Chronic liver disease is an important risk factor for worse outcomes in acute pancreatitis: a systematic review and meta-analysis.

Chronic liver diseases (CLD) affect 1.5 billion patients worldwide, with dramatically increasing incidence in recent decades. It has been hypothesized that the chronic hyperinflammation associated with CLD may increase the risk of a more severe course of acute pancreatitis (AP). This study aims to investigate the underlying impact of CLD on the outcomes of AP. A systematic search was conducted in Embase, Medline, and Central databases until October 2022. Studies investigating patients with acute pancreatitis and CLD, were included in the meta-analysis. A total of 14,963 articles were screened, of which 36 were eligible to be included. CLD was a risk factor for increased mortality with an odds ratio (OR) of 2.53 (CI 1.30 to 4.93, p = 0.01). Furthermore, renal, cardiac, and respiratory failures were more common in the CLD group, with ORs of 1.92 (CI 1.3 to 2.83, p = 0.01), 2.11 (CI 0.93 to 4.77, p = 0.062) and 1.99 (CI 1.08 to 3.65, p = 0.033), respectively. Moreover, the likelihood of developing Systemic Inflammatory Response Syndrome (SIRS) was significantly higher, with an OR of 1.95 (CI 1.03 to 3.68, p = 0.042). CLD is an important risk factor for worse outcomes in AP pancreatitis, leading to higher mortality and increased rates of local and systemic complications.

Does curcumin improve liver enzymes levels in nonalcoholic fatty liver disease? A systematic review, meta-analysis, and meta-regression.

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

In-depth assessment of steatotic liver disease awareness in high-risk groups.

OBJECTIVES: This study aims to determine the awareness levels and factors affecting it, along with prevalent misconceptions about Steatotic Liver Disease (SLD) among participants with high-risk indicators. METHODS: A questionnaire with open-ended questions was utilized. Participants were recruited from two general internal medicine outpatient clinics, focusing on those with high-risk indicators for SLD. Data collection involved a questionnaire covering demographic information, self-reported clinical conditions, and open-ended questions about SLD awareness. Key focus areas included misconceptions, thematic awareness, and the relationship between awareness and educational attainment. RESULTS: The study involved 228 participants, predominantly female (70.4%), with an average age of 53.8 years. Only 33.7% showed a comprehensive understanding of all aspects of SLD. However, 90.4% provided some accurate information, though often limited or incomplete. Higher education and awareness of SLD risks were key predictors of better understanding. The logistic regression model, with an accuracy of 0.76 and recall of 0.84, found higher education inversely related to low awareness. Common misconceptions highlighted included the belief that polypharmacy or certain medications cause SLD, fatigue as an effect, and increased water intake as a treatment. Notably, seven patients mentioned artichoke consumption as a potential treatment. CONCLUSION: The findings highlight the gap between comprehensive and partial awareness of SLD among high-risk individuals. Educational level and informed understanding of SLD risks are crucial for improving awareness, emphasizing the need for specialized educational efforts and risk communication to high-risk patients.

Association between thyroid function and nonalcoholic fatty liver disease: a dose-response meta-analysis.

Background: Thyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research. Methods: The searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD. Results: Overall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2 = 0.0%, p<0.001) in the overall meta-analysis. The continuous variable meta-analysis indicated that individuals with high levels of TSH (SMD=1.32, 95% CI 0.660 to 1.970, p<0.001) had significantly higher levels of liver fibrosis than those with low levels. Conclusions: Our findings only validate that there is a correlation between the occurrence of NAFLD and abnormal levels of THs, and it is expected that more observational studies will still be conducted in the future to further demonstrate the relationship between thyroid hormones and NAFLD. Trial registration: Registered number in PROSPERO: CRD42023405052.

The efficacy and safety of Dachaihu decoction in the treatment of nonalcoholic fatty liver disease: a systematic review and meta-analysis.

Background: Nonalcoholic fatty liver disease (NAFLD), also known as metabolic associated fatty liver disease (MAFLD), is a common liver condition characterized by excessive fat accumulation in the liver which is not caused by alcohol. The main causes of NAFLD are obesity and insulin resistance. Dachaihu decoction (DCHD), a classic formula in traditional Chinese medicine, has been proved to treat NAFLD by targeting different aspects of pathogenesis and is being progressively used in the treatment of NAFLD. DCHD is commonly applied in a modified form to treat the NAFLD. In light of this, it is imperative to conduct a systematic review and meta-analysis to assess the effectiveness and safety of DCHD in the management of NAFLD. There is a need for a systematic review and meta-analysis to assess the effectiveness and safety of modified DCHD in treating NAFLD. Objective: The objective of this meta-analysis was to systematically assess the clinical effectiveness and safety of DCHD in treating NAFLD. Methods: This meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Including seven databases, both Chinese and English databases were searched for relevant studies. The quality of included studies was carefully assessed using the bias risk assessment tool in the Cochrane Handbook. Eligible articles were the source of extracted data which was meta-analyzed by using Review Manager 5.4 and Stata 17.0. Results: A total of 10 studies containing 825 patients were included. Compared with conventional treatments, combined treatment could clearly improve the liver function of NAFLD patients, which could reduce the levels of ALT (MD = -7.69 U/L, 95% CI: -11.88 to -3.51, p < 0.001), AST (MD = -9.58 U/L, 95% CI: -12.84 to -6.33, p < 0.01), and it also had a certain impact on regulating lipid metabolism, which could reduce the levels of TC (MD = -0.85 mmol/L, 95% CI: -1.22 to 0.48, p < 0.01), TG (MD = -0.45 mmol/L, 95% CI: -0.64 to 0.21, p < 0.01). Adverse event showed that DCHD was relatively safe. Due to the inclusion of less than 10 trials in each group, it was not possible to conduct a thorough analysis of publication bias. Conclusion: According to the meta-analysis, in the treatment of the NAFLD, it is clear that the combination of DCHD was advantages over conventional treatment alone in improving liver function, regulating lipid metabolism. Additionally, DCHD demonstrates a relatively safe profile. Nevertheless, due to limitations in the quality and quantity of the studies incorporated, the effectiveness and safety of DCHD remain inconclusive. Consequently, further high-quality research is imperative to furnish more substantial evidence supporting the widespread clinical application of DCHD. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023397353, CRD42023397353.

Mettl3-m6A-YTHDF1 axis promotion of mitochondrial dysfunction in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: N6-methyladenosine (m6A) mRNA modification and mitochondrial function hold paramount importance in the advancement of metabolic dysfunction-associated steatotic liver disease (MASLD). AIM: The aim of this study was to elucidate the impact of m6A on hepatic mitochondrial dysfunction and provide a novel perspective for a more comprehensive understanding of the pathogenesis of MASLD. METHODS: High-throughput screening methods were used to identify the underlying transcriptome and proteome changes in MASLD model mice. Western blotting, blue native gel electrophoresis (BNGE), dot blot, and Seahorse analyses were conducted to identify and validate the underlying regulatory mechanisms of m6A on mitochondria. RESULTS: In vivo, abnormal m6A modification in MASLD was attributed to the upregulation of methyltransferase like 3 (Mettl3) and the downregulation of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) induced by high-fat foods. In vitro, knockdown of Mettl3 inhibited hepatic oxidative phosphorylation (OXPHOS) and the mitochondrial respiratory chain (MRC), while overexpression of Mettl3 promoted these processes. However, knockout of the reader protein YTHDF1, which plays a crucial role in the m6A modification process, counteracted the effect of Mettl3 and suppressed mitochondrial OXPHOS. CONCLUSIONS: In MASLD, damage to the MRC may be regulated by the Mettl3-m6A-YTHDF1 axis, particularly by the role of YTHDF1. Modulation of the Mettl3-m6A-YTHDF1 axis has the potential to improve mitochondrial function, alleviate MASLD symptoms, and decrease the likelihood of disease progression.

Ursodeoxycholic Acid's Effectiveness in the Management of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

Aim: This meta-analysis's objective was to assess the effectiveness of ursodeoxycholic acid (UDCA) in the management of nonalcoholic fatty liver disease (NAFLD). Methods: Electronic databases like PubMed, Embase, Scopus, and Cochrane Library were thoroughly looked for randomized controlled trials determining ursodeoxycholic acid's (UDCAs) effectiveness on the serum liver function tests in NAFLD patients. After screening, seven randomized controlled trials were incorporated overall. Utilizing a fixed effects model, quantitative data synthesis was performed in R version 4.3.1. Results: The meta-analysis showed significant reductions in alanine transaminase (ALT) (p ≤ 0.0001), aspartate transaminase (p = 0.0009), and gamma-glutamyl transferase (GGT) (p ≤ 0.0001) after UDCA therapy. However, significant reductions in bilirubin (p = 0.6989) and alkaline phosphatase (ALP) (p = 0.1172) levels were not noted. Sensitivity analysis by removing the studies with some concerns of bias was successful in demonstrating a remarkable reduction in heterogeneity for aspartate transaminase and ALP, which was also observed while performing the subgroup analyses via dosage. Conclusion: Ursodeoxycholic acid was beneficial in patients diagnosed with NAFLD as it significantly reduced aspartate transaminase, ALT and GGT levels. However, more randomized controlled trials are required to be conducted in the future to increase the certainty of the evident findings. Clinical significance: This meta-analysis strengthens the evidence about the reductions in AST, ALT, and GGT levels observed with ursodeoxycholic acid therapy in NAFLD patients by pooling the data together from the latest RCTs thus proving its hepatoprotective effects which can be beneficial in preventing the associated complications. How to cite this article: Patel VS, Mahmood SF, Bhatt KH, et al. Ursodeoxycholic Acid's Effectiveness in the Management of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis. Euroasian J Hepato-Gastroenterol 2024;14(1):92-98.

Is Aspartate Aminotransferase to Platelet Ratio Index a Better Noninvasive Score for Predicting Advanced Fibrosis in Nonalcoholic Fatty Liver Disease Patients?

Background: In the 21st century, nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disorder. The prevalence of NAFLD within the general population in India ranges from 9 to 53%. The gold standard for assessing the severity of liver fibrosis is liver biopsy. However, due to various difficulties involved with liver biopsy, it is imperative to identify different non-invasive tools that can replace liver biopsy. Methodology: A prospective observational study of 130 patients meeting the inclusion criteria for NAFLD was done for a period of 18 months. We aimed to compare the performance characteristics of different noninvasive scores [fibrosis-4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and aspartate aminotransferase to platelet ratio index (APRI)] in predicting advanced fibrosis as assessed by FibroScan. Results: In the study, 76.9% of patients were male. Advanced fibrosis was seen in 12.3% of the patients. Majority of the patients with advanced fibrosis had metabolic syndrome. Based on the area under the receiver operating characteristic curve (AUROC), the new cut-off for ruling out advanced fibrosis for FIB-4, NFS, and APRI were 1.18, -0.9, and 0.65, respectively, and APRI had the best AUROC (0.768). Conclusion: Abnormal glycemic status and metabolic syndrome were risk factors for advanced fibrosis. The newly derived cut-offs for the FIB-4 score, NFS score, and APRI score had a better Negative predictive value compared to the original cut-offs. How to cite this article: Bhayani PD, Parameswaran SA, Palaniswamy KR, et al. Is Aspartate Aminotransferase to Platelet Ratio Index a Better Noninvasive Score for Predicting Advanced Fibrosis in Nonalcoholic Fatty Liver Disease Patients? Euroasian J Hepato-Gastroenterol 2024;14(1):35-39.

Gut microbiota dysbiosis links chronic apical periodontitis to liver fibrosis in nonalcoholic fatty liver disease: Insights from a mouse model.

AIM: In this study, we investigated the systemic implications of chronic apical periodontitis (CAP). CAP may contribute to the nonalcoholic fatty liver disease (NAFLD) progression through the gut microbiota and its metabolites, which are related to the degree of fibrosis. METHODOLOGY: Sixteen 7-week-old male apolipoprotein E knockout (apoE-/-) mice were randomly divided into two groups: the CAP and Con groups. A CAP model was established by sealing the first- and second-maxillary molars with bacterium-containing cotton balls. Apical lesions were evaluated by micro-CT. Histological evaluations of NAFLD were performed using second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) assays. Additionally, we comprehensively analyzed the gut microbiota using 16S rRNA gene sequencing and explored metabolic profiles by liquid chromatography-mass spectrometry (LC-MS). Immunofluorescence analysis was used to examine the impact of CAP on tight junction proteins and mucin expression. Transcriptome assays have elucidated gene expression alterations in liver tissues. RESULTS: Micro-CT scans revealed an evident periapical bone loss in the CAP group, and the total collagen percentage was increased (Con, 0.0361 ± 0.00510%, CAP, 0.0589 ± 0.00731%, p < .05). 16S rRNA sequencing revealed reduced diversity and distinct taxonomic enrichment in the CAP group. Metabolomic assessments revealed that differentially enriched metabolites, including D-galactosamine, were enriched and that 16-hydroxyhexadecanoic acid and 3-methylindole were depleted in the CAP group. Immunofluorescence analyses revealed disruptions in tight junction proteins and mucin production, indicating intestinal barrier integrity disruption. Liver transcriptome analysis revealed upregulation of Lpin-1 expression in the CAP group. CONCLUSION: This study provides comprehensive evidence of the systemic effects of CAP on liver fibrosis in NAFLD patients by elucidating alterations in the gut microbiota composition and metabolism.

Serologic Biomarkers for Hepatic Fibrosis in Obese Children with Nonalcoholic Steatohepatitis.

Purpose: The prevalence of nonalcoholic steatohepatitis (NASH) is increasing with the increasing prevalence of childhood obesity. Although NASH has a high risk of progression to liver fibrosis and cirrhosis, few studies have reported noninvasive markers for predicting hepatic fibrosis in children. This study aimed to evaluate and compare the diagnostic accuracies of serologic biomarkers and scoring systems for hepatic fibrosis in obese children with NASH. Methods: A total of 96 children were diagnosed with NASH based on liver biopsy findings and divided into two groups according to the degree of liver fibrosis: mild (stage 0-1) or advanced (stage 2-4). Clinical and laboratory parameters and serum levels of hyaluronic acid and type IV collagen were measured. The aspartate aminotransferase/platelet ratio index (APRI) and fibrosis-4 (FIB-4) score were calculated. Results: Among the noninvasive markers, only serum type IV collagen level and FIB-4 were significantly different between the two groups. The area under the receiver operating curve of each biomarker and scoring system was 0.80 (95% confidence interval [CI]: 0.70-0.90) for type IV collagen at an optimal cutoff of 148 ng/mL (sensitivity 69.8%, specificity 84.6%), followed by 0.69 (95% CI: 0.57-0.83) for APRI, 0.68 (95% CI: 0.56-0.80) for FIB-4, and 0.65 (95% CI: 0.53-0.77) for hyaluronic acid. Conclusion: Type IV collagen as a single noninvasive serologic biomarker for hepatic fibrosis and FIB-4 as a hepatic fibrosis score are beneficial in predicting advanced hepatic fibrosis and determining proper diagnosis and treatment strategies before fibrosis progresses in obese children with NASH.

USP13 ameliorates nonalcoholic fatty liver disease through inhibiting the activation of TAK1.

BACKGROUND: The molecular mechanisms underlying nonalcoholic fatty liver disease (NAFLD) remain to be fully elucidated. Ubiquitin specific protease 13 (USP13) is a critical participant in inflammation-related signaling pathways, which are linked to NAFLD. Herein, the roles of USP13 in NAFLD and the underlying mechanisms were investigated. METHODS: L02 cells and mouse primary hepatocytes were subjected to free fatty acid (FFA) to establish an in vitro model reflective of NAFLD. To prepare in vivo model of NAFLD, mice fed a high-fat diet (HFD) for 16 weeks and leptin-deficient (ob/ob) mice were used. USP13 overexpression and knockout (KO) strategies were employed to study the function of USP13 in NAFLD in mice. RESULTS: The expression of USP13 was markedly decreased in both in vitro and in vivo models of NAFLD. USP13 overexpression evidently inhibited lipid accumulation and inflammation in FFA-treated L02 cells in vitro. Consistently, the in vivo experiments showed that USP13 overexpression ameliorated hepatic steatosis and metabolic disorders in HFD-fed mice, while its deficiency led to contrary outcomes. Additionally, inflammation was similarly attenuated by USP13 overexpression and aggravated by its deficiency in HFD-fed mice. Notably, overexpressing of USP13 also markedly alleviated hepatic steatosis and inflammation in ob/ob mice. Mechanistically, USP13 bound to transforming growth factor ß-activated kinase 1 (TAK1) and inhibited K63 ubiquitination and phosphorylation of TAK1, thereby dampening downstream inflammatory pathways and promoting insulin signaling pathways. Inhibition of TAK1 activation reversed the exacerbation of NAFLD caused by USP13 deficiency in mice. CONCLUSIONS: Our findings indicate the protective role of USP13 in NAFLD progression through its interaction with TAK1 and inhibition the ubiquitination and phosphorylation of TAK1. Targeting the USP13-TAK1 axis emerges as a promising therapeutic strategy for NAFLD treatment.

