Non-alcoholic Fatty Liver Disease Patients Research Articles

Impaired sensitivity to thyroid hormone is associated with developing non-alcoholic fatty liver disease in euthyroid diabetic subjects

Background and aimsAcquired resistance to thyroid hormone appears to exist in the general population. We aimed to evaluate the association between indices of thyroid hormone sensitivity and non-alcoholic fatty liver disease (NAFLD), and made stratified analyses by diabetic status.MethodsWe included 26,413 participants from a health screening program and 8,246 hospitalized patients with type 2 diabetes. Thyroid Feedback Quantile-based Index (TFQI), thyroid stimulating hormone index (TSHI) and thyrotroph thyroxine resistance index (TT4RI) were calculated. Advanced fibrosis risk was determined using the FIB-4 score. Multivariate logistic regression analysis was performed.ResultsTFQI was associated with an increased risk of NAFLD in patients with diabetes (fourth quartile vs. first quartile: odds ratio [OR]=1.39 and 1.82 in hospitalized and non-hospitalized patients, respectively, both P<0.001) but not non-diabetic participants (OR=0.94, P=0.40). Further adjustment for the homeostasis model assessment of insulin resistance generated similar findings in diabetes (OR=1.27, P=0.025). The TFQI-associated NAFLD risk increase in diabetic patients was confined to NAFLD with low probability of advanced fibrosis (OR 1.42, P=0.001), but not those with intermediate-to-high probability (OR=0.86, P=0.23). Also, TFQI was associated with a significantly lower risk for advanced fibrosis in the diabetic at-risk patients (OR=0.62, P=0.005) but not those non-diabetic at-risk participants, independent of the presence of NAFLD. The association was less significant for TT4RI and TSHI.ConclusionsImpaired sensitivity to thyroid hormone was associated with an increased risk of developing NAFLD but a reduced risk of advanced fibrosis limited to diabetic individuals. Our findings suggest stratified studies of NAFLD based on diabetic status are needed in the future.

Non-obese non-alcoholic fatty liver disease and the risk of chronic kidney disease: a systematic review and meta-analysis

Background Data on risk of developing chronic kidney disease (CKD) between non-obese and obese non-alcoholic fatty liver disease (NAFLD) patients are limited. We aimed to reveal the risk difference of incident CKD between non-obese and obese NAFLD patients. Methods We searched PubMed, Embase, and Web of Science databases for studies which reported the incidence of CKD in non-obese and obese NAFLD from inception to 10 March 2024. The primary and secondary outcomes were pooled. Subgroup analysis was used to examine the heterogeneity. Results A total of 15 studies were incorporated. The incidence of CKD in non-obese and obese NAFLD were 1,450/38,720 (3.74%) and 3,067/84,154 (3.64%), respectively. Non-obese NAFLD patients had a comparable risk of CKD as obese NAFLD (odds ratio [OR] 0.92, 95% confidence interval [95% CI] [0.72–1.19], I2 = 88%). No differences in estimated glomerular filtration rate and serum creatinine between non-obese and obese NAFLD were found. The mean differences (MD) and 95% CI were 0.01 [−0.02 to 0.04] and 0.50 [−0.90 to 1.90], respectively. In subgroup analyses, non-obese NAFLD had higher eGFR when diagnosed with ultrasound (MD 1.45, 95% CI [0.11–2.79], I2 = 21%). Non-obese NAFLD had higher creatinine in non-Asian (MD 0.06, 95% CI [0.01–0.11], I2 = 55%) and when taking BMI > 30 as the criterion for obesity (MD 0.06, 95% CI [0.00–0.12], I2 = 76%). The occurrence of CKD did not differ when non-obese NAFLD were categorized into overweight and normal-weight types. Conclusions Non-obese NAFLD patients experienced the same risk of CKD compared to obese NAFLD.

Sonographic Analysis of Non-Alcoholic Fatty Liver Disease (NAFLD) and Its Correlation with Obesity

