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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: Alterations in the bacteria, such as the periodontal bacteria, might be considered potential risk factors for nonalcoholic fatty liver disease (NAFLD). Most studies analyzing this association have focused mainly on a specific periodontal bacteria (Porphyromonas gingivalis) and have involved relatively small study populations (tens or hundreds of individuals). To address this gap, a sizable, nationally representative adult population was utilized to investigate the association between the incidence of NAFLD and high serum IgG antibodies for 19 periodontal bacteria. Methods: To explore this association, data from the Third National Health and Nutrition Examination Survey (NHANES III)—which provides a cross-sectional representation of the noninstitutionalized U.S. population, encompassing 33,994 individuals—were analyzed. Participants aged 40 years and above with data on NAFLD—determined by the gold standard of ultrasound examination (USON)—as well as comprehensive records of serum IgG antibodies against periodontal bacteria, were included, resulting in a final analysis subset of 6,330 individuals. Results: Using a cluster analysis based on the Socransky classification scheme for oral microorganisms, antibody titers for the 19 bacteria were grouped into four clusters—Red-Green, Orange-Blue, Yellow-Orange, and Orange-Red. When these clusters, as well as individual antibody relationships with NAFLD, were examined, the adjusted odds ratios (ORs) ranged from 0.958 [95% confidence interval (CI): 0.916, 1.003] to 1.021 [95% CI: 0.987, 1.055]. This indicated that no statistically significant associations were found (P > 0.05), underscoring the absence of a meaningful link. Conclusions: In summary, it was discovered that there is currently no evidence to correlate serum antibodies to periodontal pathogens with NAFLD in the nationally representative NHANES III. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Aims: We aimed to explore the extent to which individuals previously diagnosed with nonalcoholic fatty liver disease (NAFLD) meet the criteria fulfilled with the new nomenclature, metabolic dysfunction‐associated steatotic liver disease (MASLD), within an Asian primary clinic cohort. Additionally, we assessed the reliability of the diagnostic performance of FIB‐4 and NAFLD fibrosis score (NFS) for MASLD within the primary clinic cohort. Methods: This retrospective cross‐sectional study included participants who underwent magnetic resonance elastography and abdominal ultrasonography during their health checkups at nationwide health promotion centers (n = 6740). Results: The prevalence rates of NAFLD and MASLD diagnosed based on ultrasonography results were 36.7% and 38.0%, respectively. Notably, 96.8% of patients in the NAFLD cohort fulfilled the new criteria for MASLD. A small proportion of patients with NAFLD (n = 80, 3.2%) did not meet the MASLD criteria. Additionally, 168 patients (6.6%) were newly added to the MASLD group. The areas under the receiver operating characteristic curves for diagnosing advanced hepatic fibrosis for FIB‐4 (0.824 in NAFLD vs. 0.818 in MASLD, p = 0.891) and NFS (0.803 in NAFLD vs. 0.781 in MASLD, p = 0.618) were comparable between the MASLD and NAFLD groups. Furthermore, the sensitivity, specificity, positive predictive value, and negative predictive value of FIB‐4 and NFS for advanced fibrosis in MASLD were also comparable to those in NAFLD. Conclusions: Most patients (96.8%) previously diagnosed with NAFLD fulfilled the new criteria for MASLD in an Asian primary clinic cohort. Diagnostic performance of FIB‐4 in the MASLD cohort demonstrated satisfactory results. [ABSTRACT FROM AUTHOR]

Lipid disorders are related to the risk of nonalcoholic fatty liver disease (NAFLD). Remnant cholesterol (RC), a nonclassical and once-neglected risk factor for NAFLD, has recently received new attention. In this study, we assessed the relationship between the RC levels and NAFLD risk. We searched across PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure, with no restrictions on publication languages. Retrospective cohort studies and cross-sectional studies were enrolled from the inception of the databases until August 6, 2023. A random-effect model was applied to construct the mean difference, and a 95% confidence interval was applied to assess the relationship between the RC levels and NAFLD risk. We used two methods to estimate RC levels: Calculated-1 subtracts low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol from total cholesterol; Calculated-2 uses the Friedewald formula for LDL-C when triglycerides are <4.0 mmol/L, otherwise directly measured. A total of 265 published studies were selected through preliminary retrieval. Of these, six studies met the inclusion requirements and were enrolled in the meta-analysis. The RC level in the NAFLD group was significantly higher than that in the non-NAFLD group (mean difference: 0.18, 95% confidence interval: 0.10–0.26, P < 0.00001). We conducted subgroup analyses of computational methods and geographic regions. Notably, in the subgroup analysis of Calculation Method 2, the NAFLD group had significantly higher RC levels than the non-NAFLD group. On the other hand, in Calculation Method 1, the difference between the two groups was insignificant. In both the Asian and non-Asian populations, the RC levels were significantly higher in the NAFLD group than in the non-NAFLD group. The association of RC with an increased NAFLD risk was not dependent on the triglyceride. This meta-analysis suggests that elevated RC levels are associated with an increased risk of NAFLD. In addition to the conventional risk factors for fatty liver, clinicians should be concerned about the RC levels in the clinic. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD), more appropriately known as metabolic (dysfunction) associated fatty liver disease (MAFLD), a prevalent condition in type 2 diabetes mellitus (T2DM) patients, is a complex condition involving hepatic lipid accumulation, inflammation, and liver fibrosis. The gut-liver axis is closely linked to metabolic dysfunction, insulin resistance, inflammation, and oxidative stress that are leading to the cooccurrence of MAFLD and T2DM cardiovascular diseases (CVDs). The purpose of this review is to raise awareness about the role of the gut-liver axis in the progression of MAFLD, T2DM and CVDs with a critical analysis of available treatment options for T2DM and MAFLD and their impact on cardiovascular health. This study analysed over 100 articles on this topic, using online searches and predefined keywords, to understand and summarise published research. Numerous studies have shown a strong correlation between gut dysfunction, particularly the gut microbiota and its metabolites, and the occurrence and progression of MAFLD and type 2 diabetes mellitus (T2DM). Herein, this article also examines the impact of the gut-liver axis on MAFLD, T2DM, and related complications, focusing on the role of gut microbiota dysbiosis in insulin resistance, T2DM and obesity-related cardiovascular complications. The study suggests potential treatment targets for MAFLD linked to T2DM, focusing on cardiovascular outcomes and the molecular mechanism of the gut-liver axis, as gut microbiota dysbiosis contributes to obesity-related metabolic abnormalities. [ABSTRACT FROM AUTHOR]

