This study investigates the intricate relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and depression, emphasizing the mediating role of body fat distribution, particularly in female.

We analyzed the pairwise relationship among body fat distribution (android fat and gynoid fat), MASLD, and depression within a robust, ethnically diverse sample (n = 3332) drawn from the National Health and Nutrition Examination Survey (NHANES).

Studies have indicated that individuals with depression or MASLD exhibit significantly higher levels of android fat compared to those without these health issues. Even after controlling for confounding factors, MASLD maintained significant correlations with both depression and body fat distribution (android fat and gynoid fat). Notably, sex moderated the relationship between MASLD, depression, and body fat distribution. Among the potential mediators of the effect of MASLD on depression, android fat emerged as a significant mediator, accounting for 16.6 % of the variance and yielding statistically significant results (p < 0.05). This mediating effect was particularly pronounced in female subjects, with a mediating proportion of 17.83 %, which was also statistically significant (p < 0.05). However, it was not observed in males.

This study reveals an important association between MASLD and depression, and android fat distribution is a potential mediator in this relationship, with a particularly pronounced effect on the female population.

Background: Steatotic liver disease (SLD) represents a multisystem disease and is a common complication of childhood obesity. We studied fat content at the abdominal level (liver, subcutaneous, and visceral) and the response to childhood obesity management. Methods: In this retrospective longitudinal study, 8-18-year-olds with a body mass index (BMI) z-score above 1.28 (corresponding to a BMI above the 90th percentile), as a proxy for obesity, were offered person-centered, family-oriented obesity management in a hospital setting and in a magnetic resonance (MR) scan. Liver fat content (LFC) was assessed by MR spectroscopy, whereas subcutaneous adipose tissue and visceral adipose tissue (VAT) were assessed by MR imaging. We conducted nonparametric tests to evaluate baseline-to-follow-up changes and comparisons between participants with and without an MR assessment. Additionally, a logistic regression model examined the association between changes in LFC and BMI z-score. Results: The study group comprised 1002 children and adolescents (52% females) with an MR assessment at baseline. The median age was 13.0 years, the median BMI was 28.4, and the BMI z-score was 2.90. At baseline, 378 (38%) exhibited SLD defined by an LFC above 1.5%. Among the 322 with a follow-up MR scan, 76% of the patients with SLD reduced their LFC. BMI z-score and VAT (both p < 0.001) were reduced during intervention. Conclusions: SLD is highly prevalent (38%) in children and adolescents with obesity. A chronic care obesity management model reduced the fat content in the liver, the visceral fat, and the degree of obesity.

It has been suggested that the dietary approaches to stop hypertension (DASH) diet as a plant-based dietary pattern can be useful in improvement of risk factors of metabolic syndrome (MetS). We designed a study to evaluate the effect of the DASH diet on insulin resistance and lipid accumulation product (LAP) in subjects with MetS. 60 subjects with MetS were assigned into two groups including the intervention group and the control group. The intervention group received DASH diet and the control group received a common healthy diet for 12 weeks. We measured fasting plasma glucose (FPG), triglyceride and glucose (TyG) index, metabolic score for insulin resistance (METS-IR) and LAP before and after intervention. We utilized SPSS software version 24 and an intention-to-treat method for data analysis. A total of 59 subjects completed the trial. After intervention a significant difference was observed between groups in FPG (P < 0.001), TyG index (P < 0.001) and LAP (P = 0.01). However, there was no significant difference between groups in values of METS-IR (P = 0.27). There was a significant reduction in the intervention group compared to the control group in FPG (-7.86 ± 10.08 vs. 0.97 ± 15.51; P = 0.01), TyG index (-0.20 ± 0.14 vs. 0.02 ± 0.11; P < 0.001), METS-IR (-2.50 ± 1.99 vs. -0.53 ± 2.21; P = 0.001) and LAP (-20.06 ± 12.02 vs. -5.87 ± 15.17; P < 0.001). Adherence to DASH diet can reduce some cardiovascular risk factors in subjects with MetS. Further clinical trials are required to reach a firm conclusion.

The prevalence of obesity is increasing rapidly worldwide, particularly in Asia. Visceral obesity, characterized by intra-abdominal fat accumulation, is a precursor to metabolic syndrome, encompassing hyperglycemia, dyslipidemia, and hypertension, which elevate the risk of atherosclerosis and cardiovascular disease. A visceral fat area (VFA) of ≥100 cm2 is a recognized threshold for diagnosing obesity-related metabolic syndrome. This study aimed to identify independent risk factors for VFA ≥100 cm2 in middle-aged Chinese individuals from the general population. We analyzed data from 148 participants (mean age: 49.3 ± 10.8 years; 54% male) who underwent health check-ups. VFA and subcutaneous fat area were assessed using computed tomography, while arterial stiffness and fatty liver were evaluated via brachial-ankle pulse wave velocity (baPWV) and abdominal ultrasonography, respectively. Between-group comparisons (VFA ≥100 cm2 vs. VFA <100 cm2) were conducted using unpaired t-tests and Mann-Whitney U tests, and logistic regression analysis identified risk factors. Multivariable regression analysis revealed that baPWV ≥1,400 cm/s (odds ratio [OR] = 5.71, p = 0.011), waist circumference ≥85 cm (OR = 5.46, p = 0.026), fasting blood glucose (FBG) ≥100 mg/dL (OR = 5.69, p = 0.030), male sex (OR = 12.79, p = 0.029), and fatty liver (OR = 3.99, p = 0.042) were significant independent risk factors for VFA ≥100 cm2. Among these, baPWV ≥1,400 cm/s was the most significant, showing a positive correlation with VFA (r = 0.365, p < 0.001). Visceral obesity (VFA ≥100 cm2) is a critical target for interventions addressing metabolic syndrome, metabolic dysfunction-associated fatty liver disease (MAFLD), and cardiovascular disease, particularly in males.

Lifestyle-induced weight reduction remains crucial for managing type 2 diabetes and steatotic liver disease, but its effectiveness varies. We postulated that the G allele in the rs738409 single nucleotide polymorphism within patatin-like phospholipase domain-containing protein 3 (PNPLA3), which associates with metabolic dysfunction-associated steatotic liver disease, also modulates diet-related metabolic effects.

Participants with type 2 diabetes were randomized to 8-week hypocaloric diets (energy intake: -1,256 kJ/d of, <30 kcal% fat): high in cereal fiber and coffee excluding red meat (HF-RM + C; n = 16), or low in cereal fiber, devoid of coffee, but high in red meat (LF + RM-C; n = 15). Whole-body insulin sensitivity (M value) was assessed using [2H]glucose and hyperinsulinemic-normoglycemic clamps, hepatic lipid content (HCL) and body fat volumes by magnetic resonance spectroscopy/imaging before and after intervention.

Despite comparable weight loss, HCL decreased more in non-carriers (-65 %) than in G-allele carriers (-36 %) upon HF-RM + C diet (both p < 0.05 vs baseline and between groups), but only among non-carriers (-46 %, p < 0.05 vs baseline) upon LF + RM-C. Upon HF-RM + C diet, increase in insulin sensitivity was not different between carriers (+27 % p = 0.051 from baseline) and non-carriers (+21 %, p = 0.032 from baseline), p > 0.05 for between-group comparison. Upon LF + RM-C diet, both groups equally improved their whole-body insulin sensitivity (+42 % for non-carriers and +37 % for carriers, p < 0.05 vs baseline). Upon HF-RM + C diet, non-carriers decreased circulating interleukin-18 from baseline by -31 %, whereas, upon LF + RM-C diet, non-carriers decreased circulating anti-inflammatory interleukin-1 receptor antagonist levels by 14 % (both p < 0.05 vs baseline).

Humans with the PNPLA3 G-allele show modified dietary-induced effects on steatotic liver disease in type 2 diabetes despite body weight reduction. Registration at Clinicaltrials.gov, Identifier number: NCT01409330.

Background: The most common cause of chronic liver disease is now known to be non-alcoholic fatty liver disease (NAFLD), recently redefined as metabolic-associated fatty liver disease (MAFLD). This review aims to synthesize current evidence on the pathophysiology and clinical implications of nephrological, pulmonary, and dermatological manifestations among NAFLD/MAFLD patients. In order to find safe and efficient treatments, NAFLD/MAFLD has emerged as a primary concern for hepatologists worldwide. Methods: We conducted a comprehensive review of the literature from major databases, focusing on studies that evaluated the extrahepatic manifestations of NAFLD/MAFLD. Emphasis was placed on identifying pathophysiological mechanisms and assessing their clinical impact on renal, pulmonary, and dermatological systems. Results: Recent developments in the management of chronic viral hepatitis have lowered the mortality rate associated with chronic liver disease. However, the prevalence of NAFLD/MAFLD continues to rise, making chronic liver disease a significant health concern for the future. An increasing percentage of patients on liver transplant waiting lists now have cirrhosis and hepatocellular carcinoma due to non-alcoholic liver disease. Furthermore, the incidence and prevalence of chronic kidney disease have surged, linking NAFLD/MAFLD to higher morbidity, mortality, and healthcare costs. Conclusions: NAFLD/MAFLD is underdiagnosed and underappreciated, yet its incidence is rapidly increasing, raising concerns about a potential global epidemic. Given its multisystemic impact-extending to renal, pulmonary, and dermatological complications-it is crucial to develop interdisciplinary strategies for early detection and effective management of the disease.

Both Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and sarcopenia are associated with numerous chronic diseases, and the link between the two broad-spectrum phenotypes has been extensively researched. We focused on the relationship between the hepatic steatosis index (HSI) and hand grip strength (HGS). The Korean National Health and Nutrition Examination Surveys (2014-2019) were utilized to identify the association between estimated MASLD (eMASLD) and muscle strength. HSI determined eMASLD status, and HGS evaluated muscle strength. The HSI demonstrated a positive correlation with HGS. The alanine transaminase (ALT)/aspartate aminotransferase (AST) ratio and diabetes among the five components of HSI exhibited significant relationships with HGS in men and women. The robust linearity between HSI and HGS was observed in multivariate models and stratified analyses, particularly in older non-diabetic men with a higher body mass index (BMI) and young women without diabetes. However, younger men and older women exhibited nonlinear associations influenced by the ALT/AST ratio, BMI, and diabetes. After adjusting HGS with BMI, a significant negative association between HSI and muscle strength was observed, particularly in women. The disruption in linearity was influenced by the ALT/AST ratio, particularly in men with diabetes. Our findings highlight the complex interplay between HSI and HGS. The relationship between the two broad-range phenotypes was observed, and liver profiles influenced the linearity.

Studies on predictive markers of insulin resistance (IR) and elevated liver transaminases in children and adolescents are limited. We evaluated the predictive capabilities of the single-point insulin sensitivity estimator (SPISE) index, metabolic score for insulin resistance (METS-IR), homeostasis model assessment of insulin resistance (HOMA-IR), the triglyceride (TG)/ high-density lipoprotein cholesterol (HDL-C) ratio, and the triglyceride-glucose index (TyG) for IR and alanine aminotransferase (ALT) elevation in this population.

Data from 1,593 participants aged 10 to 18 years were analyzed using a nationwide survey. Logistic regression analysis was performed with IR and ALT elevation as dependent variables. Receiver operating characteristic (ROC) curves were generated to assess predictive capability. Proportions of IR and ALT elevation were compared after dividing participants based on parameter cutoff points.

All parameters were significantly associated with IR and ALT elevation, even after adjusting for age and sex, and predicted IR and ALT elevation in ROC curves (all P<0.001). The areas under the ROC curve of SPISE and METS-IR were higher than those of TyG and TG/HDL-C for predicting IR and were higher than those of HOMA-IR, TyG, and TG/HDL-C for predicting ALT elevation. The proportions of individuals with IR and ALT elevation were higher among those with METS-IR, TyG, and TG/ HDL-C values higher than the cutoff points, whereas they were lower among those with SPISE higher than the cutoff point.

SPISE and METS-IR are superior to TG/HDL-C and TyG in predicting IR and ALT elevation. Thus, this study identified valuable predictive markers for young individuals.

To compare outcomes of MASLD in obese and nonobese populations.

MASLD is emerging as one of the leading causes of liver failure and liver-related morbidity and mortality, with an increasing prevalence in the nonobese or lean population. The purpose of this study is to compare hepatic and oncological outcomes between MASLD patients with lean BMI and nonlean BMI.

The National Inpatient Sample (NIS) was queried from 2016 to 2020 for adult hospitalizations with MASLD. Exclusion criteria included concurrent diagnoses of viral hepatitis, alcoholic hepatitis, primary biliary cholangitis, hereditary hemochromatosis, autoimmune hepatitis, or Wilson disease. Outcomes of MASLD and its complications were compared between the lean and nonlean subgroups.

Patients with lean BMI had higher mortality rates (odds ratio: 2.10, P<0.001). The lean cohort also had higher odds of cirrhosis, portal hypertension, SBP, and ascites. The lean subgroup had higher odds of gastrointestinal malignancies including esophageal cancer, gastric cancer, pancreatic cancer, and colorectal cancer.

Hospitalized lean MASLD patients had higher odds of mortality, ​​hepatic morbidities, and gastrointestinal malignancies. These results challenge the use of BMI as a predictor of morbidity and mortality for MASLD patients. Future studies should focus on therapeutic options for MASLD and compare their efficacies between lean and nonlean populations.

