Search

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).)

This cross-sectional survey aims to determine whether cotinine exposure would enhance the relationship between blood manganese (Mn) and non-alcoholic fatty liver disease (NAFLD) in children using the NHANES database. Restricted cubic spline (RCS) and logistic regression analyses were adopted to determine the potential relationship. Besides, we tested the robustness of the results by performing trend tests and subgroup analyses. The study finally enrolled 866 children aged 18 years and below. Blood Mn was linearly linked to NAFLD and the risk of NAFLD was increased with the blood Mn elevation (P < 0.05). There was a notable relationship between blood Mn and NAFLD in crude model 1, which was still significant upon adjustment of all the identified covariates (all P < 0.05). Under Mn exposure, the cotinine-exposed group had a higher risk of NAFLD than the cotinine-unexposed group. In conclusion, blood Mn level is an independent risk factor for pediatric NAFLD, and cotinine exposure can enhance this relationship to some degree. Therefore, reducing cotinine exposure may alleviate detrimental consequences related to exposure to heavy metals in children., (© 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: Inflammation played a critical role in non-alcoholic fatty liver disease (NAFLD). Here, we aimed to explore the relationship between inflammatory biomarkers and the prevalence of NAFLD and hepatic fibrosis in US participants., Methods: Individuals with complete data from National Health and Nutrition Examination Survey (NHANES), 2017-2020 pre-pandemic cycle dataset were referred to this study. We identified NAFLD by vibration-controlled transient elastography (VCTE) on the basis of controlling attenuation parameter (CAP) ≥274dB/m. Liver fibrosis was confirmed by liver stiffness measurement (LSM) ≥8.2kPa. Multivariate logistic regression models were applied to estimate the correlations between inflammatory biomarkers and the prevalence of NAFLD and hepatic fibrosis based on sample weights., Results: All together 5026 subjects were incorporated into the study cohort. Among these subjects, 2209 were classified as having NAFLD, and 8.35 % were diagnosed with hepatic fibrosis. Pan immune inflammatory value (PIV), instead of systemic immune inflammatory index (SII), was positively correlated with the rate of NAFLD or hepatic fibrosis. Subgroup analysis for NAFLD revealed that the positive relationships of the PIV existed in males (OR=1.52, 95 % CI: 1.01-2.28, p = 0.046) and participants below 60 years of age (OR=1.49, 95 % CI: 1.05-2.1, p = 0.028). Moreover, subgroup analysis for hepatic fibrosis revealed that the positive relationships of the PIV existed in females (OR=2.09, 95 % CI: 1.2-3.63, p = 0.014) and participants below 60 years of age (OR=1.74, 95 % CI: 1.09-2.77, p = 0.023)., Conclusions: A higher PIV, but not SII, is associated with a higher likelihood of NAFLD and liver fibrosis, suggesting that the PIV is a more valuable inflammatory marker for assessing NAFLD and liver fibrosis in participants, especially for those who are below 60 years of age., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024. Published by Elsevier Masson SAS.)

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).)

Non-alcoholic fatty liver disease (NAFLD) is a common concomitant disease in adults with type 2 diabetes mellitus (T2DM) and prediabetes. Therefore, T2DM/NAFLD patient populations are at high risk for cardiovascular disease. The occurrence and progression of non-alcoholic fatty liver disease-related liver fibrosis and cardiovascular disease have a severe impact on the patient's prognosis and mortality rate. The American Diabetes Association's 2024 "Guidelines for the Standardized Management of Diabetes" put forward recommendations relevant to the screening, evaluation, treatment, and management of NAFLD in T2DM and prediabetic populations, as well as liver fibrosis. The important measures for decelerating liver inflammation and fibrosis progression and the risk of cardiovascular disease are based on improvements in lifestyle methods, weight loss, and blood sugar control.

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).)

Introduction: This study aimed to determine trends in the prevalence, incidence, and disability-adjusted life years (DALYs) of Non-alcoholic Fatty Liver Disease (NAFLD) in the US across different states and age groups between 1990 and 2019., Methods: Using the Global Burden of Disease database, this study analyzed the prevalence, incidence, and DALYs of NAFLD in the US between 1990 and 2019. We computed relative percentage changes, performed Joinpoint regression analyses of trends, and compared these between states and age groups (5-19, 20-55, and more than 55 years old)., Results: In the United States, the prevalence of NAFLD increased more than the global average over the study period (+ 30.7% vs. + 24.5%), especially in the 5-19-year-old age group. Among all states, Kansas, Washington, and California had the highest increase in prevalence and the District of Columbia followed by Massachusetts and North Carolina had the lowest increase in prevalence. The increase in incidence was greater in the US than the global average (+ 37.18% vs. + 7.28%). West Virginia, Ohio, and Kentucky had the highest increase in incidence. The increase in DALYs was greater in the US compared to the global average (+ 57.15% vs. + 12.65%). Alaska, West Virginia, and Kentucky had the highest increase in DALYs. The increased incidence and DALYs were found in all states except in the District of Columbia., Conclusion: The prevalence of NAFLD in the US has increased more rapidly than the global average, especially in the pediatric population. South and Midwest states have the highest increase in prevalence, incidence, and DALYs of NAFLD. The District of Columbia was the only state that has decreased incidence and DALYs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Both obesity and non-alcoholic fatty liver disease (NAFLD) increase the risk of metabolic abnormalities. However, the metabolic status of children suffering from NAFLD and exhibiting various subtypes of obesity is currently unclear. We aimed to explore the association between NAFLD and metabolic abnormalities in children with different weight statuses. We included 6086 participants aged 6–18 years from the China Child and Adolescent NAFLD Study (CCANS), all of whom had undergone ultrasonography or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to identify NAFLD and metabolic abnormalities, including hyperglycemia, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), high low-density lipoprotein cholesterol, high total cholesterol, and hyperuricemia. Among the participants, there were 2408 children with obesity and NAFLD, 174 with NAFLD, 2396 with obesity, and 1108 without obesity and NAFLD. The odds ratios (ORs) of suffering from individual metabolic abnormalities were significantly greater in children with obesity and NAFLD than in children without obesity and NAFLD, with ORs ranging from 6.23 (95% CI: 4.56, 8.53) to 1.77 (95% CI: 1.06, 2.94). The ORs of metabolic abnormalities, except for low HDL-C, were greater in children with NAFLD alone than in children without obesity or NAFLD, with ORs ranging from 4.36 (95% CI: 2.77, 6.84) to 2.08 (95% CI: 1.14, 3.78). Notably, obesity and NAFLD had a multiplicative effect on overall metabolic abnormalities, high TG levels, and low HDL-C levels. Children with obesity and NAFLD could be at a significantly increased risk of metabolic abnormalities. Even for children without obesity, NAFLD appears to be associated with an increased risk of experiencing a worsened metabolic status. [ABSTRACT FROM AUTHOR]