Background: The systemic immune-inflammation index (SII) and trouble sleeping are independent risk factors for nonalcoholic fatty liver disease (NAFLD). Nevertheless, studies investigating the combined effects of the SII and troubled sleeping on NAFLD are lacking. In this study, we investigated the independent relationships and interactions between trouble sleeping and the SII among patients with NAFLD. Methods: Data from seven survey cycles of the National Health and Nutrition Examination Survey (NHANES) (2005–2018) were analyzed. The SII was obtained by counting platelets, neutrophils, and lymphocytes. NAFLD was diagnosed using the US fatty liver index. Trouble sleeping was diagnosed using a sleep disorder questionnaire. The correlation between trouble sleeping and the SII in NAFLD was investigated using multiple regression analysis, subgroup stratification, interaction tests, and restricted cubic spline, and the presence or absence of additive or multiplicative interactions was determined. Additionally, mediation analyses were performed to explore the role of the SII in mediating the effects of trouble sleeping on NAFLD. Results: The survey included 10 963 participants. Multivariate logistic regression revealed that SII (OR: 1.21, 95% CI 1.08–1.35) and trouble sleeping (OR: 1.24, 95% CI 1.05–1.47) were positively correlated with NAFLD. For NAFLD, an additive but not multiplicative interaction was noted between the SII and trouble sleeping. The SII partially mediated the association between trouble sleeping and NAFLD, accounting for approximately 3.11% of the total effect (95% CI 0.01–0.05). Conclusion: The SII and trouble sleeping were independently correlated with NAFLD risk. Furthermore, a combined effect may exist between SII and trouble sleeping, which increases the risk of NAFLD. [ABSTRACT FROM AUTHOR]

Metabolic associated fatty liver disease is a chronic liver disease associated with obesity, type 2 diabetes and hyperlipidemia. The incidence of metabolic associated fatty liver disease is increasing year by year, which seriously affects the quality of life of patients and brings heavy medical burden to patients and society. Its pathogenesis involves a variety of factors, such as two-hit and multiple-hit, Helicobacter pylori infection and excessive activation of sympathetic nerves. The treatment methods include changing lifestyle. improving insulin resistance, regulating intestinal flora, and macrophage targeted therapy. This article reviews the progress in the diagnosis and treatment of metabolic associated fatty liver disease. [ABSTRACT FROM AUTHOR]

It is currently unclear whether there is a connection between Life's Essential 8 (LE8) and cardiovascular disease (CVD), as well as mortality in people with nonalcoholic fatty liver disease (NAFLD). Our goal was to explore these relationships by examining data collected in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. We identified eligible participants with NAFLD based on NHANES 2005–2018 data. CVD status was acquired through self-reported information, and using the National Death Index, mortality data were prospectively matched. The diagnosis of NAFLD relied on noninvasive biomarkers. The research involved 9094 individuals who were identified as having NAFLD, with a mean age of 52.05 years. Each incremental LE8 score exhibited a significant association, leading to a 3%, 3%, 4%, 3%, 3%, 4%, and 4% reduction in the odds of experiencing CVD, ischemic heart disease, congestive heart failure, coronary heart disease, heart attack, angina, and stroke in individuals with NAFLD. A strong correlation was found between maintaining a superior level of Cardiovascular Health (CVH), as shown by a LE8 score ranging from 80 to 100, and a reduced occurrence of CVD and its various forms in NAFLD (all p for trend < 0.0001). Likewise, LE8 demonstrated protective benefits on mortality in NAFLD, showing that following a high CVH (in contrast to low CVH) was linked to reductions of 64%, 71%, and 74% in all-cause, CVD, and cancer mortality, respectively. Restricted cubic spline analyses suggested noteworthy dose-response relationships between LE8 and CVD, specifically its types in NAFLD, and a nonlinear correlation with CVD mortality. Interaction analyses highlighted age and race as significant effect modifiers. CVH, as evaluated by LE8, demonstrated an independent association with decreased odds of CVD and mortality risk in individuals with NAFLD. Our findings substantiate that adhering to LE8 may alleviate the excessive burden of CVD and mortality in the context of NAFLD. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Although nonalcoholic fatty liver disease (NAFLD) and lipoprotein(a) [Lp(a)] are associated with cardiovascular diseases, existing data on Lp(a) in NAFLD are conflicting. The aim of this systematic review and meta‐analysis was to summarize and compare data on circulating Lp(a) between NAFLD patients and non‐NAFLD controls.A systematic literature search was performed in PubMed, Scopus, and Cochrane Library. This meta‐analysis included 18 studies containing data on 74 691 individuals (20 220 patients with NAFLD and 54 471 controls).Circulating Lp(a) was similar between patients with NAFLD and controls (standardized mean difference [SMD] 0.09; 95% confidence interval [95% CI] −0.21, 0.38). The heterogeneity among studies was high (I2 = 100%); no publication bias was detected (Egger's test P = 0.941). However, in subgroup analysis, Lp(a) was lower in NAFLD patients than controls, when Lp(a) was measured with nephelometry (SMD ‐0.26; 95% CI ‐0.46, −0.06), but not turbidimetry; this analysis also resulted in mild reduction of heterogeneity within the subgroup of nephelometry (I2 = 87%). The sensitivity analyses, based on the exclusion of studies with Newcastle‐Ottawa Scale score ≤6 (n = 5), studies in which liver biopsy was used for NAFLD diagnosis (n = 4) or studies that adopted the criteria of metabolic dysfunction‐associated fatty liver disease (n = 2), and meta‐regression analysis did not explain the high heterogeneity among studies.Overall, circulating Lp(a) was similar between NAFLD patients and non‐NAFLD controls; however, patients with NAFLD had lower circulating Lp(a) compared with controls, when Lp(a) was measured with nephelometry. These results should be cautiously interpreted, because of the high heterogeneity among studies. [ABSTRACT FROM AUTHOR]

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) represents a major clinical complication of obesity. Methods: In this study, we used magnetic resonance (MR) methods to determine the effect of obesity treatment with semaglutide, a GLP-1 receptor agonist, on the liver fat content and selected metabolic variables. We investigated whether treatment would affect the acute response of liver fat to glucose and fructose administration and whether it would affect the fatty acid profile of VLDL-triglycerides. Sixteen obese non-diabetic men underwent a 16-week dietary intervention and 16-week treatment with subcutaneous semaglutide in a crossover design without a washout period. The order of the interventions was randomized. Results: After treatment, body weight of the subjects decreased by 5% and liver fat by a third, whereas dietary intervention had no impact on these parameters. The decrease in liver fat with semaglutide did not correlate with changes in body weight and other measures of adiposity and was unrelated to improved insulin sensitivity. Conclusions: The proportion of palmitic and palmitoleic acids in VLDL-triglycerides decreased after treatment, suggesting that the beneficial effects of semaglutide on liver fat are mediated by the suppression of de novo lipogenesis. [ABSTRACT FROM AUTHOR]

