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Background: The relationship between dietary folate intake and prior mortality in adult patients with Non-alcoholic Fatty Liver Disease (NAFLD) has not been clearly studied. We aimed to examine the relationship between dietary folate intake and all-cause and cardiovascular (CVD) mortality in adult NAFLD patients in the US., Methods: Using data from National Health and Nutrition Examination Survey (NHANES) 2003-2018 and associated mortality data we conducted a cohort study of US adult NAFLD subjects. Multivariable Cox proportional hazards regression models were used to evaluate the relationship between dietary folate intake and both all-cause mortality and CVD mortality, accounting for potential confounders. The study employed restricted cubic spline analysis to investigate the non-linear association between dietary folate levels and mortality from all causes and cardiovascular disease., Results: Our final cohort consisted of 3,266 NAFLD patients, with a median follow-up of 10.3 years, 691 deaths were observed, including 221 cardiovascular deaths. Compared to participants with a folate intake in Quartile 1 (≤250 μg/d), those in Quartile 4 (≥467.5 μg/d) had multivariable-adjusted hazard ratios of 0.69 (95% CI, 0.51-0.94) for all-cause mortality (p for trend = 0.028) and 0.55 (95% CI, 0.29-1.04) for CVD mortality (p for trend = 0.107). A non-linear relationship between dietary intake and risk of death was not observed., Conclusion: Greater dietary folate intake is associated with a reduced risk of all-cause in American adults with NAFLD. Higher dietary folate intake not found to be associated with lower CVD mortality. These findings suggest that dietary folate may improve the prognosis of adult NAFLD patients. The measured-response relationship between dietary folate intake and mortality in patients with NAFLD requires further investigation., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Dong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Copper functions as an essential micronutrient influencing diverse metabolic processes in mammals, encompassing oxidative stress responses, lipid metabolism, and participation in enzymatic reactions. However, the impact of serum copper on non-alcoholic fatty liver disease (NAFLD) remains controversial. Our aim was to explore the precise correlation between serum copper and NAFLD in a large-scale population-based study. A total of 1377 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 were included in our study. The diagnosis of NAFLD and its progress to advanced liver fibrosis were based on serological indexes. One-way ANOVA, Kruskal-Wallis H test, and Chi-square test were used to access variations between quartiles groups of serum copper. We conducted multivariate-adjusted logistic regression models and subgroup analyses to investigate the association between serum copper and NAFLD, along with several metabolic diseases. Among the 1377 participants, 661 were diagnosed with NAFLD, and 141 of whom were classified into advanced liver fibrosis. Higher serum copper levels (≥ 21.00 μmol/L) were associated with an increased incidence of NAFLD (odds ratio (OR) = 2.07 (1.38-3.10), p < 0.001), as well as advanced liver fibrosis (OR = 2.40 (1.17-5.19), p = 0.025). Moreover, serum copper exhibited a positive correlation with hypertension, overweight, and abdominal obesity, all of which have been identified as risk factors of NAFLD. Additionally, female participants, under the age of 60, and with a higher body mass index (BMI) (> 24.9 kg/m 2 ) emerged as the most vulnerable subgroup concerning the relationship between serum copper and NAFLD. In the U.S. population, a notable association has been identified, linking elevated serum copper to an increased susceptibility for both the onset and progression of NAFLD, along with several metabolic disorders associated with NAFLD. The adverse effects of excess copper warrant attention in the context of public health considerations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This study investigated the potential effects of perfluoroalkyl substance (PFAS) in serum on MAFLD, NAFLD, and liver fibrosis., Methods: Our sample included 696 participants (≥ 18 years) from the 2017-2018 NHANES study with available serum PFASs, covariates, and outcomes. Using the first quartile of PFAS as the reference group, we used weighted binary logistic regression and multiple ordered logistic regression used to analyze the relationship between PFAS and MAFLD, NAFLD, and liver fibrosis and multiple ordinal logistic regression to investigate the relationship between PFAS and MAFLD, NAFLD, and liver fibrosis and calculated the odds ratio (OR) and 95% confidence interval for each chemical. Finally, stratified analysis and sensitivity analysis were performed according to gender, age, BMI, and serum cotinine concentration., Results: A total of 696 study subjects were included, including 212 NAFLD patients (weighted 27.03%) and 253 MAFLD patients (weighted 32.65%). The quartile 2 of serum PFOA was positively correlated with MAFLD and NAFLD (MAFLD, OR 2.29, 95% CI 1.05-4.98; NAFLD, OR 2.37, 95% CI 1.03-5.47). PFAS were not significantly associated with liver fibrosis after adjusting for potential confounders in MAFLD and NAFLD. Stratified analysis showed that PFOA was strongly associated with MAFLD, NAFLD, and liver fibrosis in males and obese subjects. In women over 60 years old, PFHxS was also correlated with MAFLD, NAFLD, and liver fibrosis., Conclusion: The serum PFOA was positively associated with MAFLD and NAFLD in US adults. After stratified analysis, the serum PFHxS was correlated with MFALD, NAFLD, and liver fibrosis., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The ratio of non-high-density lipoprotein cholesterol (non-HDL-C) to HDL-C (NHHR) is a novel lipid parameter used to assess the risk of cardiovascular disease. Previous studies have demonstrated an association between the NHHR and risk of non-alcoholic fatty liver disease (NAFLD). Owing to the lack of research exploring this relationship in specific populations, this study aimed to determine the potential link between the NHHR and risk of NAFLD among American adults in the United States. Data were retrieved from the National Health and Nutrition Examination Survey (NHANES) spanning 2017-2020. After excluding individuals with other liver diseases, alcohol abuse, and missing lipid data, a total of 6809 eligible adults were included for analysis. The NHHR was calculated as the ratio of (non-HDL-C) to HDL-C, while NAFLD was identified by liver steatosis detected by transient elastography. Multivariable weighted logistic regression models and restricted cubic spline (RCS) models were employed to investigate the relationship between the NHHR and risk of NAFLD. Subgroup and sensitivity analyses were also conducted to test the robustness of the results. As the NHHR increased, the prevalence of NAFLD rose progressively (5.88% vs. 8.75% vs. 12.24% vs. 15.77%, p < 0.001). In the overall population, after adjusting for confounding factors, each unit increase in the NHHR was associated with a 25% increase in NAFLD risk (OR = 1.25, 95% CI: 1.03-1.53, p = 0.0372). When the NHHR was analyzed as a categorical variable (quartiles), participants in the highest quartile had a significantly higher risk of NAFLD than those in the lowest quartile (OR = 2.6, 95% CI: 1.75-3.85, p = 0.009). RCS analysis further indicated a nonlinear dose-response relationship between the NHHR and risk of NAFLD (p non-linearity < 0.0001). This association remained significant in both subgroup and sensitivity analyses. This study confirmed that the NHHR, particularly at higher levels, was an independent risk factor for NAFLD. As a comprehensive lipid indicator, the NHHR had the potential to predict NAFLD risk. These findings provided new insights for the prevention and clinical management of NAFLD., (© 2024. The Author(s).)

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) has become a worldwide public health problem. Current evidence on the association between dietary iron intake and the risk of NAFLD is limited. The present study aimed to investigate the associations of animal-derived dietary iron (ADDI) intake, plant-derived dietary iron (PDDI) intake, and the ratio of PDDI:ADDI with NAFLD risk among U.S. adult population., Methods and Study Design: This was a repeated cross-sectional study. Data were collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. NAFLD was defined as a United States Fatty Lives Index ≥30, and dietary iron intake was assessed through two 24-h dietary recall in-terviews. Logistic regression and restricted cubic spline models were applied to examine the associations between dietary iron intake from different sources and NAFLD risk., Results: A total of 9478 participants aged ≥20 years were enrolled in the present study. After adjustment for multiple confounding factors, relative to the lowest quartile, the odds ratio (OR) and 95% confidence interval (CI) of NAFLD for the highest quartile was 1.01(95% CI, 0.82-1.24) for ADDI intake, 0.82 (95% CI, 0.64-0.99) for PDDI intake, and 1.00 (95% CI, 0.81-1.24) for the PDDI: ADDI intake ratio. In stratified analysis by sex and age, the significantly negative associations of PDDI intake with NAFLD was observed in women and participants older than 45 years. Dose-response analyses indicated that NAFLD was negatively associated with PDDI intake in a non-linear manner., Conclusions: PDDI intake was negatively associated with NAFLD in U.S. adults., Competing Interests: The authors have no competing interests to declare

Purpose: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. Phthalates have been suggested to influence the development of NAFLD due to their endocrine-disrupting properties, but studies based on nationally representative populations are insufficient, and existing studies seem to have reached conflicting conclusions. Due to changes in legislation, the use of traditional phthalates has gradually decreased, and the phthalates substitutes is getting more attention. This study aims to delve deeper into how the choice of diagnostic approach influences observed correlations and concern about more alternatives of phthalates, thereby offering more precise references for the prevention and treatment of NAFLD., Methods: A cohort of 641 participants, sourced from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 database, was evaluated for NAFLD using three diagnostic methods: the Hepatic Steatosis Index (HSI), the US Fatty Liver Indicator (US.FLI), and Vibration Controlled Transient Elastography (VCTE). The urinary metabolite concentrations of Di-2-ethylhexyl phthalate (DEHP), Di-isodecyl phthalate (DIDP), Di-isononyl phthalate (DINP), Di-n-butyl phthalate (DnBP), Di-isobutyl phthalate (DIBP), Di-ethyl phthalate (DEP) and Di-n-octyl phthalate (DnOP) were detected. The association between NAFLD and urinary phthalate metabolites was evaluated through univariate and multivariate logistic regression analyses, considering different concentration gradients of urinary phthalates., Results: Univariate logistic regression analysis found significant correlations between NAFLD and specific urinary phthalate metabolites, such as Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), Mono-2-ethyl-5-carboxypentyl phthalate (MECPP), and Mono-(carboxyisoctyl) phthalate (MCiOP), across different diagnostic criteria. In a multivariate logistic regression analysis adjusting only for demographic data, MEOHP (OR = 3.26, 95% CI = 1.19-8.94, p  = 0.029), MEHHP (OR = 3.98, 95% CI = 1.43-11.1, p  = 0.016), MECPP (OR = 3.52, 95% CI = 1.01-12.2, p  = 0.049), and MCiOP (OR = 4.55, 95% CI = 1.93-10.7, p  = 0.005) were positively related to NAFLD defined by HSI and VCTE. The correlation strength varied with the concentration of phthalates, indicating a potential dose-response relationship. Adjusting for all covariates in multivariate logistic regression, only MCiOP (OR = 4.22, 95% CI = 1.10-16.2, p  = 0.044), as an oxidative metabolite of DINP, remained significantly associated with NAFLD under the VCTE criterion, suggesting its potential role as a risk factor for NAFLD., Conclusion: This research highlights a significant association between DINP and NAFLD. These findings underscore the need for further investigation into the role of the phthalates substitutes in the pathogenesis of NAFLD and the importance of considering different diagnostic criteria in research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zou, Gu and Gu.)