Background: NAFLD is strongly associated with obesity and metabolic syndrome, arguably the most common liver disorders worldwide. To provide early diagnosis and prevention, we need to understand its predictors. Objectives: This study aimed to identify the clinical, biochemical and sonographic predictors for NAFLD in a cohort of patients with multivariate analysis. Methods: In our study, 537 patients: 340 with NAFLD as diagnosed by sonography. Clinical parameters (BMI and waist circumference) and biochemical markers (ALT, triglycerides, HDL cholesterol) were compared with demographic characteristics (age, gender and marital status). Sonographic findings involved evaluation of liver echogenicity, hepatomegaly, and steatosis. Multivariate logistic regression was used to identify odds ratios (OR) and 95% confidence intervals (CI) of NAFLD predictors. Results: All three measures (BMI, OR = 3.21, 95% CI: 1.8–5.3; waist circumference, OR = 4.02, 95% CI: 2.5–6.0; and waist/hip ratio, OR = 2.09, 95% CI: 1.3–3.3) were significantly associated with NAFLD. Elevated ALT (OR = 2.55, 95% CI: 1. The associations between NAFLD and 9–3.8), triglycerides (OR = 1.45, 95% CI: 1.2–1.9), and HDL cholesterol (OR = 0.35, 95% CI: 0.18–0.63) were lower. Sonographically, increased liver echogenicity (OR = 3.50, 95% CI: 2. Prevalence of NAFLD patients was 8–4.8 and (OR = 4.85, 95% CI: 3.2–7.1) for steatosis. Conclusion: Strong association exists between NAFLD and obesity, metabolic dysfunction, and characteristic sonographic features. Preventing disease progression requires early detection, via ultrasound, with weight loss and metabolic control interventions.

The potential of insulin resistance indices to predict non-alcoholic fatty liver disease in patients with type 2 diabetes

BackgroundThe triglyceride-glucose (TyG) index and related parameters, as well as the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), have been developed as insulin resistance markers to identify individuals at risk for non-alcoholic fatty liver disease (NAFLD). However, its use for predicting NAFLD in patients with type 2 diabetes mellitus (T2DM) remains unclear. In this study, we aimed to observe the performance of insulin resistance indices in diagnosing NAFLD combined with T2DM and to compare their diagnostic values in clinical practice.Patients and methodsOverall, 268 patients with T2DM from the Endocrinology Department of Jiangsu Provincial Hospital of Traditional Chinese Medicine were enrolled in this study and divided into two groups: an NAFLD group (T2DM with NAFLD) and a T2DM group (T2DM without NAFLD). General information and blood indicators of the participants were collected, and insulin resistance indices were calculated based on these data. Receiver operating characteristic (ROC) analysis was conducted to calculate the area under the curve (AUC) for insulin resistance-related indices, aiming to assess their ability to discriminate between T2DM patients with and without NAFLD.ResultsROC analysis revealed that among the five insulin resistance-related indices, four parameters (TyG, TyG-body mass index [BMI], TyG-waist circumference [WC], and TyG- (waist–hip ratio [WHR]) exhibited high predictive performance for identifying NAFLD, except for HOMA-IR (AUCs:0.710,0.738,0.737 and 0.730, respectivly). TyG-BMI demonstrated superior predictive value, especially in males. For males, the AUC for TyG-BMI was 0.764 (95% confidence interval [CI] 0.691–0.827). The sensitivity and specificity for male NAFLD were 90.32% and 47.89%, respectively. Moreover, in the Generalized linear regression models, there were positive associations of TyG, TyG-BMI, TyG-WC, TyG-WHR, and HOMA-IR with controlled attenuation parameter (CAP), with β values of 21.30, 0.745, 0.247, and 2.549 (all P < 0.001), respectively.ConclusionTyG-BMI is a promising predictor of NAFLD combined with T2DM, particularly in lean male patients.

Effects of dapagliflozin on liver steatosis in patients with nonalcoholic fatty liver disease: a randomized controlled trial.

Nonalcoholic fatty liver disease (NAFLD) is a common liver comorbidity with considerable global consequences. This study explores the efficacy of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor primarily used to manage type 2 diabetes, in reducing liver steatosis among NAFLD patients. This randomized, open-label, two-arm, parallel-group trial enrolled patients with NAFLD and a controlled attenuation parameter (CAP) score of ≥ 252dB/m. Participants were randomized (1:1) into either the control or dapagliflozin groups. The primary outcome was the change in CAP scores, measured with FibroScan after 24weeks. The trial included 150 patients, 20 of whom (13%) had type 2 diabetes. In week 24, the dapagliflozin group had significantly lower CAP score and fatty liver grade than did the control group (266.3 ± 57.8 50 vs 298.6 ± 59.0dB/m, respectively [p = 0.002]; 1.7 ± 0.7 vs 2.2 ± 0.8, respectively [p < 0.001]). Liver stiffness, waist circumference, and alanine transaminase levels decreased in both the dapagliflozin and control groups, but the between-group differences were nonsignificant (1.0 ± 0.3 vs 1.1 ± 0.3 [p = 0.678], 94.2 ± 12.7 vs 92.4 ± 11.1 [p = 0.382], and 28.8 ± 18.3 vs 28.3 ± 14.2 U/L [p = 0.856], respectively). In the multivariate analysis, a reduction in CAP was associated with dapagliflozin treatment (p = 0.01) and changes in BMI (p = 0.007). No adverse events were observed. Dapagliflozin can reduce CAP score and fatty liver grade in patients with moderate to severe NAFLD, regardless of their diabetes status.

