities such as insulin resistance, dyslipidemia, and hypertension significantly increase their likelihood of developing cardiovascular complications later in life, while the chronic inflammatory state associated with the disease further accelerates endothelial dysfunction, a precursor to atherosclerosis and other cardiovascular disorders [25–29]. A significant concern exists regarding the transition from pediatric to adult care, which is frequently obstructed by systemic barriers. These barriers include, but are not limited to, fragmented medical records and low follow-up rates [30–32]. A lack of awareness among healthcare providers, families, and affected individuals further delays diagnosis and treatment. On the other hand, the societal normalization of obesity, often referred to as "obesity invisibility," further obscures the risks associated with metabolic dysfunction, leading to an underestimation of its systemic impact [33–36]. Emerging evidence underscores the silent nature of this condition, with many cases progressing asymptomatically and only being identified incidentally during routine and non-routine health evaluations [37,38]. These challenges in early recognition, coupled with insufficient diagnostic criteria and the asymptomatic progression of the disease, contribute to its underdiagnosis and delayed intervention, leaving affected individuals vulnerable to severe long-term health consequences [7,39,40]. Given these severe long-term health risks, early identification and intervention are paramount to prevent disease progression and improve outcomes.
1.3Early identification of MASLD: diagnostic markers and criteriaElevated liver enzymes, such as ALT and aspartate aminotransferase (AST), are widely recognized as early markers of liver injury and disease progression [41]. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) guidelines recommend ALT thresholds of ≥26 U/L for boys and ≥22 U/L for girls, with sustained elevations over three months in overweight or obese children aged 10 years or older considered predictive of liver disease [42]. However, it is important to note that while ALT is commonly used as a biomarker for chronic liver diseases due to its ease of measurement and low cost, its diagnostic performance for identifying MASH is limited [43]. Studies have shown that ALT has a suboptimal diagnostic performance for detecting liver conditions, with an area under the receiver operating characteristic curve (AUROC) of 0.6144, sensitivity ranging from 54 to 88%, and specificity from 26 to 100% [38]. In addition, the reliance on these markers alone may overlook cases of MASLD with normal enzyme levels, highlighting the need for a more comprehensive diagnostic approach [7,45].
Body Mass Index (BMI) is a measure used to assess weight status in children and adolescents, based on age- and sex-specific percentiles from CDC growth charts. Overweight is defined as a BMI between the 85th and 95th percentiles, while obesity is classified as a BMI at or above the 95th percentile. Severe obesity is identified when BMI is at least 120% of the 95th percentile or approximately the 99th percentile. Obesity is further categorized into Class I (BMI 120%-140% of the 95th percentile or 35-40 kg/m²), Class II (BMI ≥140% of the 95th percentile or ≥40 kg/m²), and Class III obesity, which is defined as having a BMI that is at least 140% of the 95th percentile for age and sex or a BMI of 40 kg/m² or higher, whichever is lower [46].
In addition to body and liver enzyme abnormalities, metabolic syndrome serves as a critical early indicator of disease risk. This cluster of metabolic disturbances, including central obesity, insulin resistance, dyslipidemia, hypertension, and hyperglycemia, is closely linked to the development and progression of steatotic liver disease [47]. The International Diabetes Federation (IDF) defines pediatric metabolic syndrome as central obesity (waist circumference ≥90th percentile for age and sex) combined with at least two of the following: elevated triglycerides (≥150 mg/dL), reduced HDL cholesterol (<40 mg/dL for boys, <50 mg/dL for girls), elevated blood pressure (≥130/85 mmHg or above the 95th percentile for age, sex, and height), or elevated fasting glucose (≥100 mg/dL) [48]. Insulin resistance, a hallmark of metabolic syndrome, is a key driver of liver fat accumulation and fibrosis, and its presence can be assessed using Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores and fasting insulin levels [47,49]. A commonly cited cutoff for indicating insulin resistance in children includes a HOMA-IR score of 2.5 or higher [42]. Although, some studies suggest that a score above 3.0 might be more indicative of clinically significant insulin resistance in pediatric populations at higher risk, including those with obesity [50]. Furthermore, systemic inflammation, as indicated by elevated C-reactive protein (CRP) levels (range of 3 to 10 mg/L) [51], contributes to endothelial dysfunction and amplifies the risk of cardiovascular complications [8,52].
1.4Biomarkers and advanced diagnostic techniques in MASLDThe integration of liver enzyme thresholds, metabolic syndrome criteria, and other biomarkers such as genetic variants provide a comprehensive framework for early detection. Genetic variants, such as PNPLA3 and TM6SF2, are emerging as significant predictors of the condition’s progression, especially in children with obesity and metabolic disturbances [49,52]. Studies also indicate that PNPLA3 I148M variant disrupts the enzymatic activity responsible for triglyceride hydrolysis, leading to hepatic lipid accumulation and an increased risk of steatohepatitis and fibrosis. Similarly, the TM6SF2 E167K variant impairs the secretion of very-low-density lipoprotein (VLDL) particles, further exacerbating hepatic fat deposition and increasing susceptibility to advanced liver disease, including fibrosis and cirrhosis [52].
Advances in imaging technology, such as transient elastography, controlled attenuation parameter (CAP) scores for evaluating liver steatosis, and enhanced liver fibrosis (ELF) scores for assessing liver fibrosis, have emerged as promising non-invasive methods for evaluating liver health [53,54]. Liver stiffness measurements (LSM) with values exceeding 8 kPa are widely accepted as indicative of significant fibrosis risk in pediatric populations (EASL-EASD-EASO Clinical Practice Guidelines, 2024 [55]).
Lifestyle factors, including physical activity, dietary habits, and exposure to passive smoking, have also been identified as contributing factors to the development of MASLD. The prevalence of metabolic syndrome in children and adolescents has emerged as a salient public health concern, yet there are substantial knowledge gaps concerning its long-term progression and systemic effects.
This study seeks to address this pressing issue by providing a comprehensive analysis of its long-term effects, with a specific focus on determining whether these effects persist, amplify, or evolve into adulthood. A review of the current literature reveals significant gaps in research, particularly in relation to longitudinal studies that track this condition into adulthood and the absence of standardized diagnostic protocols to predict long-term health outcomes. By offering a thorough synopsis, emphasizing the significance of early identification, intervention, and ongoing care to reduce long-term health consequences, we aim to establish a foundation for future research and strategies to enhance patient outcomes.