In the United States, two out of every five adults have obesity. The obesity epidemic is a significant public health concern and a major risk factor for atherosclerotic cardiovascular disease (ASCVD), contributing to its development through a complex interplay of social, biologic and behavioral mechanisms. It exacerbates traditional cardiovascular risk factors such as dyslipidemia, hypertension, and type 2 diabetes, while visceral and epicardial fat deposition promotes inflammation and insulin resistance, thereby accelerating atherosclerosis. Beyond traditional pathophysiologic pathways, social determinants of health (SDoH) significantly contribute to obesity-related disparities, particularly among racial and ethnic minorities. SDoH factors such as socioeconomic status, access to health care, and limited availability of nutritious food and safe spaces for physical activity not only increase obesity prevalence but also exacerbate its psychological toll, including stress and anxiety, which further elevate cardiovascular risk. Environmental factors, such as limited green spaces and air pollution, further promote obesogenic behaviors and worsen cardiovascular outcomes. In this review, we explore the association between obesity and ASCVD and key mediating pathways including the role of SDoH and environmental risk factors. We also discuss potential strategies-including patient education, community engagement to address SDoH, and establishment of dedicated cardiometabolic and cardiovascular prevention clinics-to mitigate the population burden of obesity and improve downstream cardiovascular outcomes.

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) is highly prevalent among people living with severe obesity (body mass index [BMI] ≥ 35 kg/m2). However, it remains unknown how sex and adipose tissue distribution are related to MAFLD onset and progression into metabolic dysfunction-associated steatohepatitis (MASH) or advanced stages of fibrosis. Methodology: We retrospectively studied patients with severe obesity who were eligible for bariatric surgery. Demographic characteristics, biomarkers, and cardiometabolic comorbidities were reported. Anthropometric indices such as BMI, waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), neck circumference (NC), lipid accumulation product (LAP), visceral adiposity index (VAI), body adiposity index (BAI), abdominal volume index (AVI), and body roundness index (BRI) were measured or calculated. MAFLD, MASH, and stages of fibrosis (F1-F4) were established from perioperative liver biopsies. Standardized univariate and multivariate logistic regression analyses were used to examine the association between demographic variables, anthropometric indices, cardiometabolic conditions, and the risk of MASH or severe fibrosis (F2-F4). Results: A total of 2091 participants with severe obesity were included in the analyses; BMI 47.9 ± 7.3 kg/m2, age 46.2 ± 11.2 years, and 68.4% females. Overall, MAFLD prevalence was 79.5%, with 44.5% having MASH and 24.4% having severe fibrosis (Stage 2 or higher). No anthropometric indices of adiposity were associated with MASH or fibrosis severity. In this population, female sex was a risk factor for severe fibrosis (OR: 1.27, 95% CI 1.01-1.59, p < 0.05). Conclusions: MAFLD and MASH are highly prevalent in individuals living with severe obesity, but no anthropometric indices or laboratory tests are good predictors of MAFLD or MASH in this population. When MAFLD is diagnosed, our results suggest that females with severe obesity might be at higher risk of advanced stages of fibrosis.

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that can trigger the metabolic syndrome. Early prevention and treatment of NAFLD is still a huge challenge for patients and clinicians. The aim of this study was to develop and validate machine learning (ML)-based predictive models. The model with optimal performance would be developed as a set of simple arithmetic tools for predicting the risk of NAFLD individually.

Statistical analyses were performed in 2428 individuals extracted from the National Health and Nutrition Examination Survey (NHANES, cycle 2017-2020.3) database. Feature variables were selected by the least absolute shrinkage and selection operator (LASSO) regression. Seven ML algorithms, including logistic regression (LR), decision tree (DT), random forest (RF), extreme gradient boosting (XGB), K-nearest neighbor (KNN), light gradient boosting machine (LightGBM), and multilayer perceptron (MLP), were used to construct models based on the feature variables and evaluate their performance. The model with the best performance was transformed into a diagnostic predictive nomogram (DPN). The DPN was developed into an online calculator and an Excel algorithm tool. Receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and subgroup analyses were used to compare and assess the predictive abilities of the DPN and six existing NAFLD predictive models, including the ZJU index, the hepatic steatosis index (HSI), the triglyceride-glucose index (TyG), the Framingham steatosis index (FSI), the fatty liver index (FLI), and the visceral adiposity index (VAI).

Among the 2428 participants, the prevalence of NAFLD was 47.45%. LASSO regression identified eight variables from 39 variables, including body mass index (BMI), waist circumference (WC), alanine aminotransferase (ALT), triglyceride (TG), diabetes, hypertension, uric acid (UA), and race. Among the models constructed by the seven algorithms mentioned above, the LR-based model performed the best, demonstrating outstanding performance in terms of area under the curve (AUC, 0.823), accuracy (0.754), precision (0.768), specificity (0.804), and positive predictive value (0.768). It was then transformed into the DPN, which was successfully developed as an online calculator and an Excel algorithm tool. The diagnostic accuracy (AUC 0.856, 95% confidence interval (CI) 0.839-0.874, and AUC 0.823, 95% CI 0.793-0.854, respectively) and net clinical benefit of DPN in the training and validation sets were superior to those of the ZJU, HSI, TyG, FSI, FLI, and VAI. The results were maintained in subgroup analyses.

The LR model based on ML was developed, exhibiting good performance. DPN can be used as an individualized tool for rapid detection of NAFLD.

Several studies have reported associations between metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of various cancers. However, studies focusing specifically on the association between MASLD and thyroid cancer are relatively limited, and the conclusions drawn, thus, far remain inconclusive. In response, we conducted a meta-analysis of relevant cohort studies to clarify the association between MASLD and the risk of thyroid cancer. We systematically searched the Web of Science, Embase, Cochrane Library, and PubMed databases for articles published before 24 September 2024. We utilized the R software (version 4.4.1) for the comprehensive execution of all statistical analyses. Our meta-analysis included eight cohort studies (six retrospective and two prospective), comprising 18 925 396 participants. The pooled results of the eight cohort studies indicate that MASLD is linked to an increased risk of thyroid cancer (HR = 1.46; 95% CI: 1.14-1.86; I ² = 69%; P  < 0.01). A random-effects model was employed due to moderate heterogeneity ( I ² > 50%). Subgroup analyses revealed that the association between MASLD and thyroid cancer risk was stronger in the Chinese population (HR = 2.24; 95% CI: 1.32-3.81; I ² = 51%) and among overweight individuals (HR = 1.29; 95% CI: 1.02-1.63; I ² = 90%). No significant differences were identified between male and female subgroups. This meta-analysis demonstrates that MASLD increases the risk of developing thyroid cancer.