Analysis of influencing factors of exercise systolic blood pressure response in nonalcoholic fatty liver disease aged 40–60 years

ABSTRACT Objectives This study investigated the influencing factors of exercise systolic blood pressure response (ESBPR) by cardiopulmonary exercise test (CPX) in nonalcoholic fatty liver disease (NAFLD) in people aged 40–60 years. Methods A total of 603 adults were enrolled in this study. The inclusion criteria of this cross-sectional study were adults who underwent health checks and CPX. Results There were significant differences in body mass Index (BMI) (26.80 ± 2.64 VS 23.31 ± 2.41, p < 0.001) kg/m2, fasting blood glucose (FPG) (5.56 ± 0.94 VS 5.13 ± 0.55, p < 0.001) mmol/L, alanine aminotransferase (ALT), aspartate transaminase (AST), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C) (1.13 ± 0.22 VS 1.43 ± 0.33, p < 0.001) mmol/L, low-density lipoprotein-cholesterol (LDL-C) (3.21 ± 0.79 VS 2.99 ± 0.68, p = 0.001) mmol/L, resting systolic blood pressure (SBP) (123.53 ± 14.73 VS 118.79 ± 14.79, p < 0.001) mmHg, resting diastolic blood pressure (DBP) (80.29 ± 9.62 VS 75.27 ± 10.41, p < 0.001) mmHg, peak SBP (184.01 ± 23.50 VS 172.81 ± 24.95, p < 0.001) mmHg, peak DBP (87.47 ± 10.50 VS 84.01 ± 11.46, p = 0.001) mmHg, oxygen pulse (VO2/HR) (0.88 ± 0.15 VS 0.92 ± 0.16, p = 0.004) ml/beat, exercise maximum heart rate, carbon dioxide Ventilation equivalent (VE/VCO2) (25.84 ± 4.43 VS 25.12 ± 3.58, p = 0.038), peak oxygen uptake (VO2 peak) (1.78 ± 0.45 VS 1.56 ± 0.46, p < 0.001) mL/min between the NAFLD and control groups. VE/VCO2 (OR = 0.822, p = 0.036) and oxygen uptake/work rate (VO2/WR) (OR = 0.517, p = 0.021) mL/min/watt were associated with a lower risk of ESBPR in NAFLD subjects. Resting SBP was associated with a higher risk of ESBPR in NAFLD patients (OR = 1.059, p = 0.003) and overweight NAFLD subjects (OR = 1.075, p = 0.002). ESBPR (OR = 1.268, p = 0.045), skeletal-muscle mass (OR = 1.305, p < 0.001), and SMI (OR = 1.315, p < 0.001) were linked to an elevated risk of NAFLD in individuals. Conclusion Our findings indicate that ESBPR is associated with an increased risk of NAFLD in individuals aged 40–60 years. Furthermore, in NAFLD subjects, VE/VCO2 and VO2/WR were found to be correlated with a decreased risk of ESBPR, whereas resting SBP was linked to an elevated risk of ESBPR. This will provide a research basis for the NAFLD subjects who have ESBPR at risk of adverse events during exercise.

Analysis of Quality Intima-Media Thickness and Quantitative Artery Stiffness technologies on non-alcoholic fatty liver disease: a study on carotid artery structure, elasticity, and influential factors in patients.

In recent years, there have been numerous studies using Quality Intima-Media Thickness (QIMT) and Quantitative Arterial Stiffness (QAS) technology to evaluate various related factors and disease-induced changes in carotid artery (CA) elasticity. However, there is still a lack of research on the relationship between non-alcoholic fatty liver disease (NAFLD) and various indicators related to the CA. This study aimed to investigate the clinical significance of using QIMT and QAS techniques for comprehensive evaluation of CA intima-media thickness (IMT) and elasticity changes in NAFLD patients, and to analyze various factors influencing these variables. In this cross-sectional study, a total of 196 healthy adults and 285 NAFLD patients were selected from June 2021 and October 2021 in the First Affiliated Hospital of Zhejiang University School of Medicine. Body mass index (BMI), blood pressure, and triglyceride levels were collected. CA IMT and pulse wave velocity (PWV) were measured using QIMT and QAS techniques. Multiple linear regression analysis was employed to explore the relationship between parameters measured using QIMT and QAS techniques and NAFLD, while controlling for covariates, to assess the measurement effects of QIMT and QAS techniques on arterial structure and elasticity in NAFLD patients. A total of 233 males and 248 females were included in this study, with 178 males (62.46%) and 107 females (37.54%) being diagnosed with NAFLD. Gender, age, systolic blood pressure (SBP), and uric acid (UA) all are related to CA IMT (estimated value -0.031 to 0.008, P<0.0001-P=0.0450). The presence of NAFLD was not significantly related to IMT, but primarily influenced vascular elasticity indicators α, β, PWV, augmentation index (Aix), distensibility coefficient (DC), and compliance coefficient (CC). Age, SBP, diastolic blood pressure (DBP), high-density lipoprotein (HDL), and UA were all related to vascular elasticity coefficient β (estimated value -0.05 to 1.03, P<0.0001-P=0.0451); SBP and UA had a relationship with PWV (estimated value -0.001 to 0.405, P<0.0001-P=0.0027); gender, age, SBP, DBP, and UA all influenced Aix (estimated value -0.17 to 0.65, P<0.0001-P=0.0072). Ultrasound radiofrequency (RF) signal QIMT and QAS techniques can reflect changes in CA structure and elasticity function in NAFLD patients, which can be more widely applied and promoted in the changes of CA structure and elastic function in NAFLD patients.