Inflammation plays a crucial role in atherosclerosis and nonalcoholic fatty liver disease (NAFLD). We previously engineered a recombinant Lactococcus lactis strain expressing the Ling-Zhi immunomodulatory protein (L. lactis-LZ8). This study investigated the anti-atherosclerotic effects of L. lactis-LZ8 in rabbits fed a high-fat diet (HFD). Changes in body weight, serum lipid profiles, and liver function were monitored. The aorta and liver tissues were analyzed for gross pathology and histopathology. Eight-week administration of L. lactis-LZ8 with HFD ameliorated atherosclerosis by downregulating protein and gene expression associated with lipid metabolism and inflammation in the aortas. The rabbits receiving L. lactis-LZ8 exhibited a significant dose-dependent reduction in hepatic fat accumulation. RNA sequencing of the livers revealed that inflammatory genes in the L. lactis-LZ8 groups were downregulated compared to the HFD group. Disease ontology enrichment analysis indicated that these genes were involved in atherosclerosis. Gene set enrichment analysis plots revealed significant enrichment in the gene sets related to cholesterol homeostasis. CIBERSORT immune cell fraction analysis indicated significant infiltration by regulatory T cells, CD8+ T cells, activated dendritic cells, and natural killer cells in the L. lactis-LZ8 group. Our studies underscore LZ8's role in precision nutrition, providing a potential solution to the current challenges in modifying atherosclerosis and NAFLD. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a clinical syndrome that exhibits similar histopathological changes in the liver as alcoholic liver disease, despite the absence of a history of excessive alcohol consumption in patients. It encompasses a range of conditions, including simple fatty liver, non-alcoholic steatohepatitis (NASH), fatty liver cirrhosis, and hepatocellular carcinoma. NASH represents a critical stage in the progression of this disease. Such diseases have been officially named as metabolic-associated fatty liver disease, and there is a general consensus that the progression of this disease can be accurately described by its activity and degree of fibrosis. The emergence of liver fibrosis has a significant impact on the prognosis of these patients. Without timely diagnosis and treatment, the condition may gradually deteriorate, leading to liver cirrhosis and its associated complications, and there is even a possibility of developing hepatocellular carcinoma. Effective prevention and treatment of MAFLD have the potential to further halt the progression of chronic liver diseases and reduce the risks of liver cirrhosis, liver-related disabilities, and fatalities. [ABSTRACT FROM AUTHOR]

Objective: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing, presenting a treatment challenge due to limited options. Endoplasmic reticulum (ER) stress and associated lipid metabolism disorders are main causes of NAFLD, making it important to inhibit ER stress for effective treatment. Fagopyrum dibotrys has hypolipidemic, anti-inflammatory and hepatoprotective properties, showing promise in treating NAFLD. However, its effects on ER stress in NAFLD remain unclear. This study used a high-fat diet (HFD) to establish NAFLD mouse models and supplemented with Fagopyrum dibotrys extract (FDE) to evaluate its therapeutic effect and underlying mechanisms. Results: We showed that FDE supplementation reduced the severity of hepatic steatosis and lowered triglycerides (TG) and total cholesterol (TC) levels in NAFLD mice. At the molecular level, FDE supplementation reduced hepatic lipid deposition by downregulating lipogenic markers (SREBP-1c, SCD1) and upregulating fatty acid oxidase CPT1α expression. Additionally, FDE treatment inhibited the overexpression of ER stress markers (GRP78, CHOP, and P-EIF2α) in NAFLD mice livers, and blocked the activation of the PERK-EIF2α-CHOP pathway, demonstrating its role in maintaining ER homeostasis. Considering that activation of the PERK pathway could exacerbate lipid deposition, our findings suggest that FDE has a protective effect against hepatic steatosis in NAFLD mice by attenuating ER stress, and the potential mechanism is through inhibiting the PERK pathway. [ABSTRACT FROM AUTHOR]

Introduction: Non-alcoholic fatty liver disease (NAFLD) and obesity have become one of the most common chronic diseases, and the global prevalence is increasing year by year. Both are accompanied by hypersensitive C-reactive protein (hs-CRP). At present, there are many predictors of NAFLD. Exploring the relationship between hs-CRP and nonalcoholic fatty liver disease in non-obese people will be helpful for risk prediction and clinical screening in high-risk populations. Objective: To explore the relationship between levels of serum hs-CRP and the presence of NAFLD in non-obese people. Methods: A total of 6558 participants who underwent physical examination from March 2017 to November 2017. Multivariate logistic regression was utilized to analyze the risk factors associated with NAFLD. Results: This study including 4240 males and 2318 females ranging from 20 to 94 years. In 1396 patients with NAFLD, the prevalence rate was 21.3%, among which 1056 (24.9%) males and 340 (14.7%) females had NAFLD. The prevalence of NAFLD was much higher in males compared to females (χ2 = 93.748, P < 0.001). In the nonalcoholic fatty liver group, various factors including hs-CRP, age, WC, BMI, systolic blood pressure and blood pressure diastolic blood pressure were significantly higher than those in the control group. Logistic regression analysis confirmed that hs-CRP was an independent risk factor for NAFLD, even after adjusting for relevant variables. Conclusions: The prevalence of NAFLD increases with the level of hs-CRP in both men and women who are non-obese. Hs-CRP levels are an important risk factor for nonalcoholic fatty liver disease in non-obese individuals. [ABSTRACT FROM AUTHOR]

Background: Bile acids are vital regulators of liver metabolism, and their dysregulation is closely linked with the progression of nonalcoholic fatty liver disease (NAFLD). Profiling these bile acids may provide valuable diagnostic and prognostic markers for these conditions. This study aimed to evaluate bile acid profiles in NAFLD patients and assess their potential as biomarkers for diagnosing and predicting disease progression. Serum levels of 14 bile acids were measured in 25 normal healthy controls (NHC), 35patients with metabolic dysfunction–associated steatotic liver disease (MASLD), and 40 patients with NASH, categorized by the NAFLD Activity Score (NAS). Quantification was performed using high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS). Results: Primary unconjugated bile acids, CA and CDCA, along with conjugated acids GCA, GCDCA, TCA, and TCDCA, were significantly elevated in both MASLD and NASH compared to NHC (all p < 0.05). While levels increased progressively from NHC to MASLD to NASH, no significant differences were observed between MASLD and NASH except for GCA and TCA (P < 0.05). Similarly, secondary bile acids LCA, TLCA, GUDCA, and TUDCA were higher in MASLD and NASH compared to NHC (all p < 0.05). Logistic regression identified CA (odds ratio = 2.05, p = 0.02), CDCA (odds ratio = 1.58, p = 0.04), GCA (odds ratio = 1.92, p = 0.03) and DCA (odds ratio = 2.06, p = 0.04) as significant predictors of fibrosis. For active inflammation, GCA (odds ratio = 2.04, p = 0.04), and TCA (odds ratio = 1.94, p = 0.04) were significant predictors. In steatosis, CA, CDCA, GCA, DCA, TDCA, TLCA, and UDCA were notable predictors, with high odds ratios. Conclusion: The study highlights significant alterations in bile acid profiles associated with NAFLD progression. Specific bile acids, such as CA, GCA, TCA, and TCDCA are strong predictors of disease severity, indicating their potential as biomarkers for NAFLD treatment and prognosis. [ABSTRACT FROM AUTHOR]

