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Early-stage nonalcoholic fatty liver disease (NAFLD) is a silent condition, with most cases going undiagnosed, potentially progressing to liver cirrhosis and cancer. A non-invasive and cost-effective detection method for early-stage NAFLD detection is a public health priority but challenging. In this study, an adhesive, soft on-skin sensor with low electrode-skin contact impedance for early-stage NAFLD detection is fabricated. A method is developed to synthesize platinum nanoparticles and reduced graphene quantum dots onto the on-skin sensor to reduce electrode-skin contact impedance by increasing double-layer capacitance, thereby enhancing detection accuracy. Furthermore, an attention-based deep learning algorithm is introduced to differentiate impedance signals associated with early-stage NAFLD in high-fat-diet-fed low-density lipoprotein receptor knockout (Ldlr-/-) mice compared to healthy controls. The integration of an adhesive, soft on-skin sensor with low electrode-skin contact impedance and the attention-based deep learning algorithm significantly enhances the detection accuracy for early-stage NAFLD, achieving a rate above 97.5% with an area under the receiver operating characteristic curve (AUC) of 1.0. The findings present a non-invasive approach for early-stage NAFLD detection and display a strategy for improved early detection through on-skin electronics and deep learning.

BACKGROUND & AIMS: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. METHODS: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. RESULTS: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; p = 0.002). CONCLUSIONS: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. IMPACT AND IMPLICATIONS: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

BACKGROUND AND AIMS: Telehealth has emerged as an important mode of cirrhosis care delivery, but its use and satisfaction among vulnerable populations (eg, racial/ethnic minorities, socioeconomically disadvantaged, substance use disorders) are unknown. We evaluated digital capacity, telehealth use, satisfaction and associated factors among patients receiving hepatology care via telehealth (telehepatology) across 2 Veterans Affairs and 1 safety-net Healthcare systems. METHODS: English- and Spanish-speaking adults with cirrhosis (N = 256) completed surveys on telehealth use and satisfaction, quality of life, pandemic stress, alcohol use and depression. Logistic regression analyses assessed telehealth use and general linear models evaluated telehealth satisfaction. RESULTS: The mean age was 64.5 years, 80.9% were male and 35.9% Latino; 44.5% had alcohol-associated cirrhosis; 20.8% had decompensated cirrhosis; 100% had digital (phone/computer) capacity; and 75.0% used telehepatology in the prior 6 months. On multivariable analysis, participants with alcohol-associated (vs not) cirrhosis were less likely and those with greater pandemic stress were more likely to use telehepatology (odds ratio = 0.46 and 1.41, respectively; P < .05). Better quality of life was associated with higher telehepatology satisfaction and older age was associated with lower satisfaction (β = 0.01 and -0.01, respectively; P < .05). Latinos had higher satisfaction, but alcohol use disorder was associated with less satisfaction with telehepatology visits (β = 0.22 and -0.02, respectively; P

Background and aimsFatty liver disease (FLD), alcohol-associated and metabolically associated, often coexists. Increase in physical activity is associated with metabolic health and decreased FLD. We aimed to identify factors associated with physical activity and its improvement following FLD education in a racially diverse, vulnerable population.MethodsFrom February 19, 2020 to December 30, 2022, 314 adults with FLD at safety-net hepatology clinics in San Francisco were surveyed at baseline, immediately after FLD education, and at 6-month follow-up. After collecting clinical and sociodemographic data, logistic regression (adjusted for age, sex, and race/ethnicity) assessed factors associated with physical activity at baseline and its improvement following education.ResultsParticipant characteristics in those without vs with any physical activity were median age 49 vs 55 years, 64% vs 56% female, 66% vs 53% Hispanic race/ethnicity, 75% vs 55% obese, and 30% vs 22% consumed heavy alcohol, respectively. On multivariable analysis, older age was the only significant factor associated with physical activity at baseline (relative risk ratio 1.37 per decade increase, 95% confidence interval [CI] 1.07-1.75). Hispanic (vs non-Hispanic) participants had a significantly higher odds of improvement in physical activity (vs no change) 6 months after education (odds ratio 2.36, 95% CI 1.27-4.39). Among those with suboptimal or no physical activity at baseline, participants who consumed heavy alcohol (vs no drinking) had a significantly higher likelihood of achieving optimal physical activity following education (relative risk ratio 1.98, 95% CI 1.05-3.74).ConclusionDespite social and structural barriers, FLD education increased uptake of physical activity in vulnerable populations, especially among Hispanic individuals and those consuming heavy alcohol. Implementation of patient-centered education is important for FLD management.

Background: Increasing evidences suggest that nonalcoholic fatty liver disease (NAFLD) is associated with neuropsychiatric disorders. Nevertheless, whether there were causal associations between them remained vague. A causal association between neuropsychiatric disorders and NAFLD was investigated in this study. Methods: We assessed the published genome-wide association study summary statistics for NAFLD, seven mental disorder-related diseases and six central nervous system dysfunction-related diseases. The causal relationships were first assessed using two-sample and multivariable Mendelian randomization (MR). Then, sensitivity analyses were performed, followed by a reverse MR analysis to determine whether reverse causality is possible. Finally, we performed replication analyses and combined the findings from the above studies. Results: Our meta-analysis results showed NAFLD significantly increased the risk of anxiety disorders (OR = 1.016, 95% CI = 1.010–1.021, P value < 0.0001). In addition, major depressive disorder was the potential risk factor for NAFLD (OR = 1.233, 95% CI = 1.063–1.430, P value = 0.006). Multivariable MR analysis showed that the causal effect of major depressive disorder on NAFLD remained significant after considering body mass index, but the association disappeared after adjusting for the effect of waist circumference. Furthermore, other neuropsychiatric disorders and NAFLD were not found to be causally related. Conclusions: These results implied causal relationships of NAFLD with anxiety disorders and Major Depressive Disorder. This study highlighted the need to recognize and understand the connection between neuropsychiatric disorders and NAFLD to prevent the development of related diseases. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) and inflammatory periodontal disease (IPD) are both prevalent chronic conditions with growing recognition of potential interplay. Understanding their association is crucial for comprehensive disease management. Materials and Methods: A cross-sectional study was conducted among 300 participants, including 150 with NAFLD and 150 controls without NAFLD. Diagnosis of NAFLD was confirmed by liver ultrasound, while IPD was assessed through clinical periodontal examination. Demographic data, medical history, and lifestyle factors were recorded. Statistical analyses, including chi-square tests and logistic regression, were performed to determine the association between NAFLD and IPD. Results: Among participants with NAFLD, 65% were found to have IPD compared to 35% in the control group. Logistic regression analysis revealed a significant association between NAFLD and IPD (OR = 2.5, 95% CI: 1.7–3.8, p < 0.001). Additionally, individuals with NAFLD had higher mean periodontal pocket depth (4.2mm vs. 3.1mm) and greater gingival inflammation compared to controls. Conclusion: This study demonstrates a significant association between NAFLD and IPD, suggesting a potential bidirectional relationship. Comprehensive healthcare strategies addressing both conditions may be warranted to mitigate associated health risks. Further longitudinal studies are needed to elucidate the underlying mechanisms and explore therapeutic interventions targeting this comorbidity. [ABSTRACT FROM AUTHOR]

