OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are limited epidemiological studies addressing these diseases in low (LICs) and lower-middle-income countries (lower MICs). Therefore, an analysis of the trend of MASLD and cardiometabolic conditions in these countries is necessary.
METHODS: From 2000 to 2019, jointpoint regression analysis was employed to calculate the prevalence, mortality, and disability-adjusted life years (DALYs) for cardiometabolic conditions including MASLD, type 2 diabetes mellitus (T2DM), dyslipidemia (DLP), hypertension (HTN), obesity, peripheral artery disease (PAD), atrial fibrillation and flutter (AF/AFL), ischemic heart disease (IHD), stroke, and chronic kidney disease from HTN and T2DM, in LICs and lower MICs (according to the World Bank Classification 2019) using the Global Burden of Disease 2019 data.
RESULTS: Among the eleven cardiometabolic conditions, MASLD (533.65 million), T2DM (162.96 million), and IHD (76.81 million) had the highest prevalence in LICs and Lower MICs in 2019. MASLD represented the largest proportion of global prevalence in these countries (43 %). From 2000 to 2019, mortality in LICs and lower MICs increased in all cardiometabolic conditions, with obesity-related mortality having the highest increase (+134 %). During this timeframe, there were increased age-standardized death rates (ASDR) from obesity, PAD, and AF/AFL. From all conditions, the DALYs-to-prevalence ratio was higher in LICs and lower MICs than the global average.
CONCLUSIONS: The burden of MASLD and cardiometabolic conditions is increasing worldwide, with LICs and lower MICs experiencing higher disability per prevalence. As these conditions are preventable, counteracting these trends requires not only the modification of ongoing actions but also the strategizing of immediate interventions.

BACKGROUND: This study investigates the correlation between thyroid hormone levels and metabolic dysfunction in patients with type 2 diabetes mellitus (T2DM) who exhibit normal thyroid function and metabolic dysfunction associated with steatotic liver disease (MASLD).
OBJECTIVE: The objective is to identify a scientific basis for the management of T2DM complicated by MASLD, aiming to refine clinical strategies and enhance patient well-being.
METHODS: Statistical analysis was conducted using SPSS 26.0, employing independent sample t-tests for normally distributed data and logarithmic transformations for non-normal data to meet analysis prerequisites. Multifactorial logistic regression analysis elucidated the impact of various factors on the risk of MASLD in T2DM patients.
RESULTS: Elevated levels of FT3 may be associated with an increased risk of nonalcoholic fatty liver disease. Additionally, the FT3/FT4 ratio has been validated as an effective serological marker for predicting the risk of MASLD. In patients with DM2 and normal thyroid function, changes in thyroid hormone levels are closely related to the occurrence of MASLD. Elevated levels of FT3, total triiodothyronine (TT3), and thyroid-stimulating hormone are associated with an increased risk of MASLD.
CONCLUSIONS: FT3, TT3, and thyroid-stimulating hormone have important clinical value in the diagnosis of patients with T2DM complicated with MASLD.

OBJECTIVE: We aimed to explore the associations of baseline and cumulative cardiovascular health with nonalcoholic fatty liver disease (NAFLD) development and regression using the new Life\'s Essential 8 score.
METHODS: From a health screening database, participants who underwent at least 4 health examinations between 2012 and 2022 were recruited and categorized into two cohorts: (a) the NAFLD development cohort with no history of NAFLD prior to Exam 4 and (b) the NAFLD regression cohort with diagnosed NAFLD prior to Exam 4. The LE8 score was calculated from each component. The outcomes were defined as newly incident NAFLD or regression of existing NAFLD from Exam 4 to the end of follow-up.
RESULTS: In the NAFLD development cohort, of 21,844 participants, 3,510 experienced incident NAFLD over a median follow-up of 2.3 years. Compared with the lowest quartile of cumulative LE8, individuals in the highest quartile conferred statistically significant 76% lower odds (hazard ratio [HR] 0.24, 95% confidence interval [CI], 0.21-0.28) of NAFLD incidence, and corresponding values for baseline LE8 were 42% (HR 0.58, 95% CI 0.53-0.65). In the NAFLD regression cohort, of 6,566 participants, 469 experienced NAFLD regression over a median follow-up of 2.4 years. Subjects with the highest quartile of cumulative LE8 had 2.03-fold (95% CI, 1.51-2.74) higher odds of NAFLD regression, and corresponding values for baseline LE8 were 1.61-fold (95% CI, 1.24-2.10).
CONCLUSIONS: Cumulative ideal cardiovascular health exposure is associated with reduced NAFLD development and increased NAFLD regression. Improving and preserving health behaviors and factors should be emphasized as an important part of NAFLD prevention and intervention strategies.