1.5Research objectivesThe objectives of this study were to:
- 1.
Assess the prevalence and severity of MASLD (formerly NAFLD/MAFLD), in pediatric and adult populations.
- 2.
Evaluate long-term health outcomes in adults with a history of childhood MASLD (formerly NAFLD/MAFLD).
- 3.
Examine the role of early biomarkers and predictive indicators in the progression of MASLD (formerly NAFLD/MAFLD) from childhood to adulthood.
- 4.
Evaluate the Interconnected Nature of Systemic Metabolic, Cardiovascular, and Liver-Related Complications of MASLD (formerly NAFLD/MAFLD).
- 5.
Address challenges in transitioning MASLD (formerly NAFLD/MAFLD) patients from pediatric to adult care.
This systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to ensure systematic, transparent reporting and reproducibility. IRB approval was not required, as the research exclusively analyzed previously published data.
2.1Search strategyThe evolving terminology of MASLD, previously referred to as NAFLD and MAFLD, has led to variability in diagnostic criteria and reported prevalence rates, particularly in pediatric populations. This variability poses challenges in comparing studies and interpreting findings, as different definitions may capture distinct subsets of patients. Specifically, studies using the MAFLD criteria may identify children with metabolic risk factors who would not meet the NAFLD criteria, potentially leading to discrepancies in prevalence estimates. This review considers studies using all three terminologies (NAFLD, MAFLD, MASLD) to ensure comprehensive coverage and to account for the impact of these differing definitions on reported prevalence and progression data. Concordance studies have highlighted significant differences in prevalence rates, patient characteristics, and associated risk factors when applying these varying definitions in pediatric populations, emphasizing the need for standardized diagnostic criteria to ensure consistency in research and clinical practice [3,56,57]. To avoid conflating prevalence data, the term liver steatosis is used when referring to findings from studies employing NAFLD or MAFLD diagnostic criteria.
This review primarily focuses on the prevalence of disease, which refers to the proportion of individuals in a population who have the condition at a specific point in time or over a defined period. It is important to make a distinction between prevalence and incidence, which refers to the rate of new cases developing in a population during a specific time frame. This distinction is relevant for the study for comprehending the overall burden of MASLD (prevalence) in contrast to the dynamics of disease emergence (incidence). While this review emphasizes prevalence data to highlight the scope and systemic impact, further research into incidence is also necessary to better understand risk factors and disease progression.
A comprehensive search strategy was developed to identify relevant studies published between January 1, 2014, and December 31, 2024. The search was conducted across five major bibliographic databases: Medline, Scopus, Web of Science, PubMed, and the Cochrane Library. These databases were selected for their extensive coverage of biomedical and clinical research.
Given the evolving terminology of MASLD, the search terms included variations of the disease nomenclature to ensure the inclusion of all relevant studies. Specifically, MASLD was previously referred to as Nonalcoholic Fatty Liver Disease (NAFLD) and later as Metabolic Associated Fatty Liver Disease (MAFLD). The search terms included combinations of the following:
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Disease Terminology: "Nonalcoholic Fatty Liver Disease" OR "NAFLD" OR "Metabolic Associated Fatty Liver Disease" OR "MAFLD" OR "Metabolic Dysfunction-Associated Steatotic Liver Disease" OR "MASLD" OR "Nonalcoholic Steatohepatitis" OR "NASH" OR "Metabolic Dysfunction-Associated Steatohepatitis" OR "MASH"
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Population: "Children" OR "Pediatric" OR "Adolescents" OR "ages 0–18"
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Systemic Effects: "Systemic effects" OR "Cardiovascular disease" OR "Type 2 diabetes" OR "Liver fibrosis" OR "Cirrhosis" OR "Liver-related mortality"
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Biomarkers: "Biomarkers" OR "Liver enzymes" OR "Insulin resistance" OR "Inflammatory markers" OR "Liver Stiffness Measurements" OR "LSMs." OR “Patatin-Like Phospholipase Domain-Containing Protein 3” OR “PNPLA3” OR "Transmembrane 6 Superfamily Member 2” OR “TM6SF2" OR "Homeostatic Model Assessment of Insulin Resistance” OR “HOMA-IR" OR "C-Reactive Protein” OR “CRP" OR "Controlled Attenuation Parameter” OR “CAP scores" OR "Enhanced Liver Fibrosis scores or “ELF scores".
- •
Lifestyle and Environmental Factors: "Lifestyle factors" OR "Physical activity" OR "Dietary habits" OR "Processed food consumption" OR "Sugary beverage intake" OR "Passive smoking" OR "Socioeconomic disadvantage" OR "Maternal obesity"
Studies were included if they met the following criteria:
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Language: Studies published in English
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Population: Studies involving children and adolescents (ages 0–18) at baseline with follow-up into adulthood
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Study design: Longitudinal, cohort or prospective studies reporting on short-term and long-term effects of MASLD, NAFLD or MAFLD
- •
Outcomes: Studies tracking the progression of MASLD, NAFLD or MAFLD from childhood into adulthood
Studies not involving human subjects
Studies focusing solely on adults or children
Studies without clear diagnostic criteria for MASLD, MAFLD, or NAFLD
Case reports and reviews without original data
2.4Study selectionAll identified records were imported into a reference management software and duplicates were removed. Two reviewers independently screened titles and abstracts for eligibility. Discrepancies were resolved through discussion or consultation with a third reviewer, a clinical expert specializing in family medicine. A fourth reviewer, a pediatric gastroenterologist, provided additional expertise in clinical implications and contributed to resolving any remaining disagreements. The variability in diagnostic methods and study designs across the included studies was noted during the selection process. Studies using different approaches, such as ultrasound imaging, liver biopsy, and advanced imaging techniques (e.g., MRI, transient elastography), were included to provide a comprehensive overview of MASLD prevalence and progression.
