Management Of Nonalcoholic Fatty Liver Disease Research Articles

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.

Efficacy of Vitamin E Versus Pioglitazone in Treating Non-Alcoholic Fatty Liver Disease (NAFLD) without Diabetes “Decoding the Exodus of Liver Health”.

Objective: To compare the effectiveness of vitamin E in comparison with Pioglitazone in the management of NAFLD without Diabetes. Study Design: Randomized Control Trial. Setting: Outpatient Department of Allied Hospital, Faisalabad. Period: Dec 2023 to May 2024. Methods: The Ethics Review Committee of Faisalabad Medical University was taken on board and patients having the characteristics of the set Inclusion Criteria were enrolled as allowed. Selected individuals were counseled regarding the study and their consent was sought. Using a computer-generated random number table, two main groups were formed out of the participants, Group A and Group B. Group A was given 800IU of Vitamin E daily. Group B received Pioglitazone 30mg daily. Patients were monitored for efficacy over three months by tracking ALT levels as specified in the operational definition. Follow-up was ensured through contact numbers. Results: In our study of 722 cases (361 in each group), the mean age was 41.25±6.41 years in Group A and 41.23±6.56 years in Group B. Males comprised 60.11% (n=217) of Group A and 59.56% (n=215) of the Group B, while females accounted for 39.89% (n=144) out of Group A and 40.44% (n=146) of the Group B. Efficacy comparison showed that 49.72% (n=147) in Group A and 31.30% (n=113) in Group B achieved efficacy, with a p-value of 0.008, pointing out a considerable difference. Conclusion: Our study succeeded in establishing the better efficacy of Vitamin E in treating NAFLD compared to Pioglitazone.

Systematic Review and Meta-analysis of the Impact of Metabolic Surgery on Hepatic Stiffness.

Bariatric surgery is one of the effective therapeutic options for people with obesity and obesity-related co-morbidities. In addition to weight-related co-morbid diseases, including diabetes, hypertension, and hypercholesterolemia, non-alcoholic fatty liver disease (NAFLD) is common in patients with morbid obesity. Bariatric surgery is one of the therapeutic options in the management of NAFLD. Hence, this review focused on the potential role of bariatric surgery on hepatic elasticity measured through shear wave elastography. A systematic literature search was performed, and the studies regarding heterogeneity were evaluated using the random-effects model. The meta-analysis on 6 trials (3-12 months follow-up) including 350 participants showed a significant reduction of liver elasticity after surgery (WMD: -1.149, 95% CI: -1.767, -0.532, p < 0.001; I2:81.55%). Bariatric surgery is associated with decreased liver elasticity. This improvement could be related to weight loss or other mechanisms of bariatric surgery.

Research Progress on Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide. With the prevalence of overweight and obesity in the Chinese population, NAFLD is no longer a disease exclusive to Western developed countries, and has become one of the most common metabolic diseases in the world. The global prevalence of NAFLD is as high as 37.8%, and the prevalence of NAFLD in the Chinese population is 23.3%. In recent years, with the global epidemic of obesity and metabolic syndrome, the prevalence of NAFLD has gradually increased. The risk factors of NAFLD are closely related to obesity, diabetes, hypercholesterolemia, hypertriglyceridemia, hyperuricemia and other diseases. When NAFLD co-exists with these metabolic diseases, it often increases the risk of cirrhosis, liver cancer, and even death. At the same time, it can aggravate other chronic liver diseases, promote disease progression, and is closely related to the occurrence and development of atherosclerosis and type 2 diabetes. With the progression of NAFLD disease, the related clinical burden and economic burden of NAFLD and its impact on patients' quality of life are becoming more and more serious. Therefore, early identification, early diagnosis, early prevention, early treatment and standardized management of NAFLD are conducive to the control of the risk of cirrhosis, liver cancer and cardiovascular diseases. This article will review the epidemiology, hazards, and related risk factors of NAFLD.

Non-invasive Assessment of Liver Fibrosis Using Shear Wave Elastography in Patients With Type 2 Diabetes Mellitus Having Non-alcoholic Fatty Liver Disease.

Background Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) frequently coexist due to overlapping risk factors such as metabolic syndrome and obesity. T2DM exacerbates the progression of NAFLD, increasing the risk of cirrhosis and hepatocellularcarcinoma. Thus, early detection of liver fibrosis is crucial to prevent severe liver disease. A 2D shear wave elastography (2D SWE) has emerged as a reliable non-invasive method for assessing liver stiffness, potentially reducing the need for liver biopsies and facilitating prompt treatment interventions. Methods This cross-sectional study, conducted over 18 months, included 100 T2DM and NAFLD patients from the Medicine and Diabetes Outpatient Department at SRM Medical College Hospital and Research Centre, Chengalpattu, India. Participants underwent gray-scale ultrasound to classify fatty liver (Grades I, II, and III) and 2D SWE to evaluate liver stiffness. Additional data on fasting and postprandial blood glucose, glycosylated hemoglobin (HbA1c), lipid profiles, liver function tests, and body mass index (BMI) were collected. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 21 (Released 2012; IBM Corp., Armonk, New York, United States). Results The mean age of participants was 47.9 years, with 61% being male. Fatty liver Grades I, II, and III were present in 47%, 41%, and 12% of patients, respectively. SWE results showed that 30% had stiffness values <5 kPa, 53% had values between 5.1-9 kPa, 16% had values between 9.1-13 kPa, and 1% had values >13 kPa. Liver size increased significantly with fatty liver grade (p=0.029). HbA1c levels and blood glucose levels were significantly correlated with fatty liver grades (p<0.0001). Triglyceride levels were higher with increasing fatty liver grades (p<0.0001). A significant correlation was found between gamma-glutamyl transferase (GGT) levels and SWE values (p=0.04). In the lipid profile, significant correlations were noted between SWE values and triglycerides (p=0.005), cholesterol (p=0.026), and very-low-density lipoprotein (VLDL) (p=0.131). Higher levels of HbA1c, fasting blood sugar, and postprandial blood sugar were also significantly correlated with SWE values (p<0.0001). Increasing grades of hepatic steatosis significantly correlated with SWE values (p<0.0001). BMI positively correlated with SWE values (r=0.321, p=0.001). Conclusion This study highlights the prevalence of advanced liver stiffness in patients with T2DM and NAFLD, which correlates significantly with higher grades of fatty liver, elevated HbA1c, blood sugar levels, and abnormal lipid profiles. SWE is a valuable tool for assessing liver stiffness and guiding the management of NAFLD in patients with T2DM.

Changes in Gut Microbial Composition and DNA Methylation in Obese Patients with NAFLD After Bariatric Surgery.

This study investigates the effects of bariatric surgery on non-alcoholic fatty liver disease (NAFLD) by examining the interplay between gut microbiota, epigenetics, and metabolic health. A cohort of 22 patients undergoing sleeve gastrectomy (SG) was analyzed for changes in gut microbial composition and DNA methylation profiles before and six months after surgery. Correlations between gut microbial abundance and clinical markers at baseline revealed that certain genera were associated with worse metabolic health and liver markers. Following SG, significant improvements were observed in the clinical, anthropometric, and biochemical parameters of the NAFLD patients. Although alpha-diversity indices (i.e., Chao1, Simpson, Shannon) did not show significant changes, beta-diversity analysis revealed a slight shift in microbial composition (PERMANOVA, p = 0.036). Differential abundance analysis identified significant changes in specific bacterial taxa, including an increase in beneficial Lactobacillus species such as Lactobacillus crispatus and Lactobacillus iners and a decrease in harmful taxa like Erysipelotrichia. Additionally, DNA methylation analysis revealed 609 significant differentially methylated CpG sites between the baseline values and six months post-surgery, with notable enrichment in genes related to the autophagy pathway, such as IRS4 and ATG4B. The results highlight the individualized responses to bariatric surgery and underscore the potential for personalized treatment strategies. In conclusion, integrating gut microbiota and epigenetic factors into NAFLD management could enhance treatment outcomes, suggesting that future research should explore microbiome-targeted therapies and long-term follow-ups on liver health post-surgery.