Background: The prognostic value of triglyceride-glucose (TyG) related indices in non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is still unclear. This study aimed to determine the associations between TyG-related indices and long-term mortality in this population., Methods: The data came from the National Health and Nutrition Examination Survey (NHANES III) and National Death Index (NDI). Baseline TyG, TyG combining with body mass index (TyG-BMI), and TyG combining with waist circumference (TyG-WC) indices were calculated, and mortality status was determined through 31 December 2019. Multivariate Cox and restricted cubic spline (RCS) regression models were performed to evaluate the relationship between TyG-related indices and long-term mortality among participants with NAFLD/MASLD. In addition, we examined the association between TyG-related indices and all-cause mortality within subgroups defined by age, sex, race/ethnicity, and fibrosis-4 index (FIB-4)., Results: There were 10,390 participants with completed ultrasonography and laboratory data included in this study. NAFLD was diagnosed in 3672/10,390 (35.3%) participants, while MASLD in 3556/10,390 (34.2%) amongst the overall population. The multivariate Cox regression analyses showed high levels of TyG-related indices, particularly in TyG-BMI and TyG-WC indices were significantly associated with the all-cause mortality, cardiovascular mortality, and diabetes mortality in either NAFLD or MASLD. The RCS curves showed a nonlinear trend between three TyG-related indices with all-cause mortality in either NAFLD or MASLD. Subgroup analyses showed that TyG-BMI and TyG-WC indices were more suitable for predicting all-cause mortality in patients without advanced fibrosis., Conclusion: Our study highlights the clinical value of TyG-related indices in predicting the survival of the NAFLD/MASLD population. TyG-BMI and TyG-WC indices would be the surrogate biomarkers for the follow-up of the population without advanced fibrosis., (© 2024. The Author(s).)

Background: The estimated glucose disposal rate (eGDR), an effective indicator of insulin resistance, has been related to acute coronary syndrome, ischemic stroke and heart failure. This study aims to explore the relationship between eGDR and arterial stiffness, all-cause mortality and cardiovascular mortality in patients with non-alcoholic fatty liver disease (NAFLD)., Methods: Participants with NAFLD were chosen from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. The main outcomes are arterial stiffness (represented by estimated pulse wave velocity, ePWV), all-cause and cardiovascular mortality. Multiple cox regression models, restricted cubic spline, sensitivity analysis and subgroup analysis were carried out to investigate the correlation between the insulin resistance indicators and mortality and arterial stiffness. Furthermore, receiver operating characteristic curves were used to compare the predictive value of the eGDR with the triglyceride-glucose (TyG) index and the homeostasis model assessment of insulin resistance (HOMA-IR) for all-cause and cardiovascular mortality., Results: In this study, a total of 4,861 participants were included for analysis. After adjusting confounding factors in the multivariate weighted cox regression model, the eGDR was inversely associated with the all-cause mortality (Q4 vs. Q1, HR =0.65 (0.48-0.89, P=0.01) and cardiovascular mortality (Q4 vs. Q1, HR =0.35 (0.19-0.65, P<0.001). Compared with TyG index and HOMA-IR, the eGDR shows excellent predictive value in all-cause mortality (0.588 vs. 0.550 vs. 0.513, P < 0.001) and cardiovascular mortality (0.625 vs. 0.553 vs. 0.537, P < 0.001). In addition, we found a significant negative correlation between eGDR and arterial stiffness (β=-0.13(-0.14-0.11, P< 0.001). However, TyG index and HOMA-IR showed no significant correlation to arterial stiffness., Conclusions: Low eGDR (an indicator of insulin resistance) levels are related to an increased risk of arterial stiffness and mortality in NAFLD patients in the United States., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Song, Ma and Yin.)

Background: The arm circumference (AC) has been used as an important tool to access the risk of non-alcoholic fatty liver disease (NAFLD) in adults. However, the association between AC and NAFLD in children and adolescence remains unclear. This study aims to explore the relationship between AC and NAFLD in American children and adolescence., Methods: 2017-2020 National Health and Nutrition Examination Survey (NHANES) was used to carry out the cross-sectional study. The association between AC and the risk of NAFLD, and liver steatosis was analyzed using weighted multivariable logistic regression and multivariate linear regression. Additionally, a two-part linear regression model was used to identify threshold effects in this study. Subgroup analysis, interaction tests and receiver operating characteristic (ROC) curve analysis were also carried out., Results: A total of 1,559 children and adolescence aged 12-18 years old were included, and the prevalence of NAFLD was 27.3%. AC was positively correlated with the risk of NAFLD (OR = 1.25, 95% CI: 1.19, 1.32) and liver steatosis ( β  = 4.41, 95% CI: 3.72, 5.09). Subgroup analysis stratified by age and race showed a consistent positive correlation. A non-linear relationship and saturation effect between AC and NAFLD risk were identified, with an S shaped curve and an inflection point at 34.5 cm. Area under the ROC of AC to NAFLD was 0.812, with the sensitivity of 67.6%, the specificity of 83.8% and the cutoff value of 31.7 cm., Conclusion: Our study shows that AC is independently correlated with an increased risk of NAFLD and the severity of liver steatosis in American children and adolescence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Weng, Xu and Yang.)

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) and urinary incontinence (UI) are both highly prevalent and age-related diseases. Nevertheless, the link between NAFLD and UI is unclear. Hence, the study was designed to evaluate the association between the NAFLD and UI (including UI types) in a nationally representative sample of United States (US) female adults., Methods: We conducted this study used data from U.S. female adults in the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020 (pre-pandemic) cycles. The diagnosis of NAFLD is based on Vibration controlled transient elastography (VCTE) and absence of know liver diseases and significant alcohol consumption. The diagnosis and types of UI were assessment using a self-report questionnaire. Multivariable logistic regression models were used to analyze the association between NALFD and UI. Stratified analyses based on age, obesity, race, educational level, married status, PIR, and smoking status were conducted., Results: Of the 2149 participants, the mean (95% CI) age was 53.9 (52.7-55.0), 686 (61.1%) were Non-Hispanic White. UI was significantly more common in participants with NAFLD [490 (64.7%)] than those without NAFLD [552 (44.9%)]. Adjusted for age, race/ethnicity, marital status, educational level, family poverty income ratio (PIR) status, alanine aminotransferase (ALT), aspartate aminotransferase (AST), smoking status, obesity, type 2 diabetes mellitus (T2DM), hypertension and insulin resistance (IR) in a multivariable logistic regression model, NALFD were associated with UI [OR: 1.93, 95%CI 1.23-3.02, P = 0.01] and urge UI [OR: 1.55, 95%CI 1.03-2.33, P = 0.03], while patients with NAFLD did not show an increased odds in stress UI and mixed UI when compared with those without NAFLD subject (P > 0.05). In the subgroup analyses, NAFLD remained significantly associated with UI, particularly among those participants without obesity (OR: 2.69, 95% CI 1.84-4.00) and aged ≥ 60 years (OR: 2.20, 95% CI 1.38-3.51)., Conclusions: Among US female adults, NAFLD has a strong positive correlation with UI. Given that NAFLD is a modifiable disease, these results may help clinicians to target female patients with NAFLD for treatments and interventions that may help prevent the occurrence of UI and reduce the symptoms of UI., (© 2024. The Author(s).)

Background: Alterations in the bacteria, such as the periodontal bacteria, might be considered potential risk factors for nonalcoholic fatty liver disease (NAFLD). Most studies analyzing this association have focused mainly on a specific periodontal bacteria (Porphyromonas gingivalis) and have involved relatively small study populations (tens or hundreds of individuals). To address this gap, a sizable, nationally representative adult population was utilized to investigate the association between the incidence of NAFLD and high serum IgG antibodies for 19 periodontal bacteria., Methods: To explore this association, data from the Third National Health and Nutrition Examination Survey (NHANES III)-which provides a cross-sectional representation of the noninstitutionalized U.S. population, encompassing 33,994 individuals-were analyzed. Participants aged 40 years and above with data on NAFLD-determined by the gold standard of ultrasound examination (USON)-as well as comprehensive records of serum IgG antibodies against periodontal bacteria, were included, resulting in a final analysis subset of 6,330 individuals., Results: Using a cluster analysis based on the Socransky classification scheme for oral microorganisms, antibody titers for the 19 bacteria were grouped into four clusters-Red-Green, Orange-Blue, Yellow-Orange, and Orange-Red. When these clusters, as well as individual antibody relationships with NAFLD, were examined, the adjusted odds ratios (ORs) ranged from 0.958 [95% confidence interval (CI): 0.916, 1.003] to 1.021 [95% CI: 0.987, 1.055]. This indicated that no statistically significant associations were found (P > 0.05), underscoring the absence of a meaningful link., Conclusions: In summary, it was discovered that there is currently no evidence to correlate serum antibodies to periodontal pathogens with NAFLD in the nationally representative NHANES III., Clinical Trial Number: Not applicable., (© 2024. The Author(s).)

Background: To overcome the limitations of the term "non-alcoholic fatty liver disease" (NAFLD), the term metabolic-associated steatotic liver disease (MASLD) was introduced. While epidemiologic studies have been conducted on MASLD, there is limited evidence on its associated sex and ethnic variations., Aims: This study assesses the differences across sex and race-ethnicity on the prevalence, associated risk factors and adverse outcomes in individuals with MASLD., Methods: Data retrieved from the National Health and Nutrition Examination Survey between 1999 to 2018 was analyzed. Prevalence, clinical characteristics, and outcomes were evaluated according to sex and race-ethnicity. Adverse outcomes and mortality events were analyzed using multivariate analyses., Results: Of 40,166 individuals included, 37.63% had MASLD. There was a significant increase in MASLD prevalence from 1999 to 2018 among Mexican Americans (Annual Percentage Change [APC] + 1.889%, p < 0.001), other Hispanics (APC + 1.661%, p = 0.013), NH Whites (APC + 1.084%, p = 0.018), NH Blacks (APC + 1.108%, p = 0.007), and females (APC + 0.879%, p = 0.030), but not males. Females with MASLD were at lower risk of all-cause (HR: 0.766, 95%CI 0.711 to 0.825, p < 0.001), cardiovascular disease-related (CVD) (SHR: 0.802, 95% CI 0.698 to 0.922, p = 0.002) and cancer-related mortality (SHR: 0.760, 95% CI 0.662 to 0.873, p < 0.001). Significantly, NH Blacks have the highest risk of all-cause and CVD-related mortality followed by NH Whites then Mexican Americans., Conclusion: There has been an increase in prevalence in most race-ethnicities over time. While the change in definition shows no significant differences in previous associations found in NAFLD, the increased mortality in NH Whites relative to Mexican Americans remains to be explored., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The systemic immune-inflammation index (SII) and trouble sleeping are independent risk factors for nonalcoholic fatty liver disease (NAFLD). Nevertheless, studies investigating the combined effects of the SII and troubled sleeping on NAFLD are lacking. In this study, we investigated the independent relationships and interactions between trouble sleeping and the SII among patients with NAFLD., Methods: Data from seven survey cycles of the National Health and Nutrition Examination Survey (NHANES) (2005-2018) were analyzed. The SII was obtained by counting platelets, neutrophils, and lymphocytes. NAFLD was diagnosed using the US fatty liver index. Trouble sleeping was diagnosed using a sleep disorder questionnaire. The correlation between trouble sleeping and the SII in NAFLD was investigated using multiple regression analysis, subgroup stratification, interaction tests, and restricted cubic spline, and the presence or absence of additive or multiplicative interactions was determined. Additionally, mediation analyses were performed to explore the role of the SII in mediating the effects of trouble sleeping on NAFLD., Results: The survey included 10 963 participants. Multivariate logistic regression revealed that SII (OR: 1.21, 95% CI 1.08-1.35) and trouble sleeping (OR: 1.24, 95% CI 1.05-1.47) were positively correlated with NAFLD. For NAFLD, an additive but not multiplicative interaction was noted between the SII and trouble sleeping. The SII partially mediated the association between trouble sleeping and NAFLD, accounting for approximately 3.11% of the total effect (95% CI 0.01-0.05)., Conclusion: The SII and trouble sleeping were independently correlated with NAFLD risk. Furthermore, a combined effect may exist between SII and trouble sleeping, which increases the risk of NAFLD., (© 2024. The Author(s).)

