To explore the connection between metabolic parameters and the severity of hepatic steatosis determined through ultrasound in elderly individuals with metabolic dysfunction-associated fatty liver disease (MAFLD).

4,663 senior individuals who were 65 years of age or older were included in this research. They were examined physically at the Ninghai Street Community Health Service Center in Yantai City between June 7, 2021, and October 15, 2021. There were two categories of individuals identified: the MAFLD group (n = 2,985) and the non-MAFLD group (n = 1,678). Based on liver ultrasonography results, individuals in the MAFLD group were further separated into three groups: mild (n = 2,104), moderate (n = 766), and severe (n = 115). To identify indicators of risk for the severity of hepatic steatosis, metabolic data was contrasted between the groups employing logistic regression.

In comparison to the non-MAFLD group, the MAFLD group showed significantly elevated levels of body mass index (BMI), blood pressure, gender, age, lipid profile, alanine transaminase (ALT), and fasting blood glucose (FBG; p < 0.05). Among individuals with MAFLD, there was a positive correlation between BMI, FBG, ALT, and aspartate transaminase (AST) levels and the severity of hepatic steatosis (p < 0.05). Logistic regression analysis indicated that BMI, female gender, FBG, ALT, triglycerides (TG), and serum uric acid (SUA) constituted risk factors for increased severity of hepatic steatosis in MAFLD.

The severity of hepatic steatosis in elderly MAFLD patients is significantly correlated with female gender, BMI, ALT, FBG, TG, and SUA.

The historical use of the term non-alcoholic fatty liver disease (NAFLD) in obese/overweight children has been controversial as to the appropriateness of this terminology in children, and lately, in adults too. Newer game-changer terminology, metabolic (dysfunction)-associated fatty liver disease (MAFLD), for this condition signifies a positive step forward that addresses the limitations of the previous definition for both adults and children. The prevalence of MAFLD has surged in tandem with the global rise in obesity rates, establishing itself as a predominant cause of chronic liver disease in both adult and pediatric populations. The adoption of the recently proposed nomenclature reflects a more encompassing comprehension of the disease and its etiology compared to its predecessor, NAFLD. Notably, the revised terminology facilitates the recognition of MAFLD as an autonomous condition while acknowledging the potential coexistence of other systemic fatty liver disorders. Particularly in children, this includes various paediatric-onset genetic and inherited metabolic disorders, necessitating thorough exclusion, especially in cases where weight loss interventions yield no improvement or in the absence of obesity. MAFLD presents as a multifaceted disorder; evidence suggests its origins lie in a complex interplay of nutritional, genetic, hormonal, and environmental factors. Despite advancements, current non-invasive diagnostic biomarkers exhibit limitations in accuracy, often necessitating imaging and histological evaluations for definitive diagnosis. While dietary and lifestyle modifications stand as cornerstone measures for MAFLD prevention and management, ongoing evaluation of therapeutic agents continues. This article provides an overview of the latest developments and emerging therapies in the realm of paediatric MAFLD.

This study investigated the potential effects of perfluoroalkyl substance (PFAS) in serum on MAFLD, NAFLD, and liver fibrosis.

Our sample included 696 participants (≥ 18 years) from the 2017-2018 NHANES study with available serum PFASs, covariates, and outcomes. Using the first quartile of PFAS as the reference group, we used weighted binary logistic regression and multiple ordered logistic regression used to analyze the relationship between PFAS and MAFLD, NAFLD, and liver fibrosis and multiple ordinal logistic regression to investigate the relationship between PFAS and MAFLD, NAFLD, and liver fibrosis and calculated the odds ratio (OR) and 95% confidence interval for each chemical. Finally, stratified analysis and sensitivity analysis were performed according to gender, age, BMI, and serum cotinine concentration.

