Characterising the phenotypic features of individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) can help identify high-risk subpopulations within this group. High-sensitivity troponin (hs-troponin) is a significant risk factor for future cardiovascular disease events.

We studied the association of hs-troponin in the absence of cardiovascular disease with all-cause and cause-specific mortality among individuals with MASLD.

We used the National Health and Nutrition Examination Survey 1999-2004 and linked the mortality dataset through 2019. We used Cox regression models to assess the association between hs-troponin with all-cause and cause-specific mortality among individuals with MASLD and without cardiovascular disease.

During the median follow-up period of 17.5 years (IQR: 15.9-19.1), higher levels of hs-troponin T among individuals with MASLD were associated with progressively higher hazards of all-cause and cardiovascular mortality, which remained significant after adjustment for demographic, clinical, lifestyle and metabolic risk factors. There was a 29% (hazard ratio [HR]: 1.29, 95% confidence interval [CI]: 1.16-1.44) increase in all-cause mortality and a 44% (HR: 1.44, 95% CI: 1.20-1.72) increase in cardiovascular mortality for every rise in 1-standard deviation of hs-troponin T. A significant association between hs-troponin (p for trend) and cardiovascular mortality was noted with 3 hs-troponin I assays, similar to hs-troponin T. There was no significant association between hs-troponin and cancer-related mortality.

Screening hs-troponin T or I in individuals with MASLD can identify at-risk subpopulations within this group that have a higher risk for future all-cause mortality, predominantly due to cardiovascular disease-related mortality in the population without cardiovascular disease.

Increasing evidence supports a higher risk of abnormal liver function parameters due to unfavorable lifestyles. We therefore explored the synergistic effects of various lifestyle factors on liver function.

8710 participants from Guangzhou Biobank Cohort Study were included. Five lifestyle factors including non-smoking, non-alcohol use, physically active, non-central and non-general obesity were assessed and a Healthy Lifestyle Index (HLI) (0-5, a higher score indicates healthier lifestyle) was generated. Multivariable linear regression was used to examine the association of HLI with liver function parameters, yielding regression coefficients (βs) and 95% confidence intervals (CIs).

A total of 8710 participants with an average age of 64.67 years (standard deviation = 6.07) were included. Of them, 71.65% were women. After adjusting for sex, age, education, family income, and comorbidities, compared with those with HLI of zero, those with HLI scores of 1, 2, 3, 4, and 5 showed a lower ALT level by -5.85 IU/L (95% CI: -10.73, -0.97), -9.97 IU/L (95% CI: -14.53, -5.42), -11.34 IU/L(95% CI: -15.86, -6.82), -12.81 IU/L (95% CI: -17.33, -8.30), and - 14.15 IU/L (95% CI: -18.68, -9.62), respectively (P for trend < 0.001), and a lower AST level by 1.82 IU/L (95% CI: -4.85,1.21), -3.74 IU/L (95% CI: -6.57, -0.91), -4.47 IU/L (95% CI: -7.28, -1.66), -4.69 IU/L (95% CI: -7.49, -1.88), and - 4.75 IU/L (95% CI: -7.57, -1.94), respectively (P for trend < 0.001). Similar trends were observed for a higher ALB level with higher healthy lifestyle scores (P for trend = 0.003).

A healthy lifestyle was associated with optimal liver function parameters, highlighting the importance of advocating for health-conscious behaviors to potentially mitigate the incidence of liver dysfunction.

Sarcopenia, physical activity (PA), and sedentary behavior are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). The study aimed to evaluate the effects of sarcopenia and PA on the presence and severity of MASLD.

This cross-sectional study analyzed data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). Hepatic steatosis and liver fibrosis were assessed by vibration-controlled transient elastography (VCTE). Sarcopenia was defined based on the Foundation for the National Institutes of Health criteria. PA and sedentary behavior were evaluated using the Global Physical Activity Questionnaire (GPAQ).

Among 1,831 participants, 664 were diagnosed with MASLD, including 482 with severe steatosis and 89 with significant fibrosis. The prevalence of sarcopenia in the MASLD and non-MASLD populations was 11.7% and 3.8%, respectively. Multivariable-adjusted models demonstrated that sarcopenia significantly increased the risk of MASLD (OR 2.45; 95% CI: 1.33-4.52), severe steatosis (OR 2.56; 95% CI: 1.40-4.66), and significant fibrosis (OR 6.10; 95% CI: 2.08-17.84). Additionally, individuals with sarcopenia and low PA had a 7.91-fold increased risk of developing significant fibrosis (OR, 7.91; 95% CI: 1.42-44.16, P = 0.022). Sarcopenia and prolonged sedentary behavior further increased the risk of MASLD (OR 3.75; 95% CI: 1.60-8.76), severe steatosis (OR 17.58; 95% CI: 1.93-159.79), and significant fibrosis (OR 4.32; 95% CI: 1.31-14.31).

Patients with sarcopenia should increase physical activity and reduce sedentary time to decrease the risk and progression of MASLD. Increasing muscle mass and strength through resistance exercise to reduce the risk of significant fibrosis in sarcopenia patients.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) can be recapitulated in mice fed a high-fat diet. The development of MASLD and the diet per se can both perturb metabolism in key extrahepatic tissues such as the heart, kidney, and skeletal muscle. To date, these alterations have not been well described in this animal model of diet-induced MASLD. Methodology: Male C57BL/6J mice were fed either standard (SC, n = 12) or high-fat chow (HF, n = 11) for 18 weeks. Metabolites were extracted from the heart, kidney, and skeletal muscle and analyzed by 1H nuclear magnetic resonance (NMR) spectroscopy, along with multivariate and univariate statistical analyses. Results: Kidney metabolite profiles exhibited the largest differences between HF and SC diets, followed by those of skeletal muscle and then the heart. Some alterations were common across all tissues, namely decreased trimethylamine and elevated levels of linoleic acid and polyunsaturated fatty acids in HF compared to SC (p < 0.05 for all three metabolites). Overall, the metabolite variations were consistent with shifts in carbohydrate and lipid substrate selection for oxidation, increased tissue stress in the heart and kidneys, and altered choline metabolism. These findings may serve as additional important descriptors of MASLD onset and progression.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is often regarded in society as a disease caused by personal lifestyle and dietary choices. Healthcare providers who have empathy and are able to explain the disease trajectory can better engage with people with MASLD and actively work with them to improve their metabolic health on a sustainable basis. Non-invasive tests can assist in this process, but healthcare providers must ensure they explain their advantages and limitations. Discussing and setting lifestyle goals are priorities before initiating specific pharmacological treatment, since living a healthy lifestyle will remain the backbone of the multimodal management of MASLD. In this review, we discuss challenges and opportunities to actively engage with people living with MASLD in a multimodal treatment framework as a healthcare provider.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), encompasses a spectrum of liver diseases characterized by hepatic steatosis, the presence of at least one cardiometabolic risk factor, and no other apparent cause. Metabolic syndrome (MetS) is a cluster of clinical conditions associated with increased risk of cardiovascular disease, type 2 diabetes, and overall morbidity and mortality. This narrative review summarizes the changes in the management of people with MetS and NAFLD/MASLD from screening to therapeutic strategies that have occurred in the last decades. Specifically, we underline the clinical importance of considering the different impacts of simple steatosis and advanced fibrosis and provide an up-to-date overview on non-invasive diagnostic tests (i.e., imaging and serum biomarkers), which now offer acceptable accuracy and are globally more accessible. Early detection of MetS and MASLD is a top priority as it allows for timely interventions, primarily through lifestyle modification. The liver and cardiovascular benefits of a global and multidimensional approach are not negligible. Therefore, a holistic approach to both conditions, MetS and related chronic liver disease, should be applied to improve overall health and longevity.

