Biochemical and Anthropometric Indices of Insulin Resistance in Obese and Overweight Children with Metabolic Dysfunction-Associated Fatty Liver Disease.

BACKGROUND The prevalence of metabolic (dysfunction)-associated fatty liver disease (MAFLD) increases together with the epidemic of childhood obesity. An important mechanism in the phenomenon appears to be insulin resistance (IR), the assessment of which in children is problematic. The homeostatic model assessment of IR (HOMA-IR), commonly used for this, is not standardized and appears not to correlate with IR in the pediatric population. Therefore, our study aimed to evaluate potential substitute indices of IR, including the triglyceride-glucose index (TyG), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), modified TyG indices: TyG-waist circumference (TyG-WC) and TyG-body mass index (TyG-BMI) as surrogate markers of MAFLD in obese children suspected to have liver disease. MATERIAL AND METHODS The retrospective study included 264 obese children admitted to the Department to diagnose suspected liver disease. MAFLD was diagnosed according to the International Expert Consensus Statement. Anthropometric measurements and laboratory tests were made and the indices were calculated. Receiver operating characteristics analysis was performed to calculate the power of the indices. RESULTS MAFLD was diagnosed in 184 patients (70%). Obese children with MAFLD showed significantly higher activity of liver enzymes and concentration of total cholesterol, TG, WC, and waist-to-hip ratio compared to non-hepatopathic obese controls (n=80). The most important indices in identifying MAFLD were: TyG (AUC=0.641, p<0.001, cut-off =8.41, sensitivity=57.4%, specificity=68.8%), and TG/HDL-C (AUC=0.638, p<0.001, cut-off=2.5, sensitivity=48.6%, specificity=76.3%). TyG-BMI and HOMA-IR were not useful predictors. CONCLUSIONS TyG and TG/HDL-C can be considered as potential surrogate biomarkers in predicting MAFLD in obese children.

[Interpretation of the 2024 American Diabetes Association guidelines for the comprehensive management of non-alcoholic fatty liver disease combined with diabetes mellitus].

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.

Prevalence and Association of Risk Factors According to Liver Steatosis and Fibrosis Stages among Nonalcoholic Fatty Liver Disease Patients with Type 2 Diabetes Mellitus in India: A Cross-sectional Study.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are linked to the global diabetes epidemic, leading to increased disease progression and adverse health outcomes. The renaming of NAFLD to metabolic dysfunction-associated steatotic liver disease (MASLD) at the 2023 European Association for the Study of the Liver Congress highlights the complex relationship between metabolic disorders and liver health. Taking this into consideration, we aimed this study to identify prevalence and risk factors associated with the stages of NAFLD in individuals with T2DM in the Indian population. MATERIALS AND METHODS: This observational, cross-sectional study was conducted on 1,521 T2DM patients at Dr Panikar's Speciality Care Centre, Mumbai, between September 1, 2022 and October 31, 2022. Demographic parameters such as age, gender, height, weight, and anthropometric parameters such as body mass index (BMI) and waist circumference were measured. Liver fibrosis and steatosis stages were identified by vibration-controlled transient elastography (VCTE) using FibroScan®. RESULTS: The prevalence of liver steatosis was 75.1% among the 1,521 diabetes cases [S0 (24.9%), S1 (15.1%), S2 (24%), and S3 (36%)], whereas the prevalence of liver fibrosis was 28.0% [F0 (72%), F1 (19%), F2 (5%), F3 (1.5%), and F4 (3.4%)]. The S1 (p = 0.012), S3 (p = 0.001), F1 (p = 0.001), and F2 (p = 0.001) grades showed significant gender-related changes, demonstrating a positive connection. Furthermore, waist circumference was associated with disease severity in both liver steatosis and fibrosis stages (p = 0.001), but BMI was solely associated with the degree of steatosis (p = 0.001). The mean age differences between these categories, however, did not reach statistical significance (p-values of 0.149 and 0.078, respectively, for the steatosis and fibrosis grades). CONCLUSION: The study reveals a high prevalence of NAFLD (steatosis and fibrosis) in T2DM patients, increasing the risk of advanced fibrosis. In T2DM patients with risk factors including waist circumference and BMI, appropriate screening and intervention are required.