• Only 27% patients with Non-Alcoholic Fatty Liver Disease (NFALD) received statins. • Statin therapy was not associated with elevated liver enzyme levels. • ALT, total cholesterol, and LDL were significantly lower in statin users. • Findings demonstrate statin use in patients with NAFLD can reduce CVD risks. • Findings were generalized to the US population. Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular disease (CVD). Statins are recommended for treatment of dyslipidemia to reduce the overall cardiovascular risk in patients with NAFLD. However, statin treatment was underutilized and the effect of statins on liver enzymes remained unclear in this patient population. This study aimed to provide real-world evidence of the safety and effect of statin use in patients with NAFLD. We conducted a cross-sectional survey study of adults with NAFLD using pooled data from the US NHANES database 2009–2018. NAFLD was defined by Fatty Liver Index (FLI) ≥ 60 and United States Fatty Liver Index (USFLI) ≥ 30. Multivariate regression analyses adjusted for baseline clinical and demographic characteristics were performed to compare the liver enzymes and lipid profile between statin and non-statin users. The study included 2,533 adults with NAFLD, representing 22.6 million individuals in the US, with 27% receiving statin treatment between 2009 and 2018. The mean differences of liver enzymes for AST, ALT, ALP, and GGT between statin and non-statin users were -0.86 (p=0.539), -3.49 (p=0.042), -0.25 (p=0.913), and 0.57 (p=0.901), respectively. In individuals with NAFLD and dyslipidemia, total cholesterol and LDL levels were significantly lower in statin users compared to non-statin users (mean difference, -28.9; p<0.001 and -27.7; p<0.001). The use of statins was not associated with elevated liver enzymes in patients with NAFLD. Significantly lower levels of ALT, total cholesterol, and LDL were observed in statin users compared to non-statin users. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Data on the prevalence of non-alcoholic fatty liver disease (NAFLD) in subgroups of the United States (US) population are limited. This study was conducted to estimate NAFLD prevalence overall and by subgroups, and prevalence of NAFLD with advanced fibrosis., Materials and Methods: Using the National Health and Nutrition Examination Survey (NHANES) 2011-2018 data, a cross-sectional study was conducted. NAFLD was defined as having a US Fatty Liver Index (USFLI) ≥ 30 in the absence of other causes of liver disease, including excessive alcohol intake, chronic hepatitis B, and chronic hepatitis C. Likelihood for having advanced fibrosis was determined by the calculated NAFLD fibrosis score (NFS; high ≥ 0.676; low < -1.445) and fibrosis-4 index (FIB-4; high ≥ 2.67; low < 1.30)., Results: The weighted national prevalence of NAFLD in US adults was 26.7% (95% confidence interval: 25.3%-28.1%). Prevalence was higher among those aged ≥ 65 years, males, Mexican Americans, with BMI ≥ 35 kg/m 2 (class 2 and 3 obesity) and with type 2 diabetes (T2D). Of those meeting the USFLI criterion for NAFLD, 18.1% and 3.7% were determined as having a high probability of advanced fibrosis based on NFS ≥ 0.676 and FIB-4 ≥ 2.67 cut-off values, respectively., Conclusions: This study supports an increased prevalence of NAFLD in specific subpopulations (aged ≥ 65 years, males, Mexican Americans, obese population, and patients with T2D). The observed difference in the prevalence of advanced fibrosis as estimated by NFS and FIB-4 highlights the challenge of choosing optimal cut-off values., Competing Interests: Declaration of interests Annaswamy Raji, Gail Fernandes, Samuel S Engel, and Xiao Zhang are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. Yuzhi Xi was supported by a Graduate Student Fellowship from Merck & Co., Inc., Rahway, NJ, USA during the conduct of this work and is currently an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Tongtong Wang was an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, during the conduct of this work, and may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. She is currently an employee of Johnson & Johnson and may own stock and/or hold stock options in the company. Michael Crutchlow was an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, during the conduct of this work. He is currently an employee of Kallyope Inc., New York, New York., (Copyright © 2023 Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Aim: The purpose of this study was to explore the association of weight-adjusted-waist index (WWI) with non-alcoholic fatty liver disease (NAFLD) and liver fibrosis., Methods: A cross-sectional study including 6587 participants was conducted in the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression was used to validate the association of WWI with NAFLD and liver fibrosis, and smoothed curve fitting and threshold effect models were used to validate non-linear relationships. Subgroup analyses were used to verify the stability of the relationship between the independent and dependent variables in different populations., Results: There was a positive association of WWI with NAFLD and liver fibrosis. In the model adjusted for all covariates, the effect values of WWI with NAFLD and liver fibrosis were (OR = 3.44, 95% CI: 3.09-3.82) and (OR = 2.40, 95% CI: 2.05-2.79), respectively. This positive correlation became more significant as WWI increased when WWI was presented in quartiles (P for trend < 0.01). Smoothed curve fitting and threshold effects analysis suggested a non-linear correlation between WWI and NAFLD (LLR < 0.01), with the positive correlation between WWI and NAFLD becoming more significant when WWI was less than 11.44 [5.93 (95% CI: 5.04-6.98)]. However, there was a linear correlation between WWI and liver fibrosis (LLR = 0.291). When subgroup analyses were performed by indicators such as age, race and gender, we found that the positive association between WWI and the dependent variables (NAFLD and liver fibrosis) was more pronounced in white male participants aged < 40 years., Conclusions: Among adults in the United States, WWI was positively associated with the prevalence of NAFLD and liver fibrosis. Participants with a WWI less than 11.44 should be cautious about the possibility of an increased risk of NAFLD development due to a higher WWI. Meanwhile, white males younger than 40 years of age should be more cautious about the higher risk of NAFLD and liver fibrosis that might be associated with an increased WWI., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Evidence on liver injury and non-alcoholic fatty liver disease (NAFLD) from volatile organic compounds (VOCs) exposure is insufficient. A cross-sectional study including 3011 US adults from the National Health and Nutrition Examination Survey was conducted to explore the associations of urinary exposure biomarkers (EBs) for 13 VOCs (toluene, xylene, ethylbenzene, styrene, acrylamide, N,N-dimethylformamide, acrolein, crotonaldehyde, 1,3-butadiene, acrylonitrile, cyanide, propylene oxide, and 1-bromopropane) with liver injury biomarkers and the risk of NAFLD by performing single-chemical (survey weight regression) and mixture (Bayesian kernel machine regression [BKMR] and weighted quantile sum [WQS]) analyses. We found significant positive associations of EBs for toluene and 1-bromopropane with alanine aminotransferase (ALT), EBs for toluene, crotonaldehyde, and 1,3-butadiene with asparate aminotransferase (AST), EBs for 1,3-butadiene and cyanide with alkaline phosphatase (ALP), EBs for xylene and cyanide with hepamet fibrosis score (HFS), EBs for the total 13 VOCs (except propylene oxide) with United States fatty liver index (USFLI), and EBs for xylene, N,N-dimethylformamide, acrolein, crotonaldehyde, and acrylonitrile with NALFD; and significant inverse associations of EBs for ethylbenzene, styrene, acrylamide, acrolein, crotonaldehyde, 1,3-butadiene, acrylonitrile, cyanide, and propylene oxide with total bilirubin, EBs for ethylbenzene, styrene, acrylamide, acrolein, 1,3-butadiene, acrylonitrile, and cyanide with albumin (ALB), EBs for ethylbenzene, styrene, acrylamide, N,N-dimethylformamide, acrolein, crotonaldehyde, 1,3-butadiene, acrylonitrile, cyanide, and propylene oxide with total protein (TP), and EB for 1-bromopropane with AST/ALT (all P-FDR<0.05). In BKMR and WQS, the mixture of VOC-EBs was significantly positively associated with ALT, AST, ALP, HFS, USFLI, and the risk of NAFLD, while significantly inversely associated with TBIL, ALB, TP, and AST/ALT. VOCs exposure was associated with liver injury and increased risk of NAFLD in US adults. These findings highlight that great attention should be paid to the potential risk of liver health damage from VOCs exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction and Objectives: Data about 30-day readmission for patients with chronic liver disease (CLD) and their contribution to CLD healthcare burden are sparse. Patterns, diagnoses, timing and predictors of 30-day readmissions for CLD from 2010-2017 were assessed., Materials and Methods: Nationwide Readmission Database (NRD) is an all-payer, all-ages, longitudinal administrative database, representing 35 million discharges in the US population yearly. We identified unique patients discharged with CLD including hepatitis B (HBV) and C (HCV), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) from 2010 through 2017. Survey-weight adjusted multivariable analyses were used., Results: From 2010 to 2017, the 30-day readmission rate for CLD decreased from 18.4% to 17.8% (p=.008), while increasing for NAFLD from 17.0% to 19. 9% (p<.001). Of 125,019 patients discharged with CLD (mean age 57.4 years, male 59.0%) in 2017, the most common liver disease was HCV (29.2%), followed by ALD (23.5%), NAFLD (17.5%), and HBV (4.3%). Readmission rates were 20.5% for ALD, 19.9% for NAFLD, 16.8% for HCV and 16.7% for HBV. Compared to other liver diseases, patients with NAFLD had significantly higher risk of 30-day readmission in clinical comorbidities adjusted model (Hazard ratio [HR]=1.08 [95% confidence interval 1.03-1.13]). In addition to ascites, hepatic encephalopathy, higher number of coexisting comorbidities, comorbidities associated with higher risk of 30-day readmission included cirrhosis for NALFD and HCV; acute kidney injury for NAFLD, HCV and ALD; HCC for HCV, and peritonitis for ALD. Cirrhosis and cirrhosis-related complications were the most common reasons for 30-day readmission, followed by sepsis. However, a large proportion of patients (43.7% for NAFLD; 28.4% for HCV, 39.0% for HBV, and 29.1% for ALD) were readmitted for extrahepatic reasons. Approximately 20% of those discharged with CLD were readmitted within 30 days but the majority of readmissions occurred within 15 days of discharge (62.8% for NAFLD, 63.7% for HCV, 74.3% for HBV, and 72.9% for ALD). Among readmitted patients, patients with NAFLD or HCV readmitted ≤30-day had significantly higher costs and risk of in-hospital mortality (NAFLD +5.69% change [95% confidence interval, 2.54%-8.93%] and odds ratio (OR)=1.58 [1.28-1.95]; HCV +9.85% change [95%CI:6.96%-12.82%] and OR=1.31, 1.08-1.59)., Conclusions: Early readmissions for CLD are prevalent causing economic and clinical burden to the US healthcare system, especially NAFLD readmissions. Closer surveillance and attention to both liver and extrahepatic medical conditions immediately after CLD discharge is encouraged., Competing Interests: Declaration of Competing Interests ZMY has received research funds or served as consultant to Gilead Sciences, Intercept, NovoNordisk, BMS, Abbvie, Merck, Madrigal, Genfit, Siemens, BMS, Terns and Viking. All other authors have no conflict of interest to disclose., (Copyright © 2023 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent liver disease, with the highest prevalence observed in the U.S. among Hispanic/Latino adults. While physical activity and dietary behaviors have established protective associations with NAFLD and its severity, these associations have not been well-characterized in Hispanic/Latino adults. The purpose of this study was to assess the association of lifestyle behaviors with NAFLD and advanced fibrosis in US Hispanic/Latino adults., Design: We selected all Hispanic/Latino adults from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). NAFLD was defined as CAP ≥285 dB/m, and advanced fibrosis as liver stiffness measurements ≥8.6 kPa. Multivariate-adjusted logistic regression models assessed associations of physical activity and sedentary behavior (Global Physical Activity Questionnaire), as well as diet quality (Healthy Eating Index [HEI]-2015) and total energy intake (24-hour recall) with NAFLD and advanced fibrosis., Results: In Hispanic/Latino adults, the overall prevalence of NAFLD was 41.5%, while the prevalence of advanced fibrosis among those with NAFLD was 17.2%. We found that higher levels of physical activity and high diet quality were associated with lower risk of NAFLD. Compared to those reporting on average 0 metabolic equivalent (MET) hours/week of physical activity, participants reporting high levels of physical activity (≥32 MET hours/week) had 40% lower risk of NAFLD (Adjusted OR = 0.60, 95%CI 0.38, 0.93). High diet quality (HEI-2015) was associated with a 30% lower risk of NAFLD (Adjusted OR = 0.70, 95% CI 0.51, 0.97) and 72% lower risk of advanced fibrosis (Adjusted OR = 0.28, 95% CI 0.12, 0.66), as compared to those with low diet quality., Conclusions: In this population-based study, high levels of physical activity and diet quality were associated with lower risk of NAFLD in Hispanic/Latino adults. Public health and medical professionals need to concentrate efforts on lifestyle behavior change in Hispanic/Latino adults who are at high risk for serious liver disease.