Objective: Research evidence suggests that exercise is a potent therapeutic strategy for non-alcoholic fatty liver disease (NAFLD). Many investigations have delved into the curative potential of diverse exercise regimens on NAFLD. This investigation synthesizes findings from randomized controlled trials via a network meta-analysis to evaluate the efficacy of exercise-based interventions on NAFLD. Methods: We conducted a search across five electronic databases (Web of Science, EMBASE, PubMed, SCOPUS, and CNKI)to identify randomized controlled trials (RCTs) comparing the effects of different exercise modalities on metabolic profiles and liver functions in patients with NAFLD. The literature search was comprehensive up to 15, December 2023. The selected studies were subjected to a rigorous quality appraisal and risk of bias analysis in accordance with the Cochrane Handbook's guidelines, version 5.1.0. We employed Stata/MP 17 for the network meta-analysis, presenting effect sizes as standardized mean differences (SMD). Results: This study aggregated results from 28 studies, involving a total of 1,606 participants. The network meta-analysis revealed that aerobic exercise was the most effective intervention for improving BMI in patients with NAFLD, demonstrating a significant decrease in BMI (-0.72, 95%CI: -0.98 to -0.46; p < 0.05; Surface Under the Cumulative Ranking (SUCRA) = 79.8%). HIIT was the top intervention for enhancing HDL-C (0.12, 95% CI: 0.04 to 0.20; p < 0.05; SUCRA = 76.1%). Resistance exercise was the most effective for reducing LDL-C (-0.20, 95% CI: -0.33 to -0.06; p < 0.05; SUCRA = 69.7%). Mind-body exercise showed superior effectiveness in improving TC (-0.67, 95% CI: -1.10 to -0.24; p < 0.05; SUCRA = 89.7%), TG = -0.67, 95% CI: -1.10 to -0.24; p < 0.05; SUCRA = 99.6%), AST (-8.07, 95% CI: -12.88 to -3.25; p < 0.05; SUCRA = 76.1%), ALT (-12.56, 95% CI: -17.54 to -7.58; p < 0.05; SUCRA = 99.5%), and GGT (-13.77, 95% CI: -22.00 to -5.54; p < 0.05; SUCRA = 81.8%). Conclusion: This network meta-analysis demonstrates that exercise interventions positively affect various metabolic profiles and liver functions in NAFLD patients. Mind-body exercises are particularly effective, surpassing other exercise forms in improving metabolic profiles and liver functions. [ABSTRACT FROM AUTHOR]

Aims: To investigate the relationship between the level of physical activity and sedentary behavior in young adults aged 18-35 and to evaluate the effects of this relationship on musculoskeletal pain, posture, muscle shortness, and trunk muscle endurance Material and Methods: 219 students were included in this cross-sectional study. Data were obtained by using the case report form which determines the demographic characteristics and sedentary behavior of the students, The International Physical Activity Index - short form, posture analysis form, muscle shortness evaluation form, and trunk muscle endurance evaluation form. Results: In the study, 66.2% of patients were female and 33.8% were male. The ratio of highly active individuals in males, and inactive and insufficiently active individuals in females was significantly higher (p <0.05). Musculoskeletal pain was significantly higher in inactive and insufficiently active individuals (p<0.001). A statistically significant negative correlation exists between physical activity level and pain frequency, duration, and pain scores (p<0.001). There was a statistically significant positive correlation between trunk endurance tests and both physical activity level and exercise participation. In individuals who did not exercise, there was a significant shortening of the lumbar extensor muscles and gastrosoleus and an increase in thoracic kyphosis (p<0.05). It was observed that a statistically significant positive correlation exists between daily sitting time and elbow, wrist, and knee pain, an increase in lumbar lordosis (p<0.05). In those who spent more time in front of the computer, head-neck and elbow pain, the duration of pain, and pain scores, the shortness of the teres major, latissimus dorsi, rhomboideus major, and minor muscles, thoracic kyphosis, shoulder protraction, and anterior head tilt were significantly higher (p<0.05). Conclusion: In our study, we observed that students with low levels of physical activity and sedentary behavior experienced decreased trunk muscle endurance, posture disorders, increased pain, and heightened muscle shortness. [ABSTRACT FROM AUTHOR]

Backgrounds and Aims: In the pathogenesis of nonalcoholic fatty liver disease (NAFLD), inflammation plays a pivotal role. The presence of inflammatory cells is closely linked with epicardial adipose tissue (EAT). A recently identified prognostic indicator for cardiovascular disease (CVD) is the ratio of monocyte count to HDL-cholesterol (MHR). Our primary aim was to investigate the relationship between EAT and markers of inflammation in individuals with NAFLD, and to evaluate its predictability using straightforward diagnostic measures. Material-Method: This retrospective study included 218 patients who underwent thoracic computed tomography angiography between 2014 and 2021. The patients were divided into the NAFLD group (HU<48 IU) and the non-NAFLD group (HU>48 IU) according to the liver attenuation ratio. 136 patients in the NAFLD group and 82 in the non-NAFLD group. Results: The body mass index (BMI), triglyceride levels, notably the EAT volume and MHR in the NAFLD group, exhibited higher values than non-NAFLD group. Among participants in the NAFLD group, a positive correlation was observed between EAT volume and factors such as age, MHR, c-reactive protein, BMI, urea, glucose, and alanine aminotransferase. Through linear regression analysis, it was determined that MHR stood as the sole independent predictor of EAT volume in patients with NAFLD. Conclusion: EAT volume, a risk marker for CVD, can be predicted in NAFLD patients by MHR without radiological methods. Thus, easier and earlier detection of NAFLD patients in the high-risk group for CVD will be possible. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) poses a risk for numerous metabolic diseases. To date, the U.S. Food and Drug Administration has not yet approved any medications for the treatment of NAFLD, for which developing therapeutic drugs is urgent. Dihydromyricetin (DMY), the most abundant flavonoid in vine tea, has been shown to be hepatoprotective. Its application was limited by low bioavailability in vivo; Methods: In order to improve the bioavailability of DMY and achieve liver-targeted delivery, we designed a DMY-loaded stiff-soft hybrid biomimetic nano drug delivery system (DMY-hNE). The in vivo absorption, distribution, pharmacokinetic profiles, and anti-NAFLD efficacy of DMY-hNE were studied; Results: DMY-hNE was composed of a stiff core and soft shell, which led to enhanced uptake by gastrointestinal epithelial cells and increased penetration of the mucus barrier, thus improving the in vivo absorption, plasma DMY concentration, and liver distribution versus free DMY. In an early NAFLD mouse model, DMY-hNE effectively ameliorated fatty lesions accompanied with reduced lipid levels and liver tissue inflammation; Conclusions: These findings suggested that DMY-hNE is a promising platform for liver drug delivery and treatment of hepatopathy. [ABSTRACT FROM AUTHOR]