Therapeutic effects of curcumin supplementation on liver enzymes of nonalcoholic fatty liver disease patients: A systematic review and meta‐analysis of randomized clinical trials

AbstractCurcumin, as an antioxidant agent, has been proposed as a potential treatment for nonalcoholic fatty liver disease (NAFLD). The aim of the current systematic review and meta‐analysis was to summarize earlier findings regarding the effect of curcumin supplementation on liver enzymes and ALP in NAFLD patients. All studies published up to November 18, 2022, were searched through the PubMed, SCOPUS, and Web of Science databases to collect all randomized clinical trials (RCTs) on NAFLD patients in which curcumin was used as a treatment. A random‐effects model was used to measure pooled effect sizes. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were used to report pooled effect sizes. Subgroup analysis was utilized to investigate heterogeneity. A total of 14 studies were included in this systematic review and meta‐analysis. Our pooled meta‐analysis indicated a significant decrease in alanine aminotransferase (ALT) following curcumin therapy by pooling 12 effect sizes (WMD: –8.72; 95% CI: –15.16, –2.27, I2 = 94.1%) and in aspartate aminotransferase (AST) based on 13 effect sizes (WMD: –6.35; 95% CI: –9.81, –2.88, I2 = 94.4%). However, the pooled analysis of five trials indicated that there was no significant association between curcumin therapy and alkaline phosphatase (ALP) in NAFLD patients (WMD: −4.71; 95% CI: −13.01, 3.58, I2 = 64.2%). Nevertheless, subgroup analyses showed significant effects of curcumin on ALP with a longer duration of supplementation. The findings of this systematic review and meta‐analysis support the potential effect of curcumin on the management of NAFLD. Further randomized controlled trials should be conducted in light of our findings.

PNPLA3 and SAMM50 variants are associated with lean nonalcoholic fatty liver disease in Asian population

Lean adults with nonalcoholic fatty liver disease (NAFLD) have a higher risk of metabolic syndrome than lean controls. The study aimed to investigate the clinical and genetic features of lean NAFLD which remain unclear in Asian populations. This was a genetic cohort study conducted in the HAVO Health Exam Clinic in 2020-2021 in Taiwan. Adults with a body mass index less than 24 kg/m2 were enrolled. Fatty liver was defined by ultrasonography. The candidate gene approach was based on the library of the NHGRI-EBI website. After removing duplication and nonsignificant variants, rs738409 in the PNPLA3 gene and rs3761472 in the SAMM50 gene were chosen. Multiple logistic regression models and receiver operating characteristic (ROC) curves were used. A total of 1652 lean controls and 602 lean NAFLD patients were enrolled. The average age was 43.8±11.5 years. Lean NAFLD subjects were older and had a higher percentage of metabolic syndrome (case vs. control: 10.5% vs. 1.5%). The GG genotypes of PNPLA3 rs12483959 (OR: 3.06; 95% CI: 2.15-4.37) and SAMM50 rs3761472 (OR: 2.90; 95% CI: 2.04-4.14) had a higher risk of fatty liver after adjusting for BMI and metabolic syndrome. The areas under the ROC curve for PNPLA3 rs738409 and SAMM50 rs3761472 in the detection of lean NAFLD were 0.859 (95%CI: 0.841, 0.877) and 0.860 (95%CI: 0.843, 0.877), respectively. PNPLA3 rs738409 and SAMM50 rs3761472 gene polymorphisms are associated with a higher risk of fatty liver in lean individuals independent of BMI and metabolic syndrome in Asian populations.