Non-alcoholic fatty liver disease (NAFLD) is a widespread liver condition associated with diabetes, metabolic syndrome, and cardiovascular diseases, yet public awareness remains low. Early detection of risk factors is crucial, but liver biopsy, the diagnostic gold standard, is invasive and costly. Non-invasive anthropometric indices provide a safer alternative. This study examines these indices to identify the most reliable predictor of NAFLD in adults.

In the present cross-sectional study, we used the Fasa Cohort Data, conducted on about 10,000 people, of whom 1,047 were diagnosed with NAFLD. NAFLD diagnosis in this study was confirmed by physicians based on medical history and ultrasonographic evaluations, ensuring accurate and reliable identification of cases. General, anthropometric, and dietary assessments were performed using interviews, tools, and valid questionnaires. Biochemical evaluation was also done. Waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), Body mass index (BMI), a body shape index (ABSI), body roundness index (BRI), and visceral fat index (VAI) were also calculated using these measurements and formulas. This study used descriptive tests, binary logistic regression, and ROC curve analysis.

In both crude and adjusted models, significant associations were found between WHR, WHtR, BMI, and VAI with NAFLD. ROC analysis revealed that WHtR and BMI were the most accurate predictors of NAFLD in both genders (WHtR: men AUC = 0.750, women AUC = 0.702; BMI: men AUC = 0.754, women AUC = 0.701). BRI showed significant accuracy, but WHR (men: AUC = 0.727, women: AUC = 0.640) and VAI (men: AUC = 0.621, women: AUC = 0.622) were less effective. ABSI demonstrated poor predictive power (men: AUC = 0.530, women: AUC = 0.505) and is not recommended for NAFLD prediction.

Based on the findings, BMI and WHtR emerge as the most practical and accessible indicators for early screening of NAFLD in both men and women, while ABSI shows minor effectiveness in identifying the disease.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is increasing globally. Noninvasive methods, such as bioelectrical impedance analysis (BIA), which measures body composition, including visceral fat, are gaining interest in evaluating MASLD patients. Our study aimed to identify factors associated with significant liver fibrosis, compare noninvasive scores, and highlight the importance of visceral fat measurement using BIA.

MASLD patients seen in our out-patient department underwent comprehensive evaluations, including liver stiffness using transient elastography, body composition analysis using BIA, and metabolic measurements. Significant fibrosis was defined as a liver stiffness measurement of ≥8.2 kPa. Using multivariate analysis, we identified factors associated with significant liver fibrosis and compared four noninvasive scores with a novel diabetes-visceral fat 15 (DVF15) score.

We analyzed data from 609 MASLD patients seen between February 2022 and March 2023. The median age was 43 years (81% male). Among these, 78 (13%) had significant fibrosis. Patients with significant fibrosis had higher rates of type 2 diabetes (41% vs 21%, P < 0.001) and elevated levels of aspartate aminotransferase, alanine aminotransferase, hemoglobin A1c, Fibosis-4, aspartate-aminotransferase-to platelet-ratio index, and NAFLD fibrosis scores. They also exhibited higher visceral and subcutaneous fat. Binary logistic regression revealed type 2 diabetes and a visceral fat level of >15% as associated with significant liver fibrosis. Additionally, the DVF15 score, combining these factors, showed a modest area under the receiver operating characteristic curve of 0.664 (P < 0.001).

Our study identified diabetes and high visceral fat as factors associated with significant liver fibrosis in MASLD patients. We recommend that visceral fat measurement using BIA be an essential part of MASLD evaluation. The presence of either diabetes or a visceral fat level of >15% should prompt clinicians to check for significant fibrosis in MASLD patients. Further research is warranted to validate our findings and evaluate the utility of the DVF15 score in larger cohorts and diverse populations.

The associations between Chinese visceral adiposity index (CVAI) and non-alcoholic fatty liver disease (NAFLD) or hepatic fibrosis in Westerners are not obvious. Furthermore, metabolic dysfunction-associated steatotic liver disease (MASLD) is the new nomenclature of NAFLD, with significantly different diagnostic criteria. The present study aimed to investigate the relationships between CVAI and MASLD or hepatic fibrosis in an American population, as well as to assess the diagnostic value of CVAI for MASLD and fibrosis.

After excluding missing data on calculations of indices, diagnosis of MASLD, and covariates, 3242 participants were selected from the National Health and Nutrition Examination Survey 2017-2020. Multivariate logistic regression analyses and restricted cubic spline (RCS) were used to determine the associations between CVAI and MASLD or fibrosis. The diagnostic capacity was evaluated by the area under the receiver operating characteristic (AUROC) curve. Data were analyzed using R software (version 4.2.2). P<0.05 was considered statistically significant.

The risk of MASLD was increased at quartiles 2, 3, and 4 compared with quartile 1 of CVAI (OR [95% CI]=3.66 [2.44-5.63], 7.954 [5.31-12.23], and 14.84 [9.80-23.06], respectively), (P<0.001). The odds ratios (95% CI) of hepatic fibrosis risk were 1.23 [0.67, 2.30], 2.44 [1.39, 4.43], 7.46 [4.36, 13.30] for the quartiles 2, 3, and 4 compared to the lowest quartile (P<0.001). According to RCS, CVAI, MASLD, and fibrosis, all had positive relationships. CVAI had AUROCs of 0.759 and 0.771 for diagnosing MASLD and fibrosis, respectively.

The CVAI was positively related to the risk of MASLD or liver fibrosis and could be a novel biomarker for predicting MASLD and fibrosis in the American population.

Steatotic liver disease (SLD) and Hepatocellular Carcinoma (HCC) are characterised by a substantial rewiring of lipid fluxes caused by systemic metabolic unbalances and/or disrupted intracellular metabolic pathways. SLD is a direct consequence of the interaction between genetic predisposition and a chronic positive energy balance affecting whole-body energy homeostasis and the function of metabolically-competent organs. In this review, we discuss how the impairment of the cross-talk between peripheral organs and the liver stalls glucose and lipid metabolism, leading to unbalances in hepatic lipid fluxes that promote hepatic fat accumulation. We also describe how prolonged metabolic stress builds up toxic lipid species in the liver, and how lipotoxicity and metabolic disturbances drive disease progression by promoting a chronic activation of wound healing, leading to fibrosis and HCC. Last, we provide a critical overview of current state of the art (pre-clinical and clinical evidence) regarding mechanisms of action and therapeutic efficacy of candidate SLD treatment options, and their potential to interfere with SLD/HCC pathophysiology by diverting lipids away from the liver therefore improving metabolic health.

Given the known relationship between human immunodeficiency virus (HIV), antiretroviral therapies, and excess visceral adipose tissue (VAT), this review sought to characterize risk of negative health outcomes associated with excess VAT and increased waist circumference (WC) in people with HIV (PWH).