UNASSIGNED: This study was designed to compare the effects of four meal patterns on liver steatosis, fibrosis, and biochemical factors in patients with Nonalcoholic fatty liver disease (NAFLD).
UNASSIGNED: The 12-week intervention was performed on 123 patients with NAFLD who were randomly allocated into four groups: \"3-meals\", \"skipping breakfast\", \"skipping dinner\", and \" 3 meals and 3 snacks per day.\" group. The assessment of liver steatosis, fibrosis, biochemical factors, and anthropometrical evaluation were performed at baseline and at end of the study.
UNASSIGNED: A significant improvement was found in the liver steatosis and fibrosis among the patients who consumed 3 meals, 3 snacks compared to the other groups (P < 0.001). In addition, a higher reduction was observed in serum levels of alanine amino transferase (ALT) (20.93 ± 23.37 mg/dl, P < 0.001), aspartate aminotransferase (AST) (17.15 ± 16.48 mg/dl, P < 0.001), gamma-glutamyl transferase(GGT) (13.43 ± 13.41 mg/dl; P < 0.001), and alkaline phosphatase (ALK) (47.19 ± 60.51 mg/dl; P = 0.004) in patients who consumed 3 meals, 3 snacks, while the concentration of liver enzymes in patients who consumed 3 meals increased significantly. At the end of the study, there was a significant increase in the fasting blood sugar (FBS) concentration in the \"skipping breakfast\" group (17.51 ± 38.85 mg/dl; P = 0.011) and \"3-meals\" group (17.51 ± 38.85 mg/dl, P = 0.03).
UNASSIGNED: Consuming 3 meals, 3 snack per day significantly improves disease severity and biochemical factors in NAFLD patients. Further studies are warranted.
UNASSIGNED: : IRCT20201010048982N2. Name of the registry: Urmia University of Medical Sciences. Date of registration: 2021-08-22, 1400/05/31. URL of trial registry record: https://www.irct.ir/search/result?query=IRCT20201010048982N2.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40200-023-01375-2.

BACKGROUND: Although several epidemiological studies have identified an inverse association between healthy dietary patterns and metabolic dysfunction-associated steatotic liver disease (MASLD)/non-alcoholic fatty liver disease (NAFLD), little is known about the contribution of the food component to MASLD risk and the association between dietary patterns and severity of MASLD. This study aimed to investigate the association between healthy eating patterns and MASLD risk and severity of MASLD.
METHODS: A case-control study including 228 patients diagnosed with MASLD and 228 controls was conducted. The modified Alternate Healthy Eating Index (AHEI), Dietary Approaches to Stop Hypertension (DASH) score, and Alternative Mediterranean Diet (AMED) score were evaluated based on information collected via a validated food-frequency questionnaire. MASLD was confirmed if participants presented with ultrasound-diagnosed fatty liver diseases along with at least one of five cardiometabolic risk factors and no other discernible cause. The logistic regression models were applied to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of MASLD for dietary scores.
RESULTS: Compared with participants in the lowest tertile, those in the highest tertile of AHEI had a 60% reduced risk of MASLD (OR: 0.40; 95% CI: 0.25-0.66). Similar associations were also observed for DASH and AMED, with ORs comparing extreme tertiles of 0.38 (95% CI: 0.22-0.66) and 0.46 (95% CI: 0.28-0.73), respectively. Further Stratified analysis revealed that the inverse associations between AHEI and DASH with MASLD risks were stronger among women than men, and the inverse associations between AMED and MASLD risks were more pronounced among participants with normal weight (OR: 0.22; 95% CI: 0.09-0.49). For components within the dietary score, every one-point increase in vegetable score and whole grain score within the AHEI was associated with an 11% (95% CI: 5-16%) and a 6% (95% CI: 0-12%) lower MASLD risk, respectively. Similar inverse associations with those scores were observed for the DASH and AMED.
CONCLUSIONS: Greater adherence to healthy eating patterns was associated with reduced risk of MASLD, with vegetables and whole grains predominately contributing to these associations. These findings suggested that healthy eating patterns should be recommended for the prevention of MASLD.