A total of 696 study subjects were included, including 212 NAFLD patients (weighted 27.03%) and 253 MAFLD patients (weighted 32.65%). The quartile 2 of serum PFOA was positively correlated with MAFLD and NAFLD (MAFLD, OR 2.29, 95% CI 1.05-4.98; NAFLD, OR 2.37, 95% CI 1.03-5.47). PFAS were not significantly associated with liver fibrosis after adjusting for potential confounders in MAFLD and NAFLD. Stratified analysis showed that PFOA was strongly associated with MAFLD, NAFLD, and liver fibrosis in males and obese subjects. In women over 60 years old, PFHxS was also correlated with MAFLD, NAFLD, and liver fibrosis.

The serum PFOA was positively associated with MAFLD and NAFLD in US adults. After stratified analysis, the serum PFHxS was correlated with MFALD, NAFLD, and liver fibrosis.

With the rising tide of fatty liver disease related to metabolic dysfunction worldwide, the association of this common liver disease with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the old term non-alcoholic fatty liver disease (NAFLD). In 2023, a modified Delphi process was led by three large pan-national liver associations. There was consensus to change the fatty liver disease nomenclature and definition to include the presence of at least one of five common cardiometabolic risk factors as diagnostic criteria. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). The change of nomenclature from NAFLD to MAFLD and then MASLD has resulted in a reappraisal of the epidemiological trends and associations with the risk of developing CKD. The observed association between MAFLD/MASLD and CKD and our understanding that CKD can be an epiphenomenon linked to underlying metabolic dysfunction support the notion that individuals with MASLD are at substantially higher risk of incident CKD than those without MASLD. This narrative review provides an overview of the literature on (a) the evolution of criteria for diagnosing this highly prevalent metabolic liver disease, (b) the epidemiological evidence linking MASLD to the risk of CKD, (c) the underlying mechanisms by which MASLD (and factors strongly linked with MASLD) may increase the risk of developing CKD, and (d) the potential drug treatments that may benefit both MASLD and CKD.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in adolescent and adult population. However, the epidemiologic data of MAFLD in prepubertal children remain limited. This study aimed to investigate the prevalence and incidence of MAFLD and assess the role of anthropometric parameters in identifying and predicting MAFLD in this population.

Children from the Shanghai Birth Cohort Study who underwent an 8-year follow-up with anthropometric measurements and transient elastography FibroScan-502 examination (M probe, Echosens, Paris, France) were enrolled. Some of them also completed a 5-year follow-up. Diagnosis of fatty liver disease (FLD) was based on the controlled attenuation parameter (CAP) value exceeding 248 dB/m, and MAFLD was defined as FLD combined with obesity or central obesity. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic accuracy of anthropometric parameters for MAFLD.

A total of 848 children (431 boys) from the Shanghai Birth Cohort Study were followed up for 8 years, and among them, 385 children (189 boys) also participated in the 5-year follow-up. The prevalence of FLD and MAFLD at 5 years old was 3.90% and 0.52%, respectively, while at 8 years old, the prevalence rates increased to 5.07% for FLD and 3.42% for MAFLD. The 8-year-old children with MAFLD exhibited significantly higher weight, body mass index (BMI), chest circumference, waist circumference, hip circumference, waist-to-height ratio, waist-to-hip ratio, and liver stiffness measurement compared to those without MAFLD (all p < 0.05). The incidence rates of FLD and MAFLD at 8 years old, considering the 5-year follow-up data, were 3.78% (14/370) and 3.13% (12/383), respectively. Obese or centrally obese children at 5 years old had a higher incidence of FLD and MAFLD at the 8-year follow-up. Waist circumference and BMI showed significant associations with the presence and incidence of MAFLD, respectively, with the largest AUC values in ROC curve analysis. In addition, chest circumference was significantly associated with MAFLD in obese children.

This study provides insights into the incidence and prevalence of MAFLD in prepubertal children. It underscores the importance of anthropometric parameters in identifying and predicting MAFLD in this population. Further research encompassing a broader age range and incorporating these indicators and additional metabolic markers is necessary to enhance the understanding and management of MAFLD in children.