Recent studies have associated non-alcoholic fatty liver disease (NAFLD) with impaired cardiac function. However, patients with type 2 diabetes mellitus (T2DM), a high-risk group for left ventricular diastolic dysfunction (LVDD), were not analyzed as an independent study population. A systematic review was conducted to identify all published clinical trials using the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases from inception to September 14, 2022. Observational studies that reported echocardiographic parameters in T2DM patients with NAFLD compared with those without NAFLD were included for further selection. The Agency for Healthcare Research and Quality checklist was used to appraise the study quality. Ten observational studies (all cross-sectional in design) comprising 1800 T2DM patients (1124 with NAFLD, 62.4%) were included. We found that T2DM patients with NAFLD had a significantly lower E/A ratio, higher peak A velocity, higher E/e' ratio, lower e' velocity, greater left atrial maximum volume index, and greater left ventricular mass index than non-NAFLD patients. These findings reinforced the importance of NAFLD being associated with an increased risk of LVDD in the T2DM population, and NAFLD may be a sign of LVDD in patients with T2DM.PROSPERO registration numberCRD42022355844., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) is recommended for risk stratification of patients with nonalcoholic fatty liver disease (NAFLD). More recently, AGILE3 + and AGILE4 have combined LSM with clinical parameters to identify patients with advanced fibrosis and cirrhosis, respectively. However, there are limited data on prognostic performance of these scores in key at-risk subgroups such as those with diabetes and obesity compared to LSM alone., Methods: This is a retrospective cohort study including 1903 adult patients with NAFLD from tertiary care centers in the United States and Singapore undergoing VCTE between 2015 and 2022. Primary predictors were FAST, LSM, AGILE3 + , and AGILE4 scores and the primary outcome was liver-related events (LRE). Patients were further stratified by diabetes and obesity status. Prognostic performance was measured using the time-dependent area under the receiver operating characteristic curve (tAUC) at 5 years., Results: In total, 25 LRE occurred and the overall incidence rate of LRE was 4.4 per 1000 person-years. tAUC for predicting LRE in the overall group was significantly higher with AGILE3 + (0.94 [95% CI: 0.90-0.98]) and AGILE4 (0.94 [95% CI: 0.90-0.98]) compared to LSM (0.87 [95% CI: 0.80-0.94]) (p = 0.001 and 0.009, respectively) and FAST (0.73 [95% CI: 0.59-0.86]) (p < 0.001 for both). Similarly, tAUC was significantly higher in those with T2D for AGILE3 + compared to LSM (0.92 vs 0.86, respectively) (p = 0.015) and FAST (0.92 vs 0.73, respectively) (p = 0.008). Among people with obesity, tAUC was significantly higher for AGILE3 + compared to LSM (0.95 vs 0.89, respectively) (p = 0.005) and FAST (0.95 vs 0.76, respectively) (p = 0.0035). Though AGILE4 had a higher tAUC in these subgroups compared to LSM, it did not reach statistical significance., Conclusion: AGILE3 + significantly outperforms LSM and FAST for predicting LRE in patients with NAFLD including in those with diabetes or obesity., Competing Interests: Declarations Conflict of interest YJW was supported by the Nurturing Clinician Scientist Scheme, Medicine Academic Clinical Program, Singhealth. VLC was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases (K08 DK132312)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Non-alcoholic steatohepatitis (NASH) may progress to more advanced liver disease. This study aimed to characterize NASH progression and mortality in the Medicare population., Methods: Patients with NASH in 100% Medicare fee-for-service claims accrued from 2015-2021 who were ≥ 66 years old at index diagnosis, continuously enrolled for ≥ 12 months prior to and ≥ 6 months following index (unless death), and had no evidence of other causes of liver disease were included. Diagnosis codes defined severity states: non-cirrhotic NASH, compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), and liver transplant (LT). Survival analyses of disease progression and mortality were conducted for each state and by year of progression (Y1-5). Cox proportional hazards models assessed risk factors of worsening disease., Results: Mean age and follow-up were 72.2 and 2.8 years in 14,806 unique patients (n = 12,990 NASH; 1899 CC; 997 DCC; 209 HCC; 140 LT). Progression rates were highest for patients with CC (11-37% for Y1-5), followed by DCC (3-18%), NASH (3-12%), and HCC (2-4%). Mortality rates were highest for patients with HCC (41-85% for Y1-5), followed by DCC (41-76%), LT (7-33%), CC (6-26%), and NASH (2-12%). Patients with any disease progression had a 5-year mortality rate more than double that of patients without progression (41% vs. 16%). Delayed progression from NASH was associated with lower mortality risk; the 5-year mortality rate was 26% lower for patients with progression in Y2 vs. Y1 (32% vs. 43%) and further decreased for progression in Y3-Y5. Risk factors included age, nursing home use, congestive heart failure, coagulopathy, fluid/electrolyte disorders, and unexplained weight loss., Conclusion: Medicare patients ≥ 66 years with NASH experience high risk of disease progression associated with increased mortality rates. Slower disease progression is associated with lower mortality rates, suggesting that therapies that can delay or prevent NASH progression may reduce morbidity and mortality., (© 2024. The Author(s).)