Background: Chronic liver diseases (CLD), cirrhosis, and hepatocellular carcinoma (HCC) cause significant morbidity and mortality. Unfortunately, patients with CLD often go undiagnosed until progression to cirrhosis and HCC. We aimed to determine the proportion of primary care patients with severe liver disease outcomes that had missed or delayed CLD diagnoses. Methods: This retrospective cohort study evaluated primary care patients with a diagnosis of cirrhosis, HCC, or other severe liver disease outcome between 2012 and 2021. The outcomes of interest were missed and delayed diagnoses of CLD, defined as the absence of a CLD diagnosis (missed) or first appearance of CLD on the same day as the cirrhosis diagnosis (delayed). Univariate analyses were performed to describe the cohort. Multivariable logistic regression models analyzed the association of aminotransferase elevations with the outcomes of interest. Results: Of 667 patients with cirrhosis or HCC, 133 (20%) had a missed CLD diagnosis, and 243 (36%) had a delayed CLD diagnosis. Alcohol-related liver disease was the most common etiology among patients with missed/delayed diagnoses. A lower proportion of patients with missed/delayed diagnoses had an elevation in ALT or AST compared to patients with timely diagnoses (61% vs. 77%, p < 0.001). Elevated aminotransferase values were associated with lower odds of a missed/delayed diagnosis (OR 0.47; 95%CI 0.34–0.66). Conclusions: Most patients with cirrhosis or HCC had missed or delayed diagnoses of CLD in the context of probable overreliance on aminotransferase elevation for CLD detection. Enhanced screening for high prevalence CLD, especially alcohol, in primary care is needed. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is a common metabolic disease, and in recent years, the incidence rate of NAFLD is gradually increasing, which seriously threatens human health. As a traditional treatment method, external therapy of traditional Chinese medicine (TCM) has shown unique advantages and potential in the treatment of NAFLD. This article provides a detailed analysis of the TCM understanding of the etiology and pathogenesis of NAFLD, the application of TCM external therapy in clinical research, and the research on its therapeutic mechanism, in order to provide reference and guidance for further research in this field. [ABSTRACT FROM AUTHOR]

Leonurine is a natural product unique to the Lamiaceae plant Leonurus japonicus Houtt., and it has attracted attention due to its anti-oxidative stress, anti-apoptosis, anti-fibrosis, and metabolic regulation properties. Also, it plays an important role in the prevention and treatment of nonalcoholic fatty liver disease (NAFLD) through a variety of biological mechanisms, but its mechanism of action remains to be elucidated. Therefore, this study aims to preliminarily explore the mechanisms of action of leonurine in NAFLD. Mice were randomly divided into four groups: the normal control (NC) group, the Model (M) group, the leonurine treatment (LH) group, and the fenofibrate treatment (FB) group. The NAFLD model was induced by a high-fat high-sugar diet (HFHSD) for 12 weeks, and liver pathological changes and biochemical indices were observed after 12 weeks. Transcriptomic analysis results indicated that leonurine intervention reversed the high-fat high-sugar diet-induced changes in lipid metabolism-related genes such as stearoyl-CoA desaturase 1 (Scd1), Spermine Synthase (Sms), AP-1 Transcription Factor Subunit (Fos), Oxysterol Binding Protein Like 5 (Osbpl5), and FK506 binding protein 5 (Fkbp5) in liver tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results suggest that leonurine may exert its lipid-lowering effects through the AMP-activated protein kinase (AMPK) signaling pathway. Liver lipidomic analysis showed that leonurine could alter the abundance of lipid molecules related to fatty acyl (FAs) and glycerophospholipids (GPs) such as TxB3, carnitine C12-OH, carnitine C18:1-OH, and LPC (20:3/0:0). Molecular biology experiments and molecular docking techniques verified that leonurine might improve hepatic lipid metabolism through the alpha-1A adrenergic receptor (ADRA1a)/AMPK/SCD1 axis. In summary, the present study explored the mechanism by which leonurine ameliorated NAFLD by inhibiting hepatic lipid synthesis via the ADRA1a/AMPK/SCD1 axis. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease worldwide while still lacks drugs for treatment or prevention. We aimed to investigate the causal role of glucose-dependent insulinotropic polypeptide receptor agonists (GIPRAs) on NAFLD and identify the mediated risk factors by which GIPRAs exert their therapeutic effects. Genetic proxies of GIPRAs were identified as cis-SNPs of GIPR associated with both the gene expression level and HbA1c and analyses including colocalization and linkage disequilibrium (LD) were performed for validation. We then performed two-sample two-step mendelian randomization to determine the causal effect of GIPRAs on NAFLD. The MR analysis suggested genetic proxies of GIPRAs were causally associated with reduced risk of NAFLD (Odds ratio (OR): 0.46, 95 % confidence interval (95 % CI): 0.24–0.88, P = 0.02) and T2DM (OR: 0.10, 95 % CI: 0.07–0.13, P < 0.01). In addition, Mediation analysis showed evidence of indirect effect of GIPRAs on NAFLD via TRIG (0.88, [0.85–0.92], P < 0.01) and HDL-C (0.85, [0.80–0.90], P < 0.01). Our study provided strong evidence to support the causal role of GIPRAs on reducing the risk of NAFLD probably through improving lipid metabolism, especially TG and HDL-C, providing guidance for future clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Chronic liver disease (CLD) is associated with increased morbidity and mortality. Understanding health disparities can inform appropriate interventions. We aimed to study mortality outcomes of those with CLD by the income level (income-to-poverty ratio <5 as lower income and ≥5 as higher income). Methods: In this retrospective cohort study, we analyzed data of adults from the National Health and Nutrition Examination Survey, 1999–2018. CLD included viral hepatitis, nonalcoholic fatty liver disease (NAFLD), and alcohol-associated liver disease (ALD). Results: We analyzed 59,204 adults: 47,224 without CLD and 11,980 with CLD. The CLD group was older, more likely male, racial/ethnic minority groups or foreign-born, and had lower educational and income levels (p < 0.001). Most (80.02%) CLD participants did not have college degrees and had lower income (79.18%). Among CLD participants, similar differences were observed between lower and higher income groups. Lower income participants with CLD had significantly higher 10-year cumulative mortality compared to higher income CLD participants (15.26 vs. 8.00%, p < 0.001), with consistent findings in viral hepatitis and NAFLD subgroups (p < 0.001) but not ALD (p = 0.71). Adjusting for age, sex, race, birthplace, lower income CLD participants were 2.01 (hazard ratio [HR]: 2.01; 95% CI: 1.79–2.26) times more likely to die overall and in viral hepatitis (HR: 2.05; 95% CI: 1.31–3.24) and NAFLD subgroups (HR: 2.32; 95% CI: 1.69–3.18) but not ALD (HR: 1.17; 95% CI: 0.55–2.51). Conclusion: Lower income, foreign-born, and racial/ethnic minority groups were disproportionately represented among those with CLD, with lower income and CLD individuals having double the mortality risk compared to their higher income counterparts. Interventions should be culturally appropriate and address socioeconomic barriers. [ABSTRACT FROM AUTHOR]