Evidence suggests that cardiometabolic index (CMI) has been identified as a novel obesity-related index associated with diabetes, hypertension, and cardiovascular disease. Current evidence suggests that the differences in sex hormones and regional fat distribution in both sexes are directly correlated with metabolic dysfunction-associated fatty liver disease (MAFLD) risk. This study aimed to investigate the diagnostic value of CMI in MAFLD in both sexes.

This retrospective study included 6107 subjects who underwent annual health check-ups from March 2021 to January 2022. CMI was calculated by multiplying the ratio of triglycerides and high-density lipoprotein cholesterol (TG/HDL-C) by waist-to-height ratio (WHtR). Multivariable logistic regression analysis and restricted cubic spline were used to investigate the association of CMI and MAFLD risk. Receiver operating characteristic curve analysis was conducted for the exploration of the diagnostic accuracies of obesity-related indicators. Areas under the curves (AUCs) with 95% CIs were calculated.

Prevalence of MAFLD increased with elevated quartiles of CMI in both sexes. The median (IQR) age was 46.00 (18.00) years. Multivariate logistic regression analyses showed that higher CMI was independently associated with MAFLD, in which every additional standard deviation (SD) of CMI increased the risk of MAFLD (OR=2.72, 95% CI:2.35-3.15 for males; OR=3.26, 95% CI:2.36-4.51 for females). Subjects in the fourth quartile of CMI had the highest odds of MAFLD for males (OR=15.82, 95% CI:11.84-21.14) and females (OR=22.60, 95% CI:9.52-53.65)(all P for trend<0.001). Besides, CMI had a non-linearity association with MAFLD (all P for non-linearity<0.001). Furthermore, CMI exhibited the largest AUC compared to other obesity-related indexes in terms of discriminating MAFLD in males (AUC=0.796, 95% CI:0.782-0.810) and females (AUC=0.853, 95% CI:0.834-0.872).

CMI was a convenient indicator for the screening of MAFLD among Chinese adults. Females with high CMI had a better diagnostic value for MAFLD than males.

An international panel recently proposed an update to the terminology and diagnostic criteria for fatty liver disease. The experts proposed a change in the nomenclature from non-alcoholic fatty liver disease (NAFLD) to metabolic (dysfunction)-associated fatty liver disease (MAFLD). This single-letter change, we believe, heralds the dawn of a new era in clinical practice and in clinical and basic research as well. The new nomenclature with the easily applicable approach has stimulated the enthusiasm of the researchers worldwide, resulting in a large number of publications over the past two years. Several recent studies have provided tremendous evidence of the superiority of the MAFLD criteria over the NAFLD criteria. Many studies in different geographic areas of the world including the United States, Europe, and Asia on a large number of patients proved that the utility of MAFLD criteria was higher than that of the NAFLD criteria in different aspects of fatty liver diseases. Consequently, many societies, physician and nurse groups, health stakeholders, representatives of regulatory sciences, and others endorsed the new nomenclature. Here we highlight the endorsement of the new name by different societies and groups and the outcome of different studies on the new nomenclature in addition to a short discussion of the debate by some experts.

Metabolic (dysfunction)-associated fatty liver disease has taken importance during the last two years, given the new criteria for diagnosis compared to the previous criteria used to define non-alcoholic fatty liver disease. Multiple studies have also shown that this definition better adjusts to the pathogenesis and patient characteristics with fatty liver.