The function of hydroxysteroid dehydrogenase 12 (HSD17B12) in lipid metabolism is poorly understood. To study this further, we created mice with hepatocyte‐specific knockout of HSD17B12 (LiB12cKO). From 2 months on, these mice showed significant fat accumulation in their liver. As they aged, they also had a reduced whole‐body fat percentage. Interestingly, the liver fat accumulation did not result in the typical formation of large lipid droplets (LD); instead, small droplets were more prevalent. Thus, LiB12KO liver did not show increased macrovesicular steatosis with the increasing fat content, while microvesicular steatosis was the predominant feature in the liver. This indicates a failure in the LD expansion. This was associated with liver damage, presumably due to lipotoxicity. Notably, the lipidomics data did not support an essential role of HSD17B12 in fatty acid (FA) elongation. However, we did observe a decrease in the quantity of specific lipid species that contain FAs with carbon chain lengths of 18 and 20 atoms, including oleic acid. Of these, phosphatidylcholine and phosphatidylethanolamine have been shown to play a key role in LD formation, and a limited amount of these lipids could be part of the mechanism leading to the dysfunction in LD expansion. The increase in the Cidec expression further supported the deficiency in LD expansion in the LiB12cKO liver. This protein is crucial for the fusion and growth of LDs, along with the downregulation of several members of the major urinary protein family of proteins, which have recently been shown to be altered during endoplasmic reticulum stress. [ABSTRACT FROM AUTHOR]

Topiramate (TPM), a carbonic anhydrase (CA) inhibitor, is known for its anti-obesity effect. Even though, nonalcoholic fatty liver disease (NAFLD) is present in 80% of obese patients, TPM's effects on oxidant-antioxidant parameters and CA activity on fatty liver is not known. 24 Wistar albino rats were divided into four groups: control, TPM, diet, and diet + TPM. Diet groups fed with high-fat diet while control and TPM groups received standard chow for six weeks. Than 100 mg/kg/day TPM (po) was added to TPM groups for 21 days. Rats' weight and blood glucose levels were monitored weekly, and at the end of the study liver removed for biochemical and histological analysis. TPM eliminated the increases in weight and blood glucose levels caused by high-fat diet. TPM decreased CA activity in all groups. MDA levels increased significantly in TPM and DT groups (p = 0.004; p = 0.008). GSH levels were decreased in the TPM, D and DT groups (p = 0.004; p = 0.015; p = 0.003). Similarly, GPx activity levels were significantly decreased in all groups. Histological evaluation revealed notable infiltration, eosinophilia and cytoplasmic vacuolization in the TPM group. Steatosis and NAFLD activity score (NAS) were higher in the diet group. Ballooning, infiltration and NAS were higher in the diet + TPM group compared to control. CA activity negatively correlated with MDA (p < 0.001), and positively correlated with GSH (p < 0.001). TPM caused oxidant stress and liver damage, which are exacerbated in NAFLD induced rats. Therefore, use of TPM in patients with liver disease should be considered very carefully. [ABSTRACT FROM AUTHOR]

Objective: The triglyceride glucose (TyG) index and obesity are significantly closely related to the incidence of nonalcoholic fatty liver disease (NAFLD). The study aimed to investigate the relationship among the TyG index and its related parameters [TyG-waist circumference (WC) and TyG-body mass index (BMI)] with NAFLD. Methods: This was a cross-sectional study involving 8401 subjects who underwent a health examination in Karamay, Xinjiang Province, China. TyG, TyG-WC, TyG-BMI were calculated with the established formula. NAFLD was diagnosed and classified by ultrasonography. Results: The prevalence of NAFLD was markedly increased with increasing levels of TyG, TyG-WC and TyG-BMI. Logistic regression analysis suggested that WC, BMI, TyG, TyG-WC and TyG-BMI were independent risk factors for NAFLD. In receiver operating characteristic (ROC) analysis, TyG-BMI showed the largest area under the ROC curve (AUC) for the detection of NAFLD (0.856, 95% confidence interval: 0.848 ~ 0.865), and the results of sex analysis were consistent. TyG-BMI values of 176.69 (sensitivity: 86.9%, specificity: 68.1%), 193.02 (sensitivity: 73.8%, specificity: 73.6%) and 167.73 (sensitivity: 86.3%, specificity: 74.4%) were the optimal cutoff points to predict NAFLD in all participants, males and females, respectively. Conclusions: This study demonstrated that TyG and its related parameters are significantly correlated with NAFLD. TyG-BMI is an effective predictor or clinical marker for identifying NAFLD. [ABSTRACT FROM AUTHOR]

Patients with nonalcoholic fatty liver disease (NAFLD) have a higher risk of cardiac events. However, although the severity of liver fibrosis is related to worsening prognosis in patients with NAFLD, it is unclear whether the noninvasive liver fibrosis score has a predictive value for cardiac events. We evaluated 4071 patients with NAFLD diagnosed using ultrasonography. Liver fibrosis was assessed and divided into three groups based on the Fibrosis-4 (FIB4) index and NAFLD fibrosis score (NFS). The primary outcome of this study was major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, and revascularization due to coronary artery disease. The median age of the evaluated patients was 61 (52–69) years, and 2201 (54.1%) were male. During the median follow-up period of 6.6 years, 179 (4.4%) patients experienced MACE. Kaplan–Meier survival analysis demonstrated that MACE increased progressively with the FIB4 index (log-rank, p < 0.001) and NFS (log-rank, p < 0.001). Multivariable analysis showed that the higher the FIB4 index, the higher the risk for MACE (low group as reference vs. intermediate group, hazard ratio [HR]: 1.860 [95% confidence interval (CI), 1.326–2.610; p < 0.001]; vs. high group, HR:3.325 [95% CI, 2.017–5.479; p < 0.001]), as well as NFS (low NFS group as reference vs. intermediate group, HR: 1.938 [95% CI, 1.391–2.699; p < 0.001]; vs. high group, HR: 3.492 [95% CI, 1.997–6.105; p < 0.001]). The FIB4 index and NFS are associated with the probability of MACE in patients with NAFLD. The study design was approved by the ethics review board of Ogaki Municipal Hospital (approval number: 20221124–12, registration date: November 28th, 2022). https://www.ogaki-mh.jp/chiken/kenkyu.html. [Display omitted] • In patients with NAFLD, liver fibrosis status was associated with cardiac events. • The Fibrosis-4 index and NAFLD fibrosis score are both noninvasive liver fibrosis scoring indices. • These scores had significant prognostic values for the occurrence of MACE in patients with NAFLD. • Physicians should closely follow up on patients with a high liver fibrosis score. [ABSTRACT FROM AUTHOR]

Muscle quality index (MQI) is a novel indicator reflecting the quality of skeletal muscles. The association between MQI and the development of advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is unknown. We investigated the association of low MQI with advanced fibrosis among adults with NAFLD using a nationally representative sample of the US population. Adults with NAFLD who participated in the National Health and Nutrition Examination Survey (NHANES) 2011–2014 were included. Sex-specific standard was used to define low and extremely low MQI. Univariate and multivariate logistic regressions were used to assess the association between MQI level and advanced fibrosis. In the study, 3758 participants with NAFLD were included. The prevalence of low and extremely low MQI was 11.7% (95% CI 10.4–13.0%) and 2.2% (95% CI 1.6–2.8%), respectively. Among these participants, 96 were assessed to have advanced fibrosis. Individuals with low [(odds ratio (OR) 2.45, 95% confidence interval (CI) 1.22–4.91)] and extremely low MQI (OR 10.48, 95% CI 3.20–34.27) were associated with advanced fibrosis in multivariable analysis. A linear trend relationship was also observed between MQI level and the risk of advanced fibrosis (Ptrend = 0.001). Subgroup and sensitivity analyses yielded similar results to the main analyses. Decreased MQI is highly prevalent, and is associated with an increased risk of advanced fibrosis in adult US population with NAFLD. [ABSTRACT FROM AUTHOR]

