Selenium intake in relation to all-cause and cardiovascular mortality in individuals with nonalcoholic fatty liver disease: A nationwide study in nutrition.

AIMS: Limited evidence exists regarding the association of selenium with risk of death in individuals with nonalcoholic fatty liver disease (NAFLD). This study was designed to investigate the relationship between dietary selenium intake with mortality in a nationally representative sample of United States adults with NAFLD. METHODS: Dietary selenium intake was assessed in 2274 NAFLD adults younger than 60 years of age from the National Health and Nutrition Examination Survey (NHANES) III through a 24-hour dietary recall. NAFLD was diagnosed by liver ultrasound after excluding liver disease due to other causes. Cox proportional hazards models were utilized to assess the effect of dietary selenium intake on all-cause and cardiovascular mortality among individuals with NAFLD. RESULTS: At a median follow-up of 27.4 years, 577 deaths occurred in individuals with NAFLD, including 152 cardiovascular deaths. The U-shaped associations were discovered between selenium intake with all-cause (Pnolinear = 0.008) and cardiovascular mortality (Pnolinear < 0.001) in adults with NAFLD after multivariate adjustment, with the lowest risk around selenium intake of 121.7 or 125.9 µg/day, respectively. Selenium intake in the range of 104.1-142.4 µg/day was associated with a reduced risk of all-cause mortality and, otherwise, an increased risk. Selenium intake in the range of 104.1-150.6 µg/day was associated with a reduced risk of cardiovascular death and, otherwise, an increased risk. CONCLUSIONS: