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.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rising globally. Recent studies have suggested connections between exposure to endocrine disrupting chemicals (EDCs) and the development of MASLD. Phthalates, which are commonly utilized as plasticizers, in building materials and consumer items, exhibit endocrine disrupting effects and have been shown to interfere with lipid metabolism in mechanistic studies. The objective of this systematic review was to examine the association between MASLD and exposure to phthalates in the adult human populations. We searched PubMed, Scopus and Web of Science for studies published from the inception of each database until December 12, 2024. The literature search yielded 10 cross-sectional studies, which were analyzed in detail. The key findings of this study indicate a potential correlation between the prevalence of MASLD and exposure to certain phthalates. Among the phthalates examined, the metabolites of bis(2-ethylhexyl) phthalate (DEHP) - namely MECPP, MEHHP, and MEOHP, demonstrated the strongest and most frequent associations with MASLD. All the current studies followed cross-sectional study designs, which limits the possibility to establish a causal relationship between MASLD and phthalate exposure. Therefore, longitudinal studies are needed to corroborate these findings and shed light on the involvement of phthalate exposure in MASLD.

Recently, the term Metabolic-Associated Fatty Liver Disease (MAFLD) has been adopted to better reflect the underlying pathology and association with metabolic issues. Beyond dietary factors and physical activity, previous studies have suggested that persistent organic pollutants (POPs) may contribute to the etiology of MAFLD; however, this disease can also develop at very low POP exposure levels, making it challenging to discern their specific effect. This study aims to investigate the potential link between exposure to POPs and the prevalence of MAFLD. Data from the National Health and Nutrition Examination Survey (NHANES) was utilized for this cross-sectional study. Participants were categorized based on their MAFLD status and levels of various POPs measured in their blood serum. Cox regression to estimate adjusted prevalence ratio (aPR) of MAFLD was used. Hazard Index (HI), Proportion of Maximum Scaling (POMS), and Toxicity Burden Index (TBI) were applied to assess exposure to mixtures. A total of 4,224 participants were included, 47 (33-65) years, 53.0% were women, and 50.1% had MAFLD. No significant sex differences were observed in the main analysis regarding the association between individual POPs and MAFLD prevalence. However, sensitivity analyses revealed an inverse relationship between certain POPs and MAFLD prevalence, particularly in women. Higher levels of specific PCBs were associated with a lower prevalence of MAFLD in women. This study highlighted the effects of individual pollutants, mixtures, and sex-specific differences. The combined use of HI, POMS, and TBI provided a more detailed risk assessment. Findings suggest that biological sex and metabolic stressors play significant roles in how POPs influence MAFLD, warranting further investigation into mechanisms and health outcomes in different exposure ranges.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with insulin resistance (IR). However, the prognostic value of different alternative IR surrogates in patients with MASLD remains unclear. This study aimed to evaluate the association between various IR indices and all-cause mortality and cardiovascular mortality in MASLD patients.

A total of 8,753 adults aged ≥ 20 years with MASLD from the National Health and Nutrition Examination Survey (NHANES, 2003-2018) were included, and their mortality data were obtained from the National Death Index (NDI). Insulin resistance surrogates [including the triglyceride-glucose (TyG) index, TyG-body mass index (TyG-BMI), TyG-waist circumference index, TyG-waist-to-height ratio index, and Homeostatic Model Assessment for IR] were stratified into quartiles. Cox proportional hazards models, receiver operating characteristic (ROC) curve analysis, restricted cubic spline (RCS), mediation analyses, and subgroup analyses were used to explore the associations between these indices and all-cause mortality as well as cardiovascular mortality in MASLD patients.

During a median follow-up of 98 months, 1,234 deaths were observed, including 409 cardiovascular disease (CVD)-related deaths. In the fully adjusted model, higher quartiles of TyG-related indices were significantly associated with an increased risk of all-cause mortality in MASLD patients. Furthermore, the TyG-BMI index was associated with both all-cause mortality and CVD mortality [all-cause mortality: HR (95% CI) 2.84 (1.73-4.67), P < 0.001; CVD mortality: HR (95% CI) 5.32 (2.26-12.49), P < 0.001]. The RCS analyses indicated a U-shaped relationship between TyG-BMI and mortality, with a threshold value of 270.49. Subgroup analyses demonstrated that TyG-related indices had stronger associations with mortality in elderly MASLD patients.

Our findings highlight the prognostic value of IR indices, particularly TyG-BMI index, in predicting all-cause mortality and CVD mortality in MASLD patients.

The incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) is high among U.S. adults, but studies on its occurrence in different ethnic and age groups are limited. The aim of the present study was to assess MAFLD occurrence among the U.S. adults by considering demographic characteristics, physical indices, and lifestyle conditions.

This study utilized the National Health and Nutrition Examination Survey (NHANES) data 2009-2018 from 23,546 participants aged ≥ 20 years. Variables such as age, sex, race, body mass index (BMI), waist circumference (WC), blood pressure, sedentary behavior, sleep, and depression were analyzed.

Among 9933 participants, 3562 had MAFLD (34.1%), with notably higher percentages of Mexican-Americans (54.1%) and lower percentages of blacks (20.5%). The incidence of MAFLD was significantly greater (P < 0.001) in males (39%) than in females (29.2%), which was particularly evident within the 36-40 years age group. The MAFLD incidence exhibited an age-dependent pattern, initially increasing and subsequently declining (except for whites). Compared to white MAFLD patients, black MAFLD patients exhibited greater BMI, WC, systolic blood pressure (SBP), and diastolic blood pressure (DBP) values, whereas values for these measures were lower among Mexican-American patients. Logistic regression analysis adjusting for age and sex revealed that depression was more common among MAFLD patients (P < 0.001), except for severe depression (P > 0.05). Notably, the MAFLD incidence was not significantly associated with sedentary behavior or sleep duration.

The MAFLD incidence varies across different racial, age, and sex groups, and targeted interventions are essential for reducing the burden of MAFLD. However, further research is necessary to explore the correlations among MAFLD incidence, sleep patterns, and an inactive lifestyle.

The relationship between actigraphy-derived sleep parameters, day-to-day deviations in sleep parameters, and metabolic dysfunction-associated steatotic liver disease (MASLD), a new definition of nonalcoholic fatty liver disease (NAFLD), remains unclear. We aimed to explore the associations of sleep duration, midpoint, variability and irregularity with MASLD risk.

We used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Sleep duration and midpoint were estimated from 4 to 7 days of 24-hour actigraphy measurements. Sleep duration and midpoint standard deviation were used as indicators of sleep variability and irregularity, respectively. MASLD was diagnosed according to the multi-society Delphi consensus. Hepatic steatosis was defined as fatty liver index ≥ 60. Multivariable weighted logistic regression models were used to explore correlations and perform subgroup analyses.

A total of 5,316 participants were included, of whom 2,339 had MASLD. After adjusting for socio-demographic characteristics, lifestyle factors, and depression, compared to sleep variability < 60 minutes, the odds ratio (OR) [95% confidence interval (CI)] was 1.13 (0.96-1.34) for 60-90 minutes, and 1.17 (1.00-1.38) for > 90 minutes (P for trend = .034). After further adjustment for other sleep variables, short sleep duration (<7 hours) was associated with a 24% higher risk of MASLD (OR: 1.24, 95% CI: 1.01-1.53); compared to sleep irregularity < 38 minutes, OR (95% CI) was 1.27 (1.02-1.59) for 38-61 minutes and 1.43 (1.24-1.65) for > 61 minutes (P for trend = .003).