Given the global high prevalence of MASLD and its poor CVD prognosis, it is essential to perform risk stratification for MASLD patients. The specific impact of High Sensitivity Troponins (hs-cTn) on mortality in MASLD patients remains unexplored. The NHANES databases from 1999 to 2004, which include data on high-sensitivity cardiac troponin (hs-cTn) levels and comorbidities, were linked with the most recent mortality dataset. Myocardial injury was determined using the 99th upper reference limits (URL) for hs-cTn. Our study included 3460 MASLD patients. The mean follow-up duration was 192 months, during which 1074 (23%) MASLD participants died from all-cause mortality, and 363 (7.3%) died from CVD mortality. Our findings indicate that MASLD patients with elevated levels of hs-cTnT (> 99th URL) exhibit increased risks of all-cause mortality [adjusted hazard ratio (aHR) = 1.93] and CVD mortality (aHR = 2.4). Similar results were observed for hs-cTnI, where the aHRs for all-cause mortality and CVD mortality were 2.03 and 2.97, respectively. Furthermore, we identified a nonlinear dose-response relationship between hs-cTn levels and the risk of mortality (P for nonlinearity < 0.001). Our findings suggest that hs-cTn can predict mortality risk in MASLD, aiding clinicians in risk-stratifying this population. Therefore, we recommend considering hs-cTn detection in individuals with MASLD to effectively assess their future mortality risk. [ABSTRACT FROM AUTHOR]

Background: There is a contradiction in the use of microbiota-therapies, including probiotics, prebiotics, and synbiotics, to improve the condition of patients with nonalcoholic fatty liver disease (NAFLD). The aim of this review was to evaluate the effect of microbiota-therapy on liver injury, inflammation, and lipid levels in individuals with NAFLD. Methods: Using Pubmed, Embase, Cochrane Library, and Web of Science databases were searched for articles on the use of prebiotic, probiotic, or synbiotic for the treatment of patients with NAFLD up to March 2024. Results: Thirty-four studies involving 12,682 individuals were included. Meta-analysis indicated that probiotic, prebiotic, and synbiotic supplementation significantly improved liver injury (hepatic fibrosis, SMD = -0.31; 95% CI: -0.53, -0.09; aspartate aminotransferase, SMD = -0.35; 95% CI: -0.55, -0.15; alanine aminotransferase, SMD = -0.48; 95% CI: -0.71, -0.25; alkaline phosphatase, SMD = -0.81; 95% CI: -1.55, -0.08), lipid profiles (triglycerides, SMD = -0.22; 95% CI: -0.43, -0.02), and inflammatory factors (high-density lipoprotein, SMD = -0.47; 95% CI: -0.88, -0.06; tumour necrosis factor alpha, SMD = -0.86 95% CI: -1.56, -0.56). Conclusion: Overall, supplementation with probiotic, prebiotic, or synbiotic had a positive effect on reducing liver enzymes, lipid profiles, and inflammatory cytokines in patients with NAFLD. [ABSTRACT FROM AUTHOR]

Introduction: Nonalcoholic or metabolism-associated fatty liver disease (NAFLD or MAFLD) and colorectal polyps are chronic conditions strongly linked to lifestyle factors. However, the precise causal link between NAFLD or MAFLD and the development of colorectal polyps is not yet fully understood. This study aimed to evaluate the association between NAFLD or MAFLD and the risk of colorectal polyps based on a meta-analysis and two-sample Mendelian randomization (MR) analyses. Methods: PubMed, Embase, Cochrane Library databases were searched for eligible studies to be included in the meta-analysis. We conducted a thorough search of the PubMed, Embase, and Cochrane Library databases to identify eligible studies prior to 22 March 2024. Subgroup analyses were performed based on sex, age, and geographical region. Causality between NAFLD/MAFLD and colorectal polyps was explored by using two-sample Mendelian randomization (MR) analyses. Results: Based on an analysis of 17 studies encompassed within thismeta-analysis, a significant correlation was identified between the presence of NAFLD/MAFLD and elevated incidence of colorectal polyps (NAFLD: OR = 1.57, 95% CI: 1.43-1.73, I² = 38%, p = 0.06; MAFLD: OR = 1.67, 95% CI: 1.40-2.00, I² = 77%, p = 0.002). However, current evidence does not support a causal relationship between NAFLD/MAFLD and the prevalence of colorectal polyps (OR= 0.9998315, 95% CI: 0.9987566-1.000907, P = 0.7587638). Conclusion: NAFLD/MAFLD demonstrated a significant positive correlation with an elevated risk of developing colorectal polyps. However, the MR analysis suggested that no causal relationship existed between NAFLD/MAFLD and colorectal polyps. Therefore, further research is required to identify the underlying mechanism of causal link between these diseases. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the post-cessation T2DM risk in male NAFLD and NAFLD-free smokers in a 7-year cohort study. Methods: The study population was male adults who underwent annual health checkups in a 7-year cohort study. Recent quitters were categorized into four groups based on their weight gain during follow-up: < 0 kg, 0–1.9 kg, 2.0–3.9 kg, and ≥ 4.0 kg. Cox proportional hazard models, adjusted for various variables, were used to estimate hazard ratios (HRs) for the association between post-cessation weight gain and incident T2DM in NAFLD and NAFLD-free individuals. Results: At baseline, we included 1,409 NAFLD and 5150 NAFLD-free individuals. During a total of 39,259 person-years of follow-up, 222 (15.8%) NAFLD patients and 621 (12.1%) NAFLD-free participants quit smoking, with the corresponding means (standard deviations) of post-cessation weight gain being 2.24 (3.26) kg and 1.15 (3.51) kg, respectively. Among NAFLD individuals, compared to current smokers, the fully adjusted HRs (95% CI) for incident T2DM were 0.41 (0.06–3.01), 2.39 (1.21–4.70), 4.48 (2.63–7.63), and 6.42 (3.68–11.23) for quitters with weight gains < 0 kg, 0.0–1.9 kg, 2.0–3.9 kg, and ≥ 4.0 kg, respectively. For NAFLD-free individuals, we only observed a significant association between post-cessation weight gain ≥ 4.0 kg and the risk of incident T2DM (P < 0.001). Further analysis revealed that the impact of post-cessation weight gain on T2DM risk was not affected by alcohol consumption or obesity status at baseline. Conclusions: Mild post-cessation weight gain significantly increased the risk of T2DM in male NAFLD patients but not in male NAFLD-free individuals. Therefore, it is recommended that individuals with NAFLD manage their weight after quitting smoking. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver ailment worldwide, in which nonpharmacological strategies have a considerable role in the treatment. Probiotic supplementation as well as physical exercise can improve cardiometabolic parameters, but further research is needed to determine the effects of combined treatment versus exercise alone in managing NAFLD-associated biomarkers, primarily liver enzymes, lipid markers, and insulin resistance. Objectives: This systematic review and meta-analysis aimed to evaluate the effects of probiotic supplementation, combined with exercise versus exercise alone, on liver enzymes and cardiometabolic markers in patients with NAFLD. Methods: A systematic review and meta-analysis of randomized clinical trials was performed by searching PubMed, Scopus, and Web of Science databases up to April 2024. The search was restricted to articles published in the English language and human studies. Random effects models were used to calculate weighted mean differences (WMD). Results: Pooled estimates (9 studies, 615 patients, intervention durations ranging from 8 to 48 weeks) revealed that probiotics plus exercise decreased aspartate transaminase (AST) [WMD=-5.64 U/L, p = 0.02], gamma-glutamyl transferase (GGT) [WMD=-7.09 U/L, p = 0.004], low-density lipoprotein (LDL) [WMD=-8.98 mg/dL, p = 0.03], total cholesterol (TC) [WMD=-16.97 mg/dL, p = 0.01], and homeostatic model assessment for insulin resistance (HOMA-IR) [WMD=-0.94, p = 0.005] significantly more than exercise only. However, probiotics plus exercise did not significantly change high-density lipoprotein (HDL) [WMD = 0.07 mg/dL, p = 0.9], fasting insulin [WMD=-1.47 µIU/mL, p = 0.4] or fasting blood glucose (FBG) [WMD=-1.57 mg/dL, p = 0.3] compared with exercise only. While not statistically significant, there were clinically relevant reductions in alanine aminotransferase (ALT) [WMD=-6.78 U/L, p = 0.1], triglycerides (TG) [WMD=-21.84 mg/dL, p = 0.1], and body weight (BW) [WMD=-1.45 kg, p = 0.5] for probiotics plus exercise compared with exercise only. The included studies exhibited significant heterogeneity for AST (I2 = 78.99%, p = 0.001), GGT (I2 = 73.87%, p = 0.004), LDL (I2 = 62.78%, p = 0.02), TC (I2 = 72.41%, p = 0.003), HOMA-IR (I2 = 93.86%, p = 0.001), HDL (I2 = 0.00%, p = 0.9), FBG (I2 = 66.30%, p = 0.01), ALT (I2 = 88.08%, p = 0.001), and TG (I2 = 85.46%, p = 0.001). There was no significant heterogeneity among the included studies for BW (I2 = 0.00%, p = 0.9). Conclusion: Probiotic supplementation combined with exercise training elicited better results compared to exercise alone on liver enzymes, lipid profile, and insulin resistance in patients with NAFLD. Systematic Review Registration: PROSPERO registration number CRD42023424290. [ABSTRACT FROM AUTHOR]