Exposure to brominated flame retardants (BFRs) has been linked to age-related diseases. This study investigates the associations between both individual and combined BFRs exposures and phenotypic age acceleration (PhenoAgeAccel) in U.S. adults.

Data from 3,908 U.S. adults from NHANES 2005-2010 were analyzed. Generalized linear regression models (GLMs) assessed the associations between individual BFRs and PhenoAgeAccel, while weighted quantile sum (WQS) regression and Bayesian Kernel Machine Regression (BKMR) analyses were used to evaluate the effects of combined BFRs exposures.

GLMs indicated significant positive associations between several BFRs and PhenoAgeAccel, including PBDE28 (β = 0.55, 95% CI: 0.13, 0.96), PBDE85 (β = 0.42, 95% CI: 0.11, 0.74), PBDE47 (β = 0.39, 95% CI: 0.04, 0.75), PBDE99 (β = 0.38, 95% CI: 0.07, 0.68), and PBDE154 (β = 0.37, 95% CI: 0.04, 0.70). RCS analysis confirmed nonlinear dose-response relationships for PBDE47 and PBDE99 (P for nonlinearity = 0.03361 and 0.0233, respectively). Stratified analyses revealed that males were more susceptible to BFRs exposure effects, particularly for PBDE99 (P for interaction = 0.027) and PBDE209 (P for interaction = 0.005). The WQS regression showed a significant association between combined BFRs exposure and increased PhenoAgeAccel (β = 0.504, 95% CI: 0.071, 0.937), with PBB153 and PBDE153 as key contributors. BKMR analysis indicated a trend of increasing PhenoAgeAccel with higher BFR exposure levels, primarily driven by PBDE99.

This study highlights the significant positive associations between individual and combined BFR exposures and PhenoAgeAccel, with males potentially being more vulnerable to these effects.

Steatotic liver disease (SLD) is influenced by both genetics and lifestyle factors, with lifestyle effects varying by genetic susceptibility. We aimed to evaluate gene-lifestyle interactions on SLD risk.

We included 28,215 UK Biobank participants with available data. Predictors were healthy lifestyle patterns, PNPLA3-rs738409, TM6SF2-rs58542926, a 16-variant hepatic steatosis polygenic risk score (PRS), and gene-environment interactions. Primary outcome was liver fat content (LFC); secondary outcomes were cT1 (a measure of liver inflammation/fibrosis) and SLD-related events.

Lifestyle predictors, except smoking, reduced LFC, while genetic predictors increased it. Genetic predictors significantly interacted with healthy lifestyle patterns, sedentary behavior and social connection. Lifestyle effects on lower LFC were up to 6.3-fold stronger in PNPLA3-rs738409-GG vs. -CC individuals, and 1.5-7.0 times higher in the top vs. bottom PRS quartile. PRS and PNPLA3 also interacted with alcohol consumption, diet, and PNPLA3 further interacted with physical activity. These interactions were more pronounced in overweight participants. Genetic factors and physical activity interacted to influence cT1, while PRS, PNPLA3 and sleep duration were associated with cardiovascular events.

Lifestyle effects on LFC, cT1 and cardiovascular events were accentuated in individuals at higher SLD genetic risk, implying lifestyle interventions may be more impactful in these populations.

Complications from metabolic dysfunction-associated steatotic liver disease (MASLD) include liver-related and extrahepatic complications, and the all-cause mortality rate is significantly higher in patients with MASLD than in those without MASLD.

We review the complications of MASLD and their management based on the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD) guidelines as well as medical papers. For the papers, we focused on studies referenced in the EASL and AASLD guidelines. Additionally, a search was conducted in PubMed to gather relevant literature.

Identifying and managing MASLD early, before it progresses to cirrhosis, is crucial to reducing mortality rates, and collaboration among healthcare professionals, including dietitians, nurses, and physical therapists, is vital for comprehensive management. There is active development of new drugs for MASLD, and we hope that new treatments will be developed soon.

The rising intake of ultra-processed foods (UPFs) has been linked to adverse health outcomes, yet its impact on aging acceleration remains unclear.

This study aimed to examine the association between the percentage of total daily calories (%Kcal) and grams (%Gram) from UPFs and phenotypic age acceleration (PhenoAgeAccel).

Data from 12,079 adults in the NHANES 2005-2010 cycles were analyzed. The relationship between UPFs intake and PhenoAgeAccel was assessed using multivariable linear regression and restricted cubic splines, with adjustments for relevant covariates. The mediating role of body mass index (BMI) was also explored.

A significant positive linear association was observed between UPFs intake (%Gram) and PhenoAgeAccel, with the highest quartile showing an increase of 0.60 (95% CI: 0.15, 1.05; p for trend = 0.039), but no association was found between UPFs intake (%Kcal) and PhenoAgeAccel. Mediation analysis indicated that BMI mediated 27.5% of the association between UPFs intake (%Gram) and PhenoAgeAccel. Sensitivity analyses confirmed the robustness of the results.

Higher intake of UPFs intake (%Gram) is positively associated with PhenoAgeAccel, with BMI playing a significant mediating role.

Few studies have investigated the associations between perchlorate, nitrate, and thiocyanate (PNT) and biological aging. This study aimed to assess the association between PNT and biological aging among U.S. adults.

Utilizing multivariable linear regression and restricted cubic splines (RCS), we analyzed urinary PNT levels' impact on phenotypic age and biological age. Subgroup and sensitivity analyses were also conducted. Weighted Quantile Sum (WQS) and Bayesian Kernel Machine Regression (BKMR) models examined PNT mixtures.

8,368 participants were analyzed. Mean phenotypic age was 43.05 ± 0.48 years, mean biological age was 47.08 ± 0.4 years. Multivariable linear regression showed significant negative associations between higher PNT levels and phenotypic age (perchlorate β = -0.6, 95% CI: -0.93 to -0.27; nitrate β = -0.81, 95% CI: -1.19 to -0.42; thiocyanate β = -0.56, 95% CI: -0.77 to -0.34) after covariates adjusted. RCS demonstrated negative nonlinear relationships between PNT exposure and phenotypic age (nonlinear p values: 0.002, <0.001, and <0.001), with stable results in sensitivity analyses. Nitrate exposure showed a significant negative association with biological age (β = -0.78, 95% CI: -1.13 to -0.44), indicating a consistent negative linear relationship observed through RCS and remaining stable across sensitivity analyses. WQS regression revealed a negative association between the mixture and phenotypic age in both positive and negative directions, with a significant negative association with biological age in the negative direction. BKMR analysis revealed a negative association between PNT mixtures and phenotypic age, with nitrate and thiocyanate identified as the primary predictors of phenotypic age. No association found between PNT mixture and biological age.

Individual or combined PNT are negatively associated with phenotypic age. High nitrate is associated with reduced biological age, showcasing consistent outcomes.

Obesity is detrimental to liver health. Weight-adjusted waist circumference (WWI) is a new indicator of obesity that is superior to body mass index (BMI) and waist circumference (WC) in predicting obesity. There are limited studies on the relationship between Metabolic Associated Fatty Liver Disease (MASLD) and WWI. Therefore, this study aimed to investigate the association between WWI, Controlled Attenuation Parameters (CAP), and Liver Stiffness Measurement (LSM), with special attention to gender differences.

This cross-sectional study included participants from the 2017 to 2020 National Health and Nutrition Examination Survey (NHANES). The study used multiple linear regression models, smoothed curves, and threshold effects analyses to describe the relationships between variables. Multiple regression analyses were used to examine the associations between the four obesity indicators and CAP and LSM. Subject work characteristics (ROC) curves were used to assess the predictive value of WWI and other traditional obesity indicators for hepatic steatosis and liver fibrosis, and predictive power was assessed by area under the curve (AUC).

The study involved 6713 participants, including 3072 men (46%) and 3641 women (54%). The results showed that among female participants, higher WWI was associated with hepatic steatosis (OR = 1.71, 95% CI: 1.43, 2.04; P < 0.0001) and hepatic fibrosis (OR = 2.11, 95% CI: 1.58, 2.84; P < 0.0001). Smoothed curve fitting of WWI versus CAP showed a statistically significant positive correlation between WWI in male and female participants There was a statistically significant positive correlation with CAP for both male and female participants. The same significant non-linear relationship was found between WWI and LSM, with no significant difference between males and females. WWI was also a good predictor of hepatic steatosis compared to other obesity indicators and was more pronounced in male participants (AUC = 0.8224). Whereas in the comparison of WWI with LSM, wBMI was a better predictor in female participants (AUC = 0.7751).

Based on this study, WWI was significantly associated with the risk of hepatic steatosis and hepatic fibrosis in women, suggesting the potential of WWI as a screening tool. Due to the cross-sectional design, causality cannot be inferred. Longitudinal studies are needed to validate our findings.

Exercise is a key component of lifestyle management in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but neither its therapeutic effect on the active stage of the disease, that is metabolic dysfunction-associated steatohepatitis (MASH) nor the mediating mechanisms have been characterized. Therefore, we performed multi-omic phenotyping of patients with MASLD-MASH on an exercise program.

Fifteen patients with MASLD conducted high-intensity interval training (HIIT) combined with home-based training for 12 weeks. MASLD was evaluated using histology, transient elastography, and multiparametric magnetic resonance imaging (MRI) before and after the intervention. Change in maximal oxygen consumption (VO2max) and MRI-determined liver fat were compared with a control group of patients with MASLD (n = 22). RNA sequencing was performed on liver, muscle, and fat biopsies of patients in the exercise group. Stool was analyzed by shotgun metagenomics and untargeted metabolomics was performed on plasma, urine, adipose, and stool.

HIIT increased VO2max by 10.1% and improved mitochondrial metabolism in skeletal muscle, indicating improved cardiorespiratory fitness and adherence. VO2max increased significantly in the exercise group compared with controls. Histologically, no reduction in steatosis, MASH, or liver fibrosis was observed; however, transient elastography tended to improve. MRI-determined liver fat did not change in the exercise group compared with controls. HIIT induced changes in mRNA expression of genes related to beiging of adipose tissue and fibrogenesis in liver. In addition, specific gut microbial taxa and metabolites changed.

HIIT increased cardiorespiratory fitness and induced beneficial gene expression changes in muscle, adipose tissue, and liver, but without translation into histological improvement of MASLD. Longer exercise intervention trials are warranted to validate or refute current recommendations for exercise as a cornerstone treatment for MASLD-MASH.

Despite exercise being considered as a key component of lifestyle management for steatotic liver disease, neither the clinical effects nor the mechanisms involved are completely understood. We show that a high-intensity interval training (HIIT) program in 15 patients with metabolic dysfunction-associated steatotic liver disease (MASLD) improved cardiorespiratory fitness, compared with 22 control patients with MASLD who did not participate in an exercise program, however, it did not improve MASLD. HIIT induced a positive effect on fat tissue and muscle metabolism which was accompanied with changes in certain gut bacteria and metabolites in blood and urine. These findings improve our understanding of the effects of exercise on the whole-body metabolism in relation to steatotic liver disease. As such, this study provides a basis for future exercise interventions in patients with MASLD, required to thoroughly test current guideline advice for exercise as a cornerstone treatment for MASLD of all stages.

Dutch Trial Register (registration number NL7932).

Introduction: This study aims to investigate the combined association between insulin resistance (IR) levels, relative grip strength (RGS), and the incidence of nonalcoholic fatty liver disease (NAFLD), stratified by sex, using longitudinal data. Methods: The study included 1702 adult participants aged 51-88 years who completed surveys in both 2013-2014 and during a subsequent follow-up in 2019-2020. NAFLD was assessed using the hepatic steatosis index, and RGS was measured using the JAMA-5030J1 equipment (SAEHAN, Korea). To assess the interaction between RGS and IR levels and their impact on NAFLD risk, we employed a proportional hazards Cox regression model. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated for NAFLD incidence. Results: After adjusting for various confounding variables, we observed a significant decrease in NAFLD risk in the middle RGS group (HR = 0.70, 95% CI = 0.53-0.93) and high RGS group (HR = 0.31, 95% CI = 0.22-0.44) compared to the low RGS group. In addition, significant sex differences were noted in the relationship between IR, RGS levels, and NAFLD incidence across different groups. Conclusions: This study highlights that higher RGS levels are independently associated with a reduced risk of developing NAFLD. Notably, RGS emerges as a predictive indicator for assessing NAFLD risk.

Many studies have shown a link between physical activity (PA) and nonalcoholic fatty liver disease (NAFLD). However, more research is needed to investigate the relationship between different types of PA and NAFLD. This study aimed to explore the potential link between different types of PA, hepatic steatosis, and liver fibrosis.

A cross-sectional study was conducted using the data set from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. A multiple linear regression model was used to examine the linear relationship between different types of PA, the controlled attenuation parameter (CAP), and liver stiffness measurement (LSM). In addition, smoothing curve fitting and threshold effect analysis were used to depict their nonlinear relationship.

This study involved 5933 adults. Multiple linear regression analysis revealed a significantly negative correlation between leisure-time PA and CAP, while the relationship between occupation-related PA, transportation-related PA, and CAP was not significant. Subgroup analysis further revealed that leisure-time PA was significantly negatively correlated with CAP in women and younger age groups (under 60 y old), while the relationship was not significant in men and older age groups. In addition, there was a significant negative correlation between leisure-time PA and liver fibrosis in men.

Leisure-time PA can prevent hepatic steatosis, and women and young people benefit more. Occupation-related PA is not associated with hepatic steatosis and cannot replace leisure-time PA. In men, increasing leisure-time PA is more effective in preventing liver fibrosis.