In addition to sleep duration, sleep irregularity may need to be considered in the prevention of MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is understudied among US adolescents despite rising obesity rates.

This study analysed the prevalence and trends of obesity and MASLD among US adolescents aged 12-17 using data from the National Health and Nutrition Examination Survey (NHANES). We developed a new screening model utilizing FibroScan-measured controlled attenuation parameter (CAP) scores, body measurements and blood chemistry data from 2017 to 2020 to assist in analysing MASLD trends from 1999 to 2020.

Between 2017 and 2020, the prevalence of obesity and MASLD was approximately 20%, with about 70% of obese adolescents affected by MASLD. The condition was more common in boys, particularly among Mexican American adolescents. Additionally, 97.2% of those with NAFLD also had MASLD. Adolescents with MASLD had significantly higher body weight, waist circumference, triglyceride levels and alanine transaminase (ALT) levels, along with lower high-density lipoprotein (HDL) cholesterol and an increased risk of liver fibrosis. Insufficient physical activity and poor diet quality were key risk factors for developing MASLD. From 1999 to 2020, the prevalence of MASLD rose significantly, paralleling the increasing rates of obesity.

The study underscores the pressing need to screen at-risk adolescents for metabolic issues associated with steatotic liver diseases, given the rising obesity rates among adolescents. The high overlap between MASLD and NAFLD diagnoses indicates that the transition from NAFLD to MASLD can be effectively integrated into paediatric practice.

This study aimed to investigate the relationship between lung function and metabolic dysfunction-associated steatotic liver disease (MASLD), and the potential mediating role of type 2 diabetes.

Data from the 2007 to 2012 National Health and Nutrition Examination Survey were used. Logistic regression analysis was employed to assess the association between lung function parameters [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 ), FEV 1 /FVC] and MASLD prevalence while exploring type 2 diabetes mediation. Further analyses included linkage disequilibrium score regression, Mendelian randomization, and meta-analysis to examine the causal relationship between lung function and MASLD, considering type 2 diabetes mediation.

The results showed that higher FVC and FEV 1 levels were associated with decreased MASLD risk, with type 2 diabetes partially mediating this relationship. Genetic analyses supported a causal link between lung function and MASLD, with type 2 diabetes acting as an intermediary. However, no significant association was found between FEV 1 /FVC and MASLD.

The study identified a causal relationship between lung function and MASLD, with type 2 diabetes playing a partial mediating role.

Identifying metabolic dysfunction-associated steatotic liver disease (MASLD) patients at increased risk of cardiovascular mortality remains an unmet clinical need. We investigated the ability of four systemic inflammation markers to identify cardiovascular mortality risk in MASLD patients.

This cohort study included 4787 MASLD patients from the National Health and Nutrition Examination Survey (NHANES) from 2005 through 2018. The weighted Cox proportional hazards model was used to assess the relationship between four systemic indicators of inflammation and cardiovascular mortality. During a median (IQR) follow-up of 7.0 (3.8-10.3) years, 567 all-cause mortality and 174 cardiovascular mortality were recorded. Compared to the first quartile of systemic inflammation levels, the HRs of cardiovascular mortality in the fourth quartile were 3.22 (95 % CI 1.83-5.66) for SII, 2.74 (95 % CI 1.32-5.69) for SIRI, 3.69 (95 % CI 1.87-7.28) for NLR, and 1.83 (95 % CI 1.05-3.20) for PLR. For predicting 10-year cardiovascular mortality, SIRI (AUC = 0.70) and NLR (AUC = 0.69) were superior to SII (AUC = 0.60) and PLR (AUC = 0.52). Stratification of MASLD patients based on the optimal cutoff values revealed an HR of 2.67 (95 % CI 1.65-4.32) for cardiovascular mortality with SIRI > 1.23, and an HR of 2.39 (95 % CI 1.51-3.79) with NLR > 2.18. Combining systemic inflammation markers with the Fibrosis-4 Score can provide more accurate prognostic information for MASLD patients.

SIRI and NLR outperformed SII and PLR in predicting the risk of cardiovascular mortality, proving to be useful tools for risk stratification in MASLD patients.

Neutrophil-associated inflammatory markers (NPR, NHR, SII, and SIRI) have been implicated in various metabolic diseases. However, studies on these markers with metabolic dysfunction-associated steatotic liver disease (MASLD) and advanced liver fibrosis (ALF), as well as their impact on all-cause mortality, remain limited.

In this historical cohort study, data from 8051 adults aged 20 years and older were analysed. Weighted logistic regression was used to investigate the associations of neutrophil-associated inflammatory markers with MASLD and ALF. Nonlinear associations were described via restricted cubic spline regression. The diagnostic utility was assessed via receiver operating characteristic (ROC) curves. Furthermore, weighted Kaplan‒Meier survival curves and Cox proportional hazards models were employed to assess all-cause mortality risk. Sensitivity analyses were employed to guarantee the robustness of the findings.

Following adjustment for confounding factors, there was a significant positive association between the ln-transformed NPR, NHR, SII, and SIRI and the risk of MASLD (P < 0.001). Conversely, an inverse association was noted between the ln-transformed SII, SIRI and ALF (P < 0.05). Nonlinear relationships were identified between ln-transformed NPR, NHR, and SIRI and the risk of MASLD (P < 0.001), as well as between ln-transformed NPR, SII, and SIRI and the risk of ALF (P < 0.001). Furthermore, the ln-transformed NHR (cut-off value: - 2.571) exhibited the highest diagnostic accuracy for MASLD (AUC 0.71, 95% CI = 0.70, 0.72), whereas the NPR (cut-off value: - 3.857) demonstrated the highest diagnostic value for ALF (AUC 0.73, 95% CI = 0.70, 0.75). The results of the present study revealed an independent association between the ln-transformed NPR and an elevated risk of all-cause mortality in subjects diagnosed with MASLD. Subgroup analyses highlighted the underrepresentation of neutrophil-associated inflammatory markers in lean individuals with MASLD and ALF (BMI < 25 kg/m2).

Neutrophil-associated inflammatory markers are independently associated with MASLD and ALF. Specifically, the ln-transformed NHR and SII show promise as diagnostic markers for MASLD and ALF, respectively. Moreover, elevated ln-transformed NPR is independently associated with an increased risk of all-cause mortality in individuals with MASLD, highlighting the potential clinical relevance of these inflammatory markers in the context of steatotic liver disease.

The non-HDL cholesterol to HDL cholesterol ratio (NHHR) is a novel composite lipid index. However, its relationship with mortality, particularly in individuals with non-alcoholic fatty liver disease (NAFLD), remains unclear. The aim of this study was to explore the association between NHHR and both all-cause and cardiovascular mortality in adults with NAFLD in the United States.

This study included 12,648 adult participants with NAFLD from the National Health and Nutrition Examination Survey (NHANES) database (1999-2018). Multivariate Cox proportional hazards models and restricted cubic spline (RCS) methods were employed to assess all-cause and cardiovascular mortality. Subgroup analyses were performed to verify the consistency of these associations.

Over a median follow-up of 99.27 months, 1,659 participants died from all causes, including 460 from cardiovascular disease. RCS analysis revealed a U-shaped relationship between NHHR and all-cause mortality, no association was found between NHHR and cardiovascular mortality. The inflection points for all-cause mortality were 2.67. Subgroup analysis showed that a stronger association between NHHR and all-cause mortality in those with diabetes(P = 0.048).