Observational and genetic association of non-alcoholic fatty liver disease and calcific aortic valve disease.

Background: Non-alcoholic fatty liver disease (NAFLD) has emerged as a predominant driver of chronic liver disease globally and is associated with increased cardiovascular disease morbidity and mortality. However, the association between NAFLD and calcific aortic valve disease remains unclear. We aimed to prospectively investigate the association between NAFLD and incident aortic valve calcification (AVC), as well as its genetic relationship with incident calcific aortic valve stenosis (CAVS). Methods: A post hoc analysis was conducted on 4226 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) database. We employed the adjusted Cox models to assess the observational association between NAFLD and incident AVC. Additionally, we conducted two-sample Mendelian randomization (MR) analyses to investigate the genetic association between genetically predicted NAFLD and calcific aortic valve stenosis (CAVS), a severe form of CAVD. We repeated the MR analyses by excluding NAFLD susceptibility genes linked to impaired very low-density lipoprotein (VLDL) secretion. Results: After adjustment for potential risk factors, participants with NAFLD had a hazard ratio of 1.58 (95% CI: 1.03-2.43) for incident AVC compared to those without NAFLD. After excluding genes associated with impaired VLDL secretion, the MR analyses consistently showed the significant associations between genetically predicted NAFLD and CAVS for 3 traits: chronic elevation of alanine aminotransferase (odds ratio = 1.13 [95% CI: 1.01-1.25]), imaging-based NAFLD (odds ratio = 2.81 [95% CI: 1.66-4.76]), and biopsy-confirmed NAFLD (odds ratio = 1.12 [95% CI: 1.01-1.24]). However, the association became non-significant when considering all NAFLD susceptibility genes. Conclusions: NAFLD was independently associated with an elevated risk of incident AVC. Genetically predicted NAFLD was also associated with CAVS after excluding genetic variants related to impaired VLDL secretion.

Association between nonalcoholic steatohepatitis and high serum ferritin levels in type 2 diabetes mellitus.

OBJECTIVE: The aim of this study was to assess the role of elevated serum ferritin levels in the onset, pathological progression and prognosis of nonalcoholic fatty liver disease. Nonalcoholic fatty liver disease has been rapidly increasing worldwide. Despite extensive research on the pathogenesis of nonalcoholic fatty liver disease, a lack of sufficient clinical research on the relationship between nonalcoholic fatty liver disease and serum ferritin levels remains. METHODS: We analysed 968 patients with type 2 diabetes mellitus who underwent liver ultrasound examination and had their serum ferritin levels measured. The presence of nonalcoholic fatty liver disease and advanced liver fibrosis was determined through abdominal ultrasound examination and the nonalcoholic fatty liver disease fibrosis score. RESULTS: Compared to that in the non-nonalcoholic fatty liver disease group, the presence of hyperferritinemia was significantly more common in the nonalcoholic fatty liver disease group (83.3 vs. 56.3%, p=0.005). When patients with nonalcoholic fatty liver disease were stratified by the nonalcoholic fatty liver disease fibrosis score, those with advanced liver fibrosis exhibited a higher prevalence of hyperferritinemia (56.3, 78.9, and 88.9% for none, simple steatosis, and advanced fibrosis, respectively; p for trend=0.002). In multivariate logistic regression, liver fibrosis was independently associated with hyperferritinemia (odds ratio [OR] 1.45; 95% confidence interval [CI] 1.18-2.02; p=0.014), and this association remained significant in male patients after adjusting for other risk factors (OR 2.66; 95% CI 1.43-5.48; p=0.026). CONCLUSION: Identifying nonalcoholic fatty liver disease patients at a risk of developing nonalcoholic steatohepatitis and advanced fibrosis is crucial for implementing timely interventions and improving patient outcomes. This study highlights the potential utility of serum ferritin levels as a serum biomarker for identifying nonalcoholic steatohepatitis patients and those at a risk of late-stage fibrosis, particularly in male patients with nonalcoholic fatty liver disease.

Metabolic dysfunction-associated steatotic liver disease prevalence and risk factors in inflammatory bowel disease in tertiary center.