Comprehensive targeted literature searches were conducted in Medline/Embase (27 June 2022), identifying peer-reviewed articles and conference abstracts reporting on cohorts of PWH. Screening was guided by PECOS (Population, Exposure, Comparator, Outcomes, Study design) criteria. From the included studies, outcomes of interest including mortality and morbidity risk by VAT area and WC were extracted, overall, and by sex, race/ethnicity, and duration of HIV. Relationships between outcome and exposure variables were summarized.

Thirty-five studies were included (sample size range: 31-1748 PWH). Twenty-five studies characterized the relationship between increased WC and negative health outcomes-cardiovascular disease (CVD), arteriosclerosis, hypertension, diabetes, hepatic fat and fibrosis, and cognitive impairment-among PWH. Fifteen studies reported on increased VAT and negative health outcomes: all-cause mortality, CVD, atherosclerosis, hepatic fat, and fibrosis. Importantly, there was a 2.1-times higher odds of 5-year all-cause mortality among PWH with the highest amount of VAT in the only study identified reporting on mortality. Among the studies characterizing the relationship between morbidity and VAT, for example, 1 found that, for each 10-cm2 increase in VAT, the risk of prevalent CVD increased by 1.05 (95% CI: 1.0-1.1) times.

WC may be a useful and cost-effective surrogate for visceral adiposity, which is an important marker of morbidity and mortality among PWH.

Metabolic disturbances are major contributors to the onset and progression of non-alcoholic fatty liver disease (NAFLD), which includes a histological spectrum ranging from single steatosis (SS) to non-alcoholic steatohepatitis (NASH). This study aimed to identify serum metabolites and lipids enriched in different histological stages of NAFLD and to explore metabolites/lipids as non-invasive biomarkers in risk prediction of NAFLD and NASH in obese Chinese.

Serum samples and liver biopsies were obtained from 250 NAFLD subjects. Untargeted metabolomic and lipidomic profiling were performed using Liquid Chromatography-Mass Spectrometry. Significantly altered metabolites and lipids were identified by MaAsLin2. Pathway enrichment was conducted with MetaboAnalyst and LIPEA. WGCNA was implemented to construct the co-expression network. Logistic regression models were developed to classify different histological stages of NAFLD.

A total of 263 metabolites and 550 lipid species were detected in serum samples. Differential analysis and pathway enrichment analysis revealed the progressive patterns in metabolic mechanisms during the transition from normal liver to SS and to NASH, including N-palmitoyltaurine, tridecylic acid, and branched-chain amino acid signaling pathways. The co-expression network showed a distinct correlation between different triglyceride and phosphatidylcholine species with disease severity. Multiple models classifying NAFLD versus normal liver and NASH versus SS identified important metabolic features associated with significant improvement in disease prediction compared to conventional clinical parameters.

Different histological stages of NAFLD are enriched with distinct sets of metabolites, lipids, and metabolic pathways. Integrated algorithms highlight the important metabolic and lipidomic features for diagnosis and staging of NAFLD in obese individuals.

The adipose tissue of mammals represents an important energy-storing and endocrine organ, and its dysfunction is relevant to the onset of several health problems, including non-alcoholic fatty liver disease (NAFLD). However, whether treatments targeting adipose dysfunction could alleviate NAFLD has not been well-studied. Adrenomedullin 2 (ADM2), belonging to the CGRP superfamily, is a protective peptide that has been shown to inhibit adipose dysfunction. To investigate the adipose tissue-specific effects of ADM2 on NAFLD, adipose-specific ADM2-overexpressing transgenic (aADM2-tg) mice were developed. When fed a high-fat diet, aADM2-tg mice displayed decreased hepatic triglyceride accumulation compared to wild-type mice, which was attributable to the inhibition of hepatic de novo lipogenesis. Results from lipidomics studies showed that ADM2 decreased ceramide levels in adipocytes through the upregulation of ACER2, which catalyzes ceramide catabolism. Mechanically, activation of adipocyte HIF2α was required for ADM2 to promote ACER2-dependent adipose ceramide catabolism as well as to decrease hepatic lipid accumulation. This study highlights the role of ADM2 and adipose-derived ceramide in NAFLD and suggests that its therapeutic targeting could alleviate disease symptoms.

To investigate the relationship of serum uric acid (Uacid) and derived parameters as predictors of insulin resistance (IR) and elevated liver transaminases in children and adolescents METHODS: Data of 1648 participants aged 10-18 years was analyzed using nationwide survey. Logistic regression analysis was performed with IR and elevated liver transaminases as dependent variables, and odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles 2 and 3 of each parameter in comparison to tertile 1, which served as the reference. Receiver operating characteristic (ROC) curves were generated to assess predictability of the parameters for IR and elevated liver transaminases.

Hyperuricemia, IR, and elevated liver transaminases were significantly associated with each other. All Uacid and derived markers showed continuous increase in ORs and 95% CIs for IR and elevated liver transaminases across the tertiles of several biochemical and metabolic variables of interest (all p < 0.001), and were also significantly predictive in ROC curve. Overall, Uacid combined with obesity indices showed higher ORs and area under the curve (AUC) compared to Uacid alone. Uacid-body mass index (BMI) standard deviation score presented the largest AUC for IR. For elevated liver transaminases, Uacid-BMI and Uacid-waist-to-height ratio showed the largest AUC.

Uacid combined with obesity indices are robust markers for prediction of IR and elevated liver transaminases in children and adolescents. Uacid and derived markers have potential as simple markers which do not require fasting for screening of IR and elevated liver transaminases in children and adolescents.

Nonalcoholic fatty liver disease (NAFLD) is a global health challenge, with a rising rate in line with other metabolic diseases. We aimed to assess the global prevalence of NAFLD in adult and pediatric populations.

PubMed, Scopus and Web of Science databases were systematically searched up to May 2023. Heterogeneity was assessed using Cochran's Q test and I2 statistics, and random-effects model was used for meta-analysis. Analyses were performed using STATA version 18.

A total of 479 studies with 78,001,755 participants from 38 countries were finally included. The global prevalence of NAFLD was estimated to be 30.2% (95% CI: 28.7-31.7%). Regionally, the prevalence of NAFLD was as follows: Asia 30.9% (95% CI: 29.2-32.6%), Australia 16.1% (95% CI: 9.0-24.8%), Europe 30.2% (95% CI: 25.6-35.0%), North America 29% (95% CI: 25.8-32.3%), and South America 34% (95% CI: 16.9-53.5%). Countries with a higher human development index (HDI) had significantly lower prevalence of NAFLD (coefficient = -0.523, p = 0.005). Globally, the prevalence of NAFLD in men and women was 36.6% (95% CI: 34.7-38.4%) and 25.5% (95% CI: 23.9-27.1%), respectively. The prevalence of NAFLD in adults, adults with obesity, children, and children with obesity was 30.2% (95% CI: 28.8-31.7%), 57.5% (95% CI: 43.6-70.9%), 14.3% (95% CI: 10.3-18.8%), and 38.0% (95% CI: 31.5-44.7%), respectively.