Alanine aminotransferase predicts incident steatotic liver disease of metabolic etiology: Long life to the old biomarker!

Alanine aminotransferase (ALT) serum levels increase because of hepatocellular damage. Metabolic dysfunction-associated fatty liver disease (MAFLD), which identifies steatotic liver disease (SLD) associated with ≥ 2 metabolic abnormalities, has prominent sexual differences. The Metabolic Syndrome defines a cluster comprising abdominal obesity, altered glucose metabolism, dyslipidemia, and hypertension. Male sex, body mass index, glucose, lipids, ferritin, hypertension, and age independently predict ALT levels among blood donors. Over the last few decades, the reference range of ALT levels has been animatedly debated owing to attempts to update sex-specific reference ranges. With this backset, Chen et al have recently published a study which has two main findings. First, > 80% of individuals with MAFLD had normal ALT levels. Second, there was a linear increasing trend in the association between cumulative excess high-normal ALT levels and the rate of incident MAFLD. This study has biologically credible findings. However, it inaccurately considered sex differences in the MAFLD arena. Therefore, future studies on SLD owing to metabolic dysfunction should adopt locally determined and prospectively validated reference ranges of ALT and carefully consider sex differences in liver enzymes and MAFLD pathobiology.

The Beneficial Effect of Brazilian Propolis for Liver Damage through Endoplasmic Reticulum Stress.

There is evidence that propolis exhibits anti-inflammatory, anticancer, and antioxidant properties. We assessed the potential beneficial effects of Brazilian propolis on liver injury in nonalcoholic fatty liver disease (NAFLD). Our findings demonstrate that Brazilian propolis suppresses inflammation and fibrosis in the liver of mice with NAFLD by inhibiting the expression of genes involved in endoplasmic reticulum (ER) stress. Additionally, Brazilian propolis also suppressed the expression of ER stress-related genes in HepG2 cells treated with an excess of free fatty acids, leading to cell apoptosis. A deeper analysis revealed that kaempferol, one of the components present in Brazilian propolis, induces cell proliferation through the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and protects against oxidative stress. In conclusion, Brazilian propolis exhibits hepatoprotective properties against oxidative stress by inhibiting ER stress in NAFLD-induced model mice.

Association between metabolic dysfunction-associated steatotic liver disease and risk of urolithiasis: an updated systematic review and meta-analysis.

Epidemiological studies have reported an association between metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of urolithiasis. However, the magnitude of the risk and whether this risk varies with the severity of MASLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between MASLD and urolithiasis. We systematically searched PubMed, Scopus, and Web of Science from database inception to March 31, 2024, using predefined keywords to identify relevant observational studies in which imaging methods or survey questionnaires diagnosed MASLD and urolithiasis. Meta-analysis was performed using random-effects modelling. We identified seven cross-sectional studies and one prospective cohort study with aggregate data on 248,936 adults from different countries. MASLD was significantly associated with an increased risk of prevalent urolithiasis (pooled random-effects odds ratio 1.87, 95% CI 1.34-2.60; I2 = 91%). This association remained significant in those studies whose results were adjusted for age, sex, ethnicity, obesity, diabetes, and other potential confounders. There was a positive graded association between the ultrasonographic severity of MASLD and urolithiasis. Meta-analysis of the single prospective cohort study showed that MAFLD was not associated with risk of developing incident urolithiasis (pooled random-effects hazard ratio 1.08, 95% CI 0.90-1.30), although a significant association was reported in men. Sensitivity analyses did not modify these findings. The funnel plot did not reveal any significant publication bias. This updated meta-analysis provides evidence for a significant association between MASLD and the presence of urolithiasis. Whether MASLD is associated with a higher risk of developing incident urolithiasis remains to be established.