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 (P trend  = 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., (© 2024. The Author(s).)

Background: NASH is considered a contributor to atherosclerotic cardiovascular disease (ASCVD) risk; however, its contribution beyond traditional risk factors for CVD, particularly diabetes, is less clearly understood. This study aimed to quantify the cardiovascular-event risk associated with NASH, independent of diabetes status., Methods: A cross-sectional analysis was conducted using the 2017-2020 NHANES pre-pandemic cycle. NASH was defined based on presence of steatosis without other causes of liver disease, and FibroScan+AST score from vibration-controlled transient elastography (VCTE). Significant fibrosis (stages F2-F4) was identified by liver stiffness measurement from VCTE. Predicted primary CV-event risk was estimated using both the Pooled Cohort Equations (PCE) and the Framingham Risk Score (FRS). NASH patients were matched with non-NASH controls on age, sex, race/ethnicity, and diabetes status. Weighted logistic regression was conducted, modeling elevated predicted CV risk (binary) as the dependent variable and indicators for NASH / fibrosis stages as independent variables., Results: A sample of 125 NASH patients was matched with 2585 controls. NASH with significant fibrosis was associated with elevated predicted 10-year CV risk, although this association was only statistically significant in PCE analyses (odds ratio and 95% CI 2.34 [1.25, 4.36]). Analyses restricting to ages <65 years showed similar results, with associations of greater magnitude., Conclusion: Independent of diabetes, a significant association was observed between NASH with significant liver fibrosis and predicted primary CV-event risk in US adults, particularly for those <65. These findings suggest the importance of accounting for NASH and liver-fibrosis stage in predicting CV-event risk., Competing Interests: “I have read the journal’s policy and the authors of this manuscript have the following competing interests: JJW and TO are employees of Medicus Economics, LLC, a paid consultant of Madrigal Pharmaceuticals. CMP has received consulting fees from Canopy, Clue by Biowink, Collective Acumen, ConcertAI, EQRx, Evidation Health, Flatiron Health, Jazz Pharmaceuticals, Medicus Economics, Omada Health, Plinth and TTi Health Research & Economics. JF was formerly employed by and held stock options in Madrigal Pharmaceuticals. Madrigal Pharmaceuticals paid the publication charges for this piece, via reimbursement to Medicus Economics. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Woolley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The prevalence and incidence of Nonalcoholic fatty liver disease (NAFLD) are increasing worldwide, and NAFLD has emerged as a prominent global health concern. The link between serum alanine aminotransferase (ALT) to aspartate aminotransferase (AST) ratio and NAFLD remains unclear. This study investigated the association between the ALT/AST ratio and NAFLD prevalence, including liver steatosis and fibrosis levels in the population., Methods: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, including 4753 participants. Subgroup analyses, stratified by age, gender, and body mass index (BMI), were performed, along with adjusted multivariable logistic regression analyses to evaluate the relationship between ALT/AST levels and the likelihood of NAFLD, liver steatosis, and hepatic fibrosis stage. A generalized additive model examined the non-linear relationship between ALT/AST and the probability of developing NAFLD., Results: Among 4753 participants, 1508 (31.73%) were diagnosed with NAFLD. Significant positive correlations between ALT/AST and NAFLD risk were found across all models. In addition, the subgroup analysis by gender, age, and BMI suggested that ALT/AST showed a positive correlation with NAFLD. The ALT/AST ratio was positively correlated with the degree of liver steatosis and liver fibrosis. The correlation between ALT/AST and the incidence of NAFLD showed a non-linear pattern. In women, the non-linear trend is particularly evident, showing an inverted U-shaped curve with an inflection point of 1.302. A receiver operating characteristic (ROC) analysis showed that the predictive value of ALT/AST for NAFLD was better than that of traditional liver enzyme parameters., Conclusion: A higher ALT/AST ratio was independently associated with a significantly higher risk of NAFLD and liver fibrosis within American cohorts. This link is robust among females, children, and adolescents. ALT/AST ratio can be used as a simple and effective noninvasive biomarker to identify individuals with high risk of NAFLD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xuan, Wu, Zhang, Yu, Yu and Zhou.)

Background: The timing of food intake can affect the physiological and metabolic functions of the body. However, whether and how the timing of dietary antioxidant intake could influence non-alcoholic fatty liver disease (NAFLD) is largely unknown. The Composite Dietary Antioxidant Index (CDAI) serves as a comprehensive measure that encompasses various dietary antioxidants. This study aims to investigate the association between the meal timing of CDAI and NAFLD in American adults., Methods: We used data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). Dietary intake was assessed through the implementation of two non-concurrent 24-h dietary recalls. Vibration-controlled transient elastography was employed to assess the controlled attenuation as an indicator of NAFLD. CDAI across the day (total, breakfast, lunch, dinner) and Δ CDAI (Δ = dinner-breakfast) were categorized into quartiles. Weighted logistic regression models and restricted cubic splines were used to evaluate the association between the meal timing of CDAI and NAFLD., Results: Of the 6570 participants in this study, 1153 had NAFLD. Participants in the highest quartile of total CDAI levels had a lower risk of NAFLD compared with the lowest quartile (OR = 0.52; 95% CI, 0.38-0.71). More importantly, participants in the highest quartile of dinner CDAI, but not those in that of breakfast or lunch, had a lower risk of NAFLD (OR = 0.54; 95% CI, 0.40-0.73) compared with the lowest quartile. The restricted cubic splines indicated a linear relationship between total CDAI and NAFLD ( P for nonlinearity = 0.19). Stratification analyses revealed that the effect of dinner CDAI on NAFLD varied between non-Hispanic Whites and individuals of other races ( P for nonlinearity = 0.19). Stratification analyses revealed that the effect of dinner CDAI on NAFLD varied between non-Hispanic Whites and individuals of other races ( P for interaction = 0.032)., Conclusions: these findings suggest the potential beneficial effects of an antioxidant-rich diet and strategic meal timing on NAFLD.

Background: Recently, a panel of multi-society experts proposed steatotic liver disease (SLD) as an alternative terminology for metabolic dysfunction-associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD)., Aims: We compared the impact of SLD, subtype of SLD, MAFLD and NAFLD on all-cause and cause-specific mortality., Methods: A total of 7811 individuals in the third National Health and Nutrition Examination Survey and linked mortality through 2019 were analysed. SLD was defined based on ultrasonographic hepatic steatosis. SLD, subtype of SLD and MAFLD were defined using the proposed definitions. The Cox proportional hazard model assessed all-cause/cause-specific mortality., Results: During a median follow-up of 27.1 years, individuals with SLD and MAFLD experienced approximately 13%-23% higher risk of all-cause mortality (hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.02-1.29 for SLD; HR: 1.23, 95% CI: 1.09-1.38 for MAFLD; HR: 1.13, 95% CI: 1.01-1.27 for metabolic dysfunction-associated steatotic liver disease [MASLD]). Individuals with MetALD demonstrated a higher risk of all-cause (HR: 1.68, 95% CI: 1.10-2.57) and cancer-related mortality (HR: 2.40, 95% CI: 1.23-4.66). MASLD with advanced fibrosis had an increased risk of all-cause mortality compared to MASLD without advanced fibrosis., Conclusions: SLD, especially MASLD and MetALD, is associated with increased all-cause mortality among adults in the US. Given this significant association between SLD or subtype of SLD (MASLD and MetALD) and all-cause mortality, adopting the proposed SLD criteria may help identify a sub-group of individuals with SLD who are at an increased risk for all-cause mortality., (© 2024 John Wiley & Sons Ltd.)

Background: Non-alcoholic fatty liver disease (NAFLD) is a growing health crisis in the general population of the United States (U.S.), but the relationship between systemic immune-inflammation (SII) index and NAFLD is not known., Methods: We collected data from the National Health and Nutrition Examination Survey 2017-2018. Next, propensity score matching (PSM), collinearity analysis, restricted cubic spline (RCS) plot, logistic regression, quantile regression analysis, subgroup analysis, mediation analysis, and population attributable fraction were used to explore the association of the SII with risk of NAFLD., Results: A total of 665 participants including the 532 Non-NAFLD and 133 NAFLD were enrolled for further analysis after PSM analysis. The RCS results indicated that there was a linear relationship between the SII and controlled attenuation parameter (p for nonlinear = 0.468), the relationship also existed after adjustment for covariates (p for nonlinear = 0.769). The logistic regression results indicated that a high SII level was an independent risk factor for NAFLD (OR = 3.505, 95% CI: 1.092-11.249, P < 0.05). The quantile regression indicated that at higher quantiles (0.90, and 0.95) the SII was significantly associated with NAFLD (p < 0.05). Mediation analysis indicated that alanine aminotransferase (ALT), triglycerides, and blood urea nitrogen (BUN) were partially contribute to the relationship between SII and NAFLD. The population attributable fractions indicated that 23.19% (95% CI: 8.22%, 38.17%) of NAFLD cases could be attributed to SII corresponding to 133 NAFLD cases., Conclusion: There was a positive linear relationship between the SII and the risk of NAFLD. The ALT, triglycerides, and BUN had a partial mediating effect on the relationship between the SII and NAFLD., (© 2024. The Author(s).)