Non-alcoholic fatty liver disease (NAFLD), prevalent among conditions like obesity and diabetes, is globally significant. Existing ultrasound diagnosis methods, despite their use, often lack accuracy and precision, necessitating innovative solutions like AI. This study aims to validate an AI-enhanced quantitative ultrasound (QUS) algorithm for NAFLD severity assessment and compare its performance with Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF), a conventional diagnostic tool. A single-center cross-sectional pilot study was conducted. Liver fat content was estimated using an AI-enhanced quantitative ultrasound attenuation coefficient (QUS-AC) of Barreleye Inc. with an AI-based QUS algorithm and two conventional ultrasound techniques, FibroTouch Ultrasound Attenuation Parameter (UAP) and Canon Attenuation Imaging (ATI). The results were compared with MRI-PDFF values. The intraclass correlation coefficient (ICC) was also assessed. Significant correlation was found between the QUS-AC and the MRI-PDFF, reflected by an R value of 0.95. On other hand, ATI and UAP displayed lower correlations with MRI-PDFF, yielding R values of 0.73 and 0.51, respectively. In addition, ICC for QUS-AC was 0.983 for individual observations. On the other hand, the ICCs for ATI and UAP were 0.76 and 0.39, respectively. Our findings suggest that AC with AI-enhanced QUS could serve as a valuable tool for the non-invasive diagnosis of NAFLD.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common dietary disorder caused by fatty changes in the liver parenchyma and hepatocytes without alcohol consumption. The present study aimed to investigate the prevalence, characteristics, and risk factors of NAFLD in the Mashhad Persian Cohort Study population.
METHODS: The present population-based cross-sectional study included all PERSIAN Organizational Cohort study in Mashhad University of Medical Sciences (POCM), Mashhad, Iran by census sampling method. Eligible participants were divided into two groups due to their NAFLD condition (NAFLD positive or NAFLD negative). All enrolled participants were evaluated based on their clinical aspects, anthropometric measures, laboratory tests, and ultrasound features. Statistical analysis was conducted using SPSS software version 16 (SPSS Inc., Chicago, USA -version 16). A P-value less than 0.05 was considered as the significance level.
RESULTS: A total of 1198 individuals were included in the study, of which 638 (53.3%) were male and the rest were female. The mean age of the participants was 46.89 ± 8.98 years. A total of 246 patients (20.53%) were NAFLD positive, of which 122 (49.59%) were in grade 1, 112 (45.52%) were in grade 2, and 12 (4.87%) were in grade 3. The prevalence of fatty liver was significantly higher in males than in females (p < 0.001). There were significant differences between NAFLD positive and NAFLD negative participants in terms of having a history of hypertension (P = 0.044), body mass index (P < 0.001), body fat percentage (P = 0.001), waist circumference (P < 0.001), liver craniocaudal length (P = 0.012), fasting blood sugar (FBS) (P = 0.047), aspartate aminotransferase (AST) (P = 0.007), and alanine aminotransferase (ALT) (P = 0.001). Further analysis revealed a strong significant association between BMI, previous history of hypertension, higher levels of serum ALT, and NAFLD (P < 0.05).
CONCLUSIONS: It can be concluded that ultrasound findings accompanied by laboratory AST and ALT level enzymes could be a cost-benefit approach for NAFLD early diagnosis. The craniocaudal size of the liver could be a beneficent marker for estimating the severity of the disease; however, more studies are recommended to evaluate this variable for future practice against the issue.