NHHR is associated with all-cause mortality in NAFLD patients, with distinct non-linear relationships, while it is not associated with cardiovascular mortality. NHHR monitoring may be valuable for assessing mortality risk, particularly in those with diabetes.

The relationship between sodium intake and the incidence and mortality of non-alcoholic fatty liver disease (NAFLD) is underexplored in nutritional epidemiology, highlighting the need for further research.

This longitudinal cohort study analyzed data from 13,853 Participants aged 20 and older from the National Health and Nutrition Examination Survey (NHANES) (2003-2018), including 4,465 participants with NAFLD. We collected comprehensive data on mortality, dietary sodium intake, and relevant covariates. Logistic regression assessed the relationship between sodium consumption and NAFLD incidence, while Cox regression and smooth curve fitting explored sodium intake's link to all-cause mortality among Participants with NAFLD.

After adjusting for confounders, logistic regression revealed a positive association between higher sodium intake and NAFLD incidence (OR = 1.16, 95% CI = 1.11, 1.21). Adjusted odds ratios for the second (Q2), third (Q3), and fourth (Q4) quartiles of sodium intake were 0.91, 1.23, and 1.52, respectively. Smooth curve fitting and threshold analysis revealed a non-linear association between sodium intake and NAFLD risk, with an inflection point at 2.49 g/d, above which NAFLD risk significantly increased. In Cox regression, sodium intake was inversely correlated with all-cause mortality in Participants with NAFLD (HR = 0.87, 95% CI = 0.80, 0.96), with adjusted hazard ratios for Q2, Q3, and Q4 being 0.79, 0.66, and 0.63, respectively. A nonlinear model indicated a threshold effect, revealing a correlation between dietary sodium intake and mortality risk (p = 0.001). We identified a threshold intake of 3.5 grams per day (equivalent to 8.9 grams of sodium chloride): below this, each unit increase in sodium intake was associated with a 16% reduction in mortality risk (HR = 0.84, 95% CI = 0.80, 0.90). For intakes above this threshold, no significant relationship with mortality risk was observed (HR = 0.99, 95% CI = 0.90, 1.08).

This study suggests that higher sodium intake in individuals with NAFLD is associated with increased disease incidence but decreased all-cause mortality. The dose-response relationship between sodium intake and mortality risk exhibited a nonlinear pattern, with a critical inflection point around 3.5 grams per day.

Mounting evidence has established metabolic dysfunction-associated steatotic liver disease (MASLD) as an independent risk factor for heart failure (HF), particularly HFpEF. In this narrative review we explore the impact of MASLD on cardiovascular structure and function. We summarize findings from multiple cohort studies demonstrating that MASLD is associated with distinct patterns of adverse cardiac remodeling, including increased left ventricular concentricity and impaired diastolic function. These subclinical changes in cardiac structure and function often precede overt HF development and appear to occur in the context of multiple interconnected pathways involving metabolic dysfunction, systemic inflammation, adipose tissue dysregulation, vascular dysfunction, and altered hepatic hemodynamics. Early identification of cardiac structural and functional abnormalities through systematic screening may enable timely intervention in this high-risk population. Lifestyle modifications remain foundational, but achieving and maintaining significant weight loss is challenging. Recent clinical trials have shown promising results with cardiometabolic agents, particularly glucagon-like protein 1 receptor agonists, which demonstrate significant weight loss and hepatic and cardiovascular benefits. Despite these advances, key knowledge gaps remain regarding optimal screening strategies, mechanisms linking MASLD to HF, and targeted therapeutic approaches. Addressing these gaps will be essential for developing effective prevention and treatment strategies in this high-risk population.

Cardiometabolic index (CMI) was proposed ten years ago as an indicator combining obesity and dyslipidemia. This study aimed to investigate the relationships between newly modified CMI (MCMI) with non-alcoholic fatty liver disease (NAFLD) and liver fibrosis.

This cross-sectional study included participants in the 2017-2018 National Health and Nutrition Examination Survey database (NHANES). Linear regression was used to explore the relationship between MCMI and Baseline characteristics. Logistic regression was conducted to analyze the correlation among MCMI with NAFLD and liver fibrosis. Furthermore, restricted cubic spline (RCS) was performed to estimate nonlinear relationships. Receiver operating characteristic curve (ROC) was used to assess the diagnostic performance of MCMI for NAFLD and liver fibrosis.

A total of 1385 participants were enrolled in the study. After adjusting covariates, participants with high MCMI were related to increased risk of NAFLD (OR = 3.52, 95%CI: 1.44-8.61), compared with those having low MCMI. A linear association was observed between MCMI and NAFLD (p for nonlinear = 0.074), and a J-shaped nonlinear relationship was found between MCMI and liver fibrosis (p for nonlinear = 0.002). The area under the curve (AUC) for MCMI to identify NAFLD was 0.821 (95% CI 0.799-0.843), which was higher than that of CMI (AUC = 0.761, 95%CI: 0.735-0.786), fatty liver index for the U.S. population (USFLI, AUC = 0.799, 95%CI: 0.776-0.822), Triglyceride glucose index (TyG, AUC = 0.738, 95%CI: 0.712-0.765), NAFLD liver fat score (NLFS, AUC = 0.786, 95%CI: 0.761-0.810) and hepatic steatosis index (HSI, AUC = 0.799, 95%CI: 0.775-0.822).

The novel MCMI was positively corelated to the risk of NAFLD. In addition, MCMI was an effective predictor for both NAFLD and liver fibrosis.

The association between dietary indices and metabolic dysfunction-associated steatotic liver disease (MASLD) has shown inconsistent results in previous studies. Additionally, the potential mediating variables linking dietary quality to MASLD have not been adequately explored.

We analyzed data from 6,369 participants in the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Three dietary indices-Healthy Eating Index (HEI), Energy-adjusted Dietary Inflammatory Index (EDII), and Composite Dietary Antioxidant Index (CDAI)-were evaluated for their associations with MASLD using logistic regression models adjusted for a comprehensive range of covariates. Mediation analysis was performed to evaluate the roles of potential mediators from four domains: insulin resistance (homeostatic model assessment of insulin resistance, HOMA-IR; metabolic score for insulin resistance, METS-IR), systemic inflammation (systemic inflammatory response index, SIRI; systemic immune-inflammation index, SII), obesity or visceral fat distribution (a body shape index, ABSI; body roundness index, BRI), and oxidative stress (Gamma-Glutamyltransferase, GGT; Bilirubin; Uric Acid).

After adjusting for all covariates, only HEI showed a consistent inverse association with MASLD, while EDII and CDAI showed no significant associations. Mediation analysis identified METS-IR, HOMA-IR, BRI, and ABSI as significant mediators in the relationship between HEI and MASLD, with mediation proportion accounting for 47.16%, 48.84%, 52.69%, and 13.84%, respectively.

Higher HEI is associated with a reduced risk of MASLD. The findings suggest that insulin resistance and visceral fat distribution partially mediate the relationship between HEI and MASLD, providing insights into potential mechanisms linking diet and liver health.

About one-third of adults in the USA have some grade of hepatic steatosis. Coronary artery calcium (CAC) scans contain more information than currently reported. We previously reported new artificial intelligence (AI) algorithms applied to CAC scans for opportunistic measurement of bone mineral density, cardiac chamber volumes, left ventricular mass, and other imaging biomarkers collectively referred to as AI-cardiovascular disease (CVD). In this study, we investigate a new AI-CVD algorithm for opportunistic measurement of liver steatosis.