Effect of Pomegranate Peel Consumption on Liver Enzymes, Lipid Profile, Liver Steatosis, and Hs-CRP in Patients With Non-alcoholic Fatty Liver Disease: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

The most prevalent chronic liver disease for which there is currently no proven treatment is non-alcoholic fatty liver disease (NAFLD). An incomplete understanding of the underlying mechanisms of NAFLD may be the cause. The onset and development of this illness appear to be influenced by problems with lipid metabolism, insulin resistance, oxidative stress, and inflammation. Considering the antioxidant properties of pomegranate peel extract, this study was conducted to determine the effects of pomegranate peel consumption on some metabolic features in patients with NAFLD. Our hypothesis is that pomegranate peel can improve the grade of fatty liver, liver enzymes, lipid profile, serum high-sensitivity C-reactive protein (hs-CRP), and anthropometric indices. The aim of this study was to investigate the efficacy of pomegranate peel extract in NAFLD patients. This double-blind randomized clinical trial was conducted on 46 patients with NAFLD. Patients were randomly assigned to intervention group (n = 23) and placebo group (n = 23). Patients in the pomegranate peel group consumed two capsules, each containing 500 mg pomegranate peel extract daily as a part of low-calorie diet (i.e., 500-deficit calorie diet) for 10 weeks. While patients in the control group followed the low calorie diet and two capsules containing 500 mg maltodextrin. At the beginning and end of the study, demographic information, anthropometric indices, food intake, physical activity level, grade of fatty liver, liver enzymes, lipid profile, and serum high-sensitivity C-reactive protein (hs-CRP) were measured. Food intake was measured by 24-h food recall questionnaires and physical activity was measured by the International Physical Activity Questionnaire (IPAQ). Analysis of food recall questionnaire was done using Nutritionist IV program. Statistical analysis was performed using SPSS software (version 22), and a p value < 0.05 was defined as statistically significant. Of 46 patients, 42 of them completed the trial. At the end of the trial, pomegranate peel group had significantly higher reduction in TG (triglycerides), ALT(alanine aminotransferase), AST(aspartate transferase), hs-CRP and also had higher significant increase in HDL-C(high-density lipoprotein cholesterol) compared to the control group (p = 0/02, p = 0/02, p = 0/01, p = 0/01, and p = 0/04, respectively). However, changes in LDL-C, TC, ALP, GGT, and fatty liver grade were not significantly different between the two groups at the end of the study. The current study indicates that pomegranate peel extract has a favorable effect on liver enzymes, lipid profile, and serum high-sensitivity C-reactive protein (hs-CRP) in patients with NAFLD. To support these results, trials examining various dosages over longer time periods are necessary.

Impact of Nonalcoholic Fatty Liver Disease on Weight Loss Outcomes After One Anastomosis Gastric Bypass.

Obesity-associated nonalcoholic fatty liver disease (NAFLD) is a significant cause of chronic liver disease. Our study sought to investigate preoperative NAFLD and the effect at 6 months and 2 years after surgery of one anastomosis gastric bypass (OAGB) and its development 6 months after surgery regarding weight loss outcomes. A retrospective cohort study was conducted on patients with severe obesity who underwent primary OAGB at Hazrat-e-Rasool Hospital between March 2020 and June 2021. Preoperative assessments included abdominal ultrasound (US) for NAFLD grading, weight, and biochemical blood tests. Follow-up examinations were performed at 10 days and 1, 3, 6, 9, 12, and 24 months postsurgery, with subsequent US examinations at the 6-month follow-up. Two hundred thirty-one patients were included, with an average age of 40.3±10.5 years and a percentage of 78.4 women. Their mean weight and BMI were 131.2±26.8 and 48.8±8.5, respectively. Six-month grades of NAFLD showed that patients with grade 3 NAFLD had significantly lower TWL% compared with the lower grades. NAFLD grades improved in 72.3% of our patients, remained the same at 21.2%, and worsened at 6.5%. The 6-month TWL% was 28.4±4.3 in the no-change group, 28.4±5.3 for the improved group, and 25.2±14.6 in the worse group. The severity and progression of NAFLD can significantly impact weight loss outcomes post-OAGB, highlighting the importance of monitoring and managing NAFLD in patients undergoing bariatric surgery.