Semaglutide Concurrently Improves Vascular and Liver Indices in Patients With Type 2 Diabetes and Fatty Liver Disease.

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

Associations between systemic inflammation indicators and nonalcoholic fatty liver disease: evidence from a prospective study.

Background: Although inflammation has been linked to nonalcoholic fatty liver disease (NAFLD), most studies have focused only on a single indicator, leading to inconsistent results. Therefore, a large prospective study that includes a variety of well-documented single and composite indicators of inflammation is needed. This study aimed to thoroughly investigate the potential associations between different systemic inflammatory indicators and NAFLD in the UK Biobank cohort. Methods: After excluding ineligible participants, 378,139 individuals were included in the study. Associations between systemic inflammatory indicators and hepatic steatosis were assessed using multivariate logistic regression. The relationships between systemic inflammatory indicators and nonalcoholic fatty liver disease were analysed using Cox proportional hazards models, and nonlinear associations were investigated using restricted cubic splines. Results: According to the cross-sectional analysis, systemic inflammatory indicators significantly correlated with hepatic steatosis. Over a median follow-up of 13.9 years, 4,145 individuals developed NAFLD. After sufficient adjustment for confounding factors, CRP levels were found to be nonlinearly positively associated with NAFLD risk (P<0.001), representing the strongest correlation among the tested relationships; lymphocyte count and the LMR showed an L-shaped correlation; monocyte count and neutrophil count showed a linear positive correlation (all P< 0.001); and the NLR, PLR, and SII showed a U-shaped correlation (all P<0.001). Conclusions: Multiple systemic inflammatory indicators are strongly associated with the development of NAFLD, and aggressive systemic inflammation management may have a favourable impact on reducing the burden of NAFLD; further randomized controlled studies are needed.

Role of Omega-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic (DHA) as modulatory and anti-inflammatory agents in noncommunicable diet-related diseases - Reports from the last 10 years.

BACKGROUND & AIMS: Fatty acids are a fundamental component of the human diet, particularly polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The importance of omega-3 fatty acids has been studied in the context of many diseases due to their pleiotropic effects, focusing on the anti-inflammatory effects of EPA and DHA. Currently, the results of these acids in noncommunicable diseases are being increasingly assessed in a broader context than just inflammation. However, the mechanisms underlying the modulatory and anti-inflammatory effects of omega-3 fatty acids remain the subject of intensive research. Therefore, we reviewed the literature covering articles from the last decade to assess not only the anti-inflammatory but, above all, the modulatory effect of EPA and DHA acids on noncommunicable diet-related diseases. METHODS: The PubMed, Web of Science and Scopus databases were searched for studies regarding the effects of omega-3 fatty acids on diet-related disorders from the last 10 years. RESULTS: The available research shows that EPA and DHA supplementation has a beneficial impact on regulating triglycerides, total cholesterol, insulin resistance, blood pressure, liver enzymes, inflammatory markers and oxidative stress. Additionally, there is evidence of their potential benefits in terms of mitochondrial function, regulation of plasma lipoproteins, and reduction of the risk of sudden cardiovascular events associated with atherosclerotic plaque rupture. CONCLUSIONS: Omega-3 polyunsaturated fatty acids (EPA, DHA) have many beneficial effects among patients with diet-related disorders. More well-designed randomised controlled trials are needed to fully determine the usefulness of EPA and DHA in treating and preventing noncommunicable diet-related diseases.

The Association Between Neutrophil/High-Density Lipoprotein Cholesterol Ratio and Non-Alcoholic Fatty Liver Disease in a Healthy Population.