Obesity and associated morbidities, metabolic associated fatty liver disease (MAFLD) included, constitute some of the largest public health threats worldwide. Body composition and related risk factors are known to be heritable and identification of their genetic determinants may aid in the development of better prevention and treatment strategies. Recently, large-scale whole-body MRI data has become available, providing more specific measures of body composition than anthropometrics such as body mass index. Here, we aimed to elucidate the genetic architecture of body composition, by conducting genome-wide association studies (GWAS) of these MRI-derived measures. We ran both univariate and multivariate GWAS on fourteen MRI-derived measurements of adipose and muscle tissue distribution, derived from scans from 33,588 White European UK Biobank participants (mean age of 64.5 years, 51.4% female). Through multivariate analysis, we discovered 100 loci with distributed effects across the body composition measures and 241 significant genes primarily involved in immune system functioning. Liver fat stood out, with a highly discoverable and oligogenic architecture and the strongest genetic associations. Comparison with 21 common cardiometabolic traits revealed both shared and specific genetic influences, with higher mean heritability for the MRI measures (h2 = .25 vs. .13, p = 1.8x10-7). We found substantial genetic correlations between the body composition measures and a range of cardiometabolic diseases, with the strongest correlation between liver fat and type 2 diabetes (rg = .49, p = 2.7x10-22). These findings show that MRI-derived body composition measures complement conventional body anthropometrics and other biomarkers of cardiometabolic health, highlighting the central role of liver fat, and improving our knowledge of the genetic architecture of body composition and related diseases.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) affects up to a third of the global population; its burden has grown in parallel with rising rates of type 2 diabetes mellitus and obesity. MAFLD increases the risk of end-stage liver disease, hepatocellular carcinoma, death and liver transplantation and has extrahepatic consequences, including cardiometabolic disease and cancers. Although typically associated with obesity, there is accumulating evidence that not all people with overweight or obesity develop fatty liver disease. On the other hand, a considerable proportion of patients with MAFLD are of normal weight, indicating the importance of metabolic health in the pathogenesis of the disease regardless of body mass index. The clinical profile, natural history and pathophysiology of patients with so-called lean MAFLD are not well characterized. In this Review, we provide epidemiological data on this group of patients and consider overall metabolic health and metabolic adaptation as a framework to best explain the pathogenesis of MAFLD and its heterogeneity in individuals of normal weight and in those who are above normal weight. This framework provides a conceptual schema for interrogating the MAFLD phenotype in individuals of normal weight that can translate to novel approaches for diagnosis and patient care.

Cardiometabolic index (CMI) is a well promising indicator for predicting obesity-related diseases, but its predictive value for metabolic associated fatty liver disease (MAFLD) is unclear. This study aimed to investigate the relationship between CMI and MAFLD and to evaluate the predictive value of CMI for MAFLD.

A total of 943 subjects were enrolled in this cross-sectional study. CMI was calculated by multiplying the ratio of triglycerides and high-density lipoprotein cholesterol (TG/HDL-C) by waist-to-height ratio (WHtR). Multivariate logistic regression analysis was used to systematically evaluate the relationship between CMI and MAFLD. Receiver operating characteristic (ROC) curves were used to assess the predictive power of CMI for MAFLD and to determine the optimal cutoff value. The diagnostic performance of high CMI for MAFLD was validated in 131 subjects with magnetic resonance imaging diagnosis.

Subjects with higher CMI exhibited a significantly increased risk of MAFLD. The odds ratio for a 1-standard-deviation increase in CMI was 3.180 (2.102-4.809) after adjusting for various confounding factors. Further subgroup analysis showed that there were significant additive interactions between CMI and MAFLD risk in gender, age, and BMI (P for interaction < 0.05), and the area under the ROC curve(AUC) of CMI for predicting MAFLD were significantly higher in female, young, and nonobese subgroups than that in male, middle-aged and elderly, and obese subgroups (all P < 0.05). Moreover, among nonobese subjects, the AUC of CMI was significantly higher than that of waist circumference, BMI, TG/HDL-C, and TG (all P < 0.05). The best cutoff values of CMI to diagnose MAFLD in males and females were 0.6085 and 0.4319, respectively, and the accuracy, sensitivity, and specificity of high CMI for diagnosing MAFLD in the validation set were 85.5%, 87.5%, and 80%, respectively.