Preserved Ratio Impaired Spirometry (PRISm) is increasingly recognized as a precursor to Chronic Obstructive Pulmonary Disease (COPD). The impact of Ultra-Processed Foods (UPFs) intake on PRISm and lung function remains underexplored, and we aimed to explore their associations.

This study included 8,336 U.S. adults. Weighted logistic and linear regression models were employed for main analysis. Dose-response relationship was examined through restricted cubic spline (RCS) analysis, and subgroup analyses explored interactions with selected covariates.

Participants in the PRISm group were older and exhibited various adverse health characteristics. The percentage of total daily energy intake from UPFs (%Kcal) intake was associated with a non-significant increase in PRISm risk (OR 1.67, 95% CI: 0.96-2.92, p = 0.07). However, the highest quartile of UPFs (%Kcal) intake was significantly linked to increased PRISm risk (OR 1.36, 95% CI: 0.99-1.86, P for trend = 0.043). Furthermore, higher UPFs (%Kcal) intake negatively affected lung function, with participants in the highest quartile showing a significant reduction in forced expiratory volume in 1 s (FEV1) of -45.5 mL (95% CI: -87.6 to -3.4, P for trend = 0.045) and a decrease in forced vital capacity (FVC) of -139.4 mL (95% CI: -223.5 to -55.4, p < 0.001) compared to those in the lowest quartile. RCS analysis demonstrated linear relationships for both PRISm and lung function. Subgroup analysis revealed increased susceptibility primarily among individuals with occupational exposure. Additionally, sensitivity analysis indicated that a higher percentage of total daily intake from UPFs (%Grams) intake was significantly associated with an increased risk of PRISm (OR 1.86, 95% CI: 1.07-3.25, p = 0.03).

Higher intake of UPFs is linked to an increased risk of PRISm and negatively affects lung function, particularly in individuals with occupational exposure.

Nocturia is the most prevalent lower urinary tract symptom (LUTS) and is closely associated with various diseases and social burdens. Research on the relationship between physical activity and various diseases has progressed significantly. However, the association between nocturia and physical activity has received limited attention in prior studies. Thus, this study aimed to investigate the relationship between different domains of physical activity (e.g., occupation-related physical activity [OPA], transportation-related physical activity [TPA], and leisure-time physical activity [LTPA]) and nocturia. We included 5516 participants from the cross-sectional National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2012, employing survey-weighted logistic regression, restricted cubic splines (RCS), subgroup analysis, and sensitivity analysis to assess the relationship between different domains of physical activity and nocturia. Multivariable logistic regression analysis revealed a significant negative correlation between PA, LTPA, and nocturia. Specifically, PA (OR 0.7523, 95% CI 0.6307-0.8974, P = 0.002) and LTPA (OR 0.7664, 95% CI 0.6314-0.9304, P = 0.007) were negatively associated with nocturia. The RCS curve demonstrated non-linear relationships between PA, LTPA, and nocturia. Additionally, subgroup analyses and sensitivity analyses further validated this association. Based on this cross-sectional study, we suggested that PA and LTPA are associated with a reduced risk of nocturia in adults aged 20 years and older in the United States. This underscores the importance of physical activity in preventing and managing nocturia may provide valuable guidance for clinical practice.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, characterized by hepatic steatosis with at least one cardiometabolic risk factor. Patients with MASLD are at increased risk for the occurrence of cardiovascular events. Within this review article, we aimed to provide an update on the pathophysiology of MASLD, its interplay with cardiovascular disease, and current treatment strategies.

Given their high burden of cardiovascular comorbidities, patients with MASLD or MASH should undergo regular cardiovascular risk assessment using established risk models. In the absence of liver-specific therapies, therapeutic strategies should focus on improving cardiometabolic risk factors. Patients require a multimodal and multi-stakeholder treatment approach, including optimization of lifestyle, dysglycemia, obesity, and dyslipidemia. Statin treatment represents a safe and effective but often underused therapy in the management of at-risk patients with MASLD and MASH. Novel promising approaches include the use of GLP-1 receptor agonists, especially in, but not limited to, patients with cardiovascular disease and obesity. Patients with MASLD and MASH are at high cardiovascular risk requiring a multi-modal therapeutic approach including regular cardiovascular risk assessment, as well as lifestyle and pharmacological interventions. Statin therapy represents an inexpensive, safe and effective therapy across the spectrum of non-alcohol related steatotic liver diseases without major safety concerns. More prospective, randomized trials in patients with MASLD and MASH are needed.

The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), parallels the rise in sedentary lifestyles. MASLD is the most common form of steatotic liver disease (SLD), which represents the umbrella beneath which the vast majority of chronic liver diseases fall, including alcohol-related liver disease and their overlap. These conditions are the leading contributors to chronic liver disease, significantly impacting global morbidity and mortality. Despite the emergence of new pharmacotherapies, exercise represents the foundation of MASLD treatment.

This review aims to provide an updated perspective on the role of exercise in the management of SLD, highlight its molecular and clinical benefits, and explore its benefits and safety in the stage of cirrhosis.

Evidence from pre-clinical and clinical studies was reviewed to evaluate the impact of exercise on SLD (mainly MASLD), advanced chronic liver disease stages, and its relevance in the context of evolving therapies such as Resmetirom and incretin-based anti-obesity medications.

Exercise remains a cornerstone intervention in the management of MASLD, with suggested benefits even for patients who have progressed to cirrhosis. Personalized exercise regimens should be prioritized for all patients, including those receiving pharmacotherapy. Further research is needed to refine exercise protocols and investigate their impact on histologic and clinical outcomes, as well as their potential synergistic effects with emerging treatments.

The incidence of non-alcoholic fatty liver disease (NAFLD) has increased with the global increase in the outbreak of obesity, type 2 diabetes, and metabolic syndrome, reaching a 25% prevalence. However, there is currently no effective treatment for this disease apart from lifestyle modification. Furthermore, NAFLD commonly presents without symptoms, hence, leading to potentially severe and irreparable consequences.

This study was based on a systematic review. The search used the keywords "non-alcoholic fatty liver" and "risk factor" across the PubMed, Scopus, and Web of Science databases. First, the articles were evaluated based on their abstract and then on their full text. The risk factors were extracted from the articles and entered into the Excel form, and then a dataset was provided to the expert panel. The risk factors were investigated, and those related to NAFLD were selected.

The results led to the identification of 180 risk factors in 15 categories. First, the risk factors mentioned in fewer than five articles were removed. Then, the remaining 101 risk factors were presented to the expert panel, of which 39 risk factors related to NAFLD were selected.

In summary, this study shows that NAFLD is caused by various factors such as metabolic syndrome, certain diseases, demographic information, specific surgeries, drug consumption, different foods and beverages, occupation, physical activity status, and socioeconomic status. Recognizing these risk factors enables doctors to make earlier diagnoses, potentially preventing disease progression. Additionally, it is possible to develop treatment strategies aimed at reducing the risk factors of the disease, which could result in fewer patients suffering from NAFLD in the future.