Purpose: Predicting nonalcoholic fatty liver disease (NAFLD) following pancreaticoduodenectomy (PD) is challenging, which delays therapeutic intervention and makes its prevention difficult. We conducted this study to assess the potential application of preoperative computed tomography (CT) radiomics for predicting NAFLD. Methods: The subjects of this retrospective study were 186 patients with PD from a single institution. We extracted the predictors of NAFLD after PD statistically from conventional clinical and radiomic features of the estimated remnant pancreas and whole liver region on preoperative nonenhanced CT images. Based on these predictors, we developed a machine-learning predictive model, which integrated clinical and radiomic features. A comparative model used only clinical features as predictors. Results: The incidence of NAFLD after PD was 43.5%. The variables of the clinicoradiomic model included one shape feature of the pancreas, two texture features of the liver, and sex; the variables of the clinical model were age, sex, and chemoradiotherapy. The accuracy%, precision%, recall%, F1 score, and area under the curve of the two models were 75.0, 72.7, 66.7, 69.6, and 0.80; and 69.6, 68.4, 54.2, 60.5, and 0.69, respectively. Conclusions: Preoperative CT-derived radiomic features from the pancreatic and liver regions are promising for the prediction of NAFLD post-PD. Using these features enhances the predictive model, enabling earlier intervention for high-risk patients. [ABSTRACT FROM AUTHOR]

Extrahepatic malignancies are the leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Of these cancers, pancreatic cancer is one of the most lethal; however, the link between NAFLD and pancreatic cancer remains unclear. Recently, various research results have been reported on the association between NAFLD and pancreatic cancer, and the results of compiling this information revealed the following. First, the prevalence of pancreatic cancer in patients with NAFLD is at 0.26%. Second, the currently evident pathogenesis includes intrapancreatic risk factors, such as: (1) non‐alcoholic fatty pancreas disease, and (2) intraductal papillary mucinous neoplasm; and extrapancreatic risk factors, such as: (1) insulin resistance and adipocytokines, (2) proinflammatory cytokines, and (3) dysbiosis. Finally, metformin and sodium–glucose cotransporter 2 inhibitors may reduce the risk of pancreatic cancer in diabetes patients with NAFLD. In this review, we summarize the recent evidence on the epidemiology and mechanisms for NAFLD‐related pancreatic cancer. We further discuss the impact of anti‐diabetic medication on pancreatic cancer. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, and it is characterized by a series of fatty liver diseases that can lead to severe liver disease. Although no therapeutic drug has been approved as an effective therapy for NAFLD to date, dietary changes and physical activity are thought to be the cornerstone of NAFLD management. For this reason, some articles are available to analyze the studies done so far using various modifications of intermittent fasting (IF) among animals and patients with NAFLD. Data from preclinical and clinical trials suggested that IF positively impacts inflammatory and metabolic markers in both animals and humans. Inflammation and oxidative stress are the major risk factors involved in the pathogenesis of NAFLD. IF has been shown to have positive benefits in alleviating metabolic disorders, promoting the browning of white tissue, resetting circadian rhythm, and activating autophagy of cells. This review is intended to provide a detailed synopsis of the protocols, potential mechanisms of action, and supporting evidence for IF in NAFLD. We will highlight what is currently known about IF approaches in NAFLD treatments in clinical populations with mechanism insight from animal studies, and the safety concerns in certain patient groups. The protocols of intermittent fasting (IF) are various. Data from trials suggested that IF positively impacts both humans and animals. IF has been shown to have potential treatments for nonalcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is a serious disease. There are no specific drugs for it, in part because of the lack of effective models to aid drug development. However, it has been shown that three-dimensional organoid culture systems can reproduce the organ structure and maintain the gene expression profile of the original tissue. Therefore, we aimed to construct NAFLD models from liver organoids for pharmacological and mechanism studies. We successfully observed morphological changes in normal liver tissue in mouse liver organoids with positive albumin (ALB) expression and potential for differentiation toward hepatocyte-like cells. The mRNA expression of the hepatocyte markers ALB and hepatocyte nuclear factor 4 alpha increased after liver organoid differentiation. We observed free fatty acid (FFA)-induced lipid accumulation in organoids with significant increases in alanine aminotransferase, aspartate aminotransferase, total bilirubin, and triglyceride levels. Moreover, FFA-induced inflammatory cytokines (interleukin-6, tumor necrosis factor-α, and nitric oxide) and fibrosis indicators (collagen type I α1 and laminin α1) were also increased. In addition, RNA sequencing results showed that the expression of key genes [nucleotide oligomerization domain-like receptor (NLR) family apoptosis inhibitory protein, interferon regulatory factor (IRF) 3, and IRF7] involved in NAFLD metabolic abnormalities and insulin resistance in the NLR signaling pathway was altered after FFA induction of the liver organoids. Finally, we found that JC2-11 and lanifibranor limited the FFA-induced increase in oil-red lipid droplets, liver damage, inflammation, and liver fibrosis. In conclusion, tissue structure, gene expression, and the response of mouse liver organoids to drugs can partially mimic in vivo liver tissue. Liver organoids can successfully construct NAFLD models for drug discovery research. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to evaluate the prevalence of anxiety and depression traits in Italian patients with metabolic dysfunction-associated steatotic liver disease (MASLD), and the possible relation with the severity of liver disease. Methods: Demographic, anthropometric, clinical and laboratory parameters were collected in patients referred to a metabolic unit for a comprehensive evaluation of possible liver disease. Hepatic steatosis and fibrosis were evaluated by surrogate biomarkers. Imaging (controlled attenuation parameter-CAP and vibration-controlled transient elastography-VCTE). Beck depression inventory (BDI) and state-trait anxiety inventory-Y (STAI-Y) were used to define depressive/anxiety states; calorie intake and lifestyle were self-assessed by questionnaires. Results: The whole sample comprised 286 patients (61.9% females; mean age 52.0 years; BMI, 34.6 kg/m2); 223 fulfilled MASLD criteria. BDI and trait anxiety scores were lower in the MASLD cohort, and the prevalence of both moderate/severe depression and severe trait anxiety was reduced compared with non-MASLD cases, despite VCTE-diagnosed fibrosis F3–F4 present in over 15% of cases. However, after correction for demographic and anthropometric confounders, MASLD was not associated with a lower risk of moderate/severe depression or severe anxiety trait (odds ratio, 0.34; 95% confidence interval, 0.12–1.01 and 0.79, 0.27–2.34). Additional adjustment for the severity of fibrosis did not change the results. No differences in state anxiety were observed. Conclusion: The risk of anxiety and depression in MASLD is not different from that generated by diabetes and obesity per se. MASLD patients do not perceive liver disease as a specific source of psychological distress, possibly as a consequence of the unawareness of progressive liver disease. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is considered an independent risk factor for cardiovascular disease (CVD). The overall morbidity and mortality of CVD increase with higher fibrosis stage in NAFLD. Carotid atherosclerosis (CAS) is an important predictor of cardiovascular events. However, the relationship between liver fibrosis degree and the risk of CAS in NAFLD patients remains uncertain. We aimed to investigate the relationship between noninvasive liver fibrosis markers and CAS risk in patients with NAFLD. This study included 3,302 participants with NAFLD. Participants were divided into a CAS group and a non-CAS group based on carotid artery ultrasound results. They were then stratified into quartiles using various noninvasive liver fibrosis markers (fibrosis-4 (FIB-4), modified FIB-4 (mFIB-4), aminotransferase to platelet ratio index (APRI), aminotransferase to alanine aminotransferase ratio (AAR), AAR-to-platelet ratio index (AARPRI), and Forns index) to assess the associations between these markers and the risk of CAS. In the NAFLD population, individuals with CAS exhibited elevated levels of blood pressure, glucose, lipids, and noninvasive liver fibrosis markers (p < 0.001). The higher quartiles of noninvasive liver fibrosis markers, including FIB-4, mFIB-4, AAR, AARPRI, and Forns index, were significantly associated with increased risks of CAS, even after adjusting for multiple CVD risk factors. In individuals with NAFLD, increased noninvasive liver fibrosis markers were independently associated with elevated CAS risk, which may be beneficial in assessing the risk of CVD in individuals with NAFLD. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Fibroblast growth factor 19 (FGF19) is an intestinal‐derived factor that plays a role in metabolic diseases. We performed a differential study of circulating FGF19 levels and investigated the causal effects of FGF19 on metabolic diseases using Mendelian randomization (MR).Firstly, 958 subjects were included in the physical examination center of affiliated hospital from January 2019 to January 2021. Dividing the subjects into different subgroups to compare FGF19 levels. We conducted a two‐sample MR analysis of genetically predicted circulating FGF19 in relation to alcohol, cardiovascular and metabolic biomarkers and diseases, and liver function biomarkers using publicly available genome‐wide association study summary statistics data.The circulating FGF19 levels in nonalcoholic fatty liver disease (NAFLD) patients were lower than those without NAFLD (P < 0.001). The FGF19 levels in participants with obese were lower than those without obese (P < 0.001). In two‐sample MR analyses, genetically predicted higher circulating FGF19 levels was significantly associated with lower aspartate aminotransferase, γ‐glutamyltransferase, triglycerides, total cholesterol, low‐density lipoprotein, and C‐reactive protein concentrations (P < 0.05) and a negative correlation with cardiovascular disease and cirrhosis whereas a positive association with type 2 diabetes mellitus (P < 0.05).Our study found that circulating FGF19 levels were lower in NAFLD and obese populations. Additionally, our MR research results support the causal effects of FGF19 on improved liver function, lipids, and reduced the occurrence of inflammation, cardiovascular disease, and cirrhosis. We found a positive correlation with diabetes, which may indicate a compensatory increase in regulating above FGF19 resistance states in humans. [ABSTRACT FROM AUTHOR]