The prevalence of NAFLD is remarkably high, particularly in countries with lower HDI. This substantial prevalence in both adults and children underscores the need for disease management protocols to reduce the burden.

Heterogenous deposition and homeostasis roles of physiologic and ectopic adipose tissues underscore the impact of fat compartmentalization on cardiometabolic risk. We aimed to characterize the distribution of abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), epicardial adipose tissue (EAT), and liver fat on magnetic resonance imaging (MRI), and evaluate their associations with anthropometric indices and adverse cardiac remodeling.

In this cross-sectional observational study, 149 Asian adults (57.0 ± 12.8 years; 65% males) with at least one cardiometabolic risk factor underwent multiparametric fat and cardiovascular MRI. Anthropometric indices included body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and bioimpedance body fat mass (BFM). Associations between fat depots and anthropometric measures as well as cardiac remodeling features were examined as a single cohort and stratified by type 2 diabetes mellitus (T2DM) status.

VAT and SAT had opposing associations with liver fat and EAT. Therefore the VAT/SAT ratio was explored as an integrated marker of visceral adiposity. VAT/SAT was positively associated with EAT (β=0.35, P<0.001) and liver fat (β=0.32, P=0.003) independent of confounders. Of the anthropometric measurements assessed, only WHR was independently associated with VAT/SAT (β=0.17, P=0.021). Individuals with T2DM had higher VAT and lower SAT compared to those without T2DM, translating to a significantly higher VAT/SAT ratio. EAT volume was independently associated with adverse features of cardiac remodeling: increased left ventricular (LV) mass (β=0.24, P=0.005), larger myocyte volume (β=0.26, P=0.001), increased myocardial fibrosis (β=0.19, P=0.023), higher concentricity (β=0.18, P=0.035), and elevated wall stress (β=-0.18, P=0.023).

Multiparametric MRI revealed abdominal VAT and SAT have differential associations with anthropometric indices and ectopic fats in a single cohort of Asians at risk of cardiometabolic disease. People with T2DM have expanded VAT and diminished SAT, endorsing the VAT/SAT ratio beyond usual anthropometric measurements as a marker for multiorgan visceral fat composition. Among the fat depots examined, EAT is uniquely associated with adverse cardiac remodeling, suggesting its distinctive cardiometabolic properties and implications.

Nutrient metabolism is regulated by several factors. Social determinants of health with or without genetics are the primary regulator of metabolism, and an unhealthy lifestyle affects all modulators and mediators, leading to the adaptation and finally to the exhaustion of cellular functions. Hepatic steatosis is defined by presence of fat in more than 5% of hepatocytes. In hepatocytes, fat is stored as triglycerides in lipid droplet. Hepatic steatosis results from a combination of multiple intracellular processes. In a healthy individual nutrient metabolism is regulated at several steps. It ranges from the selection of nutrients in a grocery store to the last step of consumption of ATP as an energy or as a building block of a cell as structural component. Several hormones, peptides, and genes have been described that participate in nutrient metabolism. Several enzymes participate in each nutrient metabolism as described above from ingestion to generation of ATP. As of now several publications have revealed very intricate regulation of nutrient metabolism, where most of the regulatory factors are tied to each other bidirectionally, making it difficult to comprehend chronological sequence of events. Insulin hormone is the primary regulator of all nutrients' metabolism both in prandial and fasting states. Insulin exerts its effects directly and indirectly on enzymes involved in the three main cellular function processes; metabolic, inflammation and repair, and cell growth and regeneration. Final regulators that control the enzymatic functions through stimulation or suppression of a cell are nuclear receptors in especially farnesoid X receptor and peroxisome proliferator-activated receptor/RXR ligands, adiponectin, leptin, and adiponutrin. Insulin hormone has direct effect on these final modulators. Whereas blood glucose level, serum lipids, incretin hormones, bile acids in conjunction with microbiota are intermediary modulators which are controlled by lifestyle. The purpose of this review is to overview the key players in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) that help us understand the disease natural course, risk stratification, role of lifestyle and pharmacotherapy in each individual patient with MASLD to achieve personalized care and target the practice of precision medicine. PubMed and Google Scholar databases were used to identify publication related to metabolism of carbohydrate and fat in states of health and disease states; MASLD, cardiovascular disease and cancer. More than 1000 publications including original research and review papers were reviewed.

The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease (K-NAFLD) score was recently developed with the intent to operationally define nonalcoholic fatty liver disease (NAFLD). However, there remained an external validation that confirmed its diagnostic performance, especially in patients with alcohol consumption or hepatitis virus infection.

Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®. Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score, fatty liver index (FLI), and hepatic steatosis index (HSI).

K-NAFLD-moderate [adjusted odds ratio (aOR) = 2.53, 95% confidence interval (CI): 1.13-5.65] and K-NAFLD-high (aOR = 4.14, 95% CI: 1.69-10.13) groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics, and FLI-moderate and FLI-high groups revealed aORs of 2.05 (95% CI: 1.22-3.43) and 1.51 (95% CI: 0.78-2.90), respectively. In addition, the HSI was less predictive for Fibroscan®-defined fatty liver. Both K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection, and the adjusted area under curve values were comparable between K-NAFLD and FLI.

Externally validation of the K-NAFLD and FLI showed that these scores may be a useful, noninvasive, and non-imaging modality for the identification of fatty liver. In addition, these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.

The UK Biobank (UKB) imaging project is a crucial resource for biomedical research, but is limited to 100,000 participants due to cost and accessibility barriers. Here we used genetic data to predict heritable imaging-derived phenotypes (IDPs) for a larger cohort. We developed and evaluated 4,375 IDP genetic scores (IGS) derived from UKB brain and body images. When applied to UKB participants who were not imaged, IGS revealed links to numerous phenotypes and stratified participants at increased risk for both brain and somatic diseases. For example, IGS identified individuals at higher risk for Alzheimer's disease and multiple sclerosis, offering additional insights beyond traditional polygenic risk scores of these diseases. When applied to independent external cohorts, IGS also stratified those at high disease risk in the All of Us Research Program and the Alzheimer's Disease Neuroimaging Initiative study. Our results demonstrate that, while the UKB imaging cohort is largely healthy and may not be the most enriched for disease risk management, it holds immense potential for stratifying the risk of various brain and body diseases in broader external genetic cohorts.

Historical maps of racialized evaluation of mortgage lending risk (i.e., redlined neighborhoods) have been linked to adverse health outcomes. Little research has examined whether living in historically redlined neighborhoods is associated with obesity, differentially by race or gender.