Objectives: This study aimed to analyze the global profile of the literature in non-alcoholic fatty liver disease (NAFLD) research., Background: Non-alcoholic fatty liver disease is a clinically heterogeneous condition characterized by fat accumulation in the liver and the absence of significant alcohol consumption or underlying genetic disorders. These manifestations are associated with inflammation, steatosis, and fibrosis that can develop into cirrhosis and even hepatocellular carcinoma. However, a study about the research trend in NAFLD has never been reported before., Methods: The NAFLD bibliometric analysis was performed on articles indexed in the Scopus database from 1973 to 2022., Results: The total number of articles published worldwide is 28,673 documents, with an annual average of 561 documents. The United States generated the most articles (n = 6548), followed by China (n = 6180), Italy (n = 2434), and Japan (n = 2032). Since 2013, the number of publications on NAFLD has increased dramatically worldwide. The popular topics in the field include medicine, biochemistry, genetics and molecular biology, pharmacology, toxicology and pharmaceutics, and nursing., Conclusions: This study provides a unique composite picture of NAFLD research worldwide and evaluates research productivity from 1973 to 2022. This finding suggests that the prospects for interventions in NAFLD remain promising (Tab. 5, Fig. 4, Ref. 57). Text in PDF www.elis.sk Keywords: bibliometric analysis, NAFLD, Scopus.

Background: Nonalcoholic fatty liver disease (NAFLD) is closely associated with Cardiovascular disease (CVD). We aim to examine the association of Life's Essential 8 (LE8), the recently updated measurement of cardiovascular health (CVH), with the presence of NAFLD among US adults., Methods: This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey in 2017-2018 and included adults 20 years or older. LE8 score (range 0-100) was measured according to American Heart Association definitions and was categorized into low (0-49), moderate (50-79), and high (80-100) CVH. NAFLD was determined by transient elastography measured hepatic steatosis in the absence of other liver diseases and excess alcohol use. Multivariable logistic and restricted cubic spline models were used to assess the associations., Results: Among 3588 participants included (weighted mean age, 48.0 years; 95% confidence interval [CI] 46.4-49.7 years), 1839 were female (weighted percentage, 51.6%; 95% CI 49.0-54.2%) and 1483 were determined to have NAFLD (weighted percentage, 36.5%; 95% CI 33.3-39.7%). The weighted mean LE8 score of the study population was 67.9 (95% CI 66.6-69.2). After the adjustment of potential confounders, higher LE8 scores were associated with reduced odds of NAFLD (odds ratio [OR] for per 10 score increase, 0.67; 95% CI 0.59-0.76) and a nonlinear dose-response relationship was observed. Similar patterns were also identified in the association of health behavior and health factor scores with NAFLD. The inversed association of LE8 score and NAFLD was significantly stronger among younger, Asian, and participants with higher education and income level., Conclusions: LE8 and its subscales scores were negatively associated with the presence of NAFLD in non-linear fashions. Promoting adherence to optimal CVH levels may be beneficial to reduce the burden of NAFLD as well as CVD., (© 2022. The Author(s).)