Body fat distribution may impact nonalcoholic fatty liver disease (NAFLD) and significant fibrosis differently according to race/ethnicity. We determined the relationship between body fat distribution and NAFLD/significant fibrosis according to race/ethnicity.

A cross-sectional study of 2,395 participants used the National Health and Nutrition Examination Survey 2017 to 2018. NAFLD and significant fibrosis (≥F2) were defined by controlled attenuation parameter scores and liver stiffness measurements on transient elastography, respectively. Visceral and subcutaneous fat volumes were defined by dual-energy X-ray absorptiometry.

The odds ratio (OR) for NAFLD per 1-standard deviation in visceral fat volume and subcutaneous fat volume was 2.05 (95% confidence interval [CI], 1.36 to 3.09) and 1.48 (95% CI, 1.04 to 2.09) in total population, respectively. Visceral fat in non-Hispanic Blacks had the highest odds for NAFLD (OR, 2.86; 95% CI, 1.45 to 5.62), and non-Hispanic Whites (OR, 2.29; 95% CI, 1.19 to 4.40) and non-Hispanic Asians (OR, 1.61; 95% CI, 1.13 to 2.29) were in order. Significant associations between subcutaneous fat volume (OR, 2.10; 95% CI, 1.34 to 3.29; P=0.003) or visceral fat volume (OR, 1.35; 95% CI, 1.05 to 1.73; P=0.023) and significant fibrosis were noted among individuals with NAFLD. Hispanics had the highest odds for NAFLD-associated significant fibrosis (OR, 2.74; 95% CI, 1.32 to 5.70 per 1-standard deviation in subcutaneous fat volume), and non-Hispanic Whites (OR, 2.35; 95% CI, 1.11 to 4.98) and non-Hispanic Asians (OR, 2.01; 95% CI, 1.01 to 4.01) were in order.

Visceral adiposity was associated with NAFLD and significant fibrosis despite the association of subcutaneous adiposity in NAFLD and significant fibrosis. Racial/ethnic differences in the association between body fat distribution on NAFLD and significant fibrosis were noted.

Metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of chronic liver disease worldwide. Optimal dietary intervention strategies for MAFLD are not standardized. This study aimed to achieve consensus on prevention of MAFLD through dietary modification. A multidisciplinary panel of 55 international experts, including specialists in hepatology, gastroenterology, dietetics, endocrinology and other medical specialties from six continents collaborated in a Delphi-based consensus development process. The consensus statements covered aspects ranging from epidemiology to mechanisms, management, and dietary recommendations for MAFLD. The recommended dietary strategies emphasize adherence to a balanced diet with controlled energy intake and personalized nutritional interventions, such as calorie restriction, high-protein, or low-carbohydrate diets. Specific dietary advice encouraged increasing the consumption of whole grains, plant-based proteins, fish, seafood, low-fat or fat-free dairy products, liquid plant oils, and deeply colored fruits and vegetables. Concurrently, it advised reducing the intake of red and processed meats, saturated and trans fats, ultra-processed foods, added sugars, and alcohol. Additionally, maintaining the Mediterranean or DASH diet, minimizing sedentary behavior, and engaging in regular physical activity are recommended. These consensus statements lay the foundation for customized dietary guidelines and proposing avenues for further research on nutrition and MAFLD.

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects up to one-third of the global population. Since no approved pharmacotherapy for MAFLD is available, lifestyle modification remains the cornerstone of clinical care. Our study aims to evaluate the association of an overall healthy lifestyle with MAFLD risk.

We conducted an analysis of 327,387 participants from UK biobank. An overall healthy lifestyle score including six evidence-based lifestyles (diet, alcohol consumption, physical activity, sedentary behavior, sleep, and smoking) was assessed by questionnaires. MAFLD and its subtypes were diagnosed by blood biochemistry, ICD codes, and medication information from touchscreen and verbal interview. The prevalence ratios (PRs) and risk ratios (RRs) were estimated by Poisson regression models with robust variance.

In the cross-sectional analysis, the PR (95% CI) was 0.83 (0.83 to 0.84) for MAFLD, and 0.83 (0.83 to 0.84) for MAFLD-overweight/obesity (MAFLD-O), 0.68 (0.66 to 0.70) for MAFLD-lean/normal weight and metabolic dysfunction (P-value for heterogeneity < 0.001), and 0.71 (0.71 to 0.72) for MAFLD-type 2 diabetes mellitus (MAFLD-T2D); and 0.68 (0.66 to 0.71) for dual (or more) etiology fatty liver disease (MAFLD-dual) and 0.83 (0.83 to 0.84) for single etiology MAFLD (MAFLD-single) (P-value for heterogeneity < 0.001) for one additional point in the overall healthy lifestyle score. During a median follow-up of 4.4 years, the RR (95% CI) was 0.83 (0.81 to 0.85) for MAFLD, and 0.83 (0.81 to 0.85) for MAFLD-O, 0.71 (0.62 to 0.81) for MAFLD-L, and 0.68 (0.64 to 0.72) for MAFLD-T2D (P-value for heterogeneity < 0.001); and 0.83 (0.81 to 0.85) for MAFLD-dual and 0.70 (0.58 to 0.85) for MAFLD-single (P-value for heterogeneity = 0.08) for one additional point in the overall healthy lifestyle score. These findings were validated in a prospective analysis among 15,721 participants with revisit data, and also supported by fatty liver index and proton density fat fraction data.

An overall healthy lifestyle that includes six evidence-based factors was strongly associated with lower MAFLD risk, especially the subtypes with multiple etiologies.

It has been documented that regular physical activity is considered one of the most effective strategies for preventing diabetes; however, it is not the sole contributing factor. Therefore, we decided to evaluate the meditation effect of liver function and anthropometric indices on the relationship between incidence of diabetes and physical activity (PA) in the Azar cohort population.

Subjects who were diabetic in the baseline phase from 15,006 participants in study of azar cohort population were excluded and to follow up, a total of 13,253 people was included in the analysis. Demographic characteristics, physical activity, 10 anthropometric indices (AI) and seven liver indices (LI) were measured. Evaluated and displayed using Pearson correlation heatmap and canonical correlation of liver and anthropometric indices. The Generalized Structural Equation Modeling (GSEM) with the Maximum Likelihood method employed to estimate the model.

During the follow-up years, a total of 685 participants developed diabetes. The measurements of the AI were significantly higher in subjects with diabetes (P < .001). Patients with diabetes were older, had a higher proportion of women, and had lower values of PA (P < .05). Body Roundness Index (BRI) and Waist height ratio (WHtR) exhibited the largest AUCs for predicting diabetes onset risk (both AUC = 0.6989) among these anthropometric measures. The increase in AI (RR [95%CI] = 1.25 [1.22,1.29], P < .001) and liver enzyme (LE) (RR [95%CI] = 1.14 [1.08.1.19], P < .001) increase the risk of diabetes by 25% and 14%, respectively. Despite the mediation effects of AI and Liver Enzymes for an increase of one MET of PA, the risk of developing diabetes decreases by 5% (RR [95% CI] = .95 [.92,.99], P = .013). Around VAF = 53% of the association between PA and diabetes onset (Total effect: RR [95% CI] = .90 [.87,.94], P < .001) was mediated by AI and LE.