Background and Aim: The introduction of the latest nomenclature, metabolic associated steatotic liver disease (MASLD), proposed by the multi‐society without Asian society consensus statement, aims to redefine the diagnostic criteria for metabolic associated fatty liver disease (MAFLD). However, its effect on the epidemiology in Asia remains unclear. Method: We conducted a population‐based cross‐sectional survey on fatty liver disease using multistage stratified random sampling of participants from Guangzhou, a representative area in China (ChiCTR2000033376). Demographic, socioeconomic, lifestyle, and laboratory data were collected. Hepatic steatosis and the severity of fibrosis were assessed using FibroScan. Results: A total of 7388 individuals were recruited, the proportion of which meeting the definitions for nonalcoholic fatty liver disease (NAFLD), MAFLD, and MASLD were 2359 (31.9%), 2666 (36.1%), and 2240 (30.3%), respectively. One hundred and twenty (1.6%) patients had cryptogenic SLD, and 537 (7.3%) patients were diagnosed with MetALD. MASLD did not significantly differ from NAFLD and MAFLD, except that MAFLD patients had a lower proportion of males, hypertension, and diabetes and were less likely to consume tea (P < 0.05). Both cryptogenic SLD and MASLD non‐MAFLD patients exhibited milder hepatic steatosis and a lower frequency of liver injury than NAFLD, MAFLD, or MASLD patients (all P < 0.05). An increased HOMA‐IR (adjusted OR: 1.33, 95% CI: 1.10–2.03) was associated with higher risk of moderate‐to‐severe steatosis for MASLD non‐MAFLD patients, while consuming more cups of tea (P for trend = 0.015) showed inverse associations. Conclusion: Irrespective of terminology used is that fatty liver disease is highly prevalent in the Han Chinese population. Differences in insulin resistance and lifestyle risk factors are associated with redefinition disparities. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Steatotic liver disease is common in people with HIV (PWH). Identifying those with advanced fibrosis (AF, bridging fibrosis or cirrhosis), F3-4, is important. We aimed to examine the performance of FIB-4 and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) in PWH to identify those with AF assessed by liver stiffness measurement (LSM). METHODS: We prospectively collected data on adults participating in 2 National Institute of Health-sponsored HIV NAFLD networks. All had HIV on antiretroviral therapy (ART) ≥6 months with HIV RNA <200 copies/mL. Those with viral hepatitis, other liver disease, excessive alcohol use, or hepatic decompensation were excluded. Vibration-controlled transient elastrography for LSM was performed, and AF defined as ≥11 kPa was compared with FIB-4 and NFS at predefined thresholds (<1.3 and >2.67 for FIB-4 and <-1.455 and >0.675 for NFS). RESULTS: A total of 1,065 participants were analyzed: mean age 51.6 years, 74% male, 28% White, 46% Black, 22% Hispanic, with 34% overweight (body mass index 25-29 kg/m²) and 43% obese (body mass index ≥30 kg/m²). Features of the metabolic syndrome were common: hyperlipidemia 35%, type 2 diabetes 17%, and hypertension 48%. The median CD4+ T-cell count was 666 cells/mm³, 74% had undetectable HIV RNA, and duration of HIV-1 was 17 years with most taking a nucleoside reverse transcriptase inhibitor (92%) and an integrase inhibitor (83%). The mean LSM was 6.3 kPa, and 6.3% had AF. The area under the receiver characteristic curve for FIB-4 and NFS to identify AF were 0.70 and 0.75, respectively. While both had high negative predictive values (97%-98%), the sensitivity at low thresholds and specificity at high thresholds were 64% and 97% for FIB-4 and 80% and 96% for NFS, respectively. Neither FIB-4 nor NFS at either threshold had good positive predictive value to detect AF. DISCUSSION: FIB-4 and NFS have excellent specificity and negative predictive value for detecting AF, and thus can be used as screening tools in PWH to exclude those with AF who do not need further testing (LSM) or referral to hepatologist. [ABSTRACT FROM AUTHOR]