Point-of-care tools to assess advanced liver fibrosis, including the NFS, BARD, FIB-4, and APRI, are of major interest due to their noninvasive nature. However, these tools have not been investigated extensively in the Latina population. Given that the highest rate of NAFLD in Latinos and the most severe presentation of non-alcoholic fatty liver disease (NAFLD) is more common in women, we hypothesize that ethnicity may play a role in predicting liver fibrosis, particularly in women. We determined whether ethnicity alone or in association with other parameters can predict the severity of fibrosis in women with NAFLD when included in four tools. We retrospectively included 562 Latina and 133 White Caucasian women with a history of NAFLD. Associations between ethnicity and liver fibrosis severity using the four fibrosis predictor models were studied using backward selection multinomial logistic regression. Latina women compared to White showed lower body mass index (p\0.001), higher HbA1c (p\0.001), lower prevalence of bariatric surgery (p\0.001), lower likelihood to smoke (p = 0.003), and higher prevalence of chronic kidney disease stages 3-5 (p = 0.01). Some clinical variables were associated with fibrosis but not univocally in each tool. We did not find differences in the outcome of the four models when holding all other factors and examining ethnicity alone between Latina and White women. Although we did not include data on liver histology, this is the first study examining the role of ethnicity in predicting the severity of fibrosis using established noninvasive scores and documenting no association between Latina ethnicity and the severity of fibrosis in women with NAFLD. [ABSTRACT FROM AUTHOR]

Metabolism‐related diseases, including diabetes mellitus, obesity, hyperlipidemia, and nonalcoholic fatty liver disease, are becoming increasingly prevalent, thereby posing significant threats to human health and longevity. Proteins, as the primary mediators of biological activities, undergo various posttranslational modifications (PTMs), including phosphorylation, ubiquitination, acetylation, methylation, and SUMOylation, among others, which substantially diversify their functions. These modifications are crucial in the physiological and pathological processes associated with metabolic disorders. Despite advancements in the field, there remains a deficiency in contemporary summaries addressing how these modifications influence processes of metabolic disease. This review aims to systematically elucidate the mechanisms through which PTM of proteins impact the progression of metabolic diseases, including diabetes, obesity, hyperlipidemia, and nonalcoholic fatty liver disease. Additionally, the limitations of the current body of research are critically assessed. Leveraging PTMs of proteins provides novel insights and therapeutic targets for the prevention and treatment of metabolic disorders. Numerous drugs designed to target these modifications are currently in preclinical or clinical trials. This review also provides a comprehensive summary. By elucidating the intricate interplay between PTMs and metabolic pathways, this study advances understanding of the molecular mechanisms underlying metabolic dysfunction, thereby facilitating the development of more precise and effective disease management strategies. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with an average five-year survival rate in the US of 19.6%. With the advent of HBV and HCV treatment and prevention, along with the rising rates of obesity, nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are set to overtake infectious causes as the most common cause of HCC. While surgical resection and transplantation can be curative when amenable, the disease is most commonly unresectable on presentation, and other treatment approaches are the mainstay of therapy. In these patients, locoregional therapies have evolved as a vital tool in both palliation for advanced disease and as a bridge to surgical resection and transplantation. In this review, we will be exploring the primary locoregional therapies for HCC in patients with NAFLD, including transarterial chemoembolization (TACE), bland transarterial embolization (TAE), transarterial radioembolization (TARE), and percutaneous ablation. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD), recently proposed to be renamed to metabolic dysfunction-associated steatotic liver disease (MASLD), is a major global public health concern, affecting approximately 25–30% of the adult population and possibly leading to cirrhosis, hepatocellular carcinoma, and liver transplantation. The liver is involved in the actions of sex steroids via their hepatic metabolism and production of the sex hormone-binding globulin (SHBG). Liver disease, including NAFLD, is associated with reproductive dysfunction in men and women, and the prevalence of NAFLD in patients with hypogonadism is considerable. A wide spectrum of possible pathophysiological mechanisms linking NAFLD and male/female hypogonadism has been investigated. As therapies targeting NAFLD may impact hypogonadism in men and women, and vice versa, treatments of the latter may affect NAFLD, and an insight into their pathophysiological pathways is imperative. This paper aims to elucidate the complex association between NAFLD and hypogonadism in men and women and discuss the therapeutic options and their impact on both conditions. [ABSTRACT FROM AUTHOR]

Indole is a microbial metabolite produced by the gut microbiota through the degradation of dietary tryptophan, known for its well‐established anti‐inflammatory and antioxidant properties. In this study, we collected fecal samples from mice fed a high‐fat diet (HFD) and those on a standard diet (SD), then conducted 16S rRNA sequencing to analyze their gut microbiota. The analysis revealed distinct differences in the dominant bacterial species between the two groups, with a significant decrease in indole‐producing probiotics in the HFD mice compared to the SD group. Then we administered oral indole treatment to male C57BL/6J mice with HFD‐induced NAFLD and observed a significant improvement in hepatic steatosis and inflammation. Notably, indole alleviated the HFD‐induced decline in serum Angiotensin‐(1–7) [Ang‐(1–7)] levels and Angiotensin‐Converting Enzyme 2 (ACE2) expression. To further investigate the role of indole and ACE2 in NAFLD, we conducted experiments using ACE2 knockout (ACE2KO) mice that were also induced with HFD‐induced NAFLD and treated with indole. Interestingly, the protective effects of indole were compromised in the absence of ACE2. In HepG2 cells, indole similarly stimulated ACE2 expression and, in an ACE2‐dependent manner, reduced ROS generation, maintained mitochondrial membrane potential stability, and increased SIRT3 expression. In summary, our results highlight the formation of a biologically active gut‐liver axis between the gut microbiota and the liver through the tryptophan metabolite indole, which mitigates NAFLD in an ACE2‐dependent manner. Elevating dietary tryptophan and increasing indole levels may represent an effective approach for preventing and treating NAFLD. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation, steatosis and fibrosis. Sympathetic nerves play a critical role in maintaining hepatic lipid homeostasis and regulating fibrotic progression through adrenergic receptors expressed by hepatocytes and hepatic stellate cells; however, the use of sympathetic nerve-focused strategies for the treatment of NAFLD is still in the infancy. Herein, a biomimetic nanoplatform with ROS-responsive and ROS-scavenging properties was developed for the codelivery of retinoic acid (RA) and the adrenoceptor antagonist labetalol (LA). The nanoplatform exhibited improved accumulation and sufficient drug release in the fibrotic liver, thereby achieving precise codelivery of drugs. Integration of adrenergic blockade effectively interrupted the vicious cycle of sympathetic nerves with hepatic stellate cells (HSCs) and hepatocytes, which not only combined with RA to restore HSCs to a quiescent state but also helped to reduce hepatic lipid accumulation. We demonstrated the excellent ability of the biomimetic nanoplatform to ameliorate liver inflammation, fibrosis and steatosis. Our work highlights the tremendous potential of a sympathetic nerve-focused strategy for the management of NAFLD and provides a promising nanoplatform for the treatment of NAFLD. Highlights: The potential of adrenoceptor-blockade strategy was explored for reprogromming the activated hepatic stellate cells and reducing hepatic lipid accumulation in the treatment of NAFLD. A biomimetic nanoplatform with ROS-responsive and ROS-scavenging properties was tailored for achieving precise delivery of retinoic acid and adrenoceptor antagonists as well as consuming ROS to provide anti-inflammatory benefits. The biomimetic nanoplatform integrating adrenoceptor blockade exhibits excellent ability to reduce liver steatosis and alleviate inflammation and fibrosis, thereby achieving enhanced NAFLD treatment. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), poses a significant global health challenge due to its increasing prevalence and strong association with cardiovascular disease (CVD). This comprehensive review summarizes the current knowledge on the MASLD-CVD relationship, compares analysis of how different terminologies for fatty liver disease affect cardiovascular (CV) risk assessment using different diagnostic criteria, explores the pathophysiological mechanisms connecting MASLD to CVD, the influence of MASLD on traditional CV risk factors, the role of noninvasive imaging techniques and biomarkers in the assessment of CV risk in patients with MASLD, and the implications for clinical management and prevention strategies. By incorporating current research and clinical guidelines, this review provides a comprehensive overview of the complex interplay between MASLD and cardiovascular health. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) and heart failure (HF) are related conditions with an increasing incidence. However, the mechanism underlying their association remains unclear. This study aimed to explore the shared pathogenic mechanisms and common biomarkers of NAFLD and HF through bioinformatics analyses and experimental validation. Methods: NAFLD and HF-related transcriptome data were extracted from the Gene Expression Omnibus (GEO) database (GSE126848 and GSE26887). Differential analysis was performed to identify common differentially expressed genes (co-DEGs) between NAFLD and HF. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were conducted to explore the functions and regulatory pathways of co-DEGs. Protein-protein interaction (PPI) network and support vector machine-recursive feature elimination (SVM-RFE) methods were used to screen common key DEGs. The diagnostic value of common key DEGs was assessed by receiver operating characteristic (ROC) curve and validated with external datasets (GSE89632 and GSE57345). Finally, the expression of biomarkers was validated in mouse models. Results: A total of 161 co-DEGs were screened out in NAFLD and HF patients. GO, KEGG, and GSEA analyses indicated that these co-DEGs were mainly enriched in immune-related pathways. PPI network revealed 14 key DEGs, and SVM-RFE model eventually identified two genes (CD163 and CCR1) as common key DEGs for NAFLD and HF. Expression analysis revealed that the expression levels of CD163 and CCR1 were significantly down-regulated in HF and NAFLD patients. ROC curve analysis showed that CD163 and CCR1 had good diagnostic values for HF and NAFLD. Single-gene GSEA suggested that CD163 and CCR1 were mainly engaged in immune responses and inflammation. Experimental validation indicated unbalanced macrophage polarization in HF and NAFLD mouse models, and the expression of CD163 and CCR1 were significantly down-regulated. Conclusion: This study identified M2 polarization impairment characterized by decreased expression of CD163 and CCR1 as a common pathogenic pathway in NAFLD and HF. The downregulation of CD163 and CCR1 may reflect key pathological changes in the development and progression of NAFLD and HF, suggesting their potential as diagnostic and therapeutic targets. [ABSTRACT FROM AUTHOR]