2.5Data extraction and synthesisData were extracted using a standardized form, capturing study characteristics (e.g., author, year, country, sample size, follow-up duration), population demographics, diagnostic methods, long-term outcomes, and risk factors. Extracted data were organized into tables summarizing study details, diagnostic methods, biomarkers, and key findings. When discussing prevalence data derived from studies using NAFLD or MAFLD criteria, the term liver steatosis is used to ensure terminological accuracy. The variability in diagnostic methods was accounted for during data synthesis to ensure comparability across studies.
The extracted data were organized into Table 1, which was divided into three parts:
- 1.
Part 1: Study Details and Population Characteristics – This section includes information on study design, sample size, population characteristics, follow-up duration, baseline Pediatric Liver Steatosis Prevalence/Indicators, and adult liver steatosis prevalence/complications.
- 2.
Part 2: Diagnosis, Long-Term Symptoms, and Biomarkers – This section outlines the diagnostic methods used in each study, the biological systems affected at pediatric baseline and follow-up, and the assessment tools and biomarkers employed (e.g., ALT, AST, HOMA-IR scores, genetic variants, imaging techniques).
- 3.
Part 3: Key Findings, Limitations, Quality Assessments, and Predicted Long-Term Effects – This section summarizes the key findings of each study, identifies limitations (e.g., loss to follow-up, diagnostic variability), provides Newcastle–Ottawa Scale (NOS) scores for quality assessment, and predicted long-term effects (e.g., type 2 diabetes, cardiovascular disease, liver-related mortality).
Longitudinal studies tracking children into adulthood.
| Part 1. Study details and population characteristics | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Study ID | Authors | Year | Country | Study Design | Sample Size | Population Characteristics | Follow-up duration | Baseline Pediatric Liver Steatosis Prevalence/Indicators | Adult Liver Steatosis Prevalence/Complications |
| 1[47] | Yan Y, Hou D, Zhao X, et al. | 2017 | China | Longitudinal cohort | 1,350 | Children aged 6–18 years | 23.3 years | Childhood obesity | Liver steatosis: 30.5%, ALT elevation: 20.9% |
| 2[41] | Kaikkonen et al. | 2017 | Finland | Longitudinal | 3,596 | Children aged 3–18 years | 10 years | BMI, metabolic measures | 19% Liver Steatosis prevalence |
| 3[61] | Simon et al. | 2023 | Sweden | Nationwide cohort | 699 Liver Steatosis patients, 3,353 controls | 16.6 years | Median 16.6 years | Histologically confirmed Liver Steatosis | Higher rates of MACE |
| 4[65] | Wang et al. | 2016 | China | Cross-sectional | 5,306 | Adults exposed to famine | 52–93 years | Famine exposure | 55.4% Liver Steatosis prevalence in men, 51.7% in women |
| 5[59] | Daniel J. Cuthbertson et al. | 2019 | Finland | Longitudinal | 2,020 | Children aged 3–18 years | 31 years | BMI, metabolic factors | 40.5% liver steatosis prevalence in obese adults |
| 6[49] | Suomela et al. | 2016 | Finland | Longitudinal | 2,042 | Children aged 3–18 years | 31 years | BMI, insulin, genetic variants | 19% liver steatosis prevalence |
| 7[62] | Aya Bardugo, Cole et al. | 2021 | Israel | Nationwide cohort | 1,025,796 | Adolescents aged 16–19 years | 13.3 years | Liver Steatosis diagnosed | 19% type 2 diabetes prevalence |
| 8[8] | Feitong Wu et al. | 2021 | Finland | Prospective cohort | 1,315 | Children aged 3–18 years | 31 years | Passive smoking, BMI, insulin | 16.3% Liver Steatosis prevalence |
| 9[63] | Tamoore Arshad, et al. | 2021 | USA | Cross-sectional | 4,654 | Adolescents and young adults aged 12–29 years | 9 years | Obesity, metabolic syndrome | 18.5% Liver Steatosis prevalence |
| 10[54] | Draijer et al. | 2023 | Netherlands | Long-term follow-up | 51 | Adolescents with severe obesity | 10 years | Obesity severe | Prevalence 6% advanced fibrosis Steatosis (47%) |
| 11[67] | Junia N. de Brito at al. | 2023 | USA | Prospective cohort | 2,833 | Adults aged 18–30 years | 25 years | BMI, physical activity | 24% Liver Steatosis prevalence |
| 12[60] | Catherine C. Cohen, at al. | 2021 | United Kingdom | Longitudinal cohort | 1,657 | ALSPAC participants | 15 years | Body fat percentage | 20.7% Liver Steatosis prevalence |
| 13[7] | Tracey G Simon et al. | 2021 | Sweden | Nationwide cohort | 718 Liver Steatosis patients, 3,457 controls | Children and young adults aged <25 years | Median of 15.8 years | The study categorized Liver Steatosis into simple steatosis and NASH | 7.7% overall mortality among Liver Steatosis patients, 1.1% among controls; 5.26-fold higher mortality in simple steatosis, 11.51-fold higher in NASH |
| 14[70] | Tomi T Laitinen et al | 2020 | Finland | Longitudinal | 2,042 | Children aged 3–18 years | 31 years | BMI, insulin, low birth weight | 18.9% Liver Steatosis prevalence |
| 15[64] | Cantoral A, at al. | 2020 | Mexico | Cohort study | 97 | Pregnant women with singleton births; offspring tracked from birth to young adulthood. | 21–22 years | Maternal overweight/obesity | 17% Liver Steatosis prevalence |
| 16[66] | Hongyan Qi et al. | 2020 | China | Cross-sectional | 7,632 | Adults exposed to famine | 69 years | Famine exposure | 28.8% Liver Steatosis prevalence |
| 17[71] | Hannes Hagström et al. | 2021 | Sweden | Nationwide cohort | 165 Liver Steatosis cases, 717 controls | Individuals <25 years of age with biopsy-verified Liver Steatosis | 24 years | Biopsy-proven Liver Steatosis | Increased risk and severity of Liver Steatosis in offspring of obese mothers |
| 18[53] | Abeysekera et al. | 2022 | UK | Prospective cohort | 3,274 | Adolescents aged 17.8 years | 6 years | Ultrasound-defined steatosis | 20.7% Liver Steatosis prevalence, 2.4% fibrosis prevalence |
| 19[101] | Osake et al. | 2018 | Japan | Historical cohort | 1,010 | Adults diagnosed with Liver Steatosis | 10 years | Liver Steatosis diagnosis | 46% remission in men, 48.7% in women |
| 20[68] | Schnermann et al. | 2023 | Germany | Longitudinal cohort | 240 | Adolescents aged 8.5–16.5 years | 12 years | Lifestyle factors | Fatty liver indices inversely linked to healthy lifestyle |
| 21[102] | Abeysekera et al | 2021 | UK | Prospective cohort | 2,961 | Young adults (mean age 24) | 24 years | Liver Steatosis prevalence (CAP ≥248 dB/m) | 10.1% severe steatosis prevalence |
| 22[69] | Sekkarie et al. | 2021 | UK | Longitudinal cohort | 3,095 | Children aged 3 years | 21 years | Not assessed | 9.8% severe hepatic steatosis prevalence |
| 23[52] | Hagström et al. | 2016 | Sweden | Cohort study | 44,248 | Male adolescents aged 18–20 years | 39 years | BMI | Severe liver disease prevalence |
| 24[72] | Cioffi et al. | 2017 | USA | Single-center study | 44 | Pediatric Liver Steatosis patients | 4.5 years | Obesity, diabetes, fibrosis | 78% obese, 30% diabetes, progression in fibrosis for some |
| 25[10] | Golabi et al | 2020 | United States | Longitudinal cohort | 9,341 | Adults aged 20–74 years | 22.4 years | Liver Steatosis prevalence | Elevated risk of mortality, CVD, cancer |
| 26[32] | Zimmermann et al | 2015 | Denmark | Prospective cohort | 244,464 | School-aged children (7–13 years) | Up to 80 years | BMI | 2,370 Liver Steatosis cases diagnosed in adulthood |
| BMI: Body Mass Index, ALT: Alanine Aminotransferase, AST: Aspartate Aminotransferase, MACE: Major Adverse Cardiovascular Events, CAP: Controlled Attenuation Parameter, CVD: Cardiovascular Disease, UK: United Kingdom, USA: United States of America | |||||||||
MACE: Major Adverse Cardiovascular Events, CVD: Cardiovascular Disease, BMI: Body Mass Index, VPA: Vigorous Physical Activity, CAP: Controlled Attenuation Parameter, NOS: Newcastle–Ottawa Scale
To enhance clarity and usability, a separate table (Table 2) was constructed to summarize childhood risk factors that predict adult MASLD, MAFLD, or NAFLD outcomes (liver steatosis). This table links early-life indicators (e.g., Body Mass Index, maternal obesity, passive smoking, genetic predispositions) to long-term health outcomes (e.g., MASLD, MAFLD, or NAFLD prevalence, cardiovascular complications, liver-related mortality). Each risk factor is accompanied by a description of its association with adult MASLD, MAFLD, or NAFLD outcomes, supported by evidence from the included studies.
Childhood risk factors predictive of adult MASLD outcomes.
MASLD: Metabolic Dysfunction-Associated Steatotic Liver Disease, BMI: Body Mass Index, ALT: Alanine Aminotransferase, AST: Aspartate Aminotransferase, VPA: Vigorous Physical Activity, MPA: Moderate Physical Activity
The quality of the included studies was assessed using the Newcastle–Ottawa Scale (NOS) [58], a validated tool for evaluating non-randomized studies. The NOS evaluates studies based on three domains: selection of participants, comparability of study groups, and assessment of outcomes. Studies scoring ≥7 was considered high quality.
The protocol for the study selection process is delineated in the PRISMA flow diagram in Fig. 1.
3Results
A total of 26 studies were included in this review, comprising longitudinal cohort studies, cross-sectional analyses, and prospective studies. The studies are detailed in Table 1, Parts 1, 2, and 3. In order to enhance clarity and usability, a separate table (Table 2) was constructed to summarize childhood risk factors that predict adult outcomes. The findings presented in the tables, highlight the significant burden of MASLD, MAFLD, or NAFLD across various age groups as well as its long-term health implications. The sample sizes ranged from 44 to over 244,000 participants with follow-up durations of 4.5 years to 39 years. The studies were conducted across diverse geographic regions, including the United States, Finland, China, Sweden, and Mexico. Diagnostic methods varied, with ultrasound imaging, liver biopsy, and transient elastography being the most common. Biomarkers such as ALT, AST, HOMA-IR scores, and genetic variants (PNPLA3, TM6SF2) were frequently assessed to evaluate MASLD prevalence, severity, and progression. The studies primarily focused on the systemic effects of MASLD, MAFLD, or NAFLD, including metabolic, cardiovascular, and hepatic complications, as well as its persistence into adulthood. Despite variations in study types, geographic areas, populations, and healthcare systems, the prevalence of this condition and the biological systems it affects remain strikingly similar across the studies, with consistently concerning long-term health consequences.
3.1Objectives3.1.1Objective 1: assess the prevalence and severity of MASLD (formerly NAFLD/MAFLD), in pediatric and adult populationsThe prevalence of liver steatosis in children and adolescents varies widely, with rates ranging from 8% in the general population to 36.1% among obese adolescents [47,49,59]. Studies show that the condition often persists into adulthood, with prevalence increasing as individuals age. Table 1 part 1, provides detailed prevalence data across studies. For instance, study ID 147 reported a 30.5% prevalence among obese children aged 6–18 years in China, determined using NAFLD diagnostic criteria, while study ID 559 in Finland found a 40.5% prevalence of liver steatosis in obese adults using MASLD diagnostic criteria. Similarly, study ID 649, also conducted in Finland, reported a lower prevalence of 19% in adults, despite identifying similar childhood predictors such as elevated, insulin resistance, and genetic predispositions.
Longitudinal studies consistently demonstrate the persistence of liver steatosis from childhood into adulthood. For instance, study ID1260 from the Avon Longitudinal Study of Parents and Children (ALSPAC) monitored 1,657 participants over 15 years, reporting a 20.7% prevalence of this condition at age 24, with body fat percentage in childhood identified as a significant predictor. Similarly, study ID 2632 followed 244,464 school-aged children in Denmark for up to 80 years, identifying 2,370 cases diagnosed in adulthood.
The variations in prevalence across studies appear to be influenced by differences in population characteristics and the diagnostic methods employed. For instance, studies such as ID 137(China) and ID 559 (Finland) relied on ultrasound imaging, reporting prevalence rates of 30.5% and 40.5%, respectively, among obese pediatric populations. In contrast, Study ID 361 (Sweden) utilized histopathology to confirm liver steatosis diagnosis, while Study ID 1054 (Netherlands) employed advanced imaging techniques such as MRI and ELF tests, demonstrating a 6% prevalence of advanced fibrosis and 47% prevalence of liver steatosis over a 10-year follow-up period.
3.1.2Objective 2: evaluate long-term health outcomes in adults with a history of childhood MASLD (formerly NAFLD/MAFLD)Long-term health outcomes in adults with a history of childhood MASLD are influenced by the persistence of the condition, as demonstrated by longitudinal studies. As an illustration, Study ID 7 [62] conducted in Israel revealed that adolescents diagnosed with MASLD were three times more likely to develop type 2 diabetes in young adulthood. Study ID 9 [63] from the United States further demonstrated that adolescents and young adults with liver steatosis had an 18.5% prevalence of the condition over a nine-year follow-up period, with obesity and metabolic syndrome identified as key factors in disease progression. A similar finding was reported in Study ID 2332 from Sweden, which indicated that overweight male adolescents aged 18–20 exhibited a significantly higher risk of developing severe liver disease and type 2 diabetes over a 39-year follow-up period.
Cardiovascular disease is another major long-term outcome associated with this condition at childhood. Study ID 3 [61] from Sweden reported significantly higher rates of major adverse cardiovascular events (MACE), such as heart disease and heart failure, due to persistent metabolic abnormalities like insulin resistance, high cholesterol, and elevated blood pressure.
This aligns with findings from Study ID 8 [8] in Finland, which identified elevated levels of inflammatory markers in children with liver steatosis were linked to a higher risk of atherosclerosis and cardiovascular disorders in adulthood.
Hepatic complications are particularly concerning, as liver steatosis often progresses to advanced liver conditions. Study ID 1054 from the Netherlands found that 6% of adolescents with severe obesity (classified according to cut-offs for adult BMI) developed advanced fibrosis over a 10-year follow-up period. Study ID 23 [52] from Sweden demonstrated that elevated BMI in late adolescence predicted severe liver disease, including cirrhosis and liver-related mortality, later in life. Furthermore, Study from Sweden ID 13 [7] identified significant hepatic fibrosis as the strongest independent predictor of liver-related mortality, with pediatric patients exhibiting a 5.26-fold higher mortality risk in cases of simple steatosis and an 11.51-fold higher risk in cases of metabolic dysfunction-associated steatohepatitis (MASH).
Maternal obesity and early-life factors were also identified as significant contributors to disease progression. For example, Study ID 6 [49] reported that small for gestational age is a childhood risk factor on the development of liver steatosis. Study ID 15 [64] from Mexico reported a 17% prevalence of the condition in young adulthood among offspring of obese mothers, while Study ID 4 [65] and Study ID 16 [66]from China highlighted the impact of early-life famine exposure, with liver steatosis prevalence rates exceeding 50% in adults exposed to famine during childhood.
Finally, mortality risks associated with the condition are substantial. A study from Sweden ID 13 [61] found that pediatric patients with liver steatosis had a significantly higher risk of liver-related mortality, with simple steatosis increasing the risk by 5.26 times and MASH by 11.51 times. Study ID 25 [10] from the United States further demonstrated that condition significantly increases the risk of mortality, cardiovascular disease, and cancer, with individuals exhibiting a higher prevalence of systemic complications over a follow-up period of 22.4 years.
3.1.3Objective 3: examine the role of early biomarkers and predictive indicators in the progression of MASLD (formerly NAFLD/MAFLD) from childhood to adulthoodEarly biomarkers and predictive indicators, including liver enzyme levels (ALT, AST), measures of insulin resistance, and genetic variants, play a crucial role in understanding and forecasting the progression of chronic liver disease. However, ALT is more appropriately considered a biomarker of chronic liver disease rather than MASLD, as its diagnostic performance for MASH is limited [44]. Study ID 6 [49] (Finland) emphasized the relevance of insulin resistance, and genetic predispositions (e.g., PNPLA3 and TM6SF2 variants) as critical predictors of disease progression. When combined with a high body mass index (BMI) (defined as being above the 95th percentile for age and sex, based on standardized growth charts), these biomarkers significantly increase the risk of developing MASLD in adulthood. Study ID13 [47] further identified elevated fasting insulin levels and HOMA-IR scores as key indicators of liver steatosis progression.
Advanced imaging techniques, such as transient elastography and CAP scores, provide non-invasive methods for assessing liver steatosis and fibrosis. For instance, study ID 10 [65] utilized MRI and ELF tests to demonstrate that adolescents with severe obesity developed advanced fibrosis over a 10-year follow-up period. These imaging tools complement traditional biomarkers, such as ALT and AST, which are widely used for assessing chronic liver disease but exhibit poor diagnostic performance for MASH.
Lifestyle and environmental factors also serve as predictive indicators for MASLD progression. Study ID 8 [8] highlighted that childhood exposure to passive smoking, validated by serum cotinine levels (range: 0.2–15 ng/mL), was associated with an increased risk of hepatic disease in adulthood. Childhood exposure to parental smoking was determined by whether either parent smoked daily for at least one year between 1980 and 1983. Although the study did not capture the exact number of hours children were exposed to cigarette smoke, exposure was validated using serum cotinine levels, a reliable indicator. Adulthood passive smoking was assessed through self-reported daily exposure to cigarette smoke for at least one hour in various settings, such as at home, work, or other environments.
Physical activity was measured using self-reported questionnaires in Study ID 11 [67], which collected data on activity levels at multiple time points (e.g., 1985, 1992, and 2010). Vigorous activity was defined as activities requiring ≥6 metabolic equivalents (METs), such as running, swimming, or cycling, while moderate physical activity (MPA) was defined as activities requiring 3–6 METs, such as walking or light jogging. Sustained vigorous physical activity (VPA) was inversely associated with fatty liver indices in adulthood, while MPA did not show a significant association.