OBJECTIVE: The aim of this study was to evaluate the prevalence and risk factors related to metabolic dysfunction-associated steatotic liver disease in inflammatory bowel disease patients. METHODS: This is a cross-sectional study conducted on adults with inflammatory bowel disease from 2019 to 2021. Metabolic dysfunction-associated steatotic liver disease encompasses patients with steatosis and at least one cardiometabolic risk factor. Patients with alcohol consumption ≥20 g/day, chronic liver diseases, or methotrexate use were excluded. RESULTS: Almost 140 patients were included: 67.1% were female, with a mean age of 49.7±13.7 years, and 63.6% had Crohn's disease. The mean duration of inflammatory bowel disease was 9.7±7.9 years. Metabolic dysfunction-associated steatotic liver disease was observed in 44.3% and advanced liver fibrosis was excluded in 63.5% by Fibrosis-4. Patients with metabolic dysfunction-associated steatotic liver disease were older (p = 0.003) and had a higher number of metabolic syndrome components (2.9±1.1 versus 1.6±1.0; p<0.001), greater abdominal circumference (p<0.001), and body mass index (p<0.001). The only factor related to inflammatory bowel disease associated with metabolic dysfunction-associated steatotic liver disease was disease duration (11.6±9.5 versus 8.3±6.2; p = 0.017). A higher number of metabolic syndrome components and obesity increase by 2.2 times and an altered waist circumference by 2.6 times the occurrence of metabolic dysfunction-associated steatotic liver disease. CONCLUSION: A high prevalence of metabolic dysfunction-associated steatotic liver disease was observed in patients with inflammatory bowel disease, with the main risk factors being associated with metabolic syndrome predicting it, but not with inflammatory bowel disease features and/or its treatment.

The predictive role of the platelet-to-lymphocyte ratio for the risk of non-alcoholic fatty liver disease and cirrhosis: a nationwide cross-sectional study.

Background: The associations between platelet-to-lymphocyte ratio (PLR) and non-alcoholic fatty liver disease (NAFLD) and cirrhosis are unclear, and there are still no effective means for diagnosing or monitoring disease progression. Methods: Data from the National Health and Nutrition Examination Surveys were collected for analysis. Logistic regression and restricted cubic splines were used to evaluate the associations between PLR and NAFLD and cirrhosis in different populations. The Area Under Curve Receiver Operating Characteristic (AUCROC) was used to distinguish the models. Threshold analysis was performed by constructing a two-piecewise linear regression. Correlation analysis was performed separately on either side of the inflection point. Results: A total of 5724 adults were included. Logistic regression analysis revealed that the PLR was associated with NAFLD and cirrhosis (AUCROC of NAFLD: 0.803; AUCROC of cirrhosis: 0.851). The AUCROC of the PLR for predicting NAFLD incidence was 0.762 in the diabetic population and 0.804 in the nondiabetic population. High PLR predicted cirrhosis in the diabetic population, with an AUCROC of 0.824, whereas a high PLR was not associated with cirrhosis in the nondiabetic population. The restricted cubic spline revealed a negative linear correlation between the PLR and NAFLD incidence. The inflection point of the PLR for NAFLD was 180.74. A PLR ≤180.74 was statistically significant (odds ratio=0.997, 95% confidence interval=0.995-0.999). In the NAFLD population, the PLR was negatively correlated with cirrhosis at a PLR ≤130.5 (odds ratio=0.987, 95% confidence interval=0.977-0.996) and positively correlated with cirrhosis at a PLR > 130.5 (odds ratio=1.006, 95% confidence interval=1.001-1.012). Conclusions: The PLR and NAFLD were negatively correlated in the U.S. population. The PLR had a U-shaped relationship with cirrhosis in the NAFLD population. The PLR has potential value in monitoring NAFLD patient progression to cirrhosis.

The Role of CD4+T Cells in Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has become the fourth leading cause of cancer-related deaths worldwide; annually, approximately 830,000 deaths related to liver cancer are diagnosed globally. Since early-stage HCC is clinically asymptomatic, traditional treatment modalities, including surgical ablation, are usually not applicable or result in recurrence. Immunotherapy, particularly immune checkpoint blockade (ICB), provides new hope for cancer therapy; however, immune evasion mechanisms counteract its efficiency. In addition to viral exposure and alcohol addiction, nonalcoholic steatohepatitis (NASH) has become a major cause of HCC. Owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance, NASH-associated HCC patients respond much less efficiently to ICB treatment than do patients with other etiologies. In addition, abnormal inflammation contributes to NASH progression and NASH-HCC transition, as well as to HCC immune evasion. Therefore, uncovering the detailed mechanism governing how NASH-associated immune cells contribute to NASH progression would benefit HCC prevention and improve HCC immunotherapy efficiency. In the following review, we focused our attention on summarizing the current knowledge of the role of CD4+T cells in NASH and HCC progression, and discuss potential therapeutic strategies involving the targeting of CD4+T cells for the treatment of NASH and HCC.

Association between different obesity patterns and the risk of NAFLD detected by transient elastography: a cross-sectional study.

BACKGROUND: Obesity has become a major global public health challenge. Studies examining the associations between different obesity patterns and the risk of nonalcoholic fatty liver disease (NAFLD) are limited. This study aimed to investigate the relationships between different obesity patterns and the risk of NAFLD in a large male population in the US. METHODS: Data from the 2017 to March 2020 National Health and Nutrition Examination Survey (NHANES) were utilized. Liver steatosis and fibrosis were assessed with FibroScan using the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM). Steatosis was identified with a CAP value of 248 dB/m or higher. Abdominal obesity was defined by a waist circumference (WC) of 102 cm or more for males and 88 cm or more for females. Overweight was defined as a body mass index (BMI) of 24.0 kg/m2 and above. General obesity was identified with a BMI of 28.0 kg/m2 or higher. Obesity status was categorized into four types: overweight, general obesity, abdominal obesity, and combined obesity. Multivariate logistic regression, adjusting for potential confounders, was used to examine the link between obesity patterns and NAFLD risk. Subgroup analysis further explored these associations. RESULTS: A total of 5,858 adults were included. After multivariable adjustment, compared to the normal weight group, the odds ratios (ORs) [95% confidence interval (CI)] for NAFLD in individuals with overweight, general obesity, abdominal obesity, and combined obesity were 6.90 [3.74-12.70], 2.84 [2.38-3.39], 3.02 [2.02-4.51], and 9.53 [7.79-11.64], respectively. Subgroup analysis showed the effect of different obesity patterns on NAFLD risk was stable among individuals with different clinical conditions. In the fully adjusted multivariate logistic regression model, WC was positively associated with NAFLD risk (OR: 1.48; 95% CI: 1.42-1.53; P < 0.001). WC also demonstrated strong discriminatory ability for NAFLD in Receiver Operating Characteristic (ROC) analysis, achieving an Area Under the Curve (AUC) of 0.802. CONCLUSIONS: Different patterns of obesity are risk factors for NAFLD. An increase in WC significantly increased NAFLD risk. More attention should be paid to preventing different patterns of obesity among adults.

Relationship between non-alcoholic fatty liver and progressive fibrosis and serum 25-hydroxy vitamin D in patients with type 2 diabetes mellitus.

OBJECTIVE: We aimed to analyze the relationship between non-alcoholic fatty liver and progressive fibrosis and serum 25-hydroxy vitamin D (25(OH)D) in patients with type 2 diabetes mellitus. METHODS: A total of 184 patients with T2DM who were hospitalized in the Department of Endocrinology of the ShiDong Clinical Hospital between January 2023 and June 2023 were selected. We compared review of anthropometric, biochemical, and inflammatory parameters and non-invasive scores between groups defined by ultrasound NAFLD severity grades.We determine the correlation between 25(OH)D and FLI and FIB-4 scores, respectively. RESULTS: Statistically significant differences were seen between BMI, WC, C-peptide levels, FPG, ALT, serum 25(OH)D, TC, HDL, lumbar spine bone density, FLI, and FIB-4 in different degrees of NAFLD. Multivariate logistic regression analysis showed that 25(OH)D (OR = 1.26, p = 0.001), age (OR = 0.93, P < 0.001) and BMI (OR = 1.04, p = 0.007) were independent predictors of NAFLD in patients with T2DM. CONCLUSIONS: This study revealed the correlation between serum 25(OH)D levels and NAFLD in patients with T2DM. We also demonstrated that serum 25(OH)D levels were negatively correlated with FLI/FIB-4 levels in patients with T2DM with NAFLD, suggesting that vitamin D deficiency may promote hepatic fibrosis progression in T2DM with NAFLD.