Association between Weight-Adjusted Waist Index and Depression in NAFLD: the modulating roles of sex and BMI

BackgroundThe Weight-Adjusted Waist Index (WWI) is a novel indicator of obesity that accurately reflects body composition. However, the association between WWI and depression in patients with non-alcoholic fatty liver disease (NAFLD) remains unclear. This study aims to explore this relationship through a nationally representative cross-sectional analysis.MethodsThis study included adult participants diagnosed with NAFLD from NHANES 2017–2020. WWI was calculated as the waist circumference (cm) divided by the square root of body weight (kg). NAFLD diagnosis relied on vibration-controlled transient elastography (VCTE) with a controlled attenuation parameter (CAP) exceeding 248 dB/m to indicate hepatic steatosis. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), with scores ≥ 10 indicating the presence of major depression.ResultsAfter adjusting for all covariates, a significant positive association was found between WWI and depression in NAFLD (OR = 1.725, 95% CI: 1.442–2.063, p < 0.00001), with a dose-response relationship indicated by restricted cubic spline analysis. The association was stronger in men and lean/normal weight NAFLD patients. Adjusting further for BMI did not alter these findings (OR = 1.643, 95% CI: 1.357–1.989, p < 0.00001). BMI’s association with depression was negated after adjusting for WWI.ConclusionsWWI had a positive association with depression in NAFLD, independent of BMI. This association was more pronounced in men and lean/normal weight NAFLD. These findings suggest that WWI may be a novel indicator of depression in NAFLD and potentially valuable in depression prevention.

Free Cholesterol-Induced Liver Injury in Non-Alcoholic Fatty Liver Disease: Mechanisms and a Therapeutic Intervention Using Dihydrotanshinone I.

Build-up of free cholesterol (FC) substantially contributes to the development and severity of non-alcoholic fatty liver disease (NAFLD). Here, we investigate the specific mechanism by which FC induces liver injury in NAFLD and propose a novel therapeutic approach using dihydrotanshinone I (DhT). Rather than cholesterol ester (CE), we observed elevated levels of total cholesterol, FC, and alanine transaminase (ALT) in NAFLD patients and high-cholesterol diet-induced NAFLD mice compared to those in healthy controls. The FC level demonstrated a positive correlation with the ALT level in both patients and mice. Mechanistic studies revealed that FC elevated reactive oxygen species level, impaired the function of lysosomes, and disrupted lipophagy process, consequently inducing cell apoptosis. We then found that DhT protected mice on an HCD diet, independent of gut microbiota. DhT functioned as a potent ligand for peroxisome proliferator-activated receptor α (PPARα), stimulating its transcriptional function and enhancing catalase expression to lower reactive oxygen species (ROS) level. Notably, the protective effect of DhT was nullified in mice with hepatic PPARα knockdown. Thus, these findings are the first to report the detrimental role of FC in NAFLD, which could lead to the development of new treatment strategies for NAFLD by leveraging the therapeutic potential of DhT and PPARα pathway.

The Impact of Sira Vedha (Phlebotomy) at the Right Elbow Joint in the Treatment of Non-Alcoholic Fatty Liver Disease - A Research Report

ABSTRACT Non-alcoholic fatty liver disease (NAFLD) affects 9%–53% of the Indian population. No Indian studies have examined Sira Vedha (phlebotomy) for NAFLD, although it has been studied for other conditions. Sushruta recommended Sira Vedha at the right elbow joint for liver diseases, but clinical evidence for its efficacy in NAFLD is lacking. This clinical trial aimed to generate evidence for Sira Vedha in NAFLD patients. One hundred eleven patients with Grade I/II NAFLD were randomly assigned to either a control group (diet and exercise) or an intervention group (Sira Vedha, diet, and exercise). Blood samples were collected for lipid profile and liver function tests before and after treatment. Results showed significant improvements in SGOT, SGPT, cholesterol, HDL, and triglyceride levels in the intervention group compared to the control group, supporting the efficacy of Sira Vedha in NAFLD treatment. This study highlights the need for clinical evidence to confirm traditional Ayurvedic practices.

Abstract 4120912: Non-Alcoholic Fatty Liver Disease is Associated with Coronary Flow Reserve Impairment: A Pilot Meta-Analysis