Aim: Non-alcoholic steatohepatitis (NASH), or metabolic dysfunction-associated steatohepatitis (MASH), is a severe form of non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated liver disease (MASLD), that may progress to advanced liver disease. Costs associated with progression are not well characterized. This study sought to quantify costs and healthcare resource utilization (HRU) associated with NASH progression. Methods: Patients were included if diagnosed with NASH (ICD-10: K75.81) in 100% Medicare claims data (2015-2021) who were ≥66 years at index (diagnosis), continuously enrolled in Parts A, B and D for ≥12 months prior to and 6 months following index (unless death) and who had no evidence of other causes of liver disease. Patient-time was categorized into five severity states: non-cirrhotic NASH, compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC) and liver transplant (LT). Annualized HRU and costs were calculated during the study periods overall and stratified by occurrence and timing of progression. Results: In 14,806 unique patients (n = 12,990 non-cirrhotic NASH; 1899 CC; 997 DCC; 209 HCC; 140 LT), mean age and follow-up were 72.2 and 2.8 years, respectively. Average annualized costs increased from baseline following diagnosis, generally scaling with severity: $16,231 to $27,044; $25,122 to $57,705; $40,613 to $181,036; $36,549 to $165,121 and $35,626 to $108,918 in NASH; CC; DCC; HCC; and LT; respectively. Non-cirrhotic NASH and CC patients with progression had higher follow-up spending (1.6x for NASH; 1.7x for CC) than non-progressors (both p < 0.001), 2.8 and 6.1-times higher odds of an inpatient stay and 2.6 and 3.6-times higher odds to be in the top 20% of spenders, respectively, relative to non-progressors (both p < 0.001). Patients progressing within a year had costs 1.4, 1.6, 1.7 and 2.2-times more than year 2, 3, 4 and 5 progressors' costs, respectively, for non-cirrhotic NASH and 1.3, 1.8, 2.0 and 2.2-times more than year 2, 3, 4 and 5 progressors' costs, respectively, for CC. Conclusion: NASH progression is associated with high costs that increase in more severe disease states. Slower progression is associated with lower costs, suggesting a potential benefit of therapies that may delay or prevent progression.

Background: Metabolic dysfunction-associated steatohepatitis (MASH; formerly nonalcoholic steatohepatitis) is the inflammatory form of metabolic dysfunction-associated steatotic liver disease (formerly nonalcoholic fatty liver disease). MASH is a progressive disease associated with increased risk for many hepatic and extra-hepatic complications such as cirrhosis, hepatocellular carcinoma, the requirement for liver transplantation, and cardiovascular (CV)-related and kidney-related complications. It is important to understand the clinical and economic burden of MASH., Objectives: To assess and compare the clinical and economic burdens of MASH in adults with the non-MASH population in a real-world setting., Methods: This observational, retrospective study used the Healthcare Integrated Research Database (HIRD), which contains health care claims data for commercially insured and Medicare Advantage health plan members across the United States. All-cause, CV-related, and liver-related medical costs and health care resource utilization were evaluated in patients with at least 2 diagnoses of MASH during the patient identification period (October 1, 2016, to April 30, 2022) and compared with a non-MASH cohort 1:1 matched on age, Quan Charlson Comorbidity Index, region of residence, and health plan type and length of enrollment. Generalized linear regression with negative binomial and γ distribution models were used to compare health care resource utilization and medical costs, respectively, while controlling for confounders. Covariate-adjusted all-cause, CV-related, and liver-related hospitalization rate ratios and medical cost ratios were assessed and compared for the MASH and matched non-MASH cohorts., Results: A total of 18,549 patients with MASH were compared with 18,549 matched patients in the non-MASH cohort. After adjusting for covariates, MASH was associated with significantly higher rates of hospitalization and higher medical costs compared with the non-MASH cohort. When compared with the non-MASH cohort, patients with MASH had 1.22 (95% CI = 1.15-1.30; P < 0.0001) times higher rates of all-cause hospitalization, 1.13 (95% CI = 1.03-1.24; P = 0.008) times higher rates of CV-related hospitalization, and 7.22 (95% CI = 4.91-10.61; P < 0.0001) times higher rates of liver-related hospitalization. Similarly, all-cause medical costs were 1.26 (95% CI = 1.22-1.30; P < 0.0001) times higher, CV-related medical costs were 1.66 (95% CI = 1.59-1.73; P < 0.0001) times higher, and liver-related medical costs were 7.79 (95% CI = 7.42-8.17; P < 0.0001) times higher among patients with MASH., Conclusions: Compared with those of the non-MASH cohort with similar age, Quan Charlson Comorbidity Index, health plan, region of residence, and duration of enrollment, patients with MASH had significantly higher all-cause, CV-related, and liver-related hospitalizations and medical costs.

Background: There is currently limited evidence comparing the association between metabolic dysfunction-associated fatty liver disease (MAFLD), nonalcoholic fatty liver disease (NAFLD), and the risk of peripheral artery disease (PAD). This study aims to analyze the associations of MAFLD and NAFLD with incident PAD., Methods and Results: Two longitudinal studies, the UKB (UK Biobank) study (n=372 216) and the ARIC (Atherosclerosis Risk in Communities) study (n=4681), categorized participants into MAFLD/non-MAFLD groups and NAFLD/non-NAFLD groups. Subsequently, participants were classified into 4 groups: non-fatty liver disease, MAFLD-only, NAFLD-only, and both MAFLD and NAFLD groups. Cox proportional hazard model estimated associations of MAFLD/NAFLD status, subtypes, and liver fibrosis severity with PAD risk. The MAFLD group had a higher risk of incident PAD compared with the non-MAFLD group, and similarly, the NAFLD group had a higher risk compared with the non-NAFLD group. Among these 4 groups, the MAFLD-only group had the strongest association with the risk of incident PAD, while the NAFLD-only group was not independently associated. Diabetic MAFLD subtype was significantly associated with increased PAD risk, and higher level of liver fibrosis scores correlated with elevated PAD risk., Conclusions: Both MAFLD and NAFLD are significantly associated with an increased incidence of PAD, with stronger associations in MAFLD and diabetic MAFLD population. These findings emphasize that the need for screening and prevention strategies for PAD in this high-risk population is warranted. The assessment of MAFLD and its subtypes should be considered as an integral component of cardiovascular risk assessment.

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).)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic steatosis that is confirmed by imaging or histology in the setting of at least 1 metabolic risk factor in the absence of significant alcohol consumption. Nonalcoholic steatohepatitis, or NASH, was recently renamed metabolic dysfunction-associated steatohepatitis (MASH); it represents the progressive form of MASLD. MASH is defined by hepatic steatosis, lobular inflammation, and ballooning degeneration (hepatocellular injury) in a characteristic histologic pattern. Multiple pathophysiologic mechanisms underlie the development of MASLD, and multiple factors (eg, metabolic, hormonal, genetic, nutritional, and epigenetic components) are related to liver injury. MASH has a prevalence in the United States of 1% to 6%, and it is expected to rise in the next decade. Individuals living with MASH frequently suffer from comorbidities such as type 2 diabetes and cardiovascular disease. Several guidelines have been published to support the timely diagnosis of MASH that incorporate noninvasive tests that obviate the need for liver biopsy. Multiple MASH treatment options are in various stages of development. The THR-β agonist resmetirom, approved by FDA in March 2024, offers a liver-directed treatment for those patients living with moderate to severe fibrosis without cirrhosis. Considering the progressive nature of the disease and the availability of a treatment that can be initiated early to halt MASH progression, patients who have risk factors for MASH should urgently be encouraged to visit their health care providers for MASH screening.

Introduction: As of March 2024, resmetirom is the first and only therapy approved in the United States (US) for the treatment of adults with non-cirrhotic nonalcoholic steatohepatitis (NASH) with moderate-to-advanced liver fibrosis (MALF) consistent with stages F2/F3 fibrosis. Estimates of the diagnosed, treatment-eligible NASH population are poorly understood due to diagnostic variability. This study provides a contemporary estimate of the size of the US resmetirom treatment-eligible population., Methods: A dynamic population calculator was developed combining literature, screening guidelines, resmetirom study criteria, and analyses of the NHANES 2017-March 2020 cycle. It computes NASH prevalence, proportion non-cirrhotic NASH with MALF, Year 1 diagnosis, and new diagnoses in Years 2 and 3. NASH prevalence was estimated by applying the American Association of Clinical Endocrinology screening algorithm and recommended NIT cut-offs in the NHANES dataset. The proportion of non-cirrhotic NASH with MALF was informed by analyses of the Forian US integrated medical claims database using NASH and cirrhosis-specific ICD-10-CM codes and FIB-4 scores. NASH diagnosis rates were obtained from published estimates and NHANES responses. Treatment-eligible population growth was projected using published incidence data. Estimates were compared to a NASH budget-impact-analysis (BIA) from the Institute for Clinical and Economic Review (ICER)., Results: In the base case, a NASH prevalence of 4.6% was modeled (range 1.3-14.2%). This value was multiplied by the proportion estimated to have non-cirrhotic MALF (i.e., 35%). Published analyses suggest a diagnosis rate of ~ 10% (range 3.3-14.3%) and ~ 16% year-over-year growth in the treatment-eligible population. Assuming a 1-million commercial-member population, the resmetirom treatment-eligible population was estimated as 1255-1699 in Years 1-3 following approval. Sensitivity analyses were conducted and comparison to the ICER BIA was influenced by different diagnosis rates., Conclusion: Estimation of the treatment-eligible population for resmetirom depends importantly on NASH diagnosis rates, which are predicted to be < 15% in the 3 years after drug approval. Nonalcoholic steatohepatitis (NASH) is an advanced form of nonalcoholic fatty liver disease. Previously there were no treatments for NASH in the United States (US), but as of March 2024, the US Food and Drug Administration (FDA) approved resmetirom (REZDIFFRA™), a once-daily, oral therapy, in conjunction with diet and exercise, under accelerated approval for the treatment of adults (aged 18 years or older) with non-cirrhotic NASH with moderate-to-advanced liver fibrosis (MALF), consistent with stages F2-F3. It is not well understood how many diagnosed patients with NASH would be eligible for treatment with resmetirom; thus, this study aimed to estimate the size of the US resmetirom treatment-eligible population. To do so, we created a flexible population calculator that considers how many people have NASH, what proportion would be eligible for resmetirom treatment-i.e., have non-cirrhotic NASH with MALF-and of those how many people would be diagnosed. We used published literature, screening guidelines, resmetirom study criteria, and analyses of national surveys to inform our range of estimates. In the main analysis, we modeled a NASH prevalence of 4.6% (range 1.3-14.2%), which was then limited to the proportion estimated to have non-cirrhotic NASH with MALF (i.e., 35%) and diagnosed (i.e., 10%, range 3.3-14.3%). A year-over-year growth of approximately 16% in the treatment-eligible population was modeled in years following approval. Assuming a population of 1 million commercial insurance enrollees, the resmetirom treatment-eligible population was estimated to be 1255-1699 in Years 1-3 following approval. We assessed alternative scenarios and have compared our results to existing models., (© 2024. The Author(s).)

Non‑alcoholic fatty liver disease (NAFLD) is a clinically progressive illness that can advance from simple fatty liver to non-alcoholic hepatitis and liver fibrosis. Cirrhosis and hepatocellular carcinoma are two of the most common diseases caused by NAFLD. As there are no early disease biomarkers and no US Food and Drug Administration‑approved medications, treatment for NAFLD is still focused on altering lifestyle and dietary habits, which makes it difficult to treat effectively. As a result, a novel treatment is urgently needed to prevent NAFLD progression. Calcium (Ca 2+ ) channels regulate intracellular Ca 2+ homeostasis via the mediation of Ca 2+ flow. Previous studies have reported that Ca 2+ channel expression varies throughout the development and progression of NAFLD, which results in the dysregulation of intracellular Ca 2+ homeostasis, endoplasmic reticulum stress, mitochondrial dysfunction and autophagy suppression, all of which contribute to NAFLD progression. Several types of Ca 2+ channels (including two‑pore segment channel 2, transient receptor potential, inositol triphosphate receptor, voltage‑dependent anion channel 1, store‑operated Ca 2+ entry, purinergic receptor X7 and potassium Ca 2+ ‑activated channel subfamily N member 4) have been identified as potential targets for preventing NAFLD development and controlling intracellular Ca 2+ homeostasis. To achieve this, these channels can be blocked or activated, which exerts anti‑steatotic, anti‑inflammatory, anti‑fibrotic and other effects, which ultimately prevents the development of NAFLD. In the present review NAFLD therapeutics and the treatments that target Ca 2+ channels that are currently being developed were examined.