AbstractObjectivesMethodsResultsConclusionsMetabolic disorders, as multifactorial disorders, are induced by genetic susceptibility and exposure to environmental chemicals. Di (2-ethyl hexyl) phthalate (DEHP), a ubiquitous plasticizer, is well known as an endocrine-disrupting chemical in living organisms. In recent decades, researchers have focused on the potential of DEHP and its main metabolite (Mono (2-ethylhexyl) phthalate) (MEHP) to induce metabolic disorders. In the present review, we aimed to summarize studies regarding DEHP and MEHP-induced Metabolic syndrome (MetS) as well as address the involved mechanisms.A search has been carried out in Google Scholar, PubMed, Scopus, and Web of Science databases using appropriate keywords including ‘Metabolic syndrome’ or ‘Metabolic disorder’ or ‘Obesity’ or ‘Hyperglycemia’ or ‘Hyperlipidemia’ or ‘Hypertension’ or ‘Non-alcoholic fatty liver disease’ and ‘DEHP’ or ‘Di (2-ethyl hexyl) phthalate’ or ‘Bis(2-ethylhexyl) phthalate’ or ‘MEHP’ or ‘Mono (2-ethylhexyl) phthalate’. Studies were chosen based on inclusion and exclusion criteria. Inclusion criteria are in vitro, in vivo, epidemiological studies, and English-written studies. Exclusion criteria are lack of access to the full text of studies, editorial articles, review articles, and conference articles.Animal studies indicate that DEHP and MEHP disrupt insulin hemostasis, increase glucose content, and induce hyperlipidemia and hypertension as well as obesity, which could lead to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). DEHP and its metabolite induce such effects directly through influence on nuclear receptors such as peroxisome proliferator-activated receptors (PPARs) or indirectly through reactive oxygen species (ROS) production. Both events led to the disruption of several molecular signaling pathways and subsequently metabolic syndrome (MetS). Furthermore, epidemiological studies showed that there was a correlation between DEHP metabolites levels and obesity, hyperglycemia, and hypertension.According to studies, DEHP and its main metabolite have the potential to induce MetS by involving various molecular mechanisms. Epidemiological studies concerning the association of DEHP and MetS in humans are not sufficient. Therefore, more studies are needed in this regard. [ABSTRACT FROM AUTHOR]

Mitochondria and lysosomes play a very important role in maintaining cellular homeostasis, and the dysfunction of these organelles is closely related to many diseases. Recent studies have revealed direct interactions between mitochondria and lysosomes, forming mitochondria-lysosome contact sites that regulate organelle network dynamics and mediate the transport of metabolites between them. Impaired function of these contact sites is not only linked to physiological processes such as glucose and cholesterol transport but also closely related to the pathological processes of metabolic diseases. Here, we highlight the recent progress in understanding the mitochondria-lysosome contact sites, elucidate their role in regulating metabolic homeostasis, and explore the potential implications of this pathway in metabolic disorders. [ABSTRACT FROM AUTHOR]

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with obesity and insulin resistance (IR). Identifying characteristics that predict a higher risk of fibrosis using noninvasive methods is particularly important. Methods: We performed a secondary analysis of data from an RCT of 48 patients after one anastomosis gastric bypass (OAGB) surgery, supplemented with specifically formulated probiotics and micronutrients or control treatment for 12 weeks. Patients were categorized using alanine aminotransferase (ALAT; >35 U/L for women, >50 U/L for men), higher NAFLD fibrosis score (NFS) > −1.455), and IR (HOMA-IR > 2.0). This trial was registered at Clinicaltrials.gov (ID: NCT03585413). Results: Abnormal ALAT was associated with high triglycerides, blood pressure (BP), glucose, and fatty liver index (FLI). NFS > −1.455 was linked to higher age, body mass, waist circumference, and FLI, and lower albumin and platelet count. HOMA-IR > 2.0 was associated with higher BP and triglycerides, lower HDL-cholesterol, higher serum transaminases, and higher probabilities of steatosis and fibrosis. Twelve weeks postoperatively, patients with NFS > −1.455 showed greater reductions in body mass, systolic BP, serum insulin, and HbA1c, whereas those with NFS ≤ −1.455 showed improvements in FLI and lipid metabolism but had high glucose concentrations. Patients with HOMA-IR ≤ 2.0 also had high glucose concentrations. Conclusions: The evaluation of common biomarker scores for fibrosis and IR may help clinicians to recognize severe NAFLD and improve the outcomes of OAGB surgery. [ABSTRACT FROM AUTHOR]