The association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and non-alcoholic fatty liver disease in US adults: a cross-sectional study

The ratio of non-high-density lipoprotein cholesterol (non-HDL-C) to HDL-C (NHHR) is a novel lipid parameter used to assess the risk of cardiovascular disease. Previous studies have demonstrated an association between the NHHR and risk of non-alcoholic fatty liver disease (NAFLD). Owing to the lack of research exploring this relationship in specific populations, this study aimed to determine the potential link between the NHHR and risk of NAFLD among American adults in the United States. Data were retrieved from the National Health and Nutrition Examination Survey (NHANES) spanning 2017–2020. After excluding individuals with other liver diseases, alcohol abuse, and missing lipid data, a total of 6809 eligible adults were included for analysis. The NHHR was calculated as the ratio of (non-HDL-C) to HDL-C, while NAFLD was identified by liver steatosis detected by transient elastography. Multivariable weighted logistic regression models and restricted cubic spline (RCS) models were employed to investigate the relationship between the NHHR and risk of NAFLD. Subgroup and sensitivity analyses were also conducted to test the robustness of the results. As the NHHR increased, the prevalence of NAFLD rose progressively (5.88% vs. 8.75% vs. 12.24% vs. 15.77%, p < 0.001). In the overall population, after adjusting for confounding factors, each unit increase in the NHHR was associated with a 25% increase in NAFLD risk (OR = 1.25, 95% CI: 1.03–1.53, p = 0.0372). When the NHHR was analyzed as a categorical variable (quartiles), participants in the highest quartile had a significantly higher risk of NAFLD than those in the lowest quartile (OR = 2.6, 95% CI: 1.75–3.85, p = 0.009). RCS analysis further indicated a nonlinear dose–response relationship between the NHHR and risk of NAFLD (p non-linearity < 0.0001). This association remained significant in both subgroup and sensitivity analyses. This study confirmed that the NHHR, particularly at higher levels, was an independent risk factor for NAFLD. As a comprehensive lipid indicator, the NHHR had the potential to predict NAFLD risk. These findings provided new insights for the prevention and clinical management of NAFLD.

Assessing Mortality Disparities Among Non-Alcoholic Fatty Liver Disease Metabolic Dysfunction Fatty Liver Disease and Metabolic Dysfunction-Associated Liver Disease: A Comprehensive Meta-Analysis.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a major global health concern due to its association with increased mortality. While previous studies have indicated a link between NAFLD and mortality, variations in risk factors such as age, sex, and disease severity warrant a comprehensive meta-analysis to clarify these associations. This meta-analysis aimed to evaluate the overall cardiovascular disease (CVD) mortality risk associated with NAFLD, considering various subgroups defined by age, sex, disease severity, presence of cirrhosis or fibrosis, study quality, and follow-up duration. A systematic search of eight studies was conducted to assess the hazard ratios (HRs) for all-cause and CVD mortality associated with NAFLD. Heterogeneity among studies was evaluated using the I² statistic, and subgroup analyses were performed based on participant age, sex, disease severity, presence of cirrhosis or fibrosis, study quality, and follow-up duration. NAFLD was significantly associated with an increased risk of all-cause mortality (HR = 1.34, 95% CI: 1.17-1.54, I² = 80.0%). Subgroup analyses revealed that individuals aged ≥50 years (HR = 1.50, 95% CI: 1.31-1.73) and males (HR = 1.43, 95% CI: 1.29-1.59) had a higher mortality risk. Patients with nonalcoholic steatohepatitis (NASH) showed a significant association with both overall (HR = 1.37, 95% CI: 1.14-1.65) and CVD mortality (HR = 1.56, 95% CI: 1.25-1.97). The presence of cirrhosis or fibrosis further elevated the risk of mortality (HR = 3.22, 95% CI: 2.40-4.33). However, NAFLD was not significantly associated with CVD mortality in the overall analysis (HR = 1.13, 95% CI: 0.92-1.38). Heterogeneity was high across most subgroups, indicating varying effects based on study characteristics. NAFLD is significantly associated with increased all-cause mortality, particularly in older individuals, males, and those with NASH or cirrhosis/fibrosis. The association with CVD mortality was not significant in the overall analysis but was evident in specific subgroups. These findings underscore the importance of early detection and tailored management of NAFLD to mitigate its impact on mortality. Further research is needed to elucidate the mechanisms linking NAFLD with adverse health outcomes and to develop effective interventions.

Metformin: Beyond Type 2 Diabetes Mellitus.