This is a cross-sectional study to examine whether living in historically redlined neighborhoods is associated with BMI and waist circumference among Black and White adults in 1985-1986. Participants' addresses were linked to the 1930s Home Owners' Loan Corporation maps that evaluated mortgage lending risk across neighborhoods. The authors used multilevel linear regression models clustered on Census tract, adjusted for confounders to estimate main effects, and stratified, and interaction models by (1) race, (2) gender, and (3) race by gender with redlining differentially for Black versus White adults and men versus women. To better understand strata differences, they compared Census tract-level median household income across race and gender groups within Home Owners' Loan Corporation grade.

Black adults (n=2,103) were more likely than White adults (n=1,767) to live in historically rated hazardous areas and to have higher BMI and waist circumference. Redlining and race and redlining and gender interactions for BMI and waist circumference were statistically significant (p<0.10). However, in stratified analyses, the only statistically significant associations were among White participants. White participants living in historically rated hazardous areas had lower BMI (β = - 0.63 [95% CI= -1.11, -0.15]) and lower waist circumference (β = - 1.50 [95% CI= -2.62, -0.38]) than those living in declining areas. Within each Home Owners' Loan Corporation grade, residents in White participants' neighborhoods had higher incomes than those living in Black participants' neighborhoods (p<0.0001). The difference was largest within historically redlined areas. Covariate associations differed for men, women, Black, and White adults, explaining the difference between the interaction and the stratified models. Race by redlining interaction did not vary by gender.

White adults may have benefitted from historical redlining, which may have reinforced neighborhood processes that generated racial inequality in BMI and waist circumference 50 years later.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has attracted increasing attention from the scientific community because of its severe but silent progression and the lack of specific treatment. Glucolipotoxicity triggers endoplasmic reticulum (ER) stress with decreased beta-oxidation and enhanced lipogenesis, promoting the onset of MASLD, whereas regular physical exercise can prevent MASLD by preserving ER and mitochondrial function. Thus, the hypothesis of this study was that high-intensity interval training (HIIT) could prevent the development of MASLD in high-fat (HF)-fed C57BL/6J mice by maintaining insulin sensitivity, preventing ER stress, and promoting beta-oxidation. Forty male C57BL/6J mice (3 months old) comprised 4 experimental groups: the control (C) diet group, the C diet + HIIT (C-HIIT) group, the HF diet group, and the HF diet + HIIT (HF-HIIT) group. HIIT sessions lasted 12 minutes and were performed 3 times weekly by trained mice. The diet and exercise protocols lasted for 10 weeks. The HIIT protocol prevented weight gain and maintained insulin sensitivity in the HF-HIIT group. A chronic HF diet increased ER stress-related gene and protein expression, but HIIT helped to maintain ER homeostasis, preserve mitochondrial ultrastructure, and maximize beta-oxidation. The increased sirtuin-1/peroxisome proliferator-activated receptor-gamma coactivator 1-alpha expression implies that HIIT enhanced mitochondrial biogenesis and yielded adequate mitochondrial dynamics. High hepatic fibronectin type III domain containing 5/irisin agreed with the antilipogenic and anti-inflammatory effects observed in the HF-HIIT group, reinforcing the antisteatotic effects of HIIT. Thus, we confirmed that practicing HIIT 3 times per week maintained insulin sensitivity, prevented ER stress, and enhanced hepatic beta-oxidation, impeding MASLD development in this mouse model even when consuming high energy intake from saturated fatty acids.

Studies on the association between vegetarian diets and nonalcoholic fatty liver disease (NAFLD) are limited and have inconsistent results. This study aims to explore the association between vegetarian diets and NAFLD and compare the stage of fibrosis between vegetarians and nonvegetarians in a US representative sample.

Cross-sectional data from 23,130 participants aged ≥20 years were obtained from the National Health and Nutrition Examination Survey, 2005-2018. Vegetarian status was classified based on two 24-h dietary recalls. We examined the association between vegetarian diets and the risk of NAFLD using the propensity score weighting method.

Vegetarian diets were significantly associated with decreases in hepatic steatosis index (HSI), US fatty liver index and nonalcoholic fatty liver disease fibrosis score with mean differences of -2.70 (95% confidence interval [CI]: -3.69, -1.70), -3.03 (95% CI: -7.15, -0.91) and -0.12 (95% CI: -0.26, -0.01), respectively. While modelling the risk of NAFLD, we estimated that vegetarians were 53% less likely to have NAFLD assessed by HSI (odds ratios [OR]: 0.47; 95% CI: 0.34, 0.65). The effect of vegetarian diets was higher among individuals with lower waist circumferences (OR: 0.20) than among those with higher waist circumferences (OR: 0.53,p interaction ${p}_{\text{interaction}}\,$ = 0.004). However, the association was largely attenuated after adjusting for body mass index and diabetes status. No significant association was identified between vegetarian diets and advanced fibrosis.

Vegetarian diets were associated with a lower prevalence of NAFLD among US adults, and the association appeared to be stronger in people with lower waist circumferences. Further studies are warranted to replicate our findings.

Previous studies have shown that a reduced plasma concentration of the amino acid glycine (Gly) is associated with intra-abdominal obesity, but the mechanism remains unclear.

This study aimed to investigate whether lower plasma Gly concentrations in older adults are independently associated with (visceral) adiposity, age, sex, presence of chronic disease, and glucose intolerance, and whether they are caused by a reduced Gly whole-body production (WBP) and/or increased Gly disposal capacity.

We studied 102 older adults (47 males/55 females, 68.5 ± standard deviation 6.4 y) without comorbidities and 125 older adults with chronic obstructive pulmonary disease (COPD) (58 males/67 females, 69.7 ± 8.6 y). We assessed body composition and visceral adipose tissue (VAT) by dual-energy x-ray absorptiometry and muscle function by dynamometry. We measured postabsorptive plasma amino acid profile and glucose, followed by pulse administration of stable isotope-labeled Gly ([2,2-2H2]), and blood sampling was performed to measure the WBP of Gly. Results are expressed as means and 95% confidence intervals (CIs).

We found a lower plasma Gly concentration in healthy males and males with COPD than in females (Healthy: 211; 95% CI: 193,230 compared with 248; 95% CI: 225,271; COPD: 200; 95% CI: 186,215 compared with 262: 95% CI: 241, 283; P < 0.0001, respectively), with no difference between healthy and COPD groups. A negative relationship was found between unadjusted plasma Gly and VAT mass (R2: 0.16; slope: -1.7; 95% CI: -2.4, -1.2; P < 0.0021), but not with total body fat or fasting glucose. The strong association between lower plasma Gly and increased VAT mass in older adults was independent of age, sex, body weight, lean mass or body mass index, and the presence of COPD. Inclusion of these covariates increased the R2 to 0.783. We found no relation between the VAT and WBP of Gly (P = 0.35) or Gly clearance (P = 0.187) when lean mass was considered.