Purpose: Human data are limited linking magnesium (Mg) intake to the risk of non-alcoholic fatty liver disease (NAFLD). We aimed to examine the association between Mg intake and the risk of NAFLD among young adults in the US with a 25-year follow-up., Methods: This study included 2685 participants from the Coronary Artery Risk Development in Young Adult (CARDIA) study. Diet and dietary supplements were assessed at baseline (1985-1986) and exam years 7 and 20 using an interview-based dietary history. NAFLD, defined as liver attenuation ≤ 51 Hounsfield Units excluding secondary causes of liver fat accumulation, was identified by non-contrast-computed tomography scanning at exam year 25. Multivariable-adjusted logistic regression model was used to examine the associations between cumulative average total intake of Mg (dietary plus supplemental) and NAFLD odds., Results: A total of 629 NAFLD cases were documented. After adjustment for potential confounders, an inverse association between total Mg intake and NAFLD odds was observed. Compared to participants in the lowest quintile of total Mg intake, the odds of NAFLD was 55% lower among individuals in the highest quintile [multivariable-adjusted odds ratio (OR) = 0.45, 95% confidence interval (CI) (0.23, 0.85), p for trend = 0.03]. Consistently, whole-grain consumption, a major dietary source of Mg, was inversely associated with NAFLD odds (p for trend = 0.02)., Conclusions: This study suggests that higher cumulative intake of Mg throughout adulthood is associated with lower odds of NAFLD in midlife. Future studies are needed to establish a possible causal relationship., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objective: While the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and long-term cardiovascular risks has been studied, the impact of MASLD on cardiovascular events during delivery hospitalizations remains relatively unexplored. This study aims to examine the prevalence of cardiovascular diseases (CVDs) and cardiac arrhythmias in pregnant patients with MASLD and identify potential risk factors., Methods: A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted to assess maternal cardiovascular outcomes. Multivariable logistic regression models were employed, and adjusted odds ratios (AOR) were calculated to evaluate the association between MASLD and cardiovascular outcomes during pregnancy., Results: The study sample included 17 593 pregnancies with MASLD and 41 171 211 pregnancies without this condition. Women with MASLD exhibited an increased risk of congestive heart failure [AOR 3.45, 95% confidence interval (CI) 1.04-11.43], cardiac arrhythmia (AOR 2.60, 95% CI 1.94-3.49), and gestational hypertensive complications (AOR 3.30, 95% CI 2.93-3.72). Pregnancies with MASLD were also associated with a higher rate of pulmonary edema (AOR 3.30, 95% CI 1.60-6.81)., Conclusion: MASLD is an independent risk factor for cardiovascular complications during delivery hospitalizations, emphasizing the necessity for prepregnancy screening and targeted prevention strategies to manage CVD risks in expectant patients with MASLD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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: Nonalcoholic steatohepatitis (NASH) is the fastest-growing indication for liver transplantation (LT). Sex disparities among patients with cirrhosis on the LT waitlist are well known. We wanted to understand these disparities further in women with end-stage liver disease patients listed for NASH cirrhosis in a contemporary cohort., Methods: We used data from the Scientific Registry of Transplant Recipients to assess sex racial, and ethnic differences in NASH patients listed for LT. Adults transplanted from August 1997 to June 2021 were included. Inferential statistics were used to evaluate differences with univariate and multivariate comparisons, including competitive risk analysis., Results: During the study time period, we evaluated 12 844 LT for NASH cirrhosis. Women were transplanted at a lower rate (46.5% versus 53.5%; P  < 0.001) and higher model for end-stage liver disease (MELD) (23.8 versus 22.6; P < 0.001) than men. Non-White women were transplanted at a higher MELD (26.1 versus 23.1; P  < 0.001) than White women and non-White male patients (26.1 versus 24.8; P  < 0.001). Graft and patient survivals were significantly different ( P  < 0.001) between non-White women and White women and men (White and non-White)., Conclusions: Evaluation of LT candidates in the United States demonstrates women with NASH cirrhosis have a higher MELD than men at LT. Additional disparities exist among non-White women with NASH as they have higher MELD and creatinine at LT compared with White women. After LT, non-White women have worse graft and patient survival compared with men or White women. These data indicate that non-White women with NASH are the most vulnerable on the LT waitlist., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Backgruound: We aimed to investigate the association of hepatic steatosis with liver fibrosis and to assess the interactive effects of hepatic steatosis and insulin resistance on liver fibrosis in a nationally representative sample of United States adults., Methods: We conducted a cross-sectional analysis using data from National Health and Nutrition Examination Survey 2017 to 2018, which for the first time included transient elastography to assess liver stiffness and hepatic steatosis. We evaluated the association between hepatic steatosis (using controlled attenuation parameter [CAP]) and clinically significant liver fibrosis (defined as liver stiffness ≥7.5 kPa) using logistic regression with an interaction term for hepatic steatosis and insulin resistance (defined as homeostatic model assessment of insulin resistance ≥3.0)., Results: Among adults undergoing transient elastography (n=2,023), 45.9% had moderate or greater hepatic steatosis and 11.3% had clinically significant liver fibrosis. After adjustment for demographic and metabolic factors, the odds of significant liver fibrosis increased as CAP score rose (odds ratio, 1.35 per standard deviation increment; 95% confidence interval, 1.11 to 1.64). We detected a significant interaction effect between CAP score and insulin resistance on the probability of significant liver fibrosis (P=0.016 for interaction). The probability of significant liver fibrosis increased in the presence of insulin resistance with increasing CAP score, while those without insulin resistance had low probability of significant liver fibrosis, even with high CAP scores., Conclusion: Individuals with hepatic steatosis had higher odds of fibrosis when insulin resistance was present. Our findings emphasize the importance of the metabolic aspects of the disease on fibrosis risk and suggest a need to better identify patients with metabolic associated fatty liver disease.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is a growing problem in the United States and Hispanics experience the highest burden of this disease. Weight loss, physical activity (PA) and a healthy diet are the mainstay for NAFLD treatment, but patients experience barriers to behavior change. The purpose of this study was to identify barriers hindering Hispanic patients with NAFLD from making changes to PA and dietary habits., Methods: Participants referred to a multidisciplinary clinic completed self-administered questionnaires that measured barriers to greater PA engagement and eating healthier, with both close-ended and open-ended responses. One bilingual coder reviewed and categorized all open-ended responses., Results: The study population included 414 patients. The top five barriers for eating healthier were cost, perceptions that healthier food does not taste good, lack of time to cook, difficulty of cooking, and difficulty in going to the grocery store. Lack of time, feeling lazy, pain, a lack of place to exercise, and the perception that exercise is difficult were the top five barriers to PA engagement., Conclusions: Since Hispanic adults with NAFLD experience similar barriers to Hispanic adults more generally, existing behavioral lifestyle interventions may work well in this clinical population with some adaption for NAFLD-specific education.

Introduction: This study aimed to determine the burden of suspected nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) in a predominantly Hispanic patient population and explore the utility of the American Gastroenterological Association's NAFLD Clinical Care Pathway (CCP)., Methodology: Electronic medical records ( n = 223) were used to divide patients into risk groups based on the amount of metabolic risk factors they presented, diabetic status, or if they presented other liver diseases. Fribosis-4 (FIB-4) scores were used to determine the risk for advanced fibrosis., Results: Most patients (83.8%) were considered at risk for NAFLD based on CCP criteria, and about a third of patients (33.2%) were found to be at indeterminate ( n = 60; 26.9%) or high risk ( n = 14; 6.3%) for advanced fibrosis. Most indeterminate-risk patients (78.3%) were not referred for liver imaging., Discussion: This study demonstrates the potential of the CCP as a corrective tool that could help to better identify and screen patients at risk for NAFLD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The incidence of Non-alcoholic fatty liver disease (NAFLD) in China and USA is extremely high and rising. TikTok has become a popular channel for medical information dissemination and we aimed to evaluate the quality and reliability of NAFLD related videos on TikTok, in both its USA and Chinese versions., Methods: We analyzed the top 100 NAFLD videos on both the USA version and Chinese version of TikTok, a total of 200 videos, from which keywords were extracted and scored using the Global Quality Scale (GQS), modified DISCERN (mDISCERN), and Medical Quality Video Evaluation Tool (MQ-VET). Exploring the relationship between video quality and audience related factors, as well as ranking, through Spearman correlation analysis., Results: The mDISCERN scores of videos on the USA version of TikTok is higher than that on the Chinese version (P < 0.01), but there is no significant difference in the GQS and MQ-VET scores. The GQS, mDISCERN and MQ-VET scores of videos published by medical practitioners were significantly higher than those of non-medical practitioners (P < 0.001). However, there was no significant correlation between video quality and popularity indicators., Conclusion: The quality of NAFLD related short videos on TikTok is acceptable, but the reliability is mediocre, and there is still room for improvement. The videos published by USA medical practitioners are more reliable than those of Chinese medical practitioners. The most concerned topic of both countries is diet. The TikTok recommendation algorithm may limit access to high-quality health videos, and further research on other platforms and languages is necessary., Competing Interests: Declarations. Ethics approval and consent to participate: This study did not require approval by the local Research Ethics Board as it involved publicly available data only. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Metabolic dysfunction-associated steatotic liver disease affects 1 in 4 people in the United States and western Europe, with an important proportion developing metabolic dysfunction-associated steatohepatitis (MASH), the progressive subtype of metabolic dysfunction-associated steatotic liver disease. Cirrhosis caused by MASH is a leading indication for liver transplantation and the most common cause of hepatocellular carcinoma. Hitherto, there have been no specific pharmacotherapies for MASH. The recent conditional approval by the Food and Drug Administration of resmetirom for the treatment of moderate or advanced MASH presents a much-anticipated therapeutic option for patients with noncirrhotic advanced MASH. Specifically, the intended population for resmetirom are patients with MASH and fibrosis stages 2 or 3. The approval of resmetirom also presents important challenges, including how to noninvasively identify patients with fibrosis stages 2-3, and how to exclude patients with more advanced disease who should not be treated until further data emerge on the use of resmetirom in this population. Herein we consider the available literature with regard to identifying the intended population for treatment with resmetirom and in proposing criteria for stopping treatment., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Previous studies showed lutein and zeaxanthin (L and Z) may influence cognitive function by different mechanisms. Our study aimed to be the first to examine whether the risk of non-alcoholic fatty liver disease (NAFLD) mediated the possible association between the dietary intake of L and Z and cognitive function., Methods: We conducted a cross-sectional analysis of participants aged 60 years or over in the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Multivariable linear regression was used to investigate the association between the dietary intake of L and Z and cognitive function, and structural equation modeling tested the mediation effect., Results: The fatty liver index for the United States population (US FLI) acted as a mediator in the association between the higher intake of L and Z and the Animal Fluency Test, the Digit Symbol Substitution Test (DSST), and composite score and mediated 13.89%, 17.87%, and 13.79% of the total association in dietary L and Z intake (14.29%, 13.68%, and 10.34% of the total association in total L and Z intake), respectively., Conclusion: Our study indicated the potential role of the risk of NAFLD as a mediator of associations between the dietary intake of L and Z and cognitive function in the geriatric American population.