Metabolic dysfunction-associated steatotic liver disease (MASLD) (previously called nonalcoholic fatty liver disease, NAFLD) is associated with cardiometabolic risk factors and chronic kidney disease (CKD). However, evidence is lacking regarding whether the severity of fibrosis is affected by these risk factors and diseases and to what degree. We aimed to determine the correlation between these factors and vibration-controlled transient elastography-determined liver stiffness measurements (LSMs) and controlled attenuation parameter (CAP) values in a sample of the US population. Data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey were pooled. The association between LSM and cardiometabolic risk factors and CKD was assessed using generalized linear or logistic regression analyses. In multivariate regression analyses, CAP and BMI were adjusted as confounders. Of 3647 participants, 2079 (57.1%) had NAFLD/MASLD [weighted prevalence 54.8%; 95% confidence interval (CI) 51.8-57.9%]; the weighted prevalence of significant fibrosis (LSM ≥ 7.9 kPa) was 9.7% (95% CI 8.2-11.3%). Log LSM was associated with higher levels of homeostatic model assessment of insulin resistance ( β  = 2.19; P  = 0.017), hepatic steatosis (CAP > 248 dB/m) [odds ratio (OR) 3.66; 95% CI 2.22-6.02], type 2 diabetes (OR 2.69; 95% CI 1.72-4.20), and CKD (OR 1.70; 95% CI 1.24-2.34). These correlations did not change notably after adjustments were made for waist circumference, CAP, and BMI. LSM and CAP, although influenced by waist circumference and BMI, are good indicators of hepatic fibrosis and steatosis. LSM is associated with insulin resistance, diabetes, and CKD independent of hepatic steatosis and obesity., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: In the United States, 10.2% households (HH) report child food insecurity. We assessed associations between metabolic dysfunction-associated fatty liver disease (MASLD) and food insecurity among the adolescents in the United States., Methods: This cross-sectional study was performed using data from the National Health and Nutrition Examination Survey 2017-2018. Food insecurity was assessed by the US Department of Agriculture Child Food Security Survey Module. MASLD was defined by transient elastography., Results: Among 771 adolescents (aged 12-18 years) (mean age 14.7 years; 52.5% male; 50.9% White, 12.7% Black, 24.4% Hispanic, and 12.1% other), 9.8% reported food insecurity; MASLD prevalence of 10.12% (95% confidence interval [CI] 7.13%-13.20%) affecting 4.27 million adolescents; and nonalcoholic fatty liver disease prevalence of 10.77% (95% CI 7.76-13.78) affecting 4.52 million adolescents. There was near-perfect concordance between MASLD and nonalcoholic fatty liver disease (Cohen's κ coefficient of 0.971, 95% CI 0.946-0.996). The prevalence of MASLD was greater among food-insecure adolescents vs food-secure ones (17.4% vs 9.4%) and adolescents living with a low HH income vs those with a higher HH income (15.0% vs 7.2%) and living with a head of HH with a lower education level vs one with a higher education level (18.0% vs 8.2%) ( P < 0.05). The fully adjusted model showed that compared with adolescents living in a higher HH income, food-insecure adolescents living in low income HH had a 3-fold greater risk (odds ratio [OR] 3.25, 1.31-8.08) of having MASLD, while food-secure adolescents living in low-income HH had no increased risk (OR 1.58, 0.85-2.93, P = 0.139). The fully adjusted odds of having MASLD was elevated by +163% with the presence of HTN (OR 2.63, 1.02-6.78), +241% with being Hispanic (OR 3.41, 1.36-8.56), and +138% with being male (OR 2.38, 1.20-4.75). In addition, a 1-unit increase in BMI was associated with 25% increase in the odds of having MASLD (OR 1.25, 1.17-1.33) among US adolescents., Discussion: Food insecurity is associated with MASLD among US low-income adolescents especially Hispanic male individuals with obesity and hypertension. Policies addressing inequities are needed., (Copyright © 2024 by The American College of Gastroenterology.)

Background: The relationship between the triglyceride-glucose (TyG) index and its derived index, the triglyceride glucose-waist height ratio (TyG-WHtR), with mortality and cardiovascular diseases (CVDs) in patients with non-alcoholic fatty liver disease (NAFLD) remains unclear., Methods: This study enrolled 6627 adults aged 18 and above diagnosed NAFLD from the National Health and Nutrition Examination Survey (NHANES, 1999-2018). Binary weighted logistic regression analyses, cox proportional hazards model and restricted cubic spline (RCS) were used to analyze the relationship between TyG and TyG-WHtR with all-cause mortality, CVD mortality and CVDs. Mediation analysis explored the mediating role of glycohemoglobin, insulin and hypertension in the above relationships. Meanwhile, the incremental predictive value of the TyG index and TyG-WHtR was further assessed., Results: Except for no significant association between the TyG index and both all-cause mortality and chronic heart failure (CHF), both TyG and TyG-WHtR exhibited significant positive correlations or trends of positive correlation with all-cause mortality, CVD mortality, total-CVD, CHF, coronary heart disease (CHD) and angina pectoris. For all-cause mortality, CVD mortality and CHF, TyG-WHtR was a better predictor than TyG (TyG-WHtR: HR 1.31, 95%CI 1.03-1.66; HR 2.22, 95%CI 1.42-3.47; OR 3.99, 95%CI 1.79-8.93). In contrast, TyG index demonstrated a stronger association with total-CVD, CHD and angina pectoris (TyG index: OR 2.00, 95%CI 1.26-3.18; OR 1.85, 95%CI 1.19-2.91; OR 2.93, 95%CI 1.23-7.00). RCS analysis showed that after adjusting for covariates, most of the aforementioned relationships were linear(P overall < 0.0001, P-nonlinear > 0.05), while the associations of the TyG index and TyG-WHtR with all-cause mortality and CHF were non-linear(P overall < 0.0001, P nonlinear < 0.05). The addition of the TyG index and TyG-WHtR to the basic model for outcomes improved the C-statistics, net reclassification improvement value, and integrated discrimination improvement value., Conclusions: The predictive value of TyG or TyG-WHtR for all-cause mortality and cardiovascular risk in NAFLD patients was significant. The TyG index and TyG-WHtR might be valid predictors of cardiovascular outcomes of patients with NAFLD., (© 2024. The Author(s).)

Objective: This study investigated the link between triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and nonalcoholic fatty liver disease (NAFLD) and liver fibrosis in American adults., Methods: Information for 6495 participants from the National Health and Nutrition Examination Survey (NHANES) 2017-2020.03 was used for this cross-sectional study. The link between TG/HDL-C ratios and NAFLD and liver fibrosis was assessed by multiple linear regression before evaluating nonlinear correlations based on smoothed curve fitting models. Stratification analysis was then applied to confirm whether the dependent and independent variables displayed a stable association across populations., Results: TG/HDL-C ratios were positively correlated with NAFLD, with higher ratios being linked to increased prevalence of NAFLD. After adjusting for potential confounders, the odds ratios (OR) for NAFLD patients in the fourth TG/HDL-C quartile were 3.61 (95% confidence interval [CI], 2.94-4.38) ( P for trend < 0.001) in comparison with those in the first quartile after adjusting for clinical variables. However, no statistical significance was noted for the ratio for liver fibrosis after adjusting for potential confounders ( P for trend = 0.07). A nonlinear correlation between TG/HDL-C ratios and NAFLD was observed based on smoothed curve fitting models. However, a nonlinear relationship between the ratios and liver fibrosis was not established. In subgroup analyses, there was an interaction between smoking status and TG/HDL-C ratio in relation to the prevalence of liver fibrosis ( P for interaction < 0.001)., Conclusions: Among American adults, the TG/HDL-C ratio was noted to be nonlinearly positively associated with the prevalence of NAFLD; however, this relationship was not present in liver fibrosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Li, Wang, Shi, Hu, Zeng, Luo, Yang, Luo, Cao, Cai, Chen and Wang.)

Background: Obesity has become a major global public health challenge. Studies examining the associations between different obesity patterns and the risk of nonalcoholic fatty liver disease (NAFLD) are limited. This study aimed to investigate the relationships between different obesity patterns and the risk of NAFLD in a large male population in the US., Methods: Data from the 2017 to March 2020 National Health and Nutrition Examination Survey (NHANES) were utilized. Liver steatosis and fibrosis were assessed with FibroScan using the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM). Steatosis was identified with a CAP value of 248 dB/m or higher. Abdominal obesity was defined by a waist circumference (WC) of 102 cm or more for males and 88 cm or more for females. Overweight was defined as a body mass index (BMI) of 24.0 kg/m 2 and above. General obesity was identified with a BMI of 28.0 kg/m 2 or higher. Obesity status was categorized into four types: overweight, general obesity, abdominal obesity, and combined obesity. Multivariate logistic regression, adjusting for potential confounders, was used to examine the link between obesity patterns and NAFLD risk. Subgroup analysis further explored these associations., Results: A total of 5,858 adults were included. After multivariable adjustment, compared to the normal weight group, the odds ratios (ORs) [95% confidence interval (CI)] for NAFLD in individuals with overweight, general obesity, abdominal obesity, and combined obesity were 6.90 [3.74-12.70], 2.84 [2.38-3.39], 3.02 [2.02-4.51], and 9.53 [7.79-11.64], respectively. Subgroup analysis showed the effect of different obesity patterns on NAFLD risk was stable among individuals with different clinical conditions. In the fully adjusted multivariate logistic regression model, WC was positively associated with NAFLD risk (OR: 1.48; 95% CI: 1.42-1.53; P < 0.001). WC also demonstrated strong discriminatory ability for NAFLD in Receiver Operating Characteristic (ROC) analysis, achieving an Area Under the Curve (AUC) of 0.802., Conclusions: Different patterns of obesity are risk factors for NAFLD. An increase in WC significantly increased NAFLD risk. More attention should be paid to preventing different patterns of obesity among adults., (© 2024. The Author(s).)

Background and Aims: Previous studies have shown that sarcopenic obesity (SO) was associated with nonalcoholic fatty liver disease (NAFLD). However, research is limited in the context of the NAFLD renamed as metabolic dysfunction-associated steatotic liver disease (MASLD) defined by updated diagnostic criteria. The aim of this study was to use the index skeletal muscle mass to visceral fat area ratio (SVR) to describe SO in a large and representative US population (National Health and Nutrition Examination Survey 2017-2018) of adults and investigate their association with MASLD., Methods: A total of 2087 individuals were included in the analysis. SVR was calculated according to the measurement of dual-energy x-ray absorptiometry and MASLD was diagnosed with controlled attenuation parameter scores and cardiometabolic risk factors. SVR was divided into tertiles. Logistic regression adjusted for confounders was used to evaluate the association between SVR and MASLD. Several sensitivity analyses were performed to test the robustness of our findings., Results: In a multivariate logistic regression analysis, a significant association between SVR and MASLD was shown (odds ratio [OR]: 3.11, 95% confidence interval [CI]: 1.31-7.39, p = .010 for middle levels of SVR; OR: 3.82, 95% CI: 1.45-10.08, p = .007 for lowest levels of SVR). The sensitivity analyses confirmed that the association was robust., Conclusion: Our findings imply that decreased SVR is linked to MASLD., (© 2024 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Introduction: Smoking is a cause of nonalcoholic fatty liver disease (NAFLD), but the dose-response relationship between secondhand smoke exposure (SHS) and NAFLD is unclear. This study sought to determine the relationship between SHS and NAFLD risk among adult nonsmokers in the United States., Aims and Methods: Data from 7412 adult nonsmokers aged ≥20 years who participated in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016 were used in this study. SHS was defined as a nonsmoker with a serum cotinine concentration of 0.05-10.00 ng/mL. NAFLD was identified using the U.S. fatty liver index (USFLI), hepatic steatosis index (HSI), and fatty liver index (FLI). Weighted multivariable logistic regression and restricted cubic spline models were applied to evaluate the relationship between SHS and NAFLD risk., Results: The participants had a weighted mean age of 49.2 years, and 55.5% were female. SHS was associated with NAFLD (odds ratio [OR] 1.22; 95% confidence interval CI: 1.05 to 1.42), showing a linear dose-response relationship (natural log of cotinine level: OR 1.10, 95% CI: 1.05 to 1.17). Sensitivity analyses using different NAFLD definitions (HSI: OR 1.21, 95% CI: 1.01 to 1.46; FLI: OR 1.26, 95% CI: 1.06 to 1.49), excluding participants taking hepatotoxic drugs, and propensity score-adjusted analysis yielded similar results. The association between SHS and NAFLD was consistent in analyses stratified by age, sex, and race/ethnicity., Conclusions: Among this nationally representative sample of U.S. adults, SHS had a linear dose-response relationship with the risk of NAFLD, suggesting that measures to lower SHS might lower NAFLD risk., Implications: This study assessed the association between secondhand smoke exposure and the risk of nonalcoholic fatty liver disease (NAFLD) using data from 7412 adult nonsmokers aged 20 years or older who participated in the United States NHANES between 2007 and 2016. Secondhand smoke exposure was measured using serum cotinine levels. Three different noninvasive indexes were used to measure NAFLD. Secondhand smoke exposure was associated with an increased risk of NAFLD, with a linear dose-response relationship. The results of sensitivity analyses and subgroup analyses were consistent., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Limited evidence exists regarding the association of selenium with risk of death in individuals with nonalcoholic fatty liver disease (NAFLD). This study was designed to investigate the relationship between dietary selenium intake with mortality in a nationally representative sample of United States adults with NAFLD., Methods: Dietary selenium intake was assessed in 2274 NAFLD adults younger than 60 years of age from the National Health and Nutrition Examination Survey (NHANES) III through a 24-hour dietary recall. NAFLD was diagnosed by liver ultrasound after excluding liver disease due to other causes. Cox proportional hazards models were utilized to assess the effect of dietary selenium intake on all-cause and cardiovascular mortality among individuals with NAFLD., Results: At a median follow-up of 27.4 years, 577 deaths occurred in individuals with NAFLD, including 152 cardiovascular deaths. The U-shaped associations were discovered between selenium intake with all-cause (Pnolinear = 0.008) and cardiovascular mortality (Pnolinear < 0.001) in adults with NAFLD after multivariate adjustment, with the lowest risk around selenium intake of 121.7 or 125.9 μg/day, respectively. Selenium intake in the range of 104.1-142.4 μg/day was associated with a reduced risk of all-cause mortality and, otherwise, an increased risk. Selenium intake in the range of 104.1-150.6 μg/day was associated with a reduced risk of cardiovascular death and, otherwise, an increased risk., Conclusions: Both high and low selenium intake increased the risk of all-cause and cardiovascular death in adults younger than 60 years of age with NAFLD, which may help guide dietary adjustments and improve outcomes in adults with NAFLD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The link between dietary fiber intake and Non-alcoholic fatty liver disease (NAFLD) is under exploration, yielding inconsistent findings. Considering the limitations of previous research and the significance of dietary fiber in hepatic steatosis, this study investigates the association between dietary fiber intake and Controlled Attenuation Parameter (CAP) among 5935 participants from the National Health and Nutrition Examination Survey (NHANES)., Materials and Methods: Multivariable regression was used to evaluate the association between dietary fiber intake and CAP. Smoothed curve fitting and threshold effect analysis techniques were applied to illustrate non-linear relationships., Results: After adjusting for other variables, a negative correlation emerged between dietary fiber intake and CAP. Subgroup analysis by gender and race/ethnicity revealed a sustained negative association between dietary fiber intake and CAP among females and Whites. Additionally, an inverted U-shaped relationship was observed between dietary fiber intake and CAP among women and other race, with inflection points at 13.80 g/day and 33.45 g/day, respectively., Conclusion: Our research indicates that in the majority of Americans, there is an inverse relationship between dietary fiber intake and hepatic steatosis. This relationship exhibits an inverted U-shaped curve in women and other race, with a threshold effect. The findings of this study hold potential significance for clinical nutrition interventions, personalized dietary guidance, and advancing research into the diet-disease mechanism relationship., (© 2024. The Author(s).)

Background/aims:  The relationship between neutrophil-to-lymphocyte ratio (NLR) and liver fibrosis in nonalcoholic fatty liver disease remains controversial. The aim of this study was to examine the association between NLR and liver fibrosis., Materials and Methods:  We conducted a cross-sectional analysis using the National Health and Nutrition Examination Survey. Vibration-controlled transient elastography was used to assess liver fibrosis and its severity. Neutrophil-to-lymphocyte ratio was calculated as the ratio of neutrophil count to lymphocyte count., Results:  This study included 1620 US adults with a mean age of 52.9 years, of which 53.3% were male. The obese population accounted for 62.5%, 68.5% had hypertension, 31.1% had diabetes, and 16% had significant liver fibrosis. After adjusting for all covariates, a positive correlation was observed between NLR and the severity of liver fibrosis (β = 0.57, 95% CI = 0.22-0.92, P = .001), which remained stable across different subgroups., Conclusion:  This study suggests that elevated NLR levels are positively correlated with the severity of liver fibrosis in patients with nonalcoholic fatty liver disease, and these results can be well generalized to the US adult population.

The novel diagnostic term Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) requires at least one cardiovascular risk factor for diagnosis. While the relationship between gallstones and Non-Alcoholic Fatty Liver Disease (NAFLD) has been debated, the association between MASLD and gallstones remains unclear. This cross-sectional study aimed to explore this relationship using National Health and Nutrition Examination Survey (NHANES) data from 2017 to 2020. Participants were stratified into two groups based on MASLD diagnosis, and propensity score matching (PSM) was employed to reduce biases. Of 15,560 participants, 7922 met the inclusion criteria, with 2697 (34.0%) diagnosed with MASLD. Gallstone prevalence was higher in the MASLD group (14.2%) compared to the non-MASLD group (8.5%). After PSM, 4536 participants were analyzed, revealing a significant association between MASLD and gallstones (OR = 1.30, 95% CI 1.09-1.56, P = 0.003). This association remained robust across crude and adjusted analyses, with subgroup and sensitivity analyses further supporting the findings. In conclusion, MASLD is significantly associated with an increased risk of gallstones in the US population. These findings highlight the need to consider this relationship in clinical strategies for prevention and management of gallstone disease., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. The authors affirm that there are no conflicts of interest, including any commercial or financial relationships that could potentially bias the research findings., (© 2025. The Author(s).)