The excessive consumption of processed foods and sugary beverages has shown to exacerbate metabolic disturbances, contributing to the condition’s progression and systemic effects, as noted in Study ID [68] and Study ID 22 [69]. Socioeconomic factors, such as childhood disadvantage, parental education levels, and income, also play a critical role in influencing the risk of developing liver steatosis in adulthood, as demonstrated in Study ID 4 [65]. Additionally, childhood BMI, insulin levels, and parental socioeconomic status are significant predictors of adult liver disease as indicated by Study IDS 6 [49] and 14 [70]. Expanding on environmental factors, Study ID 4 [65] underscores the heightened risk of liver disease in women due to early-life famine exposure combined with adulthood obesity. In addition, Study ID 1771 provides further evidence that overweight or obesity to be a strong risk factor for increased severity of liver steatosis in offspring, highlighting the intergenerational impact of liver-related health risks.
Longitudinal studies have provided robust evidence of the predictive value of early biomarkers and indicators. Childhood Obesity (BMI > 95%) as a risk factor, with studies such as Study IDs 1 [47], 2 [41], 5 [59], 13 [47], or 23 [52] highlighting how high BMI > 95% percentile is a predictor of adult liver steatosis. Overweight/obese children are twice as likely to develop MASLD as adults, with the risk mitigated by achieving normal BMI in adulthood. On the other hand, high BMI > 95% percentile, insulin resistance, and genetic variants are reported to be predictors of adult fatty liver disease. Study ID 23 [52] revealed that overweight in late adolescence predicted the development of severe liver disease later in life, with a 39-year follow-up study of 44,248 male adolescents showing a significantly higher risk of cirrhosis and liver-related mortality in adulthood. Excessive BMI gain during childhood has been identified as a critical predictive indicator for adult MASLD outcomes. For instance, study ID 26 [32] demonstrated that BMI gain between ages 7–13 independently predicted adult liver steatosis outcomes, including severe liver disease and cirrhosis. Complementing, Study ID 12 [60] found that children with higher total body fat and trunk fat percentages are at greater risk of developing liver steatosis by age 24.
3.1.4Objective 4: evaluate the interconnected nature of systemic metabolic, cardiovascular, and liver-related complications of MASLD (formerly NAFLD/MAFLD)MASLD is a multisystem condition with interconnected metabolic, cardiovascular, and liver-related complications that begin in childhood and persist into adulthood, often intensifying over time [58]. These metabolic disturbances not only contribute to the progression of the condition but also increase the risk of type 2 diabetes and other endocrine disorders in adulthood, as highlighted by Study ID 6 [49]. The systemic inflammation driven by obesity, accelerates endothelial dysfunction, which worsens liver fibrosis and cardiovascular outcomes, as noted by Study ID 8 [8], Study ID 3 [61] and Study ID 13 [7].
3.1.5Objective 5: address challenges in transitioning MASLD (formerly NAFLD/MAFLD) patients from pediatric to adult careThe transition from pediatric to adult care for patients with MASLD is characterized by systemic barriers that hinder continuity of care. Study ID 26 [32], which followed 244,464 school-aged children in Denmark, reported a discontinuity rate of 23% among young adults, indicating significant gaps in follow-up care during this transitional period. Fragmented medical records were identified as a contributing factor, as noted in Study ID 24 [72], where reliance on pediatric records often failed to capture essential data on lifestyle changes and long-term health outcomes.
Monitoring changes during adolescence is essential for comprehensively understanding long-term health outcomes. Specifically, evidence from Study ID 23 [52] highlights that excessive BMI gain during childhood serves as a significant independent predictor of severe liver disease in adulthood. Additionally, tracking socioeconomic factors during adolescence is vital, as these determinants play a critical role in shaping care transition outcomes and influencing long-term health trajectories. For instance, findings from Study ID 8 [8] underscore that financial constraints and restricted access to health insurance represent substantial barriers to effective follow-up care for young adults. Similarly, Study ID 4 [59] revealed a significant association between childhood socioeconomic disadvantage and the prevalence of liver steatosis in adulthood, highlighting the profound impact of systemic inequities on long-term health outcomes. The absence of detailed information regarding psychosocial factors was also noted, with Study ID 24 [73] emphasizing the critical role of documenting conditions such as anxiety and depression in shaping patient engagement and adherence to ongoing care. Medical records frequently lack detailed information about the parents, adolescence, or childhood. This missing information could facilitate the establishment of links, for instance, between the intergenerational impact of maternal overweight or obesity, as indicated by Study ID 15 [64]. Finally, the transition from pediatric to adult care is further hindered by inherent disparities in care models. While pediatric care predominantly adopts a family-centered approach, adult care systems emphasize individual autonomy and responsibility. Study ID 24 [73] identified this paradigm shift as a critical factor contributing to diminished patient engagement during the transitional phase.
3.1.6Summarize childhood risk factors predictive of adult outcomesIn addition to the detailed findings presented in Table 1, Table 2 provides a focused summary of key childhood risk factors that are predictive of adult liver steatosis outcomes. These risk factors include childhood obesity, maternal obesity, passive smoking, early-life famine exposure, elevated liver enzymes, genetic variants, dietary habits, and socioeconomic disadvantage. Each risk factor is linked to specific adult health outcomes, such as increased prevalence of liver steatosis, type 2 diabetes, cardiovascular disease, and liver-related complications. For instance, childhood obesity (BMI > 95th percentile) is strongly associated with a higher likelihood of developing MASLD in adulthood, with the risk mitigated by achieving a normal BMI later in life. Similarly, maternal obesity during pregnancy has been shown to significantly increase the severity of this condition in offspring, highlighting the intergenerational impact of metabolic dysfunction. Passive smoking during childhood, validated by serum cotinine levels, is another critical predictor, as it is associated with an increased risk of advanced fibrosis, cirrhosis, and cardiovascular complications in adulthood. However, it is important to note that the prevalence data cited in these tables were derived from studies using varying diagnostic criteria, including NAFLD, MAFLD, and MASLD. This variability may influence the reported associations between childhood obesity and adult MASLD outcomes.
4DiscussionMetabolic dysfunction-associated steatotic liver disease (MASLD) poses a substantial public health concern, given its systemic impact and documented progression from childhood to adulthood. Evidence from longitudinal studies has demonstrated that childhood obesity significantly increases the likelihood of developing metabolic syndrome (MASLD) in adulthood. The systemic nature of this condition, driven by metabolic dysfunction and chronic inflammation, aligns with prior research connecting childhood obesity and metabolic syndrome to adult health risks [74–77]. This review underscores the significance of recognizing MASLD during critical developmental stages by synthesizing evidence on the long-term consequences of childhood obesity and metabolic syndrome. Early intervention targeting these risk factors can mitigate the cascading effects of disease on cardiovascular and hepatic health, ultimately reducing its long-term burden [78].
4.1Challenges in preventive educationThe findings from this study highlight significant challenges in early intervention for MASLD. The subclinical nature of metabolic syndrome in its early stages, in conjunction with societal normalization of obesity, significantly contributes to its underdiagnosis and delays in timely intervention. This issue is further exacerbated by deficiencies in public health education and prevalent misconceptions that erroneously attribute fatty liver disease solely to alcohol consumption. Consequently, healthcare providers, parents, and patients frequently possess an incomplete understanding of the substantial systemic health risks associated with childhood obesity and its connection to MASLD. Public health campaigns must prioritize raising awareness about MASLD and its systemic effects, addressing societal normalization of childhood obesity, and promoting equitable access to healthy food and physical activity programs [49,71,79].
To address these challenges, multimodal communication strategies should be employed to disseminate accurate information and engage diverse audiences effectively [80,81]. This encompasses the utilization of digital platforms, social media, community outreach programs, and educational initiatives customized to diverse age groups and cultural contexts. The utilization of these instruments can facilitate the overcoming of obstacles to awareness and ensure that key stakeholders, including parents, educators, and healthcare providers, are equipped with the knowledge and resources necessary to combat MASLD.
4.2Importance of early detection and advanced diagnostic toolsEarly detection is critical for effective MASLD management, as the disease often progresses asymptomatically. Biomarkers and predictive indicators, such as elevated liver enzymes (ALT, AST), insulin resistance (HOMA-IR scores), and genetic variants (PNPLA3, TM6SF2), are essential for forecasting the progression of MASLD from childhood to adulthood [49,71]. However, relying solely on these established predictors has limitations, as MASLD can progress even in individuals with normal enzyme levels [45] ALT, for instance, is more appropriately considered a biomarker of chronic liver disease rather than MASLD, as its diagnostic performance for metabolic dysfunction-associated steatohepatitis (MASH) is limited [38].
Emerging biomarkers, such as gene-based signature classifiers like Aldo-Keto Reductase Family 1 Member B10 (AKR1B10) and Secreted Phosphoprotein 1 (SPP1), show promise in predicting disease progression and assessing changes in the immune microenvironment [82]. Advanced imaging techniques, such as transient elastography and controlled attenuation parameter (CAP) scores, offer promising non-invasive alternatives for detecting liver steatosis and fibrosis, addressing gaps in traditional diagnostic methods like ultrasound, which may underestimate disease prevalence [55]. Healthcare providers should prioritize early screening for MASLD in children with obesity, elevated liver enzymes, or metabolic syndrome. Incorporating these advanced diagnostic tools into routine pediatric care could significantly enhance early detection and management [1,52].
4.3Socioeconomic and dietary factorsA comprehensive analysis of MASLD highlights varying prevalence rates across different population groups. Certain ethnic groups, such as Hispanic individuals, are disproportionately affected due to genetic variants [1,83,84]. Socioeconomic disparities and cultural eating habits exacerbate these differences, while early-life nutrition significantly influences offspring risk [66,71]. Emerging evidence underscores the pivotal role of dietary composition in shaping liver health, with diets high in saturated fats and refined sugars identified as key drivers of liver steatosis [85].
The widespread consumption of ultra-processed foods, characterized by excessive caloric density, artificial additives, and minimal nutritional value, has been strongly associated with an increased risk of liver disease [86]. This trend is particularly alarming for pediatric populations, who are disproportionately vulnerable to the harmful effects of these substances. Compelling experimental evidence has illuminated the harmful impact of specific food additives on liver health. Artificial sweeteners, such as saccharin and aspartame, have been implicated in the development of hepatic conditions, including transaminitis and steatosis, in preclinical rodent models [87,88]. Similarly, emulsifiers like polysorbate 80 have demonstrated hepatotoxic properties, contributing to liver degradation and cellular toxicity in animal studies [89,90]. These findings raise critical questions about the long-term safety of such additives, particularly given their widespread use in processed foods.
In stark contrast, adherence to nutrient-rich dietary patterns has emerged as a powerful strategy to counteract the progression of MASLD. The Mediterranean diet, renowned for its emphasis on whole grains, fresh fruits, vegetables, and unsaturated fats, has been consistently associated with a significant reduction in the incidence and severity of MASLD [89,90]. This dietary approach not only promotes liver health but also offers broader metabolic benefits, underscoring its potential as a cornerstone of preventive healthcare.
4.4Emerging therapies and lifestyle interventionsExploring new therapies to address the challenges posed by MASLD should include focusing on the critical role of the gut-liver axis in its pathogenesis, as gut dysbiosis significantly contributes to systemic inflammation and hepatic fat accumulation [91,92]. Microbiome-targeted therapies, such as probiotics and prebiotics, are emerging as potential strategies to mitigate disease progression, particularly in pediatric populations [93,94]. These interventions could complement existing lifestyle and pharmacological approaches. Recent pharmacological advancements, such as GLP-1 receptor agonists and dual GLP-1/GIP agonists, have shown efficacy in improving insulin sensitivity and reducing liver fat [95,96].
Lifestyle and environmental factors, including physical activity, dietary habits, and exposure to passive smoking, are critical determinants of MASLD risk. Sustained vigorous physical activity [8] has been associated with reduced disease progression, while processed food consumption and passive smoking exacerbate the condition [33,68]. Enhanced screening for liver disease in pediatric patients exposed to tobacco smoke, regardless of their weight status or obesity classification, is essential [97,98].