CMI was strongly and positively associated with the risk of MAFLD and can be a reference predictor for MAFLD. High CMI had excellent diagnostic performance for MALFD, which can enable important clinical value for early identification and screening of MAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Importantly, NAFLD increases the risk for cardiovascular disease (CVD). A causal relationship has been substantiated. Given the pandemic proportions of NAFLD, a reliable scoring system for predicting the risk of NAFLD-associated CVD is an urgent medical need. We here review cumulative evidence suggesting that systemically released organokines - especially certain adipokines, hepatokines, and cardiokines - may serve this purpose. The underlying rationale is that these signalers directly communicate between white adipose tissue, liver, and heart as key players in the pathogenesis of NAFLD and resultant CVD events. Moreover, evidence suggests that these organ-specific cytokines are secreted in a biologically predetermined, cascade-like pattern. Consequently, upon pinpointing organokines of relevance, we sketch requirements to establish an algorithm predictive of the CVD risk in patients with NAFLD. Such an algorithm, as to be consolidated in the form of an applicable equation, may be improved continuously by machine learning. To the best of our knowledge, such an option has not yet been considered. Establishing and implementing a reliable algorithm for determining the NAFLD-associated CVD risk has the potential to save many NAFLD patients from life-threatening CVD events.

In 2020, a novel comprehensive redefinition of fatty liver disease was proposed by an international panel of experts. This review aims to explore current evidence regarding the impact of this new definition on the current understanding of the epidemiology, pathogenesis, diagnosis, and clinical trials for fatty liver disease.

The effectiveness of metabolic dysfunction-associated fatty liver disease (MAFLD) was compared to the existing criteria for nonalcoholic fatty liver disease (NAFLD). Recent data robustly suggest the superior utility of MAFLD in identifying patients at high risk for metabolic dysfunction, the hepatic and extra-hepatic complications, as well as those who would benefit from genetic testing, including patients with concomitant liver diseases. This change in name and criteria also appears to have improved disease awareness among patients and physicians.

The transformation in name and definition from NAFLD to MAFLD represents an important milestone, which indicates significant tangible progress towards a more inclusive, equitable, and patient-centred approach to addressing the profound challenges of this disease. Growing evidence has illustrated the broader and specific contexts that have tremendous potential for positively influencing the diagnosis and treatment. In addition, the momentum accompanying this name change has included widespread public attention to the unique burden of this previously underappreciated disease.

Polarizing opinions have recently arisen in hepatology on the name and redefinition of fatty liver disease associated with metabolic dysfunction. In spite of growing and robust evidence of the superior utility of the term metabolic (dysfunction) associated fatty liver disease (MAFLD) definition for clinical and academic practice, controversy abounds. It should therefore come, as no surprise that the most common arguments used in contrarian op-eds is that there are no consensus on any name change. In this context, we suggest that discourse on an accurate understanding of what scientific consensus means, the various methods of achieving consensus, as well as other alternative models for reaching agreement is pivotal for the field. In this opinion piece, we provide an overview of these aspects as it applies to the case of fatty liver disease. We provide evidence that consensus on a change from non-alcoholic fatty liver disease (NAFLD) to MAFLD has already been achieved. We believe that the time has come for redirecting stakeholder focus and energy on capitalizing on the momentum generated by the debate to improve the lives of people at its centre, our patients.

Nonalcoholic fatty liver disease (NAFLD) affects about a quarter of the world's population and poses a major health and economic burden globally. Recently, there have been hasty attempts to rename NAFLD to metabolic-associated fatty liver disease (MAFLD) despite the fact that there is no scientific rationale for this. Quest for a "positive criterion" to diagnose the disease and destigmatizing the disease have been the main reasons put forth for the name change. A close scrutiny of the pathogenesis of NAFLD would make it clear that NAFLD is a heterogeneous disorder, involving different pathogenic mechanisms of which metabolic dysfunction-driven hepatic steatosis is only one. Replacing NAFLD with MAFLD would neither enhance the legitimacy of clinical practice and clinical trials, nor improve clinical care or move NAFLD research forward. Rather than changing the nomenclature without a strong scientific backing to support such a change, efforts should be directed at understanding NAFLD pathogenesis across diverse populations and ethnicities which could potentially help develop newer therapeutic options.