Objective: Non-alcoholic fatty liver disease (NAFLD) is characterized by abnormal lipid metabolism and inflammation. This study aimed to investigate the relationship between neutrophil-HDL cholesterol ratio (NHR) and NAFLD in a healthy population. Methods: 1881 healthy people who underwent a physical examination from August to December 2023 at the Hebei General Hospital were chosen for this cross-sectional study. 936 individuals were ultimately included thanks to propensity matching and exclusion criteria. Ultrasound was used to diagnose fatty liver and a t-test or Mann-Whitney test was used to compare the clinical characteristics of participants between groups with and without fatty liver. Logistic regression was used to construct a new model that included NHR. The predictive value of NHR as well as the new model for NAFLD in a healthy population was assessed using logistic regression and subject work characteristic curves. Results: NHR levels were higher among participants in the NAFLD group than those without NAFLD(P<0.05). NHR is a risk factor for NAFLD in a healthy population(P<0.05). The odds ratios (ORs) of NHR for predicting NAFLD in Model I (adjusted for sex, age, and BMI) and Model II (adjusted for sex, age, BMI, HbA1c, TC, TG, and ALT) were 1.166 (1.022, 1.331) and 1.248 (1.110, 1.402)(P<0.05). The new model created by logistic regression predicted NAFLD with an area under the curve of 0.676 (0.645, 0.706). Compared to participants in the low NHR group, the high NHR group exhibited a higher prevalence of NAFLD(p<0.05). Conclusion: NHR is associated with NAFLD, which is a good predictor of NAFLD in a healthy population.

Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic fat accumulation in individuals consuming little or no alcohol, has become highly prevalent globally. Oxidative stress plays a central role in instigating inflammation and cell death pathways driving NAFLD progression. This case-control study aimed to elucidate the association between circulating levels of the pivotal non-enzymatic antioxidants - coenzyme Q10 and vitamins E and C - and liver injury parameters among 60 Iraqi NAFLD patients versus 30 healthy controls. NAFLD diagnosis entailed over 5% hepatic steatosis on ultrasound excluding other etiologies. Patients spanned three age groups: 20-29, 30-39, and 40-49. Substantially diminished antioxidant levels concurrent with elevated alkaline phosphatase enzyme were unveiled in NAFLD patients relative to controls (all p < 0.001). Age-based analysis reinforced widespread antioxidant depletion and liver enzyme augmentation across NAFLD patients. Significant correlations also emerged between antioxidants and liver parameters. Our novel observations confirm an antioxidant inadequacy likely perpetuating pathogenic oxidative reactions in NAFLD. Restoring such deficits through lifestyle or therapeutic interventions may confer preventative and disease-modifying value.

Mapping the global research landscape on nonalcoholic fatty liver disease and insulin resistance: A visualization and bibliometric study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a liver condition that is prevalent worldwide and associated with significant health risks and economic burdens. As it has been linked to insulin resistance (IR), this study aimed to perform a bibliometric analysis and visually represent the scientific literature on IR and NAFLD. AIM: To map the research landscape to underscore critical areas of focus, influential studies, and future directions of NAFLD and IR. METHODS: This study conducted a bibliometric analysis of the literature on IR and NAFLD indexed in the SciVerse Scopus database from 1999 to 2022. The search strategy used terms from the literature and medical subject headings, focusing on terms related to IR and NAFLD. VOSviewer software was used to visualize research trends, collaborations, and key thematic areas. The analysis examined publication type, annual research output, contributing countries and institutions, funding agencies, journal impact factors, citation patterns, and highly cited references. RESULTS: This analysis identified 23124 documents on NAFLD, revealing a significant increase in the number of publications between 1999 and 2022. The search retrieved 715 papers on IR and NAFLD, including 573 (80.14%) articles and 88 (12.31%) reviews. The most productive countries were China (n = 134; 18.74%), the United States (n = 122; 17.06%), Italy (n = 97; 13.57%), and Japan (n = 41; 5.73%). The leading institutions included the Università degli Studi di Torino, Italy (n = 29; 4.06%), and the Consiglio Nazionale delle Ricerche, Italy (n = 19; 2.66%). The top funding agencies were the National Institute of Diabetes and Digestive and Kidney Diseases in the United States (n = 48; 6.71%), and the National Natural Science Foundation of China (n = 37; 5.17%). The most active journals in this field were Hepatology (27 publications), the Journal of Hepatology (17 publications), and the Journal of Clinical Endocrinology and Metabolism (13 publications). The main research hotspots were "therapeutic approaches for IR and NAFLD" and "inflammatory and high-fat diet impacts on NAFLD". CONCLUSION: This is the first bibliometric analysis to examine the relationship between IR and NAFLD. In response to the escalating global health challenge of NAFLD, this research highlights an urgent need for a better understanding of this condition and for the development of intervention strategies. Policymakers need to prioritize and address the increasing prevalence of NAFLD.