UNASSIGNED: Non-alcoholic fatty liver disease (NAFLD) is known to be associated with metabolic syndrome of which diabetes is an important component. Although diabetes is a known risk factor for dementia, studies on the association between NAFLD and dementia still produce conflicting results. This study aimed to determine whether NAFLD would be a risk factor for the development of dementia in an elderly population.
UNASSIGNED: This study included 107,369 subjects aged ≥60 years in the Korean National Health Insurance Service-Senior cohort, entered in 2009 and followed up until 2015. NAFLD was diagnosed by calculating fatty liver index (FLI). Subjects were screened for dementia at baseline using a Korean Dementia Screening Questionnaire, and dementia was diagnosed using ICD-10 codes. Controls were randomly selected at a ratio of 1:5 from individuals who were at risk of becoming the case subjects at the time of selection.
UNASSIGNED: From 107,369 subjects, 65,690 stroke- and dementia-free subjects without chronic hepatitis B or C or excessive alcohol drinking were selected for evaluation. Having NAFLD, determined by FLI, was associated with increased risk of dementia development (adjusted odds ratio [AOR] 1.493; 95% confidence interval [CI] 1.214-1.836). The increased risk of dementia in NAFLD subjects was independent of type 2 diabetes (AOR 1.421; 95% CI 1.013-1.994, in subjects with diabetes: AOR 1.540; 95% CI 1.179- 2.010, in subjects without diabetes).
UNASSIGNED: In this population-based nested case-control study, having NAFLD increased the risk of dementia in elderly individuals, independent of accompanying diabetes.

BACKGROUND: The aim of this study was to examine the association between different metabolic obesity phenotypes and the non-alcoholic fatty liver disease (NAFLD).
METHODS: This cross-sectional analysis utilized data from the baseline phase of the Ravansar non-communicable diseases (RaNCD) cohort study, which involved 8,360 adults. Participants with a Fatty Liver Index (FLI) score of ≥ 60 was classified as having NAFLD. The FLI score was calculated using liver non-invasive markers and anthropometric measurements. Participants were categorized into four phenotypes based on the presence or absence of metabolic syndrome and obesity. Logistic regression analysis was used to evaluate the association of NAFLD and obesity phenotypes.
RESULTS: According to the FLI index, the prevalence of NAFLD was 39.56%. Participants with FLI scores of ≥ 60 had higher energy intake compared to those in the FLI < 60 group (P = 0.033). In subjects with metabolically unhealthy phenotypes, the level of physical activity was lower compared to those with metabolically healthy phenotypes. The risk of NAFLD in males with the metabolically healthy-obese phenotype increased by 8.92 times (95% CI: 2.20, 15.30), those with the metabolically unhealthy-non-obese phenotype increased by 7.23 times (95% CI: 5.82, 8.99), and those with the metabolically unhealthy-obese phenotype increased by 32.97 times (95% CI: 15.70, 69.22) compared to the metabolically healthy-non-obese phenotype. Similarly, these results were observed in females.
CONCLUSIONS: This study demonstrated that the risk of NAFLD is higher in individuals with metabolically healthy/obese, metabolically unhealthy/non-obese, and metabolically unhealthy/obese phenotypes compared to those with non-obese/metabolically healthy phenotypes.

OBJECTIVE: Ginsenoside Re, a unique tetracyclic triterpenoid compound found in ginseng, has been suggested in previous reports to improve non-alcoholic fatty liver disease (NAFLD) by modulating lipid imbalance. This study aims to elucidate the potential mechanisms of Ginsenoside Re in treating NAFLD through a combination of bioinformatics analysis and biological experiments.
METHODS: Network pharmacology methods were employed to systematically depict the effective components and mechanisms of Ginsenoside Re in improving NAFLD. Molecular docking was utilized to evaluate the binding affinity of Ginsenoside Re with NAFLD-related targets and identify potential targets. NAFLD-related target genes were obtained from the GEO database for gene enrichment analysis, revealing signaling pathways, biological processes, and gene differential expression. Finally, animal experiments were conducted to verify the mechanism of action of Ginsenoside Re in NAFLD.
RESULTS: Network pharmacology analysis revealed that Ginsenoside Re improves NAFLD by modulating targets such as AKT1 and TLR4, findings corroborated by molecular docking, GEO database analysis, and experimental validation. Further investigation found that Ginsenoside Re ameliorates lipid metabolism disorders and inflammatory responses induced by NAFLD by modulating the PI3K/AKT and TLR4/NF-κB signaling pathways.
CONCLUSIONS: Our study demonstrates the pharmacological effects of Ginsenoside Re in treating NAFLD, implicating multiple components, targets, and pathways. This provides a solid foundation for considering Ginsenoside Re as an alternative therapy for NAFLD, with promising clinical applications.