Metformin was developed from an offshoot of Guanidine. It is known to be the first-line medication for type 2 diabetes mellitus, polycystic ovarian syndrome, and weight reduction. Metformin has also been shown to have effectiveness in the management of non-alcoholic fatty liver disease (NAFLD), liver cirrhosis, and various carcinomas like hepatocellular, colorectal, prostate, breast, urinary bladder, blood, melanoma, bone, skin, lung and so on. This narrative review focuses on the effect of metformin on non-alcoholic fatty liver disease, liver cirrhosis, and hepatocellular carcinoma. The search platforms for the topic were PubMed, Scopus, and Google search engine. Critical words for searching included 'Metformin,' AND 'Indications of Metformin,' AND 'Non-Alcoholic Fatty Liver Disease,' AND 'Metformin mechanism of action,' AND 'NAFLD management,' AND 'NAFLD and inflammation,' AND 'Metformin and insulin,' AND 'Metformin and inflammation,' AND 'Liver cirrhosis,' AND 'Hepatocellular carcinoma.' Lifestyle modification and the use of hypoglycemic agents can help improve liver conditions. Metformin has several mechanisms that enhance liver health, including reducing reactive oxygen species, nuclear factor kappa beta (NF-κB), liver enzymes, improving insulin sensitivity, and improving hepatic cell lipophagy. Long-term use of metformin may cause some adverse effects like lactic acidosis and gastrointestinal disturbance. Metformin long-term overdose may lead to a rise in hydrogen sulfide in liver cells, which calls for pharmacovigilance. Drug regulating authorities should provide approval for further research, and national and international guidelines need to be developed for liver diseases, perhaps with the inclusion of metformin as part of the management regime.

Leveraging adrenergic receptor blockade for enhanced nonalcoholic fatty liver disease treatment via a biomimetic nanoplatform

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.

Identification of neutrophil extracellular trap-related biomarkers in non-alcoholic fatty liver disease through machine learning and single-cell analysis

Non-alcoholic Fatty Liver Disease (NAFLD), noted for its widespread prevalence among adults, has become the leading chronic liver condition globally. Simultaneously, the annual disease burden, particularly liver cirrhosis caused by NAFLD, has increased significantly. Neutrophil Extracellular Traps (NETs) play a crucial role in the progression of this disease and are key to the pathogenesis of NAFLD. However, research into the specific roles of NETs-related genes in NAFLD is still a field requiring thorough investigation. Utilizing techniques like AddModuleScore, ssGSEA, and WGCNA, our team conducted gene screening to identify the genes linked to NETs in both single-cell and bulk transcriptomics. Using algorithms including Random Forest, Support Vector Machine, Least Absolute Shrinkage, and Selection Operator, we identified ZFP36L2 and PHLDA1 as key hub genes. The pivotal role of these genes in NAFLD diagnosis was confirmed using the training dataset GSE164760. This study identified 116 genes linked to NETs across single-cell and bulk transcriptomic analyses. These genes demonstrated enrichment in immune and metabolic pathways. Additionally, two NETs-related hub genes, PHLDA1 and ZFP36L2, were selected through machine learning for integration into a prognostic model. These hub genes play roles in inflammatory and metabolic processes. scRNA-seq results showed variations in cellular communication among cells with different expression patterns of these key genes. In conclusion, this study explored the molecular characteristics of NETs-associated genes in NAFLD. It identified two potential biomarkers and analyzed their roles in the hepatic microenvironment. These discoveries could aid in NAFLD diagnosis and management, with the ultimate goal of enhancing patient outcomes.

Baseline and change in serum lipid and uric acid level over time and incident of nonalcoholic fatty liver disease (NAFLD) in Chinese adults