4.5Future directions and global collaborationThe findings of this study have significant implications for healthcare practice, policy, and research. Future research should prioritize the validation of novel biomarkers, such as AKR1B10 and SPP1 [44], exploring pharmacological treatments for pediatric MASLD [95,96], and developing personalized prevention strategies that account for genetic predispositions and lifestyle factors. Additionally, structured transition programs, enhanced patient education, and leveraging technology to reduce fragmented medical records and improve follow-up rates should be explored [72,99].
Global collaboration is essential to address geographic and ethnic disparities in MASLD prevalence and outcomes [61]. International studies can provide valuable insights into unique risk factors and challenges faced by different populations, enabling the development of culturally tailored interventions and integrated care models. These efforts can improve long-term health outcomes and reduce societal and economic burdens associated with MASLD.
One significant gap in the existing research is the absence of longitudinal studies tracking the progression of MASLD from childhood to adulthood and its potential links to other chronic conditions, such as chronic kidney disease [24]. Current evidence indicates that MASLD may contribute to kidney dysfunction through overlapping mechanisms such as insulin resistance, systemic inflammation, and metabolic dysregulation. Addressing this gap will require large-scale, long-term studies that examine the interplay between MASLD and other systemic diseases, as well as the impact of early-life interventions on disease trajectories.
4.6Evidence-based algorithms for MASLD management in pediatric populationsBuilding on the findings of this review, we propose evidence-based algorithms for the management of MASLD in pediatric populations (see Table 3). These algorithms are designed to translate the research evidence presented into actionable clinical pathways, incorporating validated biomarkers, advanced imaging techniques, and personalized interventions to optimize early detection, prevention, and treatment outcomes.
Evidence-based algorithms for MASLD.
The recommendations and algorithms provided in the following tables are based on the evidence synthesized in this systematic review and the current understanding of MASLD. While these strategies are supported by existing studies, further research is required to validate their long-term efficacy and determine whether they represent the best approaches for managing MASLD. The authors emphasize the need for ongoing studies to refine these recommendations and address existing gaps in knowledge.
4.6.2Tables descriptionThe following tables summarize evidence-based algorithms for the early identification, management, and care transition of MASLD in pediatric populations. These algorithms are derived from the systematic review and include recommendations based on the findings.
4.7Limitations of this studyThe included studies varied significantly in diagnostic methods, follow-up durations, and study populations, making it challenging to compare findings and synthesize conclusions. For instance, reliance on ultrasound imaging may underestimate disease prevalence, while liver biopsy introduces sampling errors. Discontinuity in medical records during the transition from pediatric to adult care restricts the ability to track long-term outcomes comprehensively. This fragmentation limits the understanding of MASLD progression and the effectiveness of interventions. Many longitudinal studies reported low response rates, particularly among young adults transitioning to adult care systems. This reduces the generalizability of findings and hampers efforts to draw robust conclusions. While early biomarkers such as elevated liver enzymes (ALT, AST), insulin resistance, and genetic predispositions (e.g., PNPLA3, TM6SF2) are recognized, their long-term predictive value remains underexplored. Emerging tools like Liver Stiffness Measurements (LSM) and Enhanced Liver Fibrosis (ELF) scores require further validation. There is limited representation of diverse populations that reduces the applicability of findings to global cohorts.
Most studies focused on homogeneous populations, which may not reflect the prevalence and progression of MASLD in other ethnic or geographic groups. The diagnostic methods used to assess this condition varied widely across studies, ranging from ultrasound imaging and liver biopsy to transient elastography and CAP scores. This variability complicates efforts to establish standardized diagnostic criteria. Although lifestyle factors such as diet, physical activity, and passive although are known to influence MASLD progression, many studies failed to comprehensively account for these variables. There is also limited research on how lifestyle modifications during adolescence can mitigate long-term risks. While MASLD is now widely acknowledged as a complex disease affecting multiple systems in the body [100], the intricate connections between its systemic impacts remain insufficiently understood. For example, the interaction between cardiovascular complications and liver disease progression is not well understood. Few large-scale studies have evaluated the efficacy of lifestyle interventions, such as regular exercise and dietary changes, in diverse populations.Additionally, the role of pharmacological treatments in pediatrics are underexplored [38].
Despite these limitations, this systematic review provides valuable insights into the long-term systemic effects of MASLD in children and its progression into adulthood. By synthesizing findings from diverse studies, it highlights critical risk factors, predictive biomarkers, and the importance of early intervention. The review underscores the need for integrated care models, public health education, and targeted lifestyle interventions, offering a foundation for future research and improved management strategies. It serves as a crucial step toward addressing gaps in awareness, research, and clinical practice, ultimately contributing to better health outcomes and reduced societal and economic burdens associated with MASLD.
5ConclusionsThe studies included in this review, provided a critical framework for addressing liver steatosis, emphasizing the importance of early detection, education, and prevention. Lifestyle interventions, early screening, and integrated care models remain the foundation of its management, particularly during the transition from pediatric to adult care. However, significant gaps in research persist, including fragmented healthcare systems, underexplored biomarkers, and limited follow-up data. In addition there is a lack of studies considering the potential associations between this condition and other chronic diseases, such as chronic kidney disease.
A comprehensive evaluation of the impact of food additives, hormones, and preservatives on human health is imperative to understand their long-term effects. Future research should prioritize longitudinal studies, culturally tailored lifestyle interventions, and integrated care approaches. Additionally, the exploration of pharmacological treatments targeting metabolic dysfunction and liver fibrosis in pediatric populations could complement existing strategies and provide new avenues for managing disease progression and its systemic effects. By addressing these challenges, the healthcare community can better manage the disease, improve long-term health outcomes, and reduce societal and economic burdens.
FundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Author contributionsBR and ML: Conducted the initial screening of titles and abstracts, extracted data, and ensured adherence to inclusion/exclusion criteria. TR and ER: Provided clinical expertise, reviewed selected articles for methodological rigor, resolved discrepancies, and contributed to the interpretation of findings. All authors: Assisted in designing the study, drafting sections of the manuscript, and critically reviewing the final document for accuracy and alignment with objectives. All authors contributed to refining the study design, identifying research gaps, and proposing actionable recommendations for future research and public health strategies.
Declaration of generative AI and AI-assisted technologies in the manuscript preparation processDuring the preparation of this work, the authors used Adobe Acrobat AI Assistant in order to assist with document-related queries and tasks. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.
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