Background: The link between antioxidants and metabolic dysfunction-associated steatotic liver disease (MASLD) is a topic of considerable discussion in the field of observational studies, with the exact causal connections still being unclear., Methods: In this investigation, a cohort consisting of 17 061 participants from the National Health and Nutrition Examination Surveys was studied. Initially, a cross-sectional analysis was carried out to examine the relationship between the CDAI and MASLD. Further, Mendelian randomization (MR) was utilized to assess the possible causal links between antioxidant levels in the bloodstream and MASLD., Results: The association between the CDAI and MASLD was found to be significant in the fully adjusted logistic regression model, showing an OR of 0.95 [95% confidence interval (CI): 0.94-0.97; P  < 0.001]. The use of restricted cubic spline regression revealed no significant nonlinear association between the CDAI and the occurrence of MASLD ( Pnonlinearity  = 0.321). Additionally, MR findings did not suggest any causal connections between circulating levels of various antioxidants and MASLD. These antioxidants included vitamin A (retinol) (IVW: OR: 0.67, 95% CI: 0.33-1.36, P  = 0.272), vitamin C (ascorbate) (IVW: OR: 0.61, 95% CI: 0.34-1.09, P  = 0.094), vitamin E (α-tocopherol) (IVW: OR: 0.55, 95% CI: 0.13-2.25, P  = 0.407), vitamin E (γ-tocopherol) (IVW: OR: 0.89, 95% CI: 0.36-2.23, P  = 0.806), zinc (IVW: OR: 0.95, 95% CI: 0.82-1.09, P  = 0.449), selenium (IVW: OR: 0.98, 95% CI: 0.84-1.16, P  = 0.855), and carotene (IVW: OR: 0.80, 95% CI: 0.36-1.81, P  = 0.596)., Conclusion: The findings highlight a significant negative linear relationship between CDAI and MASLD prevalence in the observational component of the study. However, the MR analysis did not indicate any causal effects of circulating antioxidant levels on MASLD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a liver disease that is strongly associated with chronic low-grade inflammation. Stage 3 of MASLD is characterized by excessive formation of connective tissues, commonly referred to as liver fibrosis. Although numerous inflammatory markers have been identified and extensively studied, including the tumor necrosis factor-α and interleukin-6 have been studied [Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62(1 Suppl):S47-64], the lymphocyte-to-high-density lipoprotein ratio (LHR) as a new biomarker that has not been sufficiently studied. This study aims to investigate the relationship between LHR levels and MASLD, determine its potential as a predictive marker for steatosis and fibrosis stages., Methods: This was a population-based study using data from 15,560 participants in the 2017-2020 National Health and Nutrition Examination Survey (NHANES) database. The study aimed to explore the relationship between LHR and MASLD. The disease progression was tracked by continuously measuring CAP and liver stiffness measurements. Participants who exhibited a median Controlled Attenuation Parameter (CAP) of 248 dB/m or higher were deemed to have hepatic steatosis. The LHR was calculated by dividing the lymphocyte count by the high-density lipoprotein cholesterol (HDL-C) level. Multivariate linear regression models were employed to explore the linear association between LHR and MASLD. Fitted smoothing curves and threshold effect analysis were employed to display nonlinear relationships. A two-part linear regression model was employed to estimate threshold effects. Subgroup analyses were conducted to determine the consistency of this association across various demographic groups., Results: A total of 6,950 adults aged 18 years and older were enrolled in the study, with an average age of 48.15 ± 17.10 years (49.14% male, 50.86% female). The adjusted multiple logistic regression analysis revealed a significant positive correlation between LHR and MASLD (OR: 1.64, 95% CI: 1.40-1.92). Using the complex two-piece linear regression model, we observed an inverted L-shaped association between LHR and CAP, suggesting a critical inflection point at -2.58. Subgroup analyses indicated a pronounced association of the LHR index with obese individuals (OR: 1.96, 95% CI: 1.66-2.32) and females (OR: 1.76, 95% CI: 1.25-2.46). There was no significant association between LHR and clinically significant fibrosis., Conclusion: The LHR index is positively correlated with MASLD among US adults. Therefore, LHR may be a robust marker for early screening, diagnosis, and monitoring of treatment efficacy in clinical practice., Competing Interests: Declarations. Ethics approval and consent to participate: In compliance with the Declaration of Helsinki, every NHANES protocol was approved by Ethics Review Board of National Center for Health Statistics. Every participant signed the informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The correlation between serum cotinine and fatty liver index (FLI) needs further investigation for the early identification, prevention, and treatment of metabolic dysfunction-associated steatotic liver disease (MASLD)., Methods: Data from the NHANES database spanning from March 2017 to 2018 was used to perform the population-based study to assess the relationship between serum cotinine and FLI. A variance estimation strategy was applied to address the data volatility. To examine the correlation between serum cotinine and FLI, a weighted multivariate logistic regression model was used. Initial normality assessment through the Kolmogorov-Smirnov test indicated non-normal distribution. Median and interquartile range were employed for description of non-normally distributed measurement data, and group comparisons were made using the Kruskal-Wallis H test. Proportions were used for ordinal data description and comparisons, with the chi-square test used for categorical data. Smooth curve fittings and generalized additive models were used to explore the non-linear relationship between serum cotinine and FLI., Results: Finally, 2350 subjects (mean age: 49.83 ± 18.30, 1135 males and 1215 females) were selected for analysis. After adjusting for confounders, serum cotinine showed positive correlation with FLI in adults (β = 0.009, 95% CI: 0.003 to 0.014, P = 0.001). Additionally, individuals in the unexposed and passively exposed groups had lower FLI compared to those in the actively exposed group (β = -3.041, 95% CI: -4.728 to -1.353, P < 0.001; β = -2.159, 95% CI: -4.231 to -0.087, P = 0.041; respectively). Subgroup analyses by gender revealed positive associations between serum cotinine and FLI in both males (β = 0.007, 95% CI: 0.000 to 0.014, P = 0.048) and females (β = 0.012, 95% CI: 0.003 to 0.021, P = 0.007). Additionally, a positive correlation was found in "other races" subgroup (β = 0.017, 95% CI: 0.004 to 0.029, P = 0.008) rather than the subgroups of "Mexican American, Other Hispanic, Non-Hispanic White, and Non-Hispanic Black". The relationship between serum cotinine and FLI exhibited an inverted U-shaped curve with the turning point occurring at 521 ng/mL., Conclusion: This study of a nationally representative sample demonstrates a positive association between serum cotinine and FLI, characterized by an inverted U-shaped curve. Both active and passive smoking emerge as a risk factor for the development and progression of MASLD. Smoking cessation is recommended to manage MASLD and support liver and cardiovascular health., Competing Interests: Declarations. Ethics approval and consent to participate: The study received ethical approval from the National Center for Health Statistics (NCHS) and adhered to the ethical standards of the responsible committee on human experimentation, as well as the 1975 Helsinki Declaration and its amendments. All methods followed the relevant guidelines and regulations, and written informed consent was obtained from all participants or their proxies. Consent for publication: Not applicable. Conflict of interest: The authors declare that the research was conducted without any commercial or financial relationships that could be perceived as conflicts of interest. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to increased all-cause mortality due to metabolic dysfunctions like obesity, diabetes, and cardiovascular diseases. This study examines the association between Life's Essential 8 (LE8) scores and both all-cause and cardiovascular disease (CVD) mortality in MASLD participants., Methods: Data from 5,916 MASLD participants in the NHANES (2005-2018) were analyzed. Associations between LE8 scores and all-cause and CVD mortality were assessed using Cox proportional hazards models, with follow-up until December 31, 2019. Dose-response relationships and survival differences were evaluated using Kaplan-Meier survival curves and Restricted Cubic Spline models., Results: Over a median follow-up of 7.6 years, moderate and high LE8 scores were associated with 33% (HR: 0.67; 95% CI: 0.56-0.79) and 47% (HR: 0.53; 95% CI: 0.33-0.84) lower risk of all-cause mortality, respectively, compared to low scores. For CVD mortality, the adjusted HRs were 0.56 (95% CI: 0.41-0.78) and 0.35 (95% CI: 0.12-1.0). Higher LE8 scores were significantly associated with reduced cumulative incidence of all-cause and CVD mortality (log-rank P < 0.001). A 10-point increase in health behavior scores, particularly in diet, physical activity, and nicotine exposure, was linked to an 11% reduction in all-cause mortality risk and an 11% reduction in CVD mortality risk. Among health factors, only blood glucose showed a significant association with CVD mortality., Conclusion: Higher LE8 scores in MASLD patients are associated with lower mortality risk, suggesting the potential value of promoting cardiovascular health in this population. Further research is needed to confirm these associations., Competing Interests: Declarations. Ethical approval and informed consent: The survey protocol for the NHANES was approved by CDC’s National Center for Health Statistics Institutional Research Ethics Review Board, with all participants giving informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Although previous studies have established associations between specific gut microbiota (GM) and metabolic dysfunction-associated fatty liver disease (MAFLD), research examining the relationship between functional gastrointestinal symptoms and MAFLD, including advanced fibrosis, remains limited. This study aims to investigate the association between stool consistency, bowel movement frequency (BMF), and the occurrence of MAFLD and advanced fibrosis in U.S. adults., Methods: This population-based study included 9,928 adults from the 2005-2010 National Health and Nutrition Examination Survey (NHANES), with a mean age of 47.19 ± 16.65 years, comprising 47.7% males and 52.3% females. Weighted logistic regression was used to assess the association between stool consistency, BMF, and MAFLD or advanced fibrosis. A linear trend was assessed by treating BMF categories as continuous variables with ordinal values. The dose-response relationship between BMF and MAFLD was analyzed using restricted cubic splines (RCS) regression. Sensitivity and subgroup analyses were performed to confirm the robustness of the findings., Results: In the RCS regression, no significant nonlinear relationship was observed between BMF and the risk of MAFLD (p-overall < 0.0001; p-nonlinear = 0.0663). The multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for MAFLD were 0.82 (95% CI 0.69-0.98), 1.31 (95% CI 1.16-1.46), and 1.50 (95% CI 1.14-1.99) for participants with 3-6 BMs/week, 1-2 BMs/day, and > 2 BMs/day, respectively, compared to those with once/day (p-trend < 0.001). For stool consistency, hard stools were associated with a decreased risk of MAFLD (OR 0.77; 95% CI 0.62-0.95), whereas loose stools increased the risk (OR 1.37; 95% CI 1.05-1.80), relative to normal stools. A significant interaction between BMF and age was observed. No significant associations were found between stool consistency or BMF and advanced liver fibrosis. Sensitivity analyses confirmed the robustness of these findings., Conclusions: This cross-sectional study demonstrates that a BMF of 3-6 BMs/week and hard stools are associated with a reduced risk of MAFLD, whereas a BMF of more than once/day and loose stools are linked to an increased risk of MAFLD. Moreover, no significant associations were observed between stool consistency, BMF, and advanced fibrosis among individuals diagnosed with MAFLD., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: The National Center for Health Statistics review board approved the National Health and Nutrition Examination Survey. This study received an exemption from the review board of Nanjing First Hospital as the data we used were de-identified. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: This study aims to assess the prognostic value of the fatty liver index (FLI), a noninvasive tool for hepatic steatosis assessment, in predicting all-cause and disease-specific mortality., Methods: We linked data from the National Health and Nutrition Examination Survey III (1988-1994) with Public-Use Mortality Files, forming a cohort of 11 297 participants with a median follow-up period of 26.25 years. Cox proportional hazards models were used to evaluate the association between FLI and all-cause mortality, while Fine and Gray's models assessed the relationship between FLI and disease-specific mortality., Results: The FLI ≥ 60 was independently associated with an increased risk of all-cause mortality (hazard ratio = 1.24, P  < 0.001), as well as mortality from malignant neoplasms (hazard ratio = 1.18, P  = 0.048), diabetes (hazard ratio = 2.62, P  = 0.001), and cardiovascular diseases (CVDs) (hazard ratio = 1.18, P  = 0.018), compared to FLI < 30. No significant associations were found with Alzheimer's disease, influenza and pneumonia, chronic lower respiratory diseases, or renal disorders. Subgroup analyses indicated that individuals who were females aged 40-60 (hazard ratio = 1.67, P  = 0.003), non-overweight (hazard ratio = 1.75, P  = 0.007), or without abdominal obesity (hazard ratio = 1.75, P  = 0.007) exhibited a stronger association between FLI ≥ 60 and all-cause mortality., Conclusion: These findings support the prognostic value of the FLI for predicting mortality from all causes, malignant neoplasms, diabetes, and CVDs. Targeted attention is needed in postmenopausal women, non-overweight, and non-abdominally obese populations., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The association between nonalcoholic fatty liver disease and cardiovascular disease is firmly established, yet the association between noninvasive liver fibrosis scores and cardiovascular events remains a topic of uncertainty. Our study aimed to explore the association between liver fibrosis and heart failure., Methods and Results: The data set was from the National Health and Nutrition Examination Survey 2011 to 2018. Advanced hepatic fibrosis risk was assessed through 3 noninvasive liver fibrosis scores: Fibrosis-4 score (FIB-4), the nonalcoholic fatty liver disease fibrosis score (NFS), and the aspartate aminotransferase to platelet ratio index (APRI). We included 19 695 eligible participants. The national prevalence of advanced liver fibrosis risk in the United States was 4.20%, 8.06%, and 0.35% as determined by FIB-4, NFS, and APRI scores, respectively. Weighted logistic regression analysis revealed significant associations between advanced liver fibrosis risk and the prevalence of heart failure (continuous variables, FIB-4: odds ratio [OR], 1.15 [95% CI, 1.07-1.23]; NFS: OR, 1.42 [95% CI, 1.23-1.64]; APRI: OR, 1.44 [95% CI, 1.15-1.81]). When the scores were assessed as categorical variables, the results were still significant (FIB-4 ≥2.67 versus FIB-4 <1.3: OR, 2.18 [95% CI, 1.47-3.24]; NFS ≥0.675 versus NFS <-1.455: OR, 2.53 [95% CI, 1.37-4.68]). Subgroup analysis found that the association between APRI and heart failure was stronger in female patients., Conclusions: In the general US population, the prevalence of advanced liver fibrosis risk varied between 0.35% and 8.06% as indicated by noninvasive liver fibrosis scores. FIB-4, NFS, and APRI scores were linked to an elevated prevalence of heart failure.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD), trouble sleeping, and diabetes, as major public health problems, were closely related. The study examined the interaction between trouble sleeping and diabetes on MAFLD and liver fibrosis in adults with MAFLD., Methods: The data were obtained from the National Health and Nutrition Examination Survey 2017-2018. Multivariate logistic regression model and subgroup analyses were conducted to assess the relationship between either trouble sleeping or diabetes on MAFLD and liver fibrosis. Relative excess risk due to interaction (RERI), attributable proportion of interaction (AP), and synergy index (S) were utilized to assess the additive interaction., Results: Ultimately, 3747 participants were included, with 2229 known MAFLD subjects. Compared with participants without diabetes, those with diabetes had a higher risk of MAFLD [odds ratio (OR) = 5.55; 95% confidence interval (CI) = 4.07-7.56] and liver fibrosis risk (OR = 3.61; 95% CI = 2.67-4.89). We also found a significant association of trouble sleeping with an increased risk of MAFLD (OR = 1.54; 95% CI = 1.17-2.02) and liver fibrosis risk (OR = 1.51; 95% CI = 1.06-2.16), compared with those without trouble sleeping. Moreover, there was a significant interaction between diabetes and trouble sleeping on MAFLD [RERI = 1.76 (95% CI: -0.22 to 3.73), AP = 0.35 (95% CI: 0.08-0.63), S = 1.80 (95% CI: 1.02-3.16)] and liver fibrosis risk [RERI = 1.79 (95% CI: 0.37-3.21), AP = 0.44 (95% CI: 0.20-0.69), S = 2.44 (95% CI: 1.18-5.08)]., Conclusion: The findings highlight that trouble sleeping and diabetes had a synergistic effect on MAFLD and liver cirrhosis. The study highlights the importance of addressing both trouble sleeping and diabetes management in adults to mitigate the risk of MAFLD and liver fibrosis., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background/aims: With polarizing income disparities, this study investigated the prevalence and trends of liver disease in a U.S. population-based sample based on income-to-poverty ratio (IPR)., Methods: This cross-sectional study analysed survey data from the 1999-2018 National Health and Nutrition Examination Survey with highest (HIG), middle-income (MIG), and lowest income (LIG) groups defined as IPR ≤ 1, 1 < IPR <5, and IPR ≥ 5, respectively., Results: We analysed 59,204 adult participants with 48.2% male, 39.7% aged 18-39, 36.2% 40-59, and 24.1% ≥60 years. The weighted prevalence of hepatitis C (HCV), B (HBV) infection, non-alcoholic fatty liver disease (NAFLD), alcohol-associated liver disease (ALD), and advanced fibrosis in LIG were 3.9% (n = 276), 7.4% (n = 527), 33.2% (n = 714), 5.2% (n = 401), and 9.0% (n = 694), respectively, compared to lower rates for HIG: 1.0% (n = 82), 3.2% (n = 263), 29.6% (n = 798), 3.9% (n = 354), and 5.0% (n = 638). After adjusting for age, sex, race and ethnicity, education, and birthplace, HIG had the lowest odds of having any liver disease [adjusted odds ratio (aOR) 0.67, p < 0.0001], with similar findings for specific conditions including HCV, HBV, and advanced fibrosis (aOR 0.24, 0.52, and 0.64, all p < 0.0001, respectively). While viraemic HCV prevalence decreased over time for HIG, there were no changes for MIG nor LIG. Similarly, NAFLD prevalence was stable for HIG but increased for MIG and LIG., Conclusion: LIG and MIG in the United States have higher liver disease burdens than HIG, with increasing NAFLD prevalence and lack of decline in current HCV infection prevalence over time as opposed to declining or stable trend in HIG., (© 2024 John Wiley & Sons Ltd.)