We applied AI-CVD to CAC scans from 5702 asymptomatic individuals (52% female, age 62±10 years) in the Multi-Ethnic Study of Atherosclerosis. Liver attenuation index (LAI) was measured using the percentage of voxels below 40 Hounsfield units. We used Cox proportional hazards regression to examine the association of LAI with incident CVD and mortality over 15 years, adjusted for CVD risk factors and the Agatston CAC score.

A total of 751 CVD and 1343 deaths accrued over 15 years. Mean±SD LAI in females and males was 38±15% and 43±13%, respectively. Participants in the highest versus lowest quartile of LAI had greater incidence of CVD over 15 years: 19% (95% CI 17% to 22%) vs 12% (10% to 14%), respectively, p<0.0001. Individuals in the highest quartile of LAI (Q4) had a higher risk of CVD (HR 1.43, 95% CI 1.08 to 1.89), stroke (HR 1.77, 95% CI 1.09 to 2.88), and all-cause mortality (HR 1.36, 95% CI 1.10 to 1.67) compared with those in the lowest quartile (Q1), independent of CVD risk factors.

AI-enabled liver steatosis measurement in CAC scans provides opportunistic and actionable information for early detection of individuals at elevated risk of CVD events and mortality, without additional radiation.

Non-alcoholic fatty liver disease (NAFLD) represents a major public health issue, especially among individuals diagnosed with Type 2 diabetes mellitus (T2DM), where its prevalence can reach up to 70%. This research examines the relationship between the Healthy Eating Index 2020 (HEI-2020) and its individual components with the occurrence of NAFLD in T2DM patients, while also investigating the potential mediating effects of various metabolic indicators.

Data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018 were utilized. This cross-section study included 1,770 T2DM patients, who were divided into NAFLD and non-NAFLD groups using the Fatty Liver Index as a diagnostic tool. The HEI-2020, which assesses diet quality, was computed based on 24-h dietary recall data. Key metabolic indicators such as the triglyceride-glucose (TyG) index, metabolic score (MS), mean arterial pressure, uric acid levels, and total cholesterol were evaluated.

The findings indicated that higher HEI-2020 scores were associated with a lower likelihood of NAFLD (odds ratio 0.978, 95% confidence interval: 0.959-0.998), with the strongest inverse associations observed in the top quartiles of diet quality. Whole fruits, greens and beans, and saturated fat were crucial dietary factors. Mediation analysis demonstrated that the TyG index and MS accounted for 5.11 and 36.94% of the relationship between HEI-2020 and NAFLD, respectively.

Greater adherence to the HEI-2020 is associated with a lower likelihood of NAFLD in T2DM patients, with metabolic indicators partially mediating this association. Enhancing diet quality, particularly by increasing the consumption of whole fruits and greens while reducing saturated fat intake, may be important in managing metabolic health and liver function in this vulnerable population.

The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) among individuals with hyperuricemia is significantly high. The aim of this study was to identify effective biomarkers for the detection of MASLD among patients with hyperuricemia.

We conducted an analysis involving 3424 participants with hyperuricemia from the National Health and Nutrition Examination Survey (1999-2020). To identify potential significant variables, we employed Boruta's algorithm, SHapley Additive exPlanations (SHAP) and random forests. Multivariable logistic regression models were utilized to assess the odds ratio (OR) of developing MASLD. To evaluate the accuracy and clinical value of our prediction model, we employed receiver operating characteristic (ROC) curves and decision curve analysis (DCA) curves.

Among the study population of 3424 participants (mean [SD] age, 54 [20] years, 1788 [52.22%] males) with hyperuricemia, 1670 participants had MASLD. Using Boruta's algorithm, SHAP and random forests, our analysis suggested that Triglyceride Glucose-Waist Circumference (TyG_WC) was one of the most significant variables in predicting MASLD risk, with an area under the receiver operating characteristic (AUROC) of 0.865. The restricted curve spline (RCS) revealed a positive association between the odds ratio of TyG_WC and MASLD, when compared with lowest quantile of TyG_WC, the risk of MASLD for highest quantile was 137.96 times higher. The predictive strategy incorporating TyG_WC notably enhanced the clinical model, with threshold probabilities spanning from approximately 0% to 100%, resulting in a significant improvement of the net benefit.

Our analysis found that TyG_WC was one of the most significant variables in predicting MASLD risk among individuals with hyperuricemia.

Nonalcoholic fatty liver disease (NAFLD) is a pressing public health concern. NAFLD is recognized as a disease with systemic involvement. Erectile dysfunction is a prevalent condition among men. The study examined the relationship between NAFLD, assessed via U.S. Fatty Liver Index (USFLI), and erectile dysfunction. The study used cross-sectional data from the National Health and Nutrition Examination Survey conducted between 2001 and 2004 to examine the health of those over 20 years of age, collecting details on their erectile dysfunction, USFLI, and several other essential variables. A USFLI score equal to or exceeding 30 was chosen to diagnose NAFLD, while a USFLI score below 10 was utilized to exclude the presence of fatty liver. There were 3763 participants, with 29.1% (1095/3763) who experienced erectile dysfunction. After accounting for all potential covariates, USFLI was positively associated with erectile dysfunction (OR, 1.02; 95% CI, 1.02 ~ 1.03; P < 0.001). Compared with individuals with Q1 (USFLI < 10), the adjusted odds ratio values for USFLI and erectile dysfunction in Q2 (10 ≤ USFLI < 30) and Q3 (USFLI ≥ 30, NAFLD) were 1.84 (95% CI: 1.46 ~ 2.32, p < 0.001) and 2.18 (95% CI: 1.66 ~ 2.87, p < 0.001), respectively. The association USFLI and erectile dysfunction exhibited an L-shaped curve (nonlinear, P = 0.014). The odds ratio value of developing erectile dysfunction was 1.03 (95% CI: 1.021 ~ 1.04, P < 0.001) in participants with USFLI < 50.18. This study identified a positive correlation between USFLI and erectile dysfunction within the adult American population. Our findings imply that NAFLD might constitute an independent risk factor for erectile dysfunction.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver disease globally, with inflammation and nutrition playing key roles in its progression. The Advanced Lung Cancer Inflammation Index (ALI) is a novel biomarker reflecting nutritional and inflammatory status. This study aims to explore the association between ALI and the risk of liver fibrosis and prognosis in MAFLD patients.

This cross-sectional study analyzed NHANES data from the 1999-2018 on adult participants in the US. Weighted logistic regression assessed the association between ALI and liver fibrosis risk. Mortality outcomes, including all-cause, cardiovascular disease (CVD), and cancer mortality, analyzed using weighted Kaplan-Meier and Cox proportional hazards models. Restricted cubic splines (RCS) and threshold effect analyses were uesd to explore non-linear relationships. Receiver operating characteristic (ROC) curve evaluated the prognostic value of ALI, and stratified analyses examined subgroup differences.

A total of 6,858 MAFLD patients (mean age 51.38 ± 17.22 years, 54% male) were included. A non-linear relationship was found between ALI and liver fibrosis risk, with a threshold at 5.68, beyond which the risk increased significantly (OR = 2.35, 95% CI: 1.89-2.95). Stronger associations were observed in subgroups with central obesity and prediabetes (P for interaction < 0.05). ALI was inversely associated with all-cause mortality (HR = 0.64, 95% CI: 0.56-0.72) and CVD mortality (HR = 0.57, 95% CI: 0.46-0.65), but not cancer mortality. RCS analysis showed an L-shaped non-linear relationship with all-cause mortality (threshold at 5.36) and a linear relationship with CVD mortality. Low HDL cholesterol and excessive alcohol consumption influenced the association between ALI and all-cause mortality (P for interaction < 0.05). ALI demonstrated the highest predictive accuracy for CVD mortality.