A low level of PA was found to be significantly correlated with high levels of AI and LI, all of which are associated with an increased risk of developing diabetes. These analyses provide evidence that when the relationship between PA and diabetes is mediated by AI and LI this association becomes stronger, with AI playing a more significant role than LI.

The specific relationship between PA in detailed types and cognition is still unclear due to limited evidence. Our study aimed to investigate the relationship between cognitive performance and various aspects of physical activity, including overall activity, dosage, intensity levels [moderate physical activity (MPA), vigorous PA], and different domains of activity [occupational PA (OPA), transportation PA (TPA), and leisure-time PA (LTPA)] in older adults using data from the NHANES database.

This cross-sectional analysis used data from 2 cycles of NHANES (2011-2014). PA was determined through participants' self-reports using the Global Physical Activity Questionnaire (GPAQ). Cognitive performance was evaluated by the presence of psychometric mild cognitive impairment (p-MCI), identified based on a composite measure derived from three cognitive tests including the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the Animal Fluency test, and the Digit Symbol Substitution test (DSST). Logistic regression models were used to evaluate the association.

A total of 2588 participants aged 60 years or older were included, with an average age of 69.4 years and 48% being male. In the fully adjusted model, compared to no PA, performing 300 min of PA, and MPA were associated with 44%, and 33% reductions in the prevalence of p-MCI, respectively. Additionally, engaging in 1-149 min/week [OR 0.56, 95% CI (0.33-0.92)] and ≥ 300 min/week [OR 0.66, 95% CI (0.44-0.96)] of OPA, as well as ≥ 300 min/week [OR 0.56, 95% CI (0.36-0.86)] of LTPA, were also associated with a lower prevalence of p-MCI. Additionally, engaging in a diverse range of PA had better outcomes.

Our results suggested a positive association between higher levels of PA and enhanced cognitive performance. Different intensities and domains of PA have varying impacts on cognition. Future exploration, such as objectively measured PA and longitudinal studies were needed to validate our conclusion.

This systematic scoping review aimed to synthesize existing research findings on the clinical manifestations in patients with nonalcoholic fatty liver disease (NAFLD) and sarcopenia.

Adhering to scoping review guidelines, we comprehensively searched five databases for literature on sarcopenia's clinical manifestations in NAFLD patients from December 2013 to December 2023, meticulously compiling and synthesizing the findings.

A total of 312 articles were identified, with 9 studies included in the final review. Of these, 90% were cross-sectional investigations, with 70% from Asian cohorts. Comparative analysis between patients solely afflicted with NAFLD and those additionally experiencing sarcopenia revealed discernible trends. Individuals with both conditions tended to be older, have a higher body mass index, and show a higher prevalence among females, underscoring the influence of unhealthy lifestyles and obesity. Furthermore, comorbidities like metabolic syndrome, hypertension, and diabetes have been implicated in sarcopenia manifestation among NAFLD patients. Nonetheless, the lack of standardized diagnostic criteria and patterns poses an ongoing clinical challenge for this subgroup.

Our review highlights distinct clinical characteristics evident in NAFLD patients with sarcopenia. However, comprehensive investigations remain scarce, impeding accurate early detection and intervention. Future research should prioritize bridging these gaps and fostering enhanced clinical management strategies.

Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of the metabolic syndrome, posing risks to cardiovascular and hepatic health worldwide. Non-alcoholic steatohepatitis (NASH) which is a severe form of NAFLD, has a global prevalence. Therapeutic targets for NASH include THR-β, GLP-1 receptor, PPARα/δ/γ, FGF21 analogs, and FXR, a bile acid nuclear receptor pivotal for regulating bile acid synthesis and excretion. Our study aims to design the non-steroidal FXR agonist for NASH treatment, as FXR's role in the regulation of bile acid processes, rendering it a promising drug target for NASH therapy. Utilizing tropifexor as a reference molecule, we generated a shape-based pharmacophore model with seven features, identifying key binding requirements within the FXR active site. Virtual screening using this model, coupled with molecular docking studies, helped pinpoint potential ligands from diverse small molecule databases. Further analysis via MM/GBSA revealed 12 molecules with binding affinities comparable to tropifexor. Among them, DB15416 exhibited the lowest binding free energy and superior docking scores. To assess its dynamic stability, we subjected DB15416 to molecular dynamics simulations, confirming its suitability as a FXR agonist. These findings suggest that DB15416 holds promise as a FXR agonist for NASH treatment, which can be evaluated by experimental studies.

The prevalence, health and socioeconomic burden of metabolic dysfunction-associated fatty liver disease (MAFLD) is growing, increasing the need for novel evidence-based lifestyle approaches. Lifestyle is the cornerstone for MAFLD management and co-existing cardiometabolic dysfunction. The aim of this review was to evaluate the evidence for lifestyle management of MAFLD, with a specific lens on 24-hour integrated behaviour and provide practical recommendations for implementation of the evidence.

Weight loss ≥ 7-10% is central to lifestyle management; however, liver and cardiometabolic benefits are attainable with improved diet quality and exercise even without weight loss. Lifestyle intervention for MAFLD should consider an integrated '24-h' approach that is cognisant of diet, physical activity/exercise, sedentary behavior, smoking, alcohol intake and sleep. Dietary management emphasises energy deficit and improved diet quality, especially the Mediterranean diet, although sociocultural adaptations to meet preferences should be considered. Increasing physical activity and reducing sedentary behavior can prevent MAFLD, with strongest evidence in MAFLD supporting regular structured moderate-vigorous aerobic exercise for 150-240 min/week. Resistance training in addition to aerobic exercise should be considered and prioritised for those who are losing body mass via diet and/or pharmacological approaches and those with sarcopenia, to minimise bone and lean mass loss. Limited evidence suggests that sleep is important for MAFLD prevention. Emerging novel approaches to diet and exercise may address some of the key barriers to behaviour change (e.g. lack of time, access to resources and social support).

Large-scale multidisciplinary trials in people with MAFLD with long-term follow-up, that can be scaled up into mainstream healthcare, are required. Future management guidelines should consider the heterogeneity of MAFLD and specialised models of care that coordinate the health workforce to manage the increased and growing MAFLD population.

Several reports show a significant association between metabolic dysfunction-associated steatotic liver disease (MASLD) and arterial stiffness (estimated pulse wave velocity [ePWV]) as a surrogate marker of vascular age. We investigate whether ePWV as arterial stiffness in MASLD is associated with all-cause/cause-specific mortality.

This cohort study was based on the third National Health and Nutrition Examination Survey (NHANES, 1988-1994) and NHANES 2007-2014 and linked mortality datasets through 2019. Cox regression models assessed the association between ePWV categorized by quartile and all-cause/cause-specific mortality among individuals with MASLD.

During the follow-up of a median of 26.3 years (interquartile range: 19.9-27.9), higher levels of ePWV among individuals with MASLD were associated with increased all-cause mortality, which remained significant after adjusting for demographic, lifestyle, clinical, and metabolic risk factors. Furthermore, higher ePWV in MASLD was associated with higher cardiovascular mortality. There was a 44% (hazard ratio: 1.44, 95% confidence interval: 1.32-1.58) increase in all-cause mortality and a 53% (hazard ratio: 1.53, 95% confidence interval: 1.32-1.77) increase in cardiovascular mortality for every 1 m/s increase in ePWV in MASLD. However, there was no significant association between ePWV and cancer-related mortality. Sensitivity analyses using the NHANES 2007-2014 dataset showed results identical to the original analysis.