Background: While dietary intervention was an important public health strategy for the prevention and intervention of metabolic dysfunction-associated fatty liver disease (MAFLD), the effect of diet-induced inflammation on MAFLD has not been studied in detail. Therefore, we aimed to analyze the relationship between dietary inflammatory index (DII) and MAFLD., Methods: This study included data from the National Health and Nutrition Examination Survey 2017-2018. MAFLD was diagnosed based on the presence of hepatic steatosis, as determined by transient elastography, along with evidence of either overweight/obesity, type 2 diabetes mellitus, or metabolic dysfunction. DII was calculated using 27 dietary components collected through 24-hour dietary recall questionnaire. Weighted logistic regression was used to analyze the relationship between DII and MAFLD and its main components in three different models. Subgroup analyses were performed by age, sex, and alcohol use., Results: A total of 1991 participants were included, and the MAFLD group had higher DII scores. After adjusting for age, sex, race, physical activity, smoking status, and alcohol use, the highest quartile of DII was associated with increased risk of MAFLD ( OR :2.90, 95% CI s: 1.46, 5.75). Overweight/obesity, central obesity, low high density lipoprotein cholesterol (HDL-C) and high C-reactive protein (CRP) also shared the same characteristics in the main components of MAFLD. Results were consistent across subgroups (age, sex, and alcohol use)., Conclusions: A higher DII diet was positively associated with the risk of MAFLD in American adults, particularly as related to overweight/obesity, central obesity, high CRP level, and low HDL-C level.

Objective: To assess the relationship between dietary intake of α -carotene, β -carotene, β -cryptoxanthin, lycopene and lutein+zeaxanthin (LZ) and occurrence of metabolic dysfunction-associated fatty liver disease (MAFLD)., Design: Cross-sectional study design. The MAFLD diagnosis was based on hepatic steatosis and metabolic dysregulation. Carotenoid intake was adjusted for using an energy-adjusted model. Logistic regression and restricted cubic spline (RCS) analyses were used to assess the relationships, with sensitivity analysis to validate the findings. Weighted quantile sum regression (WQS) was used to explore the combined effect of these carotenoids on MAFLD. Subgroup analyses were conducted to identify population-specific associations., Setting: National Health and Nutrition Examination Survey (NHANES) 2017-March 2020., Participants: This study included 5098 individuals aged 18 years and older., Results: After adjusting for potential confounders, a weak inverse association was observed between α -carotene and β -carotene intakes and MAFLD occurrence (all P value <0·05). The highest quartile of β -carotene intake showed a significantly lower occurrence of MAFLD compared with the lowest quartile (OR = 0·65; 95 % CI: 0·44, 0·97). RCS analysis showed that a significantly lower occurrence of MAFLD was associated with a higher intake of the four carotenoids, excluding lycopene. Furthermore, the WQS analysis revealed a negative relationship between combined carotenoid intake and MAFLD occurrence (OR = 0·95, 95 % CI: 0·90, 1·00, P = 0·037). Subgroup analyses showed dietary carotenoid intake was associated with reduced MAFLD occurrence in populations aged 50-69 years, females, physically active individuals and non-drinkers., Conclusion: Higher dietary intake of carotenoids is associated with lower MAFLD occurrence. However, this relationship varies among individuals of different ages, sexes and lifestyles.

Introduction and Objectives: Fatty liver disease is a multisystem disease. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a more accurate indicator of chronic kidney disease (CKD) than nonalcoholic fatty liver disease (NAFLD). However, the relationship between recently defined metabolic dysfunction-associated steatotic liver disease (MASLD) and CKD is currently unclear. The objective of this cross-sectional study was to investigate the prevalence of CKD and albuminuria among individuals diagnosed with either MAFLD or MASLD., Patients and Methods: This study involved 5,492 participants who provided biochemical marker and liver ultrasound data from the U.S. National Health and Nutrition Examination Survey (2017-2020). Multiple logistic regression analyses were conducted to assess the independent associations of nonoverlapping MAFLD and MASLD with the presence of CKD or albuminuria (urinary albumin-to-creatinine ratio ≥ 3 mg/mmol)., Results: MAFLD and MASLD were identified in 47% and 44.5% of the participants, respectively. Individuals with MAFLD-only had a greater prevalence of CKD (24.7% vs. 8.3 %, P < 0.006) and albuminuria (18.6% vs. 5%, P < 0.01) than did those with MASLD-only. Importantly, after adjusting for factors such as sex, age, ethnicity, and alcohol use, it was demonstrated that individuals in the MAFLD-only group had a 4.73-fold greater likelihood of having prevalent CKD than those in the MASLD-only group (P < 0.03)., Conclusions: The MAFLD criteria better identify patients with CKD than do the MASLD criteria. Therefore, it is suggested that the MASLD criteria be reconsidered, as currently, the justification for changing from MAFLD to MASLD criteria may not be appropriate., Competing Interests: Conflicts of interest None., (Copyright © 2024 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To apply the new nomenclature for steatotic liver diseases (SLD), replacing nonalcoholic fatty liver disease (NAFLD) with metabolic dysfunction-associated steatotic liver disease (MASLD), in adolescents using National Health and Nutrition Examination Survey (NHANES) data., Methods: Among 1410 adolescents (12-19 years) in NHANES (2017-March, 2020), the controlled attenuation parameter (CAP) of transient elastography (TE) was used to define steatosis and fibrosis (TE ≥ 7.4 kPa). Obesity and alanine aminotransferase (ALT) ≥ 80 U/L were used to identify adolescents qualifying for hepatology referral according to practice guidelines. NAFLD was defined as liver steatosis without a specific exposure; it has no cardiometabolic risk factor requirement, unlike MASLD., Results: Steatosis (yes/no) is the first decision point in the new diagnostic protocol; however, criteria for steatosis are undefined. At the supplier (EchoSens)-recommended CAP threshold of 240 dB/m, 30.5% (95% confidence interval [CI]: 27.1%-34.0%) of adolescents had SLD and about 85% of adolescents with NAFLD met criteria for MASLD. The other 15% would receive an ambiguous diagnosis of either cryptogenic SLD or possible MASLD. At higher CAP thresholds, MASLD/NAFLD concordance increased and approached 100%. Among adolescents with MASLD-fibrosis, only 8.8% (95% CI: 0%-19.3%) had overweight/obese and ALT ≥ 80 U/L., Conclusions: The new nomenclature highlights the high prevalence of liver steatosis. At the CAP threshold of 240 dB/m, however, approximately 15% of adolescents would receive an ambiguous diagnosis, which could lead to confusion and worry. Fewer than 10% of adolescents with MASLD-fibrosis had overweight/obese and ALT ≥ 80 U/L. Revised guidelines are needed to ensure that the other 90% receive appropriate referral and liver disease care., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: Ferritin, initially acting as an iron-storage protein, was found to be associated with metabolic diseases. Our study was designed to investigate the association between serum ferritin and metabolic-associated fatty liver disease (MAFLD) using data from the National Health and Nutrition Examination Survey (NHANES) of the United State of America., Methods: A cross-sectional study was conducted, enrolling a total of 2145 participants from the NHANES in the 2017-2018 cycles. Hepatic steatosis and liver fibrosis were assessed by ultrasound images and several non-invasive indexes. Multiple regression analysis was conducted to determine the associations between serum ferritin concentration and MAFLD and liver fibrosis., Results: The analysis revealed that participants with higher serum ferritin levels (Q3 and Q4 groups) had a higher prevalence of MAFLD than those with the lowest serum ferritin levels [Q3 vs. Q1: OR=2.17 (1.33, 3.53), P<0.05 in fatty liver index (FLI); Q4 vs. Q1: OR=3.13 (1.91, 5.13), P<0.05 in FLI]. Additionally, participants with the highest serum ferritin levels (Q4 group) displayed a higher prevalence of liver fibrosis [Q4 vs. Q1: OR=2.59 (1.19, 5.62), P<0.05 in liver stiffness measurement; OR=5.06 (1.12, 22.94), P<0.05 in fibrosis-4 index], with significantly increased risk observed in participants with concomitant diabetes [OR=7.45 (1.55, 35.72), P=0.012]., Conclusion: Our study revealed that elevated serum ferritin levels are associated with a higher prevalence of MAFLD and advanced liver fibrosis in patients. Elevated serum ferritin levels combined with diabetes are important risk factors for liver fibrosis., (© 2024. Huazhong University of Science and Technology.)