Observational studies have shown that non-alcoholic fatty liver disease (NAFLD) is strongly associated with metabolic dysfunction. However, there is a paucity of research on whether changes in indicators of serum metabolism contribute to the development of NAFLD. This study was conducted with 4084 participants who underwent healthy physical examinations at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China, in 2022 and 2023. Baseline and follow-up measurements, including anthropometric data, abdominal ultrasound and blood samples were collected. The diagnosis of NAFLD was based on the 2010 Chinese Guidelines on Diagnosis and Treatment of NAFLD. Multiple logistic regression was utilized to analyze the odds ratios (ORs) for the 1-year risk of NAFLD in connection with both baseline metabolic indicators and changes in metabolic indicators observed over the course of 1 year. A total of 3425 study participants who were free of NAFLD at baseline, including 1146 men and 2279 women, were included in the final analysis. The mean age was 34.43 ± 7.20 years. Participants who developed NAFLD were older, male and had higher levels of body mass index (BMI), blood pressure, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free triiodothyronine (fT3), uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and lower levels of high-density lipoprotein cholesterol (HDL-C) and free thyroxine (fT4) (all P values < 0.05). The multivariable model showed that baseline BMI, diastolic blood pressure (DBP), TG, TC, HDL-C, LDL-C, UA, fT4, fT3, ALT and changes in TG, HDL-C, and UA were associated with the 1-year risk of developing NAFLD. The risk of NAFLD increased by 56% [OR 1.56, 95% Confidence Interval (CI) 1.32–1.87] and 40% (OR 1.40, 95% CI 1.19–1.64) for each standard deviation (SD) increase in altered TG values (1.01 mmol/L) and altered UA values (55 µmol/L) respectively. Conversely, for each SD (0.27 mmol/L) increase in HDL-C change, the 1-year risk of incident NAFLD was reduced by 50% (OR 0.50, 95% CI 0.40–0.62). The present study suggested that increases in TG and UA, and decreases in HDL-C, significantly increase the risk of developing NAFLD. Therefore, more attention should be paid to these factors in the management and prevention of NAFLD.

Sex-specific differences in NAFLD development: effect of a high-sucrose diet on biochemical, histological, and genetic markers in C57bl/6N mice

ABSTRACT Sucrose intake is a potential risk factor for non-alcoholic fatty liver disease (NAFLD). Individual characteristics such as sex, play arole in the biological variation of the disease, potentially related to genetic regulation. This research evaluated sex differences in biochemical, histopathological, and gene expression responses associated with NAFLD in C57bl/6N mice on a high sucrose diet. Female and male mice were assigned to control or high sucrose diets (50% sucrose solution) for 20 weeks. After sacrifice, blood and hepatic tissue were collected for analysis. Female mice revealed moderate-to-high NAFLD, whereas male mice showed mild-to-moderate NAFLD. Sex-specific variations were observed in Cd36 gene expression, an upregulation in females compared with the male group, and Adipor1 gene expression showed significant downregulation in the female group in response to high sucrose diet compared with the control group. These findings highlight the importance of considering gender disparities in the treatment and management of NAFLD.

The pivotal role of dysregulated autophagy in the progression of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome characterized by excessive fat deposition in hepatocytes and a major cause of end-stage liver disease. Autophagy is a metabolic pathway responsible for degrading cytoplasmic products and damaged organelles, playing a pivotal role in maintaining the homeostasis and functionality of hepatocytes. Recent studies have shown that pharmacological intervention to activate or restore autophagy provides benefits for liver function recovery by promoting the clearance of lipid droplets (LDs) in hepatocytes, decreasing the production of pro-inflammatory factors, and inhibiting activated hepatic stellate cells (HSCs), thus improving liver fibrosis and slowing down the progression of NAFLD. This article summarizes the physiological process of autophagy, elucidates the close relationship between NAFLD and autophagy, and discusses the effects of drugs on autophagy and signaling pathways from the perspectives of hepatocytes, kupffer cells (KCs), and HSCs to provide assistance in the clinical management of NAFLD.

Relationship between phase angle measured with bioelectrical impedance analysis and nonalcoholic fatty liver disease in adults

Purpose The phase angle (PhA) measured by bioelectrical impedance analysis (BIA) is associated with nutritional status and cellular health, and it is a clinically important parameter used to assess the risk of various diseases. It remains unclear whether PhA is associated with nonalcoholic fatty liver. The purpose of this study is to investigate the relationship between the BIA parameter PhA and nonalcoholic fatty liver disease (NAFLD). Design/methodology/approach This cross-sectional study was conducted with 300 adults aged 20–64 years (NAFLD: 196, normal: 104). Some biochemical findings of the participants were collected, and whole-body and segmental PhAs were measured using Tanita (MC-780) at 50 kHz. Findings The PhA values of the whole body (p = 0.003), trunk (p &lt; 0.001), right and left legs (p &lt; 0.001 for both) were found to significantly differ according to the degrees of fatty liver. It was observed that the highest PhA values were in normal individuals. Logistic regression analysis showed that the reduction in PhAs of the whole body (p = 0.038), right (p = 0.019) and left legs (p = 0.049) and trunk (p = 0.001) after adjusting for all confounding factors increased the risk of NAFLD. Additionally, whole body PhA was significantly associated with age (year, p = 0.02), BMI (kg/m2; p &lt; 0.001), fat mass (kg; p = 0.001), fat mass (%; p &lt; 0.001), albumin (g/L; p &lt; 0.001) and CRP (mg/dL; p = 0.001). Originality/value The results of this study showed that PhA can be used in the management of NAFLD. To identify potential mechanisms in the relationship between the angle of the liver and NAFLD, large-scale prospective studies are needed.