Reduced plasma Gly in older adults can be considered a marker of visceral adiposity, independent of sex, age, body composition, presence of chronic disease, and whole-body Gly production or clearance. This study was registered on clinicaltrials.gov as NCT01787682, NCT02082418, NCT02157844, NCT02770092, NCT02780219, NCT03796455, and NCT04461236.

There is currently no available information on the correlation between abdominal obesity indices and the risk of liver fibrosis progression. We aimed to investigate the relationship between the body mass index (BMI), waist circumference (WC), and the visceral adiposity index (VAI) with the progression of liver fibrosis. The study also evaluated the association between these indices and the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis. A total of 1403 subjects participated in the cross-sectional and longitudinal population-based study. Liver stiffness was assessed via transient elastography, at baseline and follow-up (median: 4.2 years). The subgroup with dysglycemia was also analyzed. In the cross-sectional study, the highest quartile of VAI, BMI ≥ 30 kg/m2, and abdominal obesity showed significant associations with the prevalence of MASLD and liver fibrosis, as well as with fibrosis progression. However, VAI showed no association with MASLD incidence. Among the dysglycemic subjects, there was no observed association between VAI and the incidence of MASLD or the progression of fibrosis. In conclusion, the BMI, WC, and the VAI are associated with an increased risk of progression to moderate-to-advanced liver fibrosis in the general population. However, the VAI does not perform better than the BMI and WC measurement.

Hepatic fat content can be non-invasively estimated by controlled attenuation parameter (CAP) during transient elastography. The aim of this study was to examine the determinants and predictors of CAP values in individuals with metabolic dysfunction.

We enrolled 1230 consecutive apparently healthy individuals (Liver-Bible-2022 cohort) with ≥3 metabolic dysfunction features. CAP was measured by Fibroscan. CAP determinants and predictors were identified using backward stepwise analysis and introduced in generalized linear models.

Participants were predominantly males (82.9%), mean age was 53.8 ± 6.4 years, 600 (48.8%) had steatosis (CAP ≥ 275 dB/m), and 27 had liver stiffness measurement (LSM) ≥ 8 kPa. CAP values correlated with LSM (p < 10-22). In multivariable analysis, fasting insulin and abdominal circumference (AC) were the main determinants of CAP (p < 10-6), together with body mass index (BMI; p < 10-4), age, diabetes, triglycerides, ferritin, and lower HDL and thyroid stimulating hormone (TSH; p < 0.05 for all). In a subset of 592 participants with thyroid hormone measurement, we found an association between higher free triiodothyronine levels, correlating with lower TSH, and CAP values, independent of TSH and of levothyroxine treatment (p = 0.0025). A clinical CAP score based on age, BMI, AC, HbA1c, ALT, and HDL predicted CAP ≥ 275 dB/m with moderate accuracy (AUROC = 0.73), which was better than that of the Fatty Liver Index and of ALT (AUROC = 0.70/0.61, respectively) and validated it in multiple cohorts.

Abdominal adiposity and insulin resistance severity were the main determinants of CAP in individuals with metabolic dysfunction and may improve steatotic liver disease risk stratification. CAP values were modulated by the hypophysis-thyroid axis.

Early detection of hepatic steatosis in people with HIV (PWH) could prevent progression and inflammation. The aim was to develop and validate a multivariable risk prediction model for hepatic steatosis in German PWH.

In this cohort study, 282 PWH were prospectively enrolled, and hepatic steatosis was defined via controlled attenuation parameter (CAP; ≥275 dB/m) using vibration-controlled transient elastography.

Three multivariable logistic regression models were conducted. Missing values were imputed with multiple imputation. Cut-offs were derived based on Youden-Indices. Performance was assessed via discriminatory and calibrative ability and accuracy via Brier Skill Score. Sensitivity, specificity, and predictive values were calculated. Internal validation was performed via bootstrapping.

The prevalence of hepatic steatosis was 35.3% (100/282). Univariate analyses revealed associations with age, waist circumference, BMI, hypertension, hyperlipidemia and gamma-gt. In multivariable analyses, male sex [odds ratio (OR) 2.07, 95% confidence interval (CI) 1.42-3.00, P  = 0.001] and BMI (OR 1.27, 95% CI 1.18-1.36, P  < 0.001) were identified as independent predictors of hepatic steatosis. The naive and optimism-corrected c -statistic of 79% showed a good discriminatory ability, the calibration was well with a slight tendency for overestimation for predicted probabilities above 70%. At the cutoff of 1.95, the specificity was 71% and the negative-predictive value 82.3%. Twenty-seven percent of the 282 patients would be misclassified, 17% as false positives and 10% as false negatives.

The developed prediction model contributes to the lack of validated noninvasive tools to predict hepatic steatosis in people with HIV. Future studies should include more candidate predictors and externally validate the model.

Aims: To evaluate and compare lipid accumulation product (LAP) with alanine aminotransferase (ALT), aspartate aminotransferase (AST), visceral adiposity index (VAI) and triglyceride-glucose index (TyG) as biomarkers for hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Methods: LAP, ALT, AST, VAI and TyG were measured in 52 biopsy-proven NAFLD patients and 21 control subjects. Additionally, LAP was also measured in 448 ultrasound-proven NAFLD patients and 1009 control subjects. Results: LAP was positively associated with hepatic steatosis and inflammation in biopsy-proven NAFLD. The risk of NAFLD was positively related to LAP and TyG, but LAP showed a better area under the receiver operating characteristic curve for hepatic steatosis and NAFLD. LAP also performed well in recognizing ultrasound-proven NAFLD. Conclusion: LAP is an ideal biomarker of hepatic steatosis and NAFLD.

Obesity often leads to severe medical complications. However, existing FDA-approved medications to combat obesity have limited effectiveness in reducing adiposity and often cause side effects. These medications primarily act on the central nervous system or disrupt fat absorption through the gastrointestinal tract. Adipose tissue enlargement involves adipose hyperplasia and hypertrophy, both of which correlate with increased reactive oxygen species (ROS) and hyperactivated X-box binding protein 1 (XBP1) in (pre)adipocytes. In this study, we demonstrate that KT-NE, a nanoemulsion loaded with the XBP1 inhibitor KIRA6 and α-Tocopherol, simultaneously alleviates aberrant endoplasmic reticulum stress and oxidative stress in (pre)adipocytes. As a result, KT-NE significantly inhibits abnormal adipogenic differentiation, reduces lipid droplet accumulation, restricts lipid droplet transfer, impedes obesity progression, and lowers the risk of obesity-associated non-alcoholic fatty liver disease in female mice with obesity. Furthermore, diverse administration routes of KT-NE impact its in vivo biodistribution and contribute to localized and/or systemic anti-obesity effectiveness.