Higher ePWV in MASLD was associated with a higher risk of all-cause and cardiovascular mortality beyond traditional cardiovascular risk factors. Screening for ePWV in individuals with MASLD may be an effective and beneficial approach to reducing all-cause and cardiovascular mortality.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.

Muscle quality index (MQI) is a novel indicator reflecting the quality of skeletal muscles. The association between MQI and the development of advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is unknown. We investigated the association of low MQI with advanced fibrosis among adults with NAFLD using a nationally representative sample of the US population. Adults with NAFLD who participated in the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were included. Sex-specific standard was used to define low and extremely low MQI. Univariate and multivariate logistic regressions were used to assess the association between MQI level and advanced fibrosis. In the study, 3758 participants with NAFLD were included. The prevalence of low and extremely low MQI was 11.7% (95% CI 10.4-13.0%) and 2.2% (95% CI 1.6-2.8%), respectively. Among these participants, 96 were assessed to have advanced fibrosis. Individuals with low [(odds ratio (OR) 2.45, 95% confidence interval (CI) 1.22-4.91)] and extremely low MQI (OR 10.48, 95% CI 3.20-34.27) were associated with advanced fibrosis in multivariable analysis. A linear trend relationship was also observed between MQI level and the risk of advanced fibrosis (Ptrend = 0.001). Subgroup and sensitivity analyses yielded similar results to the main analyses. Decreased MQI is highly prevalent, and is associated with an increased risk of advanced fibrosis in adult US population with NAFLD.

The co-morbidity of non-alcoholic fatty liver disease (NAFLD) in patients with bipolar disorder (BD) has a negative impact on patient treatment and prognosis. This study aimed to identify the prevalence of NAFLD in patients with BD and investigate the risk factors of NAFLD.

A total of 678 patients with BD were included in the study. Clinical data were obtained from the hospital's electronic health record system. Data included fasting blood glucose, alanine aminotransferase, triglycerides, aspartate aminotransferase, high-density lipoprotein cholesterol (HDL), alkaline phosphatase, total cholesterol, glutamine transpeptidase, uric acid, apolipoprotein A1, apolipoprotein B, and liver ultrasound findings.

The prevalence of NAFLD was 43.66% in patients with BD. Significant differences in body mass index (BMI), mean age, diabetes prevalence, course of BD, fasting blood glucose, alanine aminotransferase, HDL, alkaline phosphatase, triglycerides, aspartate aminotransferase, uric acid, glutamine transpeptidase, apolipoprotein B, total cholesterol, and apolipoprotein A1 were seen between the groups (all P<0.01). Male sex, age, BMI, course of BD, alanine aminotransferase, fasting blood glucose, aspartate aminotransferase, diabetes, glutamine transpeptidase, total cholesterol, alkaline phosphatase, triglycerides, uric acid, apolipoprotein B, HDL, and apolipoprotein A1 levels were correlated with NAFLD (all P<0.05). In patients with BD, diabetes (OR=6.412, 95% CI=1.049-39.21), BMI (OR=1.398, 95% CI=1.306-1.497), triglycerides (OR=1.456, 95% CI=1.036-2.045), and apolipoprotein A1 (OR=0.272, 95% CI=0.110-0.672) were risk factors for NAFLD (all P<0.05).

Risk factors for NAFLD in patients with BD include diabetes, BMI, course of BD, and a low level of apolipoprotein A1. A proactive approach to disease management, such as appropriate physical activity and adoption of a healthy diet, and regular monitoring of changes in patient markers should be adopted to reduce the prevalence of NAFLD.

Metabolic dysfunction-associated steatotic liver disease management guidelines have been published worldwide; we aimed to summarize, categorize, and compare their lifestyle intervention recommendations.

We searched metabolic dysfunction-associated steatotic liver disease/NAFLD management guidelines published between January 1, 2013, and June 31, 2024, through databases including PubMed/MEDLINE, Cochrane, and CINAHL. In total, 35 qualifying guidelines were included in the final analysis. Guideline recommendations were categorized into 5 domains (ie, weight reduction goals, physical activity, nutrition, alcohol, and tobacco smoking) and were ranked based on how frequently they appeared. A recommendation was defined as widely adopted if recommended in ≥24 (≥66.6%) of the guidelines. These included increasing physical activity; reducing body weight by 7%-10% to improve steatohepatitis and/or fibrosis; restricting caloric intake; undertaking 150-300 or 75-150 minutes/week of moderate or vigorous-intensity physical activity, respectively; and decreasing consumption of commercially produced fructose. The least mentioned topics, in ≤9 of the guidelines, evaluated environmental determinants of health, mental health, referring patients for psychological or cognitive behavioral therapy, using digital health interventions, and assessing patients' social determinants of health.

Most guidelines recommend weight reduction through physical activity and improving nutrition, as these have proven positive effects on health outcomes when sustained. However, gaps regarding mental health and the social and environmental determinants of metabolic dysfunction-associated steatotic liver disease were found. To optimize behavioral modifications and treatment, we recommend carrying out studies that will provide further evidence on social support, environmental factors, and mental health, as well as further exploring digital health interventions.

Metabolic dysfunction-associated fatty liver disease (MAFLD), a globally prevalent disease, is closely linked to insulin resistance (IR). Physical activity (PA) is closely linked to both MAFLD and IR. We aim to explore the dose-response relationship between metabolic score for IR (METS-IR)/homeostasis model assessment of IR (HOMA-IR) and MAFLD, and investigate the relationship between PA, IR and MAFLD.

Participants from the NHANES study were included in this cross-section study. Logistic regression and the receiver operating characteristic were used to assess the predictive performance of METS-IR/HOMA-IR for MAFLD. Restrictive cubic splines were performed to visualize their dose-response relationship. Decision tree analysis was used to identify high-risk populations of MAFLD. PA's mediating effect in the association between METS-IR/HOMA-IR and MAFLD was also examined.

Of all 1,313 participants, 693 had MAFLD (52.78%). There were a positive association between METS-IR (OR = 1.162, 95% CI = 1.126-1.199) and HOMA-IR (OR = 1.630, 95% CI = 1.431-1.856) and MAFLD risk. The AUCs of the METS-IR and HOMA-IR were 0.831 (0.809, 0.853) and 0.767 (0.741, 0.791), respectively, with significantly different predictive performance (P < 0.001). Adding METS-IR/HOMA-IR to the basic model greatly improved the statistical significance for MAFLD. Five high-risk subgroups were identified for MAFLD. PA mediated about 0.81% and 0.78% (indirect effect/total effect) in the association between METS-IR/HOMA-IR and MAFLD.

MAFLD risk might be predicted by METS-IR/HOMA-IR, among which METS-IR performed better. And PA mediated the association between them. More attention should be paid to the therapeutic effect of lifestyle changes on MAFLD.