Evaluating Bempedoic Acid for Non-alcoholic Fatty Liver Disease: A Review of Preclinical and Clinical Research.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disorder globally, characterized by fat accumulation in liver cells, which can progress to inflammation, fibrosis, and cirrhosis. The disease predominantly affects individuals with obesity and high body mass index (BMI). It is a globally prevalent condition, with variations in incidence across different regions. The pathophysiology of NAFLD involves insulin resistance, metabolic disturbances, and genetic and gut microbial factors. Current treatments primarily focus on lifestyle modifications and a limited range of pharmacological options. Bempedoic acid (BA), a novel cholesterol-lowering agent, targets adenosine triphosphate (ATP)-citrate lyase to reduce low-density lipoprotein (LDL) cholesterol and has shown potential in managing NAFLD by decreasing liver fat accumulation and improving lipid profiles. BA's unique mechanism offers a promising add-on therapy, particularly for the patient's intolerant to statins. Despite its potential, comprehensive clinical and preclinical studies are needed to further elucidate its efficacy and safety compared to other NAFLD treatments. Future research should focus on comparing BA with existing and emerging therapies to optimize its role in NAFLD management and enhance patient outcomes.

Clinical cohort of nonalcoholic fatty liver disease in a primary care setting.

Nonalcoholic fatty liver disease (NAFLD) is increasingly common, and primary care physicians (PCPs) are often the first to diagnose NAFLD. While guidelines on NAFLD management in primary care exist, there are limited data on clinical practice patterns. We gathered data from over 370,000 patients with at least one PCP visit between July 2016 and September 2023. Using ICD-10 codes to identify patients with a diagnosis of NAFLD or Nonalcoholic Steatohepatitis (NASH), we extracted demographics, comorbidities, laboratory results, prescriptions, imaging orders, and referrals to describe their care. We identified 10,334 patients with a diagnosis code of NAFLD (93.1%) and/or NASH (16.7%) during a PCP visit. Just over half (54.8%) were female, mean age was 52.8 years, and mean BMI was 33.2 kg/m2 with 90% having overweight or obese. More than 50% had hypertension and hyperlipidemia, and 38% had diabetes. At the diagnosis visit, 2.7% had ultrasound elastography ordered, 2.7% liver biopsy, and less than 1% magnetic resonance elastography. During follow-up ranging from 0 to 7 years, patients had a mean of 15 encounters, during which 4% were diagnosed with fibrosis or cirrhosis. Only 24.2% of patients were referred to a nutritionist and 18% had an appointment, and only 0.7% were referred to hepatology and 3.8% saw a hepatologist. PCPs have not widely implemented clinical practice guidelines for NAFLD, resulting in suboptimal care including for the substantial minority with fibrosis or cirrhosis. Patients might benefit from targeted NAFLD education for PCPs and improved decision and management support.

The effect of myo-inositol supplementation on AMPK/PI3K/AKT pathway and insulin resistance in patients with NAFLD.

Insulin resistance (IR) is the pivotal pathological hit in non-alcoholic fatty liver disease (NAFLD). There is specific attention to combination/conjugated therapies for NAFLD management. As myo-inositol (MI) has been shown to improve IR in animal and human trials, this study aimed to investigate the influence of MI supplementation on glycemic response and IR through AMPK/PI3K/AKT signaling pathway in obese patients with NAFLD. This double-blinded placebo-controlled randomized clinical trial was conducted on 48 obese (BMI = 30-40 kg/m2) patients with NAFLD who were randomly assigned to receiving either MI (4 g/day) or placebo (maltodextrin 4 g/day) group for 8 weeks. Before and after the trial, weight, height, serum glycemic parameters (inc. fasting glucose and insulin) as well as IR indices were assessed. Moreover, the mRNA expression levels of AMPK, AKT, and PDK-1 in peripheral blood mononuclear cells (PBMCs) were determined. MI supplementation resulted in significant increases in the fold changes of AMPK, AKT, and PDK-1 genes (p = .019, p = .049, and p = .029, respectively). Indeed, IR improved in terms of all IR indices in MI group (p < .05) after adjusting for the confounders, apart from quantitative insulin sensitivity check index (QUICKI). The results showed that MI supplementation not only upregulated AMPK, AKT, and PDK-1 mRNA in PBMCs but also improved IR in obese patients with NAFLD.