Background: The current study aims to assess cardiovascular risk factors (CVRFs) among diabetic versus nondiabetic nonalcoholic fatty liver disease (NAFLD) patients. NAFLD is the most common hepatic disorder worldwide which is directly associated with diverse CVRFs such as type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS). Materials and Methods: The current cross-sectional population-based study has been conducted on 1031 NAFLD patients. After excluding 340 prediabetes patients, the NAFLD patients were divided into T2DM and normal blood glucose (NBG). Then, CVRFs were compared between the two groups. Results: Out of 691 NAFLD cases included in the study, 337 (48.8%) patients had T2DM. In the T2DM and NBG groups, the body mass index (BMI) was 31.2 ± 4.6 and 29.9 ± 4.3 kg/m2, respectively (P = 0.001). The waist circumference was 102.2 ± 10.2 and 97.6 ± 10.6 cm, respectively (P < 0.001). The systolic blood pressure was 123.3 ± 15.6 and 119.6 ± 13.6 mmHg, respectively (P = 0.043). The triglyceride levels were 191.9 ± 104.7 and 176.5 ± 89.6 mg/dL, respectively (P = 0.042). Generally, these factors were significantly higher among the diabetic patients. Besides, cardiovascular disease (CVD), hypertension, and MS were statistically more prevalent in NAFLD patients with T2DM (P < 0.001) than nondiabetic NAFLD patients. In multiple logistic regression models, the odds ratio of CVD, hypertension, and MS was 2.18, 2.12, and 6.63 for patients with T2DM compared with NBG, respectively. Adjustment was made for age, sex, BMI, smoking, and physical activity. Conclusion: CVRFs were higher in NAFLD patients with T2DM than NAFLD patients with NBG. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) affects over a third of the US population and 25% globally, with current treatments proving ineffective. This study investigates whether manipulating brown adipose tissue (BAT) and beige fat activity by housing C57BL/6J mice at thermoneutral (27 °C) or standard temperatures (22 °C) impacts NAFLD development. Male mice were fed either a chow diet (CHD) or a "fast food" diet (FFD) for 10 weeks. Mice at 27 °C had reduced food intake but increased body weight and plasma leptin levels. FFD-fed mice at 27 °C had greater liver weight (2.6 vs. 1.8 g), triglyceride content (7.6 vs. 3.9 mg/g), and hepatic steatosis compared to those at 22 °C. Gene expression of fatty acid synthase, sterol regulatory element-binding protein 1, and fatty acid translocase CD36 was elevated in FFD-fed mice at 27 °C, but not in CHD-fed mice. Thermoneutral housing also reduced expression of thermogenic markers in BAT and inguinal white adipose tissue (WAT) and caused BAT whitening. In conclusion, thermoneutrality inhibits thermogenic markers and exacerbates NAFLD. Activating BAT or promoting WAT browning via cold exposure or other stimuli may offer a strategy for managing NAFLD. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease is the most prevalent chronic liver disease globally and is linked to augmented susceptibility to type 2 diabetes mellitus (DM), cardiovascular disease, and microvascular complications inherent to DM, such as nephropathy, neuropathy, and retinopathy. The fibrosis-4 (FIB-4) scoring system, a noninvasive tool, is useful for predicting the extent of liver fibrosis across diverse pathologies. This study aimed to assess the potential predictive role of FIB-4 scores in microvascular complications associated with diabetes. The medical records of patients with type 2 DM admitted to our endocrinology clinic between February 2019 and December 2020 were retrospectively evaluated. Parameters including demographic attributes, fasting blood glucose, glycated hemoglobin, aspartate aminotransferase, alanine aminotransferase, thrombocyte levels, and microvascular complications were recorded. The FIB-4 score was computed, and patients were categorized based on these scores (<1.3 and ≥ 1.3). The analysis included 312 patients with a median age of 60 (50–68 years); 39.7 % were men. The median duration of diabetes was 10 years (5–20 years), and the median FIB-4 score was 0.93 (0.63–1.34). Neuropathy, nephropathy, and retinopathy were observed in 50.6 %, 31.4 %, and 34 % of the patients, respectively. Although the FIB-4 score did not differ significantly between patients with and without neuropathy or retinopathy, patients with nephropathy exhibited higher FIB-4 scores. Notably, patients with FIB-4 scores ≥ 1.3 demonstrated a significantly higher prevalence of nephropathy. Logistic regression analysis demonstrated that higher FIB-4 scores were significantly associated with an increased risk of nephropathy. The FIB-4 score is a cost-effective and straightforward tool with potential applicability in predicting nephropathy in individuals with type 2 DM. [ABSTRACT FROM AUTHOR]

Background: GLP-1 receptor agonists (GLP-1 RAs) have been shown to improve glycemic control and insulin sensitivity and reduce body weight in obese patients with type 2 diabetes mellitus (T2D). This trial sought to evaluate the therapeutic effect of oral and subcutaneous semaglutide in NAFLD and its sequelae in obesity and/or T2D. Methods: In an open-labelled intervention study, the sample was 180 patients classified into three parallel groups (1:1:1): group I received oral semaglutide, group II patients received injectable semaglutide, and group III received pioglitazone and/or vitamin E. Patients were evaluated at 6 and 12 months. Results: There was a substantial improvement in lipid profile, liver enzymes, and body mass index, especially in group II. As for HDL, only group II showed a consistent increase at both 6 months (51 ± 4.62 mg/dL) and 12 months (50.08 ± 2.45 mg/dL) compared with baseline (45.6 ± 6.37 mg/dL) (p-value < 0.001). Despite the non-significant difference in NAFLD fibrosis score (NFS) (p-value = 0.45 and 0.63), group II had significantly lower scores of the fibrosis-4 score (FIB-4), liver stiffness measurement (LSM), and controlled attenuation parameter (CAP) at 6 and 12 months (p-value < 0.001). Conclusions: Semaglutide improves lipid profile, liver steatosis, and fibrosis parameters and reduces the BMI in T2D and obese patients with NAFLD. [ABSTRACT FROM AUTHOR]

The aim of this meta‐analysis is to investigate the sources of heterogeneity in randomized clinical trials examining the effects of curcumin supplementation on liver aminotransferases in subjects with nonalcoholic fatty liver disease (NAFLD). We conducted a systematic search of the PubMed, SCOPUS, and Web of Science databases for randomized clinical trials and identified 15 studies (n = 835 subjects). We used random‐effects models with DerSimonian‐Laird methods to analyze the serum levels of alanine aminotransferase and aspartate aminotransferase enzymes. Our results indicate that curcumin did not affect serum alanine aminotransferase, but it did reduce aspartate aminotransferase levels. Notably, both outcomes showed high heterogeneity (p < 0.01). Subgroup analysis revealed that adding piperine to curcumin did not benefit aminotransferase levels in NAFLD patients. Additionally, we found a negative correlation between the duration of the intervention and the relative (mg/kg/day) curcumin dose with the reduction in liver aminotransferases. In summary, the sources of heterogeneity identified in our study are likely attributed to the duration of the intervention and the relative dose of curcumin. Consequently, longer trials utilizing high doses of curcumin could diminish the positive impact of curcumin in reducing serum levels of aminotransferases in patients with NAFLD. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is a disorder in which excess fat accumulates in hepatocytes and can lead to serious complications. Oxidative stress is one of the leading causes of NAFLD. Pomegranates are considered antioxidant‐rich fruit. This systematic review study was aimed to investigate the impact of pomegranate on NAFLD. PubMed, Scopus, and Google Scholar databases/search engines (from inception up to July 2023) were searched for interventional studies (human and animal) that examined the effects of supplementation with different parts of pomegranate including fruits, peels, seeds, or flower on NAFLD outcomes. A total of 222 articles were retrieved following the initial search. After excluding duplicates, the title and abstract of 114 articles were screened. Afterward, irrelevant articles were removed and the full texts of the remaining 27 articles were reviewed. Eventually, 19 articles (16 animal and three human interventional studies) that met the inclusion criteria, published between 2009 and 2023, were included in this systematic review. Our study indicates the potential beneficial effects of different parts of pomegranate on the improvement of NAFLD. However, given that the majority of the included articles were animal studies, further investigations in the form of human clinical trials are warranted to suggest a clinical indication of such interventions. [ABSTRACT FROM AUTHOR]