The term non-alcoholic fatty liver disease (NAFLD), and its definition, have limitations for both adults and children. The definition is most problematic for children, for whom alcohol consumption is usually not a concern. This problematic definition has prompted a consensus to rename and redefine adult NAFLD associated with metabolic dysregulation to metabolic (dysfunction)-associated fatty liver disease (MAFLD). Similarities, distinctions, and differences exist in the causes, natural history, and prognosis of fatty liver diseases in children compared with adults. In this Viewpoint we, an international panel, propose an overarching framework for paediatric fatty liver diseases and an age-appropriate MAFLD definition based on sex and age percentiles. The framework recognises the possibility of other coexisting systemic fatty liver diseases in children. The new MAFLD diagnostic criteria provide paediatricians with a conceptual scaffold for disease diagnosis, risk stratification, and improved clinical and multidisciplinary care, and they align with a definition that is valid across the lifespan.

Metabolic-associated fatty liver disease (MAFLD) is the most common liver disease globally, and affects about a quarter of the general population. Autoimmune hepatitis (AIH) is a severe (sometimes fatal) liver disease that affects children and adults, with a rising prevalence. Thus, not surprisingly, both conditions can frequently coexist, with potential synergistic impact on the course of the disease and response to therapy of both entities.

In this work, the authors aimed to provide a narrative updated review on this interaction, diagnosis, and management of MAFLD/AIH and the current challenges.

Clarifying the nature of the complex interaction between the two diseases was hampered by a myriad of factors, particularly the previous diagnosis of exclusion for fatty liver disease associated with metabolic dysfunction. The recent redefinition of fatty liver disease that led to the development of positive diagnostic criteria for MAFLD has the premise to help in circumventing some of these challenges.

The World Health Organization (WHO) set a goal to eliminate hepatitis C (HCV) infection globally by 2030, with specific targets to reduce new viral hepatitis infections by 80% and reduce related deaths by 65%. However, an overlooked aspect that may hinder these efforts is the impact other liver diseases could have by continuing to drive liver disease progression and offset the beneficial impact of DAAs on end-stage liver disease and hepatocellular carcinoma (HCC). In particular, the decrease in HCV prevalence has been countered by a marked increase in the prevalence of metabolic-associated fatty liver disease (MAFLD).

To review the potential interaction of HCV and MAFLD.

We have reviewed the literature relating to an arrange of interaction of HCV, metabolic dysfunction and MAFLD.

In this viewpoint, international experts suggest a holistic and multidisciplinary approach for the management of the growing number of treated HCV patients who achieved SVR, taking into consideration the overlooked impact of MAFLD for reducing morbidity and mortality in people who have had HCV.

This will strengthen and improve the continuum of care cascade for patients with liver disease(s) and holds the potential to alleviate the cost burden of disease; and increase quality of life for patients following DAAs treatment.

Recently, the new definition of Metabolic (dysfunction) associated fatty liver disease (MAFLD) has gained remarkable scientific interest. We aimed to evaluate the effectiveness of MAFLD definition in selecting obese children at higher cardiovascular risk.

A total of 954 obese children and adolescents was retrospectively enrolled. Clinical, biochemical, and metabolic evaluations were performed. Hepatic steatosis was assessed by liver ultrasound. According to the metabolic status, the population was divided in three groups. Group 1 included obese patients without both non-alcoholic fatty liver disease (NAFLD) and metabolic dysregulation; group 2 included patients with obesity and NAFLD (then encompassing one MAFLD criterion); group 3 included patients with obesity, NAFLD and evidence of metabolic dysregulation (then encompassing more than 1 MAFLD criteria).

Patients of Group 3 showed a worse cardiometabolic profile, as also proven by the higher percentage of prediabetes (defined as the presence of impaired fasting glucose or impaired glucose tolerance) compared to other groups (p = 0.001).

MAFLD criteria in obese children seem to be less accurate in identifying patients having an intrinsic higher cardiometabolic risk. This suggests the need for a more accurate definition in the context of pediatric obesity.