1. Positive associations were found between METS-IR and HOMA-IR and MAFLD risk. 2. METS-IR has better predictive performance for MAFLD risk than HOMA-IR. 3.Two high-risk subgroups were identified for MAFLD by METS-IR: individuals with METS-IR ≥ 40; Hispanic black individuals with 34 ≤ METS-IR < 40 and aged ≥ 46. 4. In the significant association between METS-IR/HOMA-IR and MAFLD, about 0.81% and 0.78% (indirect effect/total effect), respectively, were mediated by physical activity.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a growing threat leading to substantial disease burden globally. Poor sleep and physical inactivity are common in modern societies and independently associated with MAFLD, however, their joint effects on MAFLD remains unclear.

This population-based cross-sectional study was conducted in Xinjiang Uygur Autonomous Region, China, between July 2019 and September 2021. Self-reported sleep behaviors and physical activity (PA) were assessed using validated questionnaires. The primary outcome was radiological diagnosis of MAFLD.

Of the 10 089 participants aged 47.0 (9.1) years (51.6% men), 3854 (38.2%) individuals had MAFLD. Poor sleep quality and physical inactivity were independently and jointly associated with an increased prevalence of MAFLD, independent of traditional risk factors (P < 0.05). Compared to subjects with guideline-recommended moderate-to-vigorous PA (MVPA) and good sleep quality, individuals with no recommended MVPA and poor sleep had the highest possibility of MAFLD (odds ratio = 2.36, 95% confidence interval: 1.81 - 3.08). Enhancing sleep quality substantially attenuated MAFLD prevalence regardless of the volume of PA, whereas, engaging in PA well above current guidelines did not adequately counteract the adverse impacts of poor sleep on MAFLD.

Public health awareness and strategies concurrently targeting both sleep quality and PA should be encouraged to curb the climbing prevalence of MAFLD.

Steatotic liver disease (SLD) is a prevalent metabolic disease. While single component movement behaviors have been related to its development, comprehensive assessments of their joint associations are scarce.

To investigate the single-component and multi-component associations of moderate and vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior (SB), and sleep with prevalent SLD in Brazilian adults.

A cross-sectional analysis using data from the third wave of the ELSA-Brasil cohort (2017-2019). Participants wore an ActiGraph wGT3X-BT in the waist for seven days and completed a sleep diary. SLD was defined by a Fatty Liver Index ≥ 60. To investigate single-component and multi-component associations, we used three exposure modeling approaches based on Poisson models: multivariable-adjusted regression, restricted cubic splines, and compositional data analysis.

Among 8569 participants (55.7% women, mean age 59.2 ± 8.60), 43.9% had SLD. Total activity volume adjusted for covariates was inversely associated with prevalent SLD. Every 1 mg/day increase in total activity volume was associated with a PR of 0.95 in individuals sleeping < 7 h/day (95% CI 0.94-0.97) and 0.95 (95% CI 0.93-0.96) in those sleeping ≥ 7 h/day. Increasing 30 min/day of MVPA was associated with decreasing prevalence of SLD (sleep ≥ 7 h/day [PR 0.83; 95% CI 0.77-0.89]; sleep ≥ 7 h/day [PR 0.78; 95% CI 0.74-0.83]). Sleep, SB, and LPA were not associated with SLD. Associations of total activity volume and MVPA were more pronounced among females. Adjustment with adiposity markers attenuated the associations.

In adults, total activity volume and MVPA were inversely associated with SLD in a dose-response fashion. Substituting lower-intensity behaviors with MVPA was associated with a lower prevalence of SLD independent of sleep duration, sex, and age.

Various lifestyle factors including smoking, alcohol, physical activity, sedentary behavior, diet quality, sleep behavior, and overweight have been related to metabolic dysfunction-associated steatotic liver disease (MASLD); however, their joint impact on risk of MASLD is not well known. We prospectively investigated the association between a combination of lifestyle factors and risk of MASLD.

This prospective cohort study included 13,303 participants (mean age: 39.1 ± 11.3 years, female: 60.1%) in China. A novel healthy lifestyle score was created combining seven healthy factors: not smoking, no alcohol intake, regular physical activity, short sedentary time, healthy diet, healthy sleep, and healthy weight. Incident MASLD cases were ascertained annually by liver ultrasound and cardiometabolic risk factors. Multivariable Cox proportional hazards regression models were used to estimate the association of healthy lifestyle score with risk of MASLD.

Within 48,036 person-years of follow-up, 2823 participants developed MASLD. After adjusting for age, sex, education, occupation, household income, personal and family history of disease, and total energy intake, compared with participants with 0-2 healthy lifestyle factors, the multivariable hazard ratios (95% confidence interval) of MASLD were 0.81 (0.73, 0.89), 0.67 (0.61, 0.75), and 0.55 (0.49, 0.62) for healthy lifestyle score of 3, 4, and 5-7, respectively (P for trend <0.0001). Such associations were consistent across subgroup and sensitivity analyses.

Our results indicate that a higher healthy lifestyle score is associated with a lower risk of MASLD.

Noninvasive and early assessment of liver fibrosis is of great significance and is challenging. We aimed to evaluate the predictive performance and cost-effectiveness of the LiverRisk score for liver fibrosis and liver-related and diabetes-related mortality in the general population.

The general population from the NHANES 2017-March 2020, NHANES 1999-2018, and UK Biobank 2006-2010 were included in the cross-sectional cohort (n = 3,770), along with the NHANES follow-up cohort (n = 25,317) and the UK Biobank follow-up cohort (n = 17,259). The cost-effectiveness analysis was performed using TreeAge Pro software. Liver stiffness measurements ≥10 kPa were defined as compensated advanced chronic liver disease (cACLD).

Compared to conventional scores, the LiverRisk score had significantly better accuracy and calibration in predicting liver fibrosis, with an area under the receiver operating characteristic curve (AUC) of 0.76 (0.72-0.79) for cACLD. According to the updated thresholds of LiverRisk score (6 and 10), we reclassified the population into three groups: low, medium, and high risk. The AUCs of LiverRisk score for predicting liver-related and diabetes-related mortality at 5, 10, and 15 years were all above 0.8, with better performance than the Fibrosis-4 score. Furthermore, compared to the low-risk group, the medium-risk and high-risk groups in the two follow-up cohorts had a significantly higher risk of liver-related and diabetes-related mortality. Finally, the cost-effectiveness analysis showed that the incremental cost-effectiveness ratio for LiverRisk score compared to FIB-4 was USD $18,170 per additional quality-adjusted life-year (QALY) gained, below the willingness-to-pay threshold of $50,000/QALY.

The LiverRisk score is an accurate, cost-effective tool to predict liver fibrosis and liver-related and diabetes-related mortality in the general population.

The National Natural Science Foundation of China (nos. 82330060, 92059202, and 92359304); the Key Research and Development Program of Jiangsu Province (BE2023767a); the Fundamental Research Fund of Southeast University (3290002303A2); Changjiang Scholars Talent Cultivation Project of Zhongda Hospital of Southeast University (2023YJXYYRCPY03); and the Research Personnel Cultivation Program of Zhongda Hospital Southeast University (CZXM-GSP-RC125).