ALI is associated with an increased risk of liver fibrosis and reduced all-cause and CVD mortality, highlighting its potential value in assessing MAFLD prognosis, particularly CVD-related mortality.

High oxidative balance score (OBS) may mitigate inflammation levels and thereby alleviate the adverse health effects induced by toxic metals. We assessed the independent, joint effects as well as their interactions of toxic metals and OBS on mortality among individuals with non-alcoholic fatty liver diseases (NAFLD).

Participants with NAFLD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included. Mortality and underlying causes of death were certain by National Death Index records through 31 December 2019. Cox regression models were used to estimate hazard ratios (HRs) for all-cause and disease-specific mortality. Additionally, we assessed multiplicative and additive interactions of OBS and toxic metals on mortality.

Among 5263 patients with NAFLD, 1097 deaths occurred during a mean follow-up of 10.27 years. Compared with those in the OBS tertile 1, participants in tertile 3 had lower risk of all-cause mortality (HR=0.79, 95 %CI: 0.64, 0.96). Compared with individuals in the lowest lead concentration in blood, those in the highest had an increased risk of mortality, with the HRs (95 %CIs) being 1.23 (1.01, 1.51), 1.53(1.06, 2.20) and 1.94(1.25, 3.01) for all-cause, CVD and cancer mortality, respectively. Similar results were also found for blood cadmium level. Joint associations analyses found that individuals with low lead and high-OBS levels had the lowest risk of all-cause, CVD and cancer mortality, with the HRs(95 %CIs) being 0.58(0.40, 0.85), 0.45(0.21, 0.93) and 0.35(0.15, 0.81), respectively. Multiplicative interactions between OBS and blood cadmium on all-cause death (HR=0.87, 95 %CI: 0.78, 0.97) and CVD death (HR=0.81, 95 %CI: 0.67, 0.99) were found.

High OBS and low exposure to toxic metals were associated with lower risk of mortality among participants with NAFLD. Adopting anti-oxidative lifestyle could alleviate the harmful effects of toxic metals in NAFLD patients. Comprehensive strategies are essential to decrease the risk of mortality and potentially mitigate the overall burden of NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is associated with multiple factors, yet the relationship between NAFLD and thyroid-related biomarkers remains unclear. This study aims to elucidate this potential linkage.

Utilizing data from the US National Health and Nutrition Examination Survey (NHANES), we explored the possible associations between thyroid-related biomarkers and NAFLD through multivariable logistic regression, subgroup analysis, and interaction tests. A bidirectional Mendelian randomization (MR) approach complemented by various sensitivity analyses was then employed to ascertain these relationships' causality.

Our NHANES analysis indicated significant associations between elevated levels of free triiodothyronine (FT3) [odds ratio (OR): 2.59, 95% confidence interval (CI): 1.50-4.49] and total triiodothyronine (TT3) (OR: 2.01, 95% CI: 1.27-3.18) with the prevalence of NAFLD. MR findings reinforced the causal relationship, demonstrating that NAFLD may elevate FT3 (β: 0.05, 95% CI: 0.01-0.09) and TT3 (β: 0.08, 95% CI: 0.02-0.14) levels. Additionally, thyroid-stimulating hormone (TSH) was confirmed as an independent risk factor for NAFLD (OR: 1.10, 95% CI: 1.04-1.18), with specific MR sensitivity analyses supporting the robustness of these results.

This study indicates potential elevations in FT3, TT3, and thyroglobulin levels associated with NAFLD, while also identifying TSH as a risk factor for NAFLD. These findings underscore the importance of routine thyroid function monitoring both in the general population and particularly in individuals with NAFLD.

Metabolic-associated fatty liver disease (MASLD) is a growing global health concern. From the standpoint of preventive and personalized medicine, understanding the early determinants and modifiable risk factors is essential for targeted prevention and personalized treatment strategies. This study aimed to evaluate the specific association between probiotics/prebiotics and the occurrence of MASLD, contributing to the development of innovative preventive measures and personalized therapeutic approaches.

Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. The study employed logistic regression analysis to examine the relation between MASLD and probiotics/prebiotics. The efficacy of various MASLD predictive models was assessed using receiver operating characteristic (ROC) curves. A meta-analysis was conducted by searching databases up to 4 May 2024. The analysis included randomized controlled trials of liver function in patients with MASLD or nonalcoholic steatohepatitis treated with probiotics, prebiotics, or yogurt for a minimum of 6 months.

A total of 5014 adults from NHANES were included in this study, with a weighted prevalence of MASLD observed at 24.47%. MASLD adults who consumed both probiotics and prebiotics exhibited a reduced risk of MASLD (OR = 0.71, 95% CI: 0.53 to 0.94). The use of probiotics/prebiotics can enhance the simplicity and practicality of the model. Model 1, adjusted for sex, BMI, race, and HEI-2015, achieved an area under the curve (AUC) of 0.8544, while Model 2, adjusted for sex, BMI, race, and prebiotics/probiotics use, showed a similar AUC of 0.8537. The comparison between the two models revealed no statistically significant difference (0.8544 vs. 0.8537; 95% CI: - 0.0010 to 0.0025; Z = 0.8332; p = 0.4047). Subgroup analysis of the NHANES data revealed that individuals aged 40 and older benefit from consuming probiotics or prebiotics. Furthermore, the meta-analysis demonstrated that probiotic or prebiotic interventions resulted in significant improvements in biochemical markers, including alanine aminotransferase, aspartate aminotransferase, low-density lipoprotein cholesterol, and triglycerides.

The consumption of probiotics/prebiotics has been linked to a reduced risk of developing MASLD in adults. Integrating probiotics/prebiotics into early intervention and personalized treatment plans may facilitate targeted prevention and management of MASLD, promoting a more individualized approach to disease prevention and care.

The online version contains supplementary material available at 10.1007/s13167-025-00398-4.

Some studies have found that high dietary inflammatory index (DII) increases stroke risk, but previous studies have mostly been conducted in the general population, and the exact relationship between DII and stroke in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) is not clear.

This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (2009-2016) to investigate the association between the DII and stroke. DII was computed according to established methods. Participants were categorized into tertiles of DII (Q1-Q3). Multivariate weighted logistic regression analysis, smooth curve fitting, and subgroup analysis were employed to explore this relationship. Subgroup analyses were conducted based on demographic and clinical variables.

A total of 2426 individuals were enrolled in our study. The overall prevalence of stroke in the study population was 4.66%. The smooth curve fitting analysis indicated a J-shaped relationship between DII and stroke among individuals with MASLD. In multivariate weighted logistic regression analysis, the odds ratio (OR) of DII is 1.17 (95% CI: 1.03-1.38) for stroke, with a turning point of 1.89. After the turning point, the OR (95% CI) was 1.22 (1.08-2.56). In subgroup analysis, DII still increased the risk of stroke independently.

Our study highlighted a J-shaped association between DII and stroke in adults with MASLD from USA.

Previous researches have revealed the potential association between dietary niacin intakes and several diseases, but studies assessing the association between dietary niacin intakes and nonalcoholic fatty liver disease (NAFLD) is limited and remains unclear. This study was performed to explore the association.

In this study, 10,528 participants (male: 5,257) in the 10 National Health and Nutrition Examination Survey (NHANES) cycles (1999-2018) from the NHANES database were selected for the analyses. We built three logistic regression models to explore the independent association between dietary niacin intakes and NAFLD and to explore whether such association exists. Finally, a restricted cubic spline model was applied to simulate the potential nonlinear association between dietary niacin intakes and the occurrence of NAFLD.