Aims: To examine whether an extended lifestyle metrics incorporating sleep quality improves risk stratification for metabolic dysfunction-associated fatty liver disease (MAFLD), at-risk metabolic dysfunction-associated steatohepatitis (MASH) and significant fibrosis., Methods: A total of 5011 participants with abdominal ultrasound from Imaging sub-cohort of South China Cohort (ISSCC) and 3672 participants underwent vibration controlled transient elastography from US National Health and Nutrition Examination Survey (US NHANES) were included. Liver Essential 5 was constructed by incorporating sleep quality into traditional healthy lifestyles (HLS)., Results: A total of 4.66-17.72% of the association between traditional HLS and MAFLD was mediated by sleep quality regardless of the detection techniques, and their joint associations on MAFLD were significant in both cohorts. ORs for individuals with poor sleep and unfavorable HLS were 1.72 (1.29-2.30) in ISSCC and 2.25 (1.55-3.26) in US NHANES, respectively. Around half of the participants previously considered as following a favorable HLS were re-classified by Liver Essential 5 with significantly higher prevalences of MAFLD in both cohorts (P < 0.001). Similar results were also found on at-risk MASH and significant fibrosis in US NHANES. ORs of participants with per one increment increase in Liver Essential 5 were 0.82 (0.77-0.89) and 0.79 (0.70-0.88) for MAFLD in ISSCC and US NHANES, 0.62 (0.48-0.78) for at-risk MASH and 0.78 (0.65-0.93) for significant fibrosis., Conclusions: Liver Essential 5, which incorporates sleep quality and traditional lifestyle factors, provides additional risk stratification for MAFLD-related outcomes., (© 2024. The Author(s).)

Liver diseases, including non-alcoholic fatty liver disease (NAFLD), are a growing global health issue. Environmental exposure to toxic metals can harm the liver, increasing the risk of NAFLD. Essential elements are vital for liver health, but imbalances or deficiencies can contribute to the development of NAFLD. Therefore, understanding the interplay between toxic metals and essential elements in liver disease is important. This study aims to assess the individual and combined effects of toxic metals (lead(Pb), cadmium (Cd), mercury (Hg)), and essential elements (manganese and selenium) on the risk of liver disease. Methods: We assessed the individual and combined effects of Pb, Cd, Hg, manganese (Mn), and selenium (Se) on liver disease risk using data from the National Health and Nutrition Examination Survey between 2017 and 2018. We performed descriptive statistics and linear regression analysis and then utilized Bayesian Kernel Machine Regression (BKMR) techniques such as univariate, bivariate, and overall effect analysis. BKMR enabled the assessment of non-linear exposure-response functions and interactions between metals and essential elements. Posterior Inclusion Probabilities (PIPs) were calculated to determine the importance of each metal and essential element in contributing to liver disease. Regarding our study results, the regression analysis of liver injury biomarkers ALT, AST, ALP, GGT, total bilirubin, and the FLI-an indicator of NAFLD-with toxic metals and essential elements, adjusting for covariates such as age, sex, BMI, alcohol consumption, ethnicity, income, and smoking status, demonstrated the differential effects of these contaminants on the markers of interest. Our BKMR analysis provided further insights. For instance, the PIP results underscored Pb's consistent importance in contributing to liver disease (PIP = 1.000), followed by Hg (PIP = 0.9512), Cd (PIP = 0.5796), Se (PIP = 0.5572), and Mn (PIP = 0.4248). Our univariate analysis showed a positive trend with Pb, while other exposures were relatively flat. Our analysis of the single-variable effects of toxic metals and essential elements on NAFLD also revealed that Pb significantly affected the risk of NAFLD. Our bivariate analysis found a positive (toxic) trend when Pb was combined with other metals and essential elements. For the overall exposure effect of exposure to all the contaminants together, the estimated risk of NAFLD showed a steady increase from the 60th to the 75th percentile. In conclusion, our study indicates that Pb exposure, when combined with other toxic metals and essential elements, plays a significant role in bringing about adverse liver disease outcomes.

Backgrounds: Insulin resistance (IR) plays a vital role in the pathogenesis of the metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether triglyceride-glucose (TyG) related parameters, which serve as useful biomarkers to assess IR, have prognostic effects on mortality outcomes of MASLD., Methods: Participants in the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018 years were included. TyG and its related parameters [TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR)] were calculated. Kaplan-Meier curves, Cox regression analysis, and restricted cubic splines (RCS) were conducted to evaluate the association between TyG-related indices with the all-cause and cardiovascular mortality of adults with MASLD. The concordance index (C-index) was used to evaluate the prediction accuracy of TyG-related indices., Results: A total of 8208 adults (4209 men and 3999 women, median age 49.00 years) with MASLD were included in this study. Multivariate-adjusted Cox regression analysis revealed that high quartile levels of TyG-related indices were significantly associated with the all-cause mortality of participants with MASLD [ TyG adjusted hazard ratio (aHR) = 1.25, 95% confidence interval (CI) 1.05-1.50, P = 0.014; TyG-WC aHR for all-cause mortality = 1.28, 95% CI 1.07-1.52, P = 0.006; TyG-WHtR aHR for all-cause mortality = 1.50, 95% CI 1.25-1.80, P < 0.001; TyG-WC aHR for cardiovascular mortality = 1.81, 95% CI 1.28-2.55, P = 0.001; TyG-WHtR aHR for cardiovascular mortality = 2.22, 95% CI 1.55-3.17, P < 0.001]. The C-index of TyG-related indices for predicting all-cause mortality was 0.563 for the TyG index, 0.579 for the TyG-WC index, and 0.585 for the TyG-WHtR index, respectively. Regarding cardiovascular mortality, the C-index was 0.561 for the TyG index, 0.607 for the TyG-WC index, and 0.615 for the TyG-WHtR index, respectively. Nonlinear trends were observed between TyG and TyG-WC indices with all-cause mortality of MASLD (P < 0.001 and = 0.012, respectively). A non-linear relationship was observed between the TyG index and cardiovascular mortality of MASLD (P = 0.025). Subgroup analysis suggested that adults aged < 65 years old and those without comorbidities were more sensitive to the mortality prediction of TyG-related indices., Conclusion: Findings of this study highlight the predictive value of TyG-related indices, especially the TyG-WHtR index, in the mortality outcomes of adults with MASLD. TyG-related indices would be surrogate biomarkers for the clinical management of MASLD., (© 2024. The Author(s).)

Background: The global obesity pandemic has led to an alarming rise in the prevalence of metabolic-associated fatty liver disease (MAFLD), making it a substantial clinical and economic burden on society. Early detection and effective treatment of MAFLD are imperative to mitigate its impact., Methods: This cross-sectional study was conducted involving 4634 adults from the National Health and Nutrition Examination Surveys (NHANES) 2017-2018 cycle. Transient elastography (TE) was used to diagnose MAFLD and assess the extent of liver steatosis and fibrosis. Multivariate logistic regression models were utilized to examine the association between the triglyceride and glucose index-waist circumference (TyG-WC) and the risk of MAFLD, liver fibrosis, and steatosis., Results: A positive association between TyG-WC and MAFLD persisted across all three models: model1: OR = 8.44, 95% CI: 6.85-10.38 (unadjusted), model2: OR = 8.28, 95% CI: 6.53-10.50 (partially adjusted), and model3: OR = 7.98, 95% CI: 4.11-15.46 (fully adjusted). Further investigation through interaction and stratified analysis revealed that this association was more pronounced in the non-obese and Non-Hispanic White persons groups. Moreover, a non-linear relationship analysis unveiled threshold and saturation effects between TyG-WC and MAFLD. Specifically, a TyG-WC value of approximately 600 may represent the threshold effect for MAFLD risk, while 1200 may signify the saturation effect of MAFLD risk. Finally, a robust correlation between TyG-WC and the severity of liver steatosis and fibrosis was found., Conclusions: The findings suggest that the TyG-WC index exhibits excellent predictive value for MAFLD in the general American population.

Background and Aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) has been proposed as an alternative for the validated definition of metabolic dysfunction-associated fatty liver disease (MAFLD). We compared the abilities of MAFLD and MASLD to predict the risk of atherosclerotic cardiovascular disease (ASCVD)., Methods: Six thousand and ninety six participants from the 2017 to 2020 National Health and Nutrition Examination Survey cohort who received a thorough medical health check-up were chosen for the study. The associations between fatty liver status and coronary risk surrogates, such as 10-year ASCVD risk and self-reported cardiovascular events, were analysed., Results: MAFLD and MASLD were identified in 2911 (47.7%) and 2758 (45.2%) patients, respectively. MAFLD (odds ratio [OR]: 2.14, 95% confidence interval [CI], 1.78-2.57, p < .001) was more strongly independently associated with high ASCVD risk than MASLD (OR: 1.82, 95% CI, 1.52-2.18, p < .001) was in comparison with the absence of each condition. However, compared with MAFLD, MASLD alone was not associated with increased ASCVD risk. Multiple logistic regression revealed that MAFLD alone was significantly more strongly associated with a high risk of ASCVD (OR: 2.82; 95% CI: 1.13-7.01; p < .03) than MASLD alone., Conclusions: Although both MAFLD and MASLD were associated with different ASCVD risks, MAFLD predicted the ASCVD risk better than MASLD. The higher predictive ability of MAFLD compared to MASLD was attributed to metabolic dysfunction rather than moderate alcohol use., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction and Objectives: Our objective was to measure and compare the intake of macro and micronutrients in a cohort of individuals with Metabolic Syndrome Associated Steatotic Liver Disease (MASLD) compared with matched controls to identify areas of further research in this area; we identified nutrition-associated associations with MASLD in the United States general population., Materials and Methods: We used the 2017 - 2018 NHANES dataset. Elastography Controlled Attenuation Parameter (CAP score>280) in the absence of other liver disease was defined as MASLD in adults (>18). Advanced fibrosis was defined by transient elastography >10 kPa. Controls were adults without liver disease., Results: 1648 MASLD cases (11.4 % advanced fibrosis) and 2527 controls were identified. MASLD cases were older (P<0.001), more likely males (P = 0.01), less likely to have a college education (P = 0.04) and more likely married (P = 0.002). MASLD cases were more likely to be of Mexican American or Hispanic ethnicity (P = 0.002), have higher BMI, and have higher prevalence of diabetes, hyperlipidemia and hypertension (P<0.001 for all). MASLD cases had higher hs-CRP (P = 0.02) and ferritin (P = 0.02). MASLD cases had lower total (P = 0.004) and added vitamin E in their diet (P = 0.002), lower vitamin K intake (P = 0.005), and higher selenium intake (P = 0.03). Caloric intake (P = 0.04), carbohydrate intake (P = 0.02), cholesterol intake (P = 0.03) and saturated fatty acid intake (P = 0.05) were higher in MASLD. Individuals with MASLD were more likely to be on a diet (P<0.001), sedentary (P = 0.008) and less likely to participate in moderate or vigorous recreational activities (P<0.001)., Conclusions: The deficiencies of micronutrients and excess of macronutrients point to oxidative stress, pro-inflammatory state, and lipotoxicity as pathways linking the US diet to MASLD. MASLD patients are more often on special diets, which may reflect prior provider counseling on diet changes to improve health., Competing Interests: Declaration of interests None., (Published by Elsevier España, S.L.U.)