Over the past few decades, the scientific community has been highly concerned about the obesity epidemic. Artificial sweeteners are compounds that mimic the sweet taste of sugar but have no calories or carbohydrates; hence, they are very popular among patients suffering from diabetes or obesity, aiming to achieve glycemic and/or weight control. There are four different types of sweeteners: artificial, natural, rare sugars, and polyols. Artificial and natural sweeteners are characterized as non-nutritional sweeteners (NNSs) since they do not contain calories. The extended use of sweeteners has been reported to have a favorable impact on body weight and glycemic control in patients with type 2 diabetes (T2DM) and on tooth decay prevention. However, there is concern regarding their side effects. Several studies have associated artificial sweeteners' consumption with the development of insulin resistance, nonalcoholic fatty liver disease (NAFLD), gastrointestinal symptoms, and certain types of cancer. The present review focuses on the description of different types of sweeteners and the benefits and possible deleterious effects of the chronic consumption of NNSs on children's health. Additionally, possible underlying mechanisms of the unfavorable effects of NNSs on human health are described. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder strongly linked to type 2 diabetes mellitus (T2DM). Understanding the predictive value of lipid parameters in identifying abnormal glucose metabolism in NAFLD patients is crucial for early intervention. Methods: This study analyzed data from the National Health and Nutrition Examination Survey(NHANES) database (2017-2020) involving 1066 NAFLD patients. Participants were categorized into three groups: T2DM (n=414), prediabetes mellitus (pre-DM) (n=507), and normoglycemia (NG) (n=145). Traditional lipid parameters [triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)] and nontraditional lipid parameters [atherogenic index of plasma (AIP), residual cholesterol (RC), and non-high-density lipoprotein cholesterol (non-HDL-C)] were evaluated for their association with T2DM and pre-DM. Results: Elevated TG levels were significantly associated with an increased risk of T2DM and pre-DM, whereas high HDL-C demonstrated a protective effect. Among nontraditional lipid parameters, increased AIP and RC were most strongly associated with T2DM risk, while high non-HDL-C was best associated with the development of pre-DM. Stratified analyses revealed that these associations were stronger in younger, non-obese, smoking, and female NAFLD patients. Conclusion: Nontraditional lipid parameters, particularly AIP and RC, show superior predictive value over traditional lipid parameters in identifying abnormal glucose metabolism in NAFLD patients. Incorporating these novel biomarkers into clinical practice could enhance early detection and prevention strategies for T2DM and pre-DM in this high-risk population. [ABSTRACT FROM AUTHOR]

Background: Observational data posits a correlation between reproductive traits and nonalcoholic fatty liver disease (NAFLD), but their causal inference is still unclear. This investigation seeks to elucidate the causal influence of reproductive traits on NAFLD and determine the intervening role of health condition and socioeconomic status in these connections. Methods: Utilizing a Mendelian Randomization (MR) approach, this research leveraged a comprehensive dataset from the Genome-wide Association Study (GWAS) database. The study incorporated body mass index, major depression, educational level, household income and Townsend deprivation index as intermediary variables. Initially, a bidirectional two-sample MR study was conducted to explore the genetic associations between reproductive traits and NAFLD. Then, two-step MR analyses were implemented to quantify the extent of mediation by these indicators. The weighted inverse variance method was the primary analytical approach, complemented by several sensitivity analyses to affirm the robustness of the MR assumptions. Finally, these findings were validated in the FinnGen research. Results: The bidirectional MR analysis indicated that earlier reproductive traits (age at menarche, age at first sexual intercourse, and age at first birth) were associated with an elevated risk of NAFLD, absent any evidence of the reverse relationship. Body mass index accounted for 35.64% of the association between premature menarche and NAFLD. Additionally, body mass index, major depression, educational level and household income mediated 41.65%, 14.35%, 37.88%, and 18.59% of the connection between early sexual intercourse and NAFLD, respectively. Similarly, these same variables elucidated 36.36%, 15.58%,41.56%, and 22.73% of the correlation between younger age at first birth and NAFLD. Conclusion: Our study elucidated the causal relationships between reproductive traits and NAFLD. Potential underlying mechanisms may involve factors such as body mass index, major depression, educational attainment and household income. [ABSTRACT FROM AUTHOR]

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 increasing prevalence of metabolic diseases poses a significant threat to public health, highlighting the urgent need to identify effective therapeutic targets. Humanin (HN), a 24-amino acid linear peptide synthesized from mitochondrial DNA, has been previously acknowledged for its neuroprotective properties. Recent research indicates that HN can regulate glucose and lipid metabolism and has shown promise in treating metabolic disorders in animal models using either HN or its analogs. This review outlines the fundamental biological functions and signal transduction mechanisms of HN, and comprehensively evaluates its role and therapeutic potential in type 2 diabetes mellitus, nonalcoholic fatty liver disease, atherosclerosis and polycystic ovary syndrome, aiming to examine the potential of HN as a target for the prevention and treatment of metabolic diseases. [ABSTRACT FROM AUTHOR]

Background and Aim: This study estimated the prevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD) according to cardiometabolic risk factors. The long‐term impacts of MASLD on all‐cause and cardiometabolic‐specific mortality were evaluated. Methods: We enrolled 343 816 adults aged ≥30 years who participated in a health screening program from 1997 through 2013. MASLD was identified on the basis of abdominal ultrasonography and metabolic profiles. The participants were further categorized by liver enzyme elevation. Baseline cardiometabolic comorbidities were classified on the basis of self‐reported medication use and clinical seromarkers. All‐cause and cardiometabolic‐specific deaths were determined through computerized data linkage with nationwide death certifications until December 31, 2020. Results: The overall prevalence of MASLD was 36.4%. Among patients with MASLD, 35.9% had abnormal liver enzyme levels. Compared with patients without MASLD, abnormal liver enzymes were positively associated with cardiometabolic comorbidities in patients with MASLD (Pfor trend < 0.001). After follow‐up, patients with MASLD had a 9%–29% higher risk of all‐cause, cardiovascular‐related, or diabetes‐related mortality. In the groups with MASLD and elevated and normal liver enzyme levels, the multivariate‐adjusted hazard ratios for cardiovascular deaths were 1.14 (1.05–1.25) and 1.10 (1.03–1.17), respectively, and those for diabetes deaths were 1.42 (1.05–1.93) and 1.24 (0.98–1.57), respectively, compared with those in the non‐MASLD group (Pfor trend < 0.001). Discussion: Individuals with MASLD and elevated liver enzyme levels exhibited significantly higher risks of all‐cause and cardiometabolic deaths and should be monitored and given consultation on cardiometabolic modifications. [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]