The result of the fully-adjusted model suggested that ln-transformed dietary niacin intakes were significantly associated with the reduced occurrence of NAFLD. The odd ratio (OR) of the model and its 95% confidence interval (CI) were 0.81 (0.73, 0.90). When taking the lowest quartile as a reference, the level of niacin in the highest quartile was associated with decreased prevalence of NAFLD (OR: 0.76, 95% CI: 0.63, 0.91). The restricted cubic spline plot presented a negative dose-response association between levels of daily niacin consumption and the occurrence of NAFLD (p for nonlinearity = 0.762).

According to the results of this study, dietary niacin intakes may have a negative association with NAFLD, and more well-designed cohort studies are required in the future to confirm the obtained finding.

Environmental factors, or exposome, are non-negligible contributors to the occurrence and progression of metabolic dysfunction-associated fatty liver disease (MAFLD). Therefore, this environment-wide association study (EWAS) aimed to investigate the associations between multifarious environmental factors and MAFLD among the general adult population in the United States.

Eligible participants were obtained from the National Health and Nutrition Examination Survey 2005-2020 cycles. Survey-weighted multivariate logistic regression models were constructed to identify and tentatively validate MAFLD-associated environmental factors. The least absolute shrinkage and selection operator (LASSO) regression was conducted to identify tentatively validated environmental factors with stronger associations with MAFLD. Moreover, the importance, discrimination power, correlation patterns, subgroup-specific differences, and survey cycle heterogeneity of the identified factors were further examined by multiple statistical strategies.

A total of 14,416 participants were included in this EWAS. Among 511 candidate environmental factors, 167 were identified and tentatively validated, and 45 were preserved after the LASSO selection and correlation evaluation. In this study, most previously known factors were replicated with reduced bias, and several poorly studied environmental factors were discovered, for example, upper leg length, access to care, mid-upper arm circumference, and total trabecular bone score. Their importance, discrimination ability, pairwise correlations, subgroup variations, and heterogeneity across survey cycles were further systematically and rigorously evaluated.

This EWAS comprehensively explored the associations between environmental factors and MAFLD in the general adult population from a panoramic perspective. The findings may provide clues for further understanding this disease and promote early prevention and risk prediction strategies in the future.

Steatotic liver disease (SLD) is a common chronic liver disease without effective therapeutic options. Some studies suggest potential health benefits of dietary live microbes. This study aims to investigate the association between dietary live microbes intake and metabolic dysfunction-associated steatotic liver disease (MASLD) / metabolic alcohol-related liver disease (MetALD) / alcoholic liver disease (ALD) in adults. Data from the National Health and Nutrition Examination Survey 1999-2018 were analyzed. MASLD was defined according to the latest Delphi Consensus standard. Participants were grouped based on estimated dietary live microbe intake: low (< 104 CFU/g), moderate (104-107 CFU/g), and high (> 107 CFU/g). Multivariable logistic regression analysis was employed to assess the impact of dietary live microbes on MASLD/MetALD/ALD, along with further investigations into non-dietary probiotic/prebiotic relationships. Participants had a weighted mean age of 47.05 years (SE, 0.24) and 50.59% were female. MASLD proportions differ among low (21.76%), moderate (22.24%), and high (18.96%) microbe groups. Similarly, for MetALD, proportions are 7.75%, 6.95%, and 6.44%, and for ALD, 5.42%, 3.59%, and 2.97% in respective groups. The high dietary live microbe intake group was associated with a 16% lower risk of MASLD compared to those in the low intake group (trend test, P = 0.02), while the risk of ALD was reduced by 25% in the moderate intake group. A lack of association was identified between non-dietary prebiotic/probiotic and MASLD/MetALD/ALD. Our study suggests that a relatively high intake of live microbes diets in adults is associated with a lower risk of SLD.

The Life's Essential 8 (LE8) is a recently introduced assessment of cardiovascular health (CVH) by the American Heart Association (AHA). Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease and is associated with an increased risk of stroke. We aimed to explore the association of LE8 with stroke in NAFLD using a national cross-sectional study.

Eligible participants with NAFLD aged 20-85 years in NHANES 2005-2018 were included. LE8 was assessed according to AHA criteria and categorized into metabolic and behavioral factors. US Fatty Liver Index (USFLI) ≥ 30 and exclusion of other chronic liver diseases suggested NAFLD. Stroke was diagnosed according to self-report on standardized questionnaires.

After adjusting for all confounders, each point increase in LE8, LE8 metabolic factors, and LE8 behavioral factors was associated with a 4.4 %, 1.8 %, and 2.5 % reduction in stroke prevalence in NAFLD, respectively. Both moderate and high CVH assessed by LE8 and LE8 behavioral factors were associated with reduced odds of stroke compared with low CVH. Stroke prevalence declined progressively with increasing number of ideal LE8 components, with the lowest odds of stroke at 3 + ideal LE8 components for both LE8 metabolic and behavioral factors. Restricted cubic spline suggested dose-response associations. Race/ethnicity was a significant effect modifier, and this association was present only among non-Hispanic white population and other Hispanic population. FLI as a diagnostic indicator of NAFLD yielded generally consistent results.

Higher LE8 score, especially LE8 behavioral factors, was associated with reduced prevalence of stroke in NAFLD, especially among non-Hispanic white population and other Hispanic population. The odds of stroke declined progressively with increased ideal LE8 component number. These findings underscore the preventive value of adherence to high CVH for stroke prevention in NAFLD.

The association between Life's Essential 8 (LE8) score and all-cause mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unknown.

This population-based prospective cohort study analyzed data of participants aged 20-79 years in the National Health and Nutrition Examination Survey from 2005 to 2018, with linked mortality information until 2019. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between different cardiovascular health (CVH) scores and all-cause mortality in participants with MASLD.

Among 11,988 participants, 4109 (34.3 %) were diagnosed with MASLD. During the median 7.8 years of follow-up, 912 deaths were recorded. Unexpectedly, the total LE8 CVH score was not associated with all-cause mortality in patients with MASLD (all P > .05). However, individuals with MASLD with moderate and poor LE8 health behaviors scores exhibited an increased risk of all-cause mortality (moderate: HR, 1.51; 95 % CI, 1.05-2.17; poor: HR, 2.32; 95 % CI, 1.64-3.30), particularly among patients with advanced fibrosis (moderate: HR, 1.77; 95 % CI, 1.07-2.92; poor: HR, 2.43; 95 % CI, 1.23-4.78). Population-attributable fraction estimates suggest that 35.0 % of all-cause mortality attributed to poor or moderate health behaviors scores could be avoided if ideal CVH metrics were achieved in all patients with MASLD.

These findings demonstrate a significant association between the LE8 health behaviors score and all-cause mortality in patients with MASLD, highlighting the usefulness of this score in optimizing risk management strategies for MASLD in future clinical practice.

Oxidative stress contributes to the progression of non-alcoholic fatty liver disease (NAFLD). Antioxidants from food can reduce NAFLD incidence, and the Composite Dietary Antioxidant Index (CDAI) measures total antioxidant capacity (TAC). However, the relationship between CDAI and NAFLD in the US adult population remains unclear.

To assess whether CDAI is associated with NAFLD in US adults.

This population-based cross-sectional study used data on US adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2016 cycles. Data were analyzed from January to February 2024.

CDAI obtained from the dietary intake questionnaire.

The main outcome was NAFLD which defined by the US fatty liver score (USFLI) ≥30. Sampling weights were calculated according to NHANES guidelines.