The purpose of the present clinical trial was to determine the impact of zinc supplementation on serum liver enzymes, steatosis severity, lipid profile, and inflammatory status in overweight or obese children with nonalcoholic steatohepatitis (NASH). This randomized controlled trial was conducted by enrolling 60 children with NASH, aged 10–18 years old. The participants were randomly assigned to two groups that received either 30 mg/day of elemental zinc or placebo for 16 weeks. The severity of liver steatosis was evaluated using liver ultrasonography. Fasting blood samples were collected from each patient at the beginning and after 16 weeks of intervention to measure biochemical parameters. Following a 16-week intervention, zinc supplementation compared with placebo significantly decreased serum alanine aminotransferase (ALT) concentrations and high-sensitivity C-reactive protein and considerably enhanced HDL-cholesterol values. However, zinc intake had no considerable impact on aspartate aminotransferase, the severity of liver steatosis, anthropometric parameters, and other lipid indices versus the placebo group. Overall, zinc supplementation showed a promising impact on serum ALT, HDL-cholesterol, and inflammatory status in overweight or obese children suffering from NASH. Zinc supplementation may be a new strategy for the amelioration of NASH in overweight or obese children. This trial has been registered on the Iranian website for registration of clinical trials with the special ID of IRCT20200531047614N1 (https://www.irct.ir/trial/48543). [ABSTRACT FROM AUTHOR]

Context The cardiovascular benefits of semaglutide are established; however, its effects on surrogate vascular markers and liver function are not known. Objective To investigate the effects of semaglutide on vascular, endothelial, and liver function in patients with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD). Methods Overall, 75 consecutive subjects with T2DM and NAFLD were enrolled: 50 patients received semaglutide 1 mg (treatment group) and 25 patients received dipeptidyl peptidase 4 inhibitors (control group). All patients underwent a clinical, vascular, and hepatic examination with Fibroscan elastography at 4 and 12 months after inclusion in the study. Results Treatment with semaglutide resulted in a reduction of Controlled Attenuation Parameter (CAP) score, E fibrosis score, NAFLD fibrosis score, Fibrosis-4 (FIB-4) score and perfused boundary region (PBR) at 4 and at 12 months (P <.05), contrary to controls. Patients treated with semaglutide showed a greater decrease of central systolic blood pressure (SBP) (−6% vs −4%, P =.048 and −11% vs −9%, P =.039), augmentation index (AIx) (−59% vs −52%, P =.041 and −70% vs −57%, P =.022), and pulse wave velocity (PWV) (−6% vs −3.5%, P =.019 and −12% vs −10%, P =.036) at 4 and at 12 months, respectively. In all patients, ΔPWV and ΔPBR were correlated with a corresponding reduction of CAP, E fibrosis, NAFLD fibrosis, and FIB-4 scores. Conclusion Twelve-month treatment with semaglutide simultaneously improves arterial stiffness, endothelial function, and liver steatosis and fibrosis in patients with T2DM and NAFLD. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) constitutes an independent risk factor for the development of coronary heart disease. Low-grade inflammation has been shown to play an important role in the development of atherosclerosis and NAFLD. Free fatty acid receptor 4 (FFAR4/GPR120), which is involved in damping inflammatory reactions, may represent a promising target for the treatment of inflammatory diseases. Our objective was to evaluate the effect of TUG-891, the synthetic agonist of FFAR4/GPR120, on fatty liver in vivo. Methods: The effect of TUG-891 on fatty liver was investigated in apoE−/− mice fed a high-fat diet (HFD), using microscopic, biochemical, molecular, and proteomic methods. Results: Treatment with TUG-891 inhibited the progression of liver steatosis in apoE−/− mice, as evidenced by histological analysis, and reduced the accumulation of TG in the liver. This action was associated with a decrease in plasma AST levels. TUG-891 decreased the expression of liver genes and proteins involved in de novo lipogenesis (Srebp-1c, Fasn and Scd1) and decreased the expression of genes related to oxidation and uptake (Acox1, Ehhadh, Cd36, Fabp1). Furthermore, TUG-891 modified the levels of selected factors related to glucose metabolism (decreased Glut2, Pdk4 and Pklr, and increased G6pdx). Conclusion: Pharmacological stimulation of FFAR4 may represent a promising lead in the search for drugs that inhibit NAFLD. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the immunogenicity of the hepatitis B virus (HBV) vaccine by applying a normal and high-dose hepatitis B virus vaccination program in the mice modeling of non-alcoholic fatty liver disease (NAFLD). NAFLD was induced in mouse livers via diet. At the 10-week mark, both groups were divided into 3 subgroups. While the standard dose vaccination program was applied on days 0, 7, and 21, two high-dose programs were applied: one was applied on days 0 and 7, and the other was applied on days 0, 7, and 21. All mice were euthanized. Blood samples from anti-HB titers; T follicular helper, T follicular regulatory, CD27+, and CD38+ cells; and the liver, spleen, and thymus were taken for histopathologic evaluation. NAFLD subgroups receiving high doses showed higher hepatocyte ballooning scores than normal-dose subgroup. There were differences in CD27+ and CD27+CD38+ cells in animals fed on different diets, without any differences or interactions in terms of vaccine protocols. In the NAFLD group, a negative correlation was observed between anti-HB titers and T helper and CD27+ cells, while a positive correlation was observed with CD38+ cells. NAFLD induced changes in immune parameters in mice, but there was no difference in vaccine efficacy among the applied vaccine protocols. Based on this study's results, high-dose vaccination protocols are not recommended in cases of NAFLD, as they do not enhance efficacy and may lead to increased liver damage. [ABSTRACT FROM AUTHOR]

Purpose: The need to investigate the pathogenesis and treatment of nonalcoholic fatty liver disease (NAFLD) has led to the development of multiple mouse models. The aim of this study was to validate a fast food diet (FFD) mouse model that is introduced as being close to the human disease. Methods: Eight to nine weeks old male and female C57BL/6 J mice were randomly allocated to a FFD group or to a chow diet (CD) group. Every four weeks, mice were weighed, and blood samples were collected for the measurement of glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TGs) and total cholesterol. After 25 weeks, mice were sacrificed, and liver tissue was histologically evaluated. Results: FFD mice gained more weight (p = 0.049) and presented a higher liver-to-body weight ratio (p < 0.001) compared to CD mice. FFD group presented with greater steatosis, hepatocellular ballooning and NAFLD activity score (NAS), whereas lobular inflammation and fibrosis were not significantly different compared to CD. When stratified by sex, NAS was different between FFD and CD groups in both male and female mice. Group by time interaction was significant for weight, ALT and cholesterol, but not for glucose, AST and TGs. Conclusion: FFD mice presented with morphologic and biochemical features of NAFLD and with greater hepatic steatosis, hepatocellular ballooning and NAS, but not lobular inflammation and fibrosis, compared to CD mice. These results only partly validate the FFD mouse model for NAFLD, at least for a 6-month feeding period. [ABSTRACT FROM AUTHOR]