MiR-218-5p promotes hepatic lipogenesis through targeting Elovl5 in non-alcoholic fatty liver disease

Investigating and identifying pathogenic molecules of non-alcoholic fatty liver disease (NAFLD) has become imperative, which would serve as effective targets in the future. We established high-fat diet (HFD)-induced NAFLD model in mice and palmitic acid (PA)-induced model in mouse AML12 cells. The level of miR-218-5p was examined by qRT-PCR, and Elovl5 was identified as the potential target gene of miR-218-5p. The binding relationship between miR-218-5p and Elovl5 was validated by double luciferase reporter gene assay, and inhibition/overexpression of miR-218-5p in vitro. The functional mechanisms of miR-218-5p/Elovl5 in regulating lipogenesis in NAFLD were investigated in vivo and in vitro through gain- and loss-of-function studies. MiR-218-5p was significantly increased, and Elovl5 was decreased in model group. According to the double luciferase reporter and gene interference experiments in AML12 cells, Elovl5 was a target gene of miR-218-5p and its expression was regulated by miR-218-5p. The SREBP1-mediated lipogenesis signaling pathway regulated by Elovl5 was upregulated in model group. Moreover, silencing of miR-218-5p significantly upregulated Elovl5 expression, and suppressed SREBP1 signaling pathway in PA-induced AML-12 cells. Correspondingly, the cell injury, elevated TC, TG contents and lipid droplet accumulation were ameliorated. Furthermore, the effect of miR-218-5p on lipogenesis in vitro and in vivo was obstructed by si-Elovl5, implicating that miR-218-5p promotes lipogenesis by targeting ELOVL5 in NAFLD. miR-218-5p could promote fatty acid synthesis by targeting Elovl5, thereby accelerating the development of NAFLD, which is one of the key pathogenic mechanisms of NAFLD and provides a new molecular target for the management of NAFLD.

Analysis of Probiotic Role in Non-Alcoholic Fatty Liver Disease (NAFLD) Management: A Meta-Analysis

Background: Non-alcoholic fatty liver disease (NAFLD) is an increasing global health problem. Probiotics have emerged as a potential therapy for NAFLD, but evidence for their efficacy remains mixed. This meta-analysis aims to evaluate the effectiveness of probiotics in the management of NAFLD. Methods: A comprehensive literature search was performed on PubMed, Embase, Cochrane Library, and Web of Science databases until December 2023. Randomized controlled trials (RCTs) evaluating the effects of probiotics in NAFLD patients were included. The main outcomes evaluated were changes in liver enzymes (ALT, AST), insulin resistance index (HOMA-IR), and hepatic steatosis score. Meta-analysis was performed using a random effects model, and heterogeneity was assessed using the I² statistic. Results: Twenty-five RCTs involving 1845 patients met inclusion criteria. Meta-analysis showed that probiotics significantly reduced ALT (MD -8.45; 95% CI -12.67 to -4.23; p&lt;0.0001) and AST (MD -6.89; 95% CI -10.11 to -3.67; p&lt;0.0001) levels compared with placebo. Significant reductions were also observed in HOMA-IR (MD -0.68; 95% CI -1.02 to -0.34; p&lt;0.0001) and hepatic steatosis scores (SMD -0.45; 95% CI -0.71 to -0.19; p=0.0008). Subgroup analysis showed that the effects of probiotics were more pronounced in patients with NAFLD non-alcoholic steatohepatitis (NASH) and those receiving multi-strain probiotics. Conclusion: This meta-analysis provides strong evidence that probiotics have beneficial effects on biochemical and imaging parameters in NAFLD patients. Probiotics may be considered as an adjunct therapy for NAFLD, especially in patients with NASH. However, more research is needed to determine the optimal probiotic strain, dosage, and duration of treatment.