Among 9,746 adults included in this study [mean age, 48.3 years; 4,662 (47.6%) males], 3,324 (33.0%) were classified as having NAFLD using USFLI. In the fully adjusted of multivariable logistic regression, CDAI was negatively associated with NAFLD (odds ratio [OR], 0.95; 95% CI, 0.93-0.98). Furthermore, individuals in the highest quartile of CDAI were 34% less likely to have NAFLD compared to those in the lowest quartile (OR, 0.66; 95% CI, 0.52-0.85). In subgroup analyses, CDAI was inversely associated with NAFLD among participants with a BMI <25 (OR, 0.89; 95% CI, 0.83-0.95) and without metabolic syndrome (OR, 0.93; 95% CI, 0.91-0.96). The interaction tests revealed significant differences in these subgroups (P for interaction = 0.04 for BMI and 0.003 for metabolic syndrome). Sensitivity analyses confirmed this association using the hepatic steatosis index (HSI) to define NAFLD, applying unweighted logistic regression, adjusting for physical activity or after excluding non-Hispanic Black participants, and after excluding medications known for their potential hepatotoxic effects.

In this cross-sectional study based on six cycles (2005-2016) of the NHANES, CDAI was negatively associated with NAFLD in US adult population. This association highlights the potential for dietary interventions to reduce NAFLD incidence and underscores the need for future research, including clinical trials and mechanistic studies, to further explore the role of dietary antioxidants in NAFLD prevention and management.

Multifaceted factors play a crucial role in the prevention and treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to utilize multifaceted indicators to construct MASLD risk prediction machine learning models and explore the core factors within these models.

MASLD risk prediction models were constructed based on seven machine learning algorithms using all variables, insulin-related variables, demographic characteristics variables, and other indicators, respectively. Subsequently, the partial dependence plot(PDP) method and SHapley Additive exPlanations (SHAP) were utilized to explain the roles of important variables in the model to filter out the optimal indicators for constructing the MASLD risk model.

Ranking the feature importance of the Random Forest (RF) model and eXtreme Gradient Boosting (XGBoost) model constructed using all variables found that both homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride glucose-waist circumference (TyG-WC) were the first and second most important variables. The MASLD risk prediction model constructed using the variables with top 10 importance was superior to the previous model. The PDP and SHAP methods were further utilized to screen the best indicators (including HOMA-IR, TyG-WC, age, aspartate aminotransferase (AST), and ethnicity) for constructing the model, and the mean area under the curve value of the models was 0.960.

HOMA-IR and TyG-WC are core factors in predicting MASLD risk. Ultimately, our study constructed the optimal MASLD risk prediction model using HOMA-IR, TyG-WC, age, AST, and ethnicity.

Exposure to brominated flame retardants (BFRs) may negatively impact human health. The association of BFRs with nonalcoholic fatty liver disease (NAFLD) in the general population is unclear. Meanwhile, limited studies have investigated the potential role of oxidative stress and inflammation in this link.

We included 4110 adults from the 2009-2014 National Health and Nutrition Examination Survey (NHANES). NAFLD was diagnosed by serum alanine aminotransferase (ALT), hepatic steatosis index (HSI), and United States fatty liver index (USFLI). The link between a single BFR exposure and NAFLD was estimated using weighted logistic regression and restricted cubic splines (RCS). The quantile-based g-computation (QGC), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were applied to evaluate the overall correlation of BFRs mixtures with NAFLD and identify significant compounds. Furthermore, we investigated the potential mediation function of oxidative stress and inflammation.

Our study demonstrated that specific concentrations of BFRs are related to an increased risk of NAFLD, both individually and when combined. PBB153, PBDE28, PBDE209, and PBDE153 exhibited the highest importance for NAFLD and were potential risk factors worthy of concern. Additionally, mediation analysis showed that absolute neutrophil cell count (ANC) and lymphocyte count (LC) (inflammation markers) have significantly mediated influences on the correlations of PBB153, PBDE85, and PBDE28 with N AFLD risk. Albumin (ALB) (oxidative stress marker) has notably mediated influences on the correlations of PBDE99, PBDE154, and PBDE85 with NAFLD risk. Men had higher serum BFRs concentrations than women, and the association between BFRs and NAFLD was also more prominent in men, which may be related to physiological differences between the sexes.

Our findings offer evidence for single and mixed associations of BFRs and NAFLD in ordinary US adults. Furthermore, oxidative stress and chronic inflammation may mediate the effects of BFR exposure on NAFLD development.

The diagnostic criteria for Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) and Metabolic Associated Steatotic Liver Disease (MASLD) aim to refine the classification of fatty liver diseases previously grouped under Non-Alcoholic Fatty Liver Disease (NAFLD). This study evaluates the applicability of the MAFLD and MASLD frameworks in NAFLD patients, exploring their clinical utility in identifying high-risk patients. A total of 369 NAFLD patients were assessed using MAFLD and MASLD diagnostic criteria. Baseline characteristics, metabolic profiles, hepatic fibrosis, and cardiovascular risks were compared across the groups. Among NAFLD patients, 97.55% (n = 359) met MASLD criteria, and 97.01% (n = 357) fulfilled MAFLD criteria. Both frameworks MAFLD and MASLD captured overlapping populations, with MASLD encompassing slightly more cases. No significant differences were observed in metabolic risk factors, fibrosis indices (APRI, FIB-4, NAFLD fibrosis score), or cardiovascular risk (10-year ASCVD score). A small subset of lean NAFLD patients (10 cases) with distinct profiles remained uncategorized by either framework. Pure NAFLD cases (n = 10) were with mild insulin resistance (HOMA-IR: 3.07 ± 0.33) and slightly elevated LDL (102.5 ± 42.87 mg/dL), while fibrosis indices indicated low fibrosis risk. Steatosis indices supported the diagnosis of early-stage NAFLD with preserved liver function. These patients do not meet the criteria for inclusion in the MAFLD or MASLD frameworks, highlighting a gap in the current diagnostic systems. MAFLD and MASLD criteria align closely with NAFLD in capturing patients with metabolic risk with MASLD-enhanced inclusivity. Further refinement is required to address heterogeneity, particularly in lean NAFLD patients. Hypertension prevalence was comparable (17.4% in NAFLD, 18.2% in MAFLD, 17.8% in MASLD; p = 0.960), as was diabetes mellitus (36.7%, 37.8%, and 37.6%, respectively; p = 0.945). Body mass index was also similar across groups, with medians of 33.25, 33.6, and 33.4 kg/m2 (p = 0.731). Non-invasive markers of hepatic fibrosis, including APRI, FIB-4, and NAFLD fibrosis scores, did not differ significantly, with median FIB-4 scores around 1.05 (p = 0.953). Similarly, were the results of hepatic steatosis index and ASCVD score.