Background: Non-alcoholic fatty liver disease (NAFLD) is estimated to affect approximately 25% of the global population. Significant epidemiological data links NAFLD to an increased risk of coronary artery disease. Both, coronary artery disease and NAFLD are linked to underlying insulin resistance and inflammation as drivers of the disease. Coronary flow reserve parameters including coronary flow reserve velocity (CFRV), baseline diastolic peak flow velocity (DPFV), and hyperemic DPFV are non-invasive markers of coronary microvascular circulation. The existing literature contains conflicting findings for these parameters in NAFLD patients. Aim: This meta-analysis aimed to compare CFRV, baseline DPFV, and hyperemic DPFV in between NAFLD patients and healthy controls. Methods: A comprehensive systematic search was conducted on PubMed, Embase, Cochrane Library, and Google Scholar from inception until 8th May 2024 to identify relevant studies. We pooled the standardized mean differences (SMD) with the 95% confidence intervals (CI) using the inverse variance random-effects model. A p-value of less than 0.05 was considered statistically significant. Results: We included 4 studies with 1139 participants (226: NAFLD and 913: controls). The mean age in the NAFLD group was 54.55 ± 7.62 years and in the control group was 54.2 ± 7.6 years. NAFLD was associated with a significantly lower CFRV [SMD: -0.77; 95% CI: -1.19, -0.36; p&lt;0.0002] and hyperemic DPFV [SMD: -0.73; 95% CI: -1.03, -0.44; p&lt;0.00001] compared to the controls. NAFLD demonstrated a statistically insignificant trend towards reduction in the baseline DPFV [SMD: -0.09; 95% CI: -0.38, 0.19; p=0.52] as compared to healthy controls. Conclusion: NAFLD patients are at a higher risk of coronary microvascular dysfunction as demonstrated by reduced CFRV and hyperemic DPFV. The presence of abnormal coronary flow reserve in NAFLD patients provides insights into the higher rates of cardiovascular disease in these patients. Early aggressive targeted interventions towards impaired coronary flow reserve in NAFLD subjects may lead to improvement in clinical outcomes.

Risk factors of hepatocellular carcinoma associated with nonalcoholic fatty liver disease: Systematic review and meta-analysis.

Nonalcoholic fatty liver disease (NAFLD) is currently an important chronic liver disease threatening human life and health. To investigate the risk factors of hepatocellular carcinoma (HCC) associated with nonalcoholic fatty liver disease (NAFLD) by systematic review. We conducted a systematic review and meta-analysis. A systematic search of Chinese and English databases (PubMed, Web of Science, Cochrane Library, China national knowledge infrastructure (CNKI), Wanfang database, and VIP database) was performed until June 30, 2023. Studies were included to investigate the risk factors for HCC in patients with NAFLD. Quality evaluation was performed using the Newcastle-Ottawa Literature Quality Evaluation Scale, and then hazard ratios (HRs) for different influencing factors were combined. We reviewed the results of 12 high-quality cohort studies involving 738,934 patients with NAFLD and 1,480 developed HCC. A meta-analysis based on a random-effects model showed that advanced age (HR = 1.81, 95% CI: 1.51-2.17), male gender (HR = 2.51, 95% CI: 1.67-3.78), hypertension (HR = 1.87, 95% CI: 1.05-3.33), and diabetes (HR = 2.27, 95% CI: 1.63-3.16) were risk factors for HCC in NAFLD, and the differences were statistically significant. However, there was no statistically significant effect of current smoking (HR = 1.45, 95% CI: 0.72-2.92) and dyslipidemia (HR = 1.03, 95% CI: 0.72-1.47) on HCC incidence in this study. Age, sex, hypertension and diabetes are risk factors for HCC in NAFLD patients. Diabetic NAFLD patients have a 2.27-fold increased risk of HCC, and health education and intervention for elderly, male, NAFLD patients with diabetes and hypertension need to be strengthened to promote a reduction in the risk of HCC.

The effect of ertugliflozin in patients with nonalcoholic fatty liver disease associated with type 2 diabetes mellitus: A randomized controlled trial.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with liver inflammation, fibrosis, and cirrhosis and is associated with a greater risk of hepatocarcinoma. Nonalcoholic steatohepatitis (NASH) is a persistent and progressive form of NAFLD. Recent evidence suggested that ertugliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2), suppresses NAFLD development in patients with type 2 diabetes mellitus (T2DM). The objective of this study was to determine the impact of ertugliflozin on improving NAFLD in patients with T2DM and the function of liver enzymes. This prospective, randomized, double-blind, placebo-controlled, interventional study aimed to determine the effectiveness of 15 mg of ertugliflozin versus 30 mg of the standard therapy pioglitazone versus placebo in NAFLD patients with T2DM. The study was established based on patient randomization in three groups: ertugliflozin, pioglitazone, and a placebo. This study was registered under the Australian New Zealand Clinical Trial Registry (Trial ID: ACTRN12624000032550). The impact of therapy was determined in the treatment groups by utilizing liver ultrasonography and biochemical parameters. After 24 weeks of clinical study, the results revealed significant improvement in the grades of fatty liver, especially in the ertugliflozin group. The number of patients with hepatic steatosis significantly decreased among the respective groups classified according to fatty liver grade. Among patients in the ertugliflozin and pioglitazone groups, 45% to 23.4% and 41.7% to 26.6%, respectively, decreased in the Grade 2 group. The aspartate aminotransferase and alanine aminotransferase levels were significantly lower in all the study groups, especially in the ertugliflozin group (P ≤ .001). The present study revealed that the concomitant use of ertugliflozin has favorable effects on liver enzymes, as it decreases liver fat intake and reduces complications in patients with NAFLD-associated T2DM. However, more in-depth studies will be required to observe every aspect of ertugliflozin.