Background: Elevated serum ferritin levels (SFLs) was previously reported to be related with hepatic histologic severity and advanced liver fibrosis among non-alcoholic fatty liver disease (NAFLD) patients. However, whether NAFLD influences SFLs remains uncertain and needs more clinical evidences. This study explored the differences of SFLs in US adults with or without NAFLD., Methods: We conducted a cross-sectional study of 3689 participants aged 18-80 years using the National Health and Nutrition Examination Survey (NHANES) 2017-2018 cycle. NAFLD status was confirmed based on controlled attenuation parameter (CAP) values ≥274 dB/m through vibration controlled and transient elastography (VCTE). We performed weighted multivariable logistic regression models to evaluate the associations between NAFLD and SFLs in different age and gender., Results: There was a positive association between NAFLD and SFLs in all three models (model 1:β = 23.07, 95% CI: 10.32, 35.81; model 2:β = 23.68, 95% CI: 10.86, 36.50; model 3:β = 13.86, 95% CI: 0.29, 27.43). After adjusting for the covariates, this positive association persisted in females (β = 16.22, 95% CI: 2.81, 29.62). Further, relationships between NAFLD and SFLs were significantly different in various age groups. In the subgroup stratified by gender, their associations further differed. In males, the positive association was more prominent in 50-64 age group (β = 70.89, 95% CI: 25.14, 116.64). In females, this positive association was more prominent in 18-34 age group (β = 20.72, 95% CI: 7.45, 33.99). However, no correlations between severe steatosis, significant fibrosis, advanced fibrosis, cirrhosis, and SFLs in adults with NAFLD were found., Conclusion: This study indicated that US adults suffered with NAFLD had significantly higher SFLs compared with their counterparts in non-NAFLD group. Moreover, the associations between NAFLD and SFLs further differed by age and gender., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

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).)

Background: For individuals with a coronary artery calcium (CAC) score of 0, CAC rescans at appropriate timings are recommended, depending on individual risk profiles. Although nonalcoholic fatty liver disease, recently redefined as metabolic-associated fatty liver disease, is a risk factor for atherosclerotic cardiovascular disease events, its relationship with the warranty period of a CAC score of 0 has not been elucidated., Methods: A total of 1944 subjects from the MESA (Multi-Ethnic Study of Atherosclerosis) with a baseline CAC score of 0, presence or absence of nonalcoholic hepatic steatosis, and at least 1 follow-up computed tomography scan were included. Nonalcoholic hepatic steatosis was defined using nonenhanced computed tomography and liver/spleen attenuation ratio <1. The association between nonalcoholic hepatic steatosis and new CAC incidence (CAC score >0) was evaluated using a Weibull survival model., Results: Nonalcoholic hepatic steatosis was identified in 268 (14%) participants. Participants with nonalcoholic hepatic steatosis had higher CAC incidence than those without nonalcoholic hepatic steatosis. Nonalcoholic hepatic steatosis was independently associated with new CAC incidence after adjustment for atherosclerotic cardiovascular disease risk factors (hazard ratio, 1.28 [95% CI, 1.05-1.57]; P =0.015). Using a 25% testing yield (25% of participants with zero CAC at baseline would be expected to have developed a CAC score >0), the warranty period of a CAC score of 0 in participants with nonalcoholic hepatic steatosis was shorter than in those without nonalcoholic hepatic steatosis (4.7 and 6.3 years). This association was consistent regardless of sex, race/ethnicity, age, and 10-year atherosclerotic cardiovascular disease risk., Conclusions: Nonalcoholic hepatic steatosis had an impact on the warranty period of a CAC score of 0. The study suggests that the time period until a CAC rescan should be shorter in those with nonalcoholic hepatic steatosis and a CAC score of 0., Competing Interests: All authors declare no conflicts of interest associated with this article.

Nonalcoholic steatohepatitis (NASH)/metabolic dysfunction-associated steatohepatitis (MASH) is an advanced form of liver disease that can lead to significant morbidity and mortality primarily due to hepatic complications including fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure, as well as cardiovascular disease. As the development of NASH/MASH is closely linked to cardiometabolic risk factors such as obesity and type 2 diabetes mellitus, its prevalence is increasing along with the prevalence of those conditions. Identifying at-risk patients or those early in the disease process is essential to optimizing care and may prevent future complications. Current treatment options include disease-modifying interventions, off-label use of US Food and Drug Administration (FDA)-approved medications for comorbid conditions, and resmetirom, the recently first-ever FDA-approved medication specifically for use in NASH/MASH. There is also considerable continued activity in related drug development research with several other potential emerging treatments. With the increasing prevalence of NASH/MASH and emerging treatments, it is important for managed care organizations (MCOs) to be prepared to assist in patient care and implement equitable treatment management. Understanding patient perspectives and their experience with NASH/MASH provides insights for MCOs such as the need for education of both health care providers and patients to encourage early diagnosis and for enhancing access to individualized care including resources and support. Additionally, MCOs can consider potential management strategies for new and emerging treatments.