Liver enzymes are associated with liver function, but their relationship with body mass index (BMI) remains unclear. This cross-sectional study aimed to identify correlations between serum liver enzyme levels and BMI in the general population. The data were derived from the Dryad Digital Repository. Smooth curve and multiple linear regression analyses were performed to evaluate the associations between BMI and serum liver enzyme levels. A total of 15,464 participants, including 8430 males (54.5%), were included in the study, with a median age of 43.7 years. Smooth curve regression revealed that BMI followed U-shaped curves with respect to serum levels of liver enzymes (AST, ALT, and GGT). For AST serum levels, the turning points were BMI = 19.0 and 23.3 kg/m2; for ALT serum levels, the inflection points were BMI = 19.0 and 23.1 kg/m2; and for GGT serum levels, the inflection point was BMI = 19.5 kg/m2. In addition, stratified analysis revealed that sex, fatty liver, and smoking status as covariates modified the associations between BMI and AST and ALT serum levels in participants with higher BMIs (all interactions P < 0.01). Specifically, in the higher BMI range, the positive associations between BMI and liver enzymes were more robust in men (AST and ALT), participants with fatty liver disease (AST and ALT), and participants with a history of smoking (AST, ALT, and GGT). Interestingly, alcohol consumption modified the association between BMI and GGT serum levels, regardless of BMI. Our study is the first to identify a U-shaped association between BMI and serum levels of liver enzymes in the general population, which suggests a new target for regulating liver enzyme levels.

To estimate the individual and combined influences of phthalates and biological aging on insulin resistance (IR), prediabetes, and diabetes in population with metabolic dysfunction-associated steatotic liver disease (MASLD).

Data on 3,045 US adults with MASLD were collected to outline the individual and mixed effects of urinary phthalate metabolites on prevalent IR, prediabetes, and diabetes by survey-weighted logistic regression and weighted quantile sum (WQS) regression, as well as the interaction effects between phthalates and biological aging.

We discovered positive relationships - odds ratio (OR) and 95 % confidence interval [CI] - of mono-2-ethyl-5-carboxypentyl phthalate 1.147 [1.041;1.264], mono-(2-ethyl-5-hydroxyhexyl) phthalate 1.175 [1.073;1.288], and mono-(2-ethyl-5-oxohexyl) phthalate 1.140 [1.040;1.250] with IR, and of mono-isobutyl phthalate with prediabetes 1.216 [1.064;1.390] (all FDR-adjusted P < 0.05). WQS analyses indicated significantly mixed effects of phthalate metabolites on the elevated risks of IR 1.166 [1.034;1.315], prediabetes 1.194 [1.006;1.416], and diabetes 1.214 [1.026;1.437]. Biological age (BA) and phenotypic age (PA) were positively associated with IR, prediabetes, and diabetes and further significantly interacted with phthalates on the outcomes; typically, compared to participants with low levels of phthalates mixture and PA, those with high levels of phthalates mixture and PA had the highest risks of IR 2.468 [1.474;4.133] (Pinteraction = 0.031), prediabetes 1.975 [1.189;3.278] (Pinteraction = 0.009), and diabetes 6.065 [3.210;11.460] (Pinteraction = 0.013).

Phthalates exposure of MASLD adults was related to increased risks of IR, prediabetes, and diabetes, which were interactively aggravated by biological aging. Controlling phthalates exposure and biological aging probably hold significant relevance for the prevention of diabetes in the MASLD population.

The American Heart Association has updated the cardiovascular health (CVH) assessment tool, referred to as the Life's Essential 8 (LE8). Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common chronic liver disease worldwide and is linked to an elevated risk of mortality. We aimed to explore the association of LE8 with all cause and cause-specific mortality in MASLD in a prospective cohort study. A total of 10,050 participants with MASLD from the NHANES 2005-2018 dataset were included in the study. LE8 was evaluated by combining four health behaviors and four health factors, with scores of 0-49 categorized as low CVH, 50-79 as moderate CVH, and 80-100 as high CVH. In the fully adjusted model, each one-point increase in the LE8 score corresponded to a 2.7, 2.7, and 1.6% decrease in all-cause, CVD, and cancer mortality risk, respectively, in people with MASLD. Compared to low CVH, being in moderate/high CVH was negatively associated with most mortality outcomes, while health factors lost significant association with cancer mortality.

There are no studies discussing the significance of neutrophil-to-lymphocyte ratio (NLR), neutrophil-percentage-to-albumin ratio (NPAR), and systemic immune-inflammation index (SII) in predicting poor prognosis in patients with metabolic dysfunction associated steatotic liver disease (MASLD); this study aimed to investigate the relationship between these three inflammatory markers and all-cause mortality and cardiovascular disease (CVD) mortality in patients with MASLD. Survival data for 3970 participants were obtained from National Death Index (NDI) records associated with the National Health and Nutrition Examination Survey (NHANES) dataset, the associations of NPAR, NLR, and SII with all-cause and CVD mortality were analyzed using multivariate COX regression modeling, restricted cubic spline (RCS) was used to explore nonlinear relationships and to determine the inflection point, regrouping was done according to the nonlinear inflection point, using multivariate COX regression modeling, subgroup analysis, and the Kaplan-Meier survival curves to evaluate differences in risk of death between the two groups. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to assess the predictive efficacy of NPAR, NLR, and SII on survival outcomes. Multivariate COX regression and RCS analyses revealed a positive linear correlation between NLR and all-cause and CVD mortality, whereas a nonlinear relationship was found between NPAR and SII and all-cause and CVD mortality. Further reclassified into two groups according to the inflection point, multivariate COX regression analyses showed a significant difference in the risk of death between the two NPAR groups (HR 1.37, 95% CI = (1.01, 1.86) for all-cause mortality and HR 2.03, 95% CI = (1.24, 3.32) for CVD mortality ) and no difference in the risk of death between the two SII groups (HR 1.11, 95% CI = (0.87, 1.42) for all-cause mortality and HR 1.35, 95% CI = (0.86, 2.12) for CVD mortality), and Kaplan-Meier survival curves showed that both all-cause and CVD mortality rates were higher in patients with MASLD above the NPAR inflection point (log-rank P < 0.05). Subgroup analyses showed that the associations between high levels of NPAR and all-cause mortality were generally consistent across populations (P interaction > 0.05). Also, COPD subgroups had a significant effect on the correlation between high levels of NPAR and CVD mortality (P interaction < 0.05). Time-dependent ROC show the predictive value of NPAR, NLR, and SII for all-cause and CVD mortality in MASLD patients. The correlation between NPAR and mortality was nonlinear, and NLR was linearly and positively correlated with mortality, Measuring NPAR and NLR may be useful in assessing risk and predicting prognosis in populations of patients with MASLD.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease in human history and it is expected to surpass other causes of liver disease mortality by 2030. Therefore, finding an alternative way to diagnose steatosis in the early stage when imaging modalities are not available is crucial. This study decided to validate the optimal cut-off points and the sensitivity and specificity of the Fatty Liver Index (FLI) based on the Iranian population compared to ultrasonography.

The data of 367 individuals, 108 males and 259 females over 35, were analyzed. Hepatic steatosis was identified by ultrasound. FLI was determined from waist circumference, gamma-glutamyl transferase, triglyceride, and body mass index data. The receiver operating characteristic curve (ROC) was used to determine the best FLI index cut point for diagnosing nonalcoholic fatty liver. The sensitivity and specificity indices were calculated for the determined cut point.

The AUC of the FLI index in diagnosing NAFLD in the total population was 0.733 (95% CI: 0.68-0.77, specificity = 0.6705, sensitivity = 0.7320) with the optimal COP of 40.6. There was a statistically significant association between non-alcoholic liver disease and FLI-based ultrasound (p < 0.0001). Furthermore, the sex-specific optimal COPs of FLI was 33.4, specificity = 0.6071, sensitivity = 0.8462 in men vs. 27.8, sensitivity = 0.8233, specificity = 0.7655 in women.

FLI is a reliable tool for identifying individuals with NAFLD. It has the potential to aid in detecting and managing this condition in large-scale populations while other methods are not available. We also determine an optimal COP of 40.6 with sensitivity and specificity of 73.20% and 67.05% in the general population, respectively.