Refining the predictive utility of aspartate aminotransferase to platelet ratio index in nonalcoholic fatty liver disease patients with COVID-19.

Refining the predictive utility of aspartate aminotransferase to platelet ratio index in nonalcoholic fatty liver disease patients with COVID-19.

Lack of Efficacy of Pomegranate Supplementation on Insulin Resistance and Sensitivity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The objective of this study is to assess the impact of pomegranate supplements on insulin resistance (IR) and insulin sensitivity through a systematic review and meta-analysis of randomized controlled trials (RCTs). Additionally, we aim to analyze the differences in efficacy among various pomegranate extracts and the sensitivity of different diseases to pomegranate supplementation. We conducted searches in PubMed, Embase, Web of Science, and Cochrane Library up to October 30, 2023, for relevant studies published in English. The treatment group required the intake of pomegranate extract for a minimum of 4 weeks, with no restrictions on the extract type. The control group received a placebo or a treatment excluding pomegranate extract. The primary outcome was homeostatic model assessment for insulin resistance (HOMA-IR) and fasting insulin (FI), and the secondary outcome was quantitative insulin sensitivity check index (QUICKI). RoB 2 was used to assess the risk of bias in the original studies. We pre-specified subgroup analyses based on types of intervention, intervention duration, health condition, and intervention dose. Sensitivity analysis was conducted to validate result stability, utilizing Begg's test and Egger's test for publication bias. Data synthesis and analysis were performed using Stata 15.1 software. This study included a total of 15 RCTs with 673 participants conducted in 7 countries. Risk of bias results indicated an overall low risk of bias of the articles. Participants included healthy individuals, overweight and obese individuals, non-alcoholic fatty liver disease (NAFLD) patients, type 2 diabetes (T2DM) patients, polycystic ovary syndrome (PCOS) patients, metabolic syndrome (MS) patients, and individuals with hyperlipidemia. Pomegranate extract variations included pomegranate juice (PJ), pomegranate seed oil (PSO) capsule, pomegranate/pomegranate peel (PP) extract capsule, and pomegranate peel-added bread. The control groups primarily received placebo treatments with varying dosage and frequency. No adverse reactions were reported in any of the studies. The summary results showed that compared to the control groups, pomegranate extract had no significant impact on improving HOMA-IR levels in participants (WMD = -0.03, 95%CI: -0.37 to 0.31, and p = 0.851) and FI (WMD = -0.03, 95%CI: -0.42 to 0.36, and p = 0.862). Additionally, there was no significant advantage of pomegranate extract on QUICKI changes in T2DM and PCOS patients (WMD = 0.00, 95%CI: 0.00 to 0.01, and p = 0.002). Subgroup analysis results indicated that pomegranate extract could improve HOMA-IR levels in PCOS patients (WMD = -0.42, 95%CI: -0.54 to -0.29, and p < 0.001) and FI levels in T2DM, PCOS, and NAFLD patients. Our results indicate that pomegranate extract only improves HOMA-IR and FI levels in PCOS patients and FI levels in T2DM and NAFLD patients. No significant difference has been found for HOMA-IR, FI, or QUICKI in other metabolic diseases. The current evidence suggests that we should interpret the value of pomegranate extract in regulating IR and sensitivity cautiously. In the future, there is a need for more rigorously designed RCTs to specifically evaluate the impact of pomegranate supplementation on insulin sensitivity in patients with NAFLD, PCOS, and T2DM.

Association of serum klotho with cognitive function among individuals with nonalcoholic fatty liver disease.

This study investigated the potential link between serum klotho levels and cognitive function in patients with non-alcoholic fatty liver disease (NAFLD). Utilizing NHANES data from 2011 to 2014, the research included 356 eligible participants. NAFLD was identified with the United States Fatty Liver Index (US-FLI), and cognition was measured by various tests including the Animal Fluency Test (AFT), Digit Symbol Substitution Test (DSST), Immediate Recall Test (IRT), and Delayed Recall Test (DRT). Weighted logistic regression and restricted cubic splines were employed to analyze the relationship between klotho levels and cognitive scores. A significant nonlinear association was observed between klotho levels and the performance in DSST and Delayed Recall Test (DRT). After controlling for confounding factors, the study found a positive association between higher serum klotho levels and improved cognitive performance in both AFT and DSST. However, there was no significant relationship between klotho levels and the IRT or DRT, regardless of whether the natural logarithm or quartile was considered. The findings suggest that a higher serum klotho level may be positively correlated with better cognitive performance in NAFLD patients.