Clinical and genetic risk factors for progressive fibrosis in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: Fibrosis-4 (FIB4) is a recommended noninvasive test to assess hepatic fibrosis among patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we used FIB4 trajectory over time (ie, "slope" of FIB4) as a surrogate marker of liver fibrosis progression and examined if FIB4 slope is associated with clinical and genetic factors among individuals with clinically defined MASLD within the Million Veteran Program Cohort. METHODS: In this retrospective cohort study, FIB4 slopes were estimated through linear regression for participants with clinically defined MASLD and FIB4 <2.67 at baseline. FIB4 slope was correlated with demographic parameters and clinical outcomes using logistic regression and Cox proportional hazard models. FIB4 slope as a quantitative phenotype was used in a genome-wide association analysis in ancestry-specific analysis and multiancestry meta-analysis using METAL. RESULTS: FIB4 slopes, generated from 98,361 subjects with MASLD (16,045 African, 74,320 European, and 7996 Hispanic), showed significant associations with sex, ancestry, and cardiometabolic risk factors (p < 0.05). FIB4 slopes also correlated strongly with hepatic outcomes and were independently associated with time to cirrhosis. Five genetic loci showed genome-wide significant associations (p < 5 × 10-8) with FIB4 slope among European ancestry subjects, including 2 known (PNPLA3 and TM6SF2) and 3 novel loci (TERT 5.1 × 10-11; LINC01088, 3.9 × 10-8; and MRC1, 2.9 × 10-9). CONCLUSIONS: Linear trajectories of FIB4 correlated significantly with time to progression to cirrhosis, with liver-related outcomes among individuals with MASLD and with known and novel genetic loci. FIB4 slope may be useful as a surrogate measure of fibrosis progression.

TG/HDL-C ratio is positively associated with risk and severity of CHD among NAFLD patients: a case control study.

Objective: This study aimed to explore the association between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and the risk and severity of CHD among NAFLD patients. Methods: This retrospective study included 278 patients with NAFLD and chest pain. The TG/HDL-C ratio was calculated and coronary angiography performed. All individuals were divided into NAFLD + CHD and NAFLD groups. The severity of coronary artery stenosis is quantified using the Gensini score based on angiographic results. In NAFLD patients, the association between the TG/HDL-C ratio and the risk and severity of CHD was explored. Results: CHD was detected in 139 of 278 patients. Compared to NAFLD group, multivariate logistic regression showed that TG/HDL-C ratio was a risk factor for CHD among NAFLD patients after adjustment for confounding factors with the odds ratio (OR 1.791, 95% CI 1.344-2.386, P<0.001). Further analysis using multivariate logistic regression based on tertiles revealed that, after adjusting for confounding factors, compared to the T1 group, the risk of CHD in the T2 group was 2.17-fold higher (OR, 2.17; 95% CI, 1.07-4.38; P = 0.031). Similarly, the risk of CHD in the T3 group increased by 2.84-fold (OR, 2.84; 95% CI, 1.36-5.94; P = 0.005). The multifactor linear regression analysis showed each 1-unit increase in TG/HDL-C ratio in the NAFLD + CHD group was associated with a 7.75-point increase in Gensini score (ß=7.75, 95% CI 5.35-10.15, P<0.001). Conclusion: The TG/HDL-C ratio was positively correlated with CHD risk and reflected coronary atherosclerosis severity in NAFLD patients.

Correlation between controlled attenuation parameter values with SYNTAX score in patients with significant coronary artery disease.

Non-alcoholic fatty liver disease (NAFLD) is an emerging cause of chronic liver disease, with coronary artery disease (CAD) as the main cause of death in NAFLD patients. However, correlation between the severity of liver steatosis and coronary atherosclerosis is yet to be understood. Here we aim to explore the correlation between controlled attenuation parameter (CAP) values and SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score in adult patients with significant CAD, defined as ≥ 50% stenosis of the left main coronary artery, or ≥ 70% stenosis of the other major coronary arteries. A cross-sectional study was conducted on 124 adult patients with significant CAD who underwent coronary angiography. Transient elastography with CAP was used to assess liver steatosis severity, resulting in a mean CAP value of 256.5 ± 47.3 dB/m, with 52.5% subjects had significant steatosis (CAP value of ≥ 248 dB/m). Median SYNTAX score was 22. A statistically significant correlation was observed between CAP value and SYNTAX score (r = 0.245, p < 0.0001). The correlation was more pronounced in patients with prior history of PCI (r = 0.389, p = 0.037). Patients with high-risk SYNTAX score (> 32) had the highest CAP value (285.4 ± 42.6 dB/m), and it was significantly higher than those with low-risk SYNTAX score (0-22), with a mean difference of 38.76 dB/m (p = 0.006). Patients with significant liver steatosis should undergo periodic CAD assessment and lifestyle modification, especially those with severe liver steatosis.

A comprehensive approach to lifestyle intervention based on a calorie-restricted diet ameliorates liver fat in overweight/obese patients with NAFLD: a multicenter randomized controlled trial in China.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a globally increasing health epidemic. Lifestyle intervention is recommended as the main therapy for NAFLD. However, the optimal approach is still unclear. This study aimed to evaluate the effects of a comprehensive approach of intensive lifestyle intervention (ILI) concerning enhanced control of calorie-restricted diet (CRD), exercise, and personalized nutrition counseling on liver steatosis and extrahepatic metabolic status in Chinese overweight and obese patients with NAFLD. METHODS: This study was a multicenter randomized controlled trial (RCT) conducted across seven hospitals in China. It involved 226 participants with a body mass index (BMI) above 25. These participants were randomly assigned to two groups: the ILI group, which followed a low carbohydrate, high protein CRD combined with exercise and intensive counseling from a dietitian, and a control group, which adhered to a balanced CRD along with exercise and standard counseling. The main measure of the study was the change in the fat attenuation parameter (FAP) from the start of the study to week 12, analyzed within the per-protocol set. Secondary measures included changes in BMI, liver stiffness measurement (LSM), and the improvement of various metabolic indexes. Additionally, predetermined subgroup analyses of the FAP were conducted based on variables like gender, age, BMI, ethnicity, hyperlipidemia, and hypertension. RESULTS: A total of 167 participants completed the whole study. Compared to the control group, ILI participants achieved a significant reduction in FAP (LS mean difference, 16.07 [95% CI: 8.90-23.25] dB/m) and BMI (LS mean difference, 1.46 [95% CI: 1.09-1.82] kg/m2) but not in LSM improvement (LS mean difference, 0.20 [95% CI: -0.19-0.59] kPa). The ILI also substantially improved other secondary outcomes (including ALT, AST, GGT, body fat mass, muscle mass and skeletal muscle mass, triglyceride, fasting blood glucose, fasting insulin, HbA1c, HOMA-IR, HOMA-ß, blood pressure, and homocysteine). Further subgroup analyses showed that ILI, rather than control intervention, led to more significant FAP reduction, especially in patients with concurrent hypertension (p < 0.001). CONCLUSION: In this RCT, a 12-week intensive lifestyle intervention program led to significant improvements in liver steatosis and other metabolic indicators in overweight and obese Chinese patients suffering from nonalcoholic fatty liver disease. Further research is required to confirm the long-term advantages and practicality of this approach. TRIAL REGISTRATION: This clinical trial was registered on ClinicalTrials.gov (registration number: NCT03972631) in June 2019.

Diagnostic role of SPP1 and collagen IV in a rat model of type 2 diabetes mellitus with MASLD.

Type 2 diabetes mellitus combined with metabolic dysfunction-associated steatotic liver disease (MASLD) leads to an increasing incidence of liver injury year by year, and patients are at a significantly higher risk of developing cirrhosis or even liver failure. No drugs have emerged to specifically treat this disease. The aim of this study is to investigate the mechanisms and causative hub genes of type 2 diabetes combined with MASLD. The data were obtained through the GEO platform for bioinformatics analysis and validated by in vitro experiments to find the causative targets of type 2 diabetes mellitus combined with MASLD, which will provide some theoretical basis for the development of future therapeutic drugs. GSE23343 and GSE49541 were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) in type 2 diabetes mellitus combined with MASLD for functional enrichment analysis. And STRING database and Cytoscape software were used to construct Protein-Protein Interaction (PPI) and hub gene networks. And GO (gene ontology, GO) analysis and KEGG (Kyoto encyclopedia of genes and genomes, KEGG) enrichment analysis were performed on target genes. A total of 185 co-expressed DEGs were obtained by differential analysis, and 20 key genes involved in the development and progression of type 2 diabetes were finally screened. These 20 key genes were involved in 529 GO enrichment results and 20 KEGG enrichment results, and were mainly associated with ECM-receptor interaction, Focal adhesion, Human papillomavirus infection, PI3K-Akt signaling pathway, and the Toll-like receptor signaling pathway. A total of two target genes (SPP1, collagen IV) were found to be highly correlated with type 2 diabetes mellitus combined with MASLD. Real time PCR results showed that there was a significant difference in SPP1 and collagen IV mRNA expression among the three groups (P < 0.05). SPP1 and Collagen IV may be candidate biomarkers for type 2 diabetes mellitus combined with MASLD, as verified by bioinformatics screening and in vitro experiments. Our findings provide new targets for the treatment of type 2 diabetes combined with MASLD.

Decreased Hepatic and Serum Levels of IL-10 Concur with Increased Lobular Inflammation in Morbidly Obese Patients.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Accumulating evidence in animal models suggests that loss of interleukin-10 (IL-10) anti-inflammatory actions might contribute to lobular inflammation, considered one of the first steps toward NASH development. However, the role of IL-10 in lobular inflammation remains poorly explored in humans. We examined mRNA and protein levels of IL-10 in liver biopsies and serum samples from morbidly obese patients, investigating the relationship between IL-10 and lobular inflammation degree. Materials and Methods: We prospectively enrolled morbidly obese patients of both sexes, assessing the lobular inflammation grade by the Brunt scoring system to categorize participants into mild (n = 7), moderate (n = 19), or severe (n = 13) lobular inflammation groups. We quantified the hepatic mRNA expression of IL-10 by quantitative polymerase chain reaction and protein IL-10 levels in liver and serum samples by Luminex Assay. We estimated statistical differences by one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. Results: The hepatic expression of IL-10 significantly diminished in patients with severe lobular inflammation compared with the moderate lobular inflammation group (p = 0.01). The hepatic IL-10 protein levels decreased in patients with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.008 and p = 0.0008, respectively). In circulation, IL-10 also significantly decreased in subjects with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.005 and p < 0.0001, respectively). Conclusions: In liver biopsies and serum samples of morbidly obese patients, the protein levels of IL-10 progressively decrease as lobular inflammation increases, supporting the hypothesis that lobular inflammation develops because of the loss of the IL-10-mediated anti-inflammatory counterbalance.

Relationship between thyroid hormone levels and metabolic dysfunction associated steatotic liver disease in patients with type 2 diabetes: A clinical study.

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. CONCLUSION: FT3, TT3, and thyroid-stimulating hormone have important clinical value in the diagnosis of patients with T2DM complicated with MASLD.

NON-ALCOHOLIC FATTY LIVER DISEASE AND EXTRA-HEPATIC CANCER: A NARRATIVE REVIEW.

BACKGROUND: Recently, significant associations between non-alcoholic fatty liver disease (NAFLD) and extra-hepatic cancer have been reported. OBJECTIVE: To carry out a comprehensive review of the current evidence in the literature on the association between NAFLD and extra-hepatic cancer. METHODS: A narrative literature review was performed through an online search for the MeSH terms "fatty liver" and "cancer" in MEDLINE (via PubMed) and LILACS (via BVS). Original studies that described the impact of NAFLD on different types of extra-hepatic malignancies were included. RESULTS: After careful analysis, nine prospective cohort studies, one retrospective cohort study, three case-control studies, and three cross-sectional studies were selected. CONCLUSION: There is consistent evidence on the association between NAFLD and extra-hepatic carcinogenesis, especially in relation to colorectal, gastric, pancreatic, breast, prostate, and bladder cancers.