Background and Aims: This study examines the relationships between epicardial adipose tissue (EAT), nonalcoholic fatty liver disease (NAFLD), and coronary artery calcium score (CACS) using non‐ECG‐gated CT scans. It aims to determine the effectiveness of EAT measurements and NAFLD as predictors for coronary artery disease (CAD). Methods: This cross‐sectional study was conducted at a specialized center, focusing on individuals who underwent non‐ECG‐gated chest CT scans without contrast. We evaluated EAT thickness and density in three areas: the right atrioventricular groove, the free wall of the right ventricle, and the central area of the right anterior interventricular groove. Additionally, we measured CACS and determined the presence of NAFLD by comparing liver‐to‐spleen density ratios. Statistical analyses, including regression models, were performed using SPSS (version 26). Results: In this study, we enrolled 365 participants, including 203 males with an average age of 47 ± 17.93 years. EAT thickness was 6.28 ± 1.62 mm, and EAT density was −96.07 ± 12.47 Hounsfield units (HU). The mean CACS was 22.27 ± 79.01, and the mean liver density was 50.01 ± 10.76 HU. A significant positive correlation was observed between EAT thickness and CACS (r = 0.208, p < 0.001). EAT density showed a significant negative correlation with CACS (r = −0.155, p = 0.003). No correlation was found between NAFLD and CACS. Univariate logistic regression analysis identified significant predictors of increased CACS, including EAT thickness (OR: 1.803), EAT density (OR: 0.671), diabetes mellitus (DM) (OR: 5.921), and hypertension (HTN) (OR: 7.414). Multivariate analysis confirmed the significance of EAT thickness (OR: 0.682), DM (OR: 3.66), and HTN (OR: 2.79) as predictors of elevated CACS. Conclusion: Our findings demonstrate that increased EAT thickness and decreased density are associated with higher CACS. Also, both DM and HTN significantly contribute to increased CACS. These results support the inclusion of EAT measurements in cardiovascular risk assessment models to enhance diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in patients with diabetes; limited data suggested that statins may reduce the risk of NAFLD progression. This study aimed to examine the association between statins and the development or progression of NAFLD in veterans with diabetes. In a new-user negative control design, we conducted a retrospective propensity score (PS)-matched cohort study of patients with diabetes between 2003 and 2015. After excluding patients with other causes of liver disease, we formed PS using 85 characteristics. The primary outcome was a composite NAFLD progression outcome. Primary analysis examined odds of outcome in PS-matched cohort. Post-hoc analysis included a PS-matched cohort of statin users with intensive lowering of low-density lipoprotein-cholesterol (LDL-C) vs low-intensity lowering. We matched 34,102 pairs from 300,739 statin users and 38,038 non-users. The composite outcome occurred in 8.8% of statin users and 8.6% of non-users (odds ratio (OR) 1.02, 95% confidence interval (95% CI) 0.97–1.08). In the post-hoc analysis, intensive lowering of LDL-C compared to low-intensity showed increased NAFLD progression (OR 1.21, 95% CI 1.13–1.30). This study showed that statin use in patients with diabetes was not associated with decreased or increased risk of NAFLD progression. Intensive LDL-C lowering, compared to low-intensity LDL-C lowering, was associated with an increased risk of NAFLD progression. [ABSTRACT FROM AUTHOR]

Purpose To explore the relationship between liver fat content (LFC) and nonalcoholic fatty liver disease (NAFLD) and determine the new threshold of LFC to diagnose NAFLD. Methods The data from questionnaire survey, general physical examination, laboratory examination, and image examination were collected. Multivariate regression analysis, receiver operating characteristic curve analysis, smooth curve fitting, and threshold effect analysis were performed using the R software to investigate the relationship between LFC and NAFLD and to identify the new threshold of LFC to diagnose NAFLD. Results The prevalence of NAFLD was 30.42%, with a significantly higher prevalence in men than in women. Regression analyses demonstrated that LFC odds ratio [95% confidence interval (CI)] was 1.28 (95% CI: 1.24–1.31) in fully-adjust model. Analysis of the LFC quartile, with Q1 as a reference, revealed that the odds ratios of NAFLD were 1.47 (95% CI: 1.08–1.99), 2.29 (95% CI: 1.72–3.06), and 10.02 (95% CI: 7.45–13.47) for Q2, Q3, and Q4 groups, respectively. Smooth curve fitting and threshold effect analysis displayed a nonlinear relationship between LFC and NAFLD, and the threshold was 4.5%. The receiver operating characteristic curve indicated that when LFC was 4.5%, the area under curve (95% CI) was 0.80 (0.79–0.82), and the sensitivity and specificity of LFC in diagnosing NAFLD were 0.64% and 0.82%, respectively. Conclusion The relationship between LFC and NAFLD was sigmoidal, with an inflection point of 4.5%. What is already known on this topic At present, there is no standard and uniform threshold for QCT diagnosis of hepatic steatosis, and its threshold is based on MRI. Therefore, this study aimed to explore the correlation between LFC and NAFLD and establish a novel threshold of LFC to diagnose NAFLD. What this study adds This is the first study to report a sigmoidal relationship between LFC and NAFLD with a threshold effect. When LFC was higher than 4.5%, the risk of NAFLD was significantly increased. LFC can be quantified by QCT, which can be a valuable tool for evaluating the NAFLD risk. How this study might affect research, practice, or policy The results of this study have important implications for research, practice, and policy. QCT can be utilized as a noninvasive technique for quantitatively assessing hepatic steatosis, providing a valuable reference for screening, diagnosing, and evaluating the treatment effect of NAFLD. [ABSTRACT FROM AUTHOR]

Background: Although gut microbiota and serum metabolite composition have been observed to be altered in patients with non-alcoholic fatty liver disease (NAFLD), previous observational studies have demonstrated inconsistent results. As this may be influenced by factors such as confounders and reverse causality, we used Mendelian randomization to clarify the causal effect of gut microbiota and blood metabolites on NAFLD. Methods: In this research, we performed a two-step Mendelian randomization analysis by utilizing genome-wide association study (GWAS) data obtained from MiBioGen and UK Biobank. To mitigate potential errors, we employed False Discovery Rate (FDR) correction and linkage unbalanced regression (LDSC) analysis. Sensitivity analyses including cML-MA and bidirectional Mendelian randomization were performed to ensure the robustness of the results. Results: In this study, a total of nine gut microbiota and seven metabolites were found to be significantly associated with NAFLD. MR analysis of the above findings revealed a causal relationship between Ruminococcus2 and cysteine-glutathione disulfide (OR = 1.17, 95%CI = 1.006–1.369, P = 0.041), as well as 3-indoleglyoxylic acid (OR = 1.18, 95%CI = 1.011–1.370, P = 0.036). For each incremental standard deviation in Ruminococcus2 abundance, there was a corresponding 26% reduction in NAFLD risk (OR = 0.74, 95%CI = 0.61–0.89, P = 0.0012), accompanied by a 17% increase in cysteine-glutathione disulfide levels (OR = 1.17, 95%CI = 1.01–1.37, P = 0.041) and an 18% increase in 3-indoleglyoxylic acid levels (OR = 1.18, 95%CI = 0.81-1.00, P = 0.036). The proportion mediated by cysteine-glutathione disulfide is 11.2%, while the proportion mediated by 3-indoleglyoxylic acid is 7.5%. Conclusion: Our study suggests that increased abundance of specific gut microbiota may reduce the risk of developing NAFLD, and this relationship could potentially be mediated through blood metabolites. [ABSTRACT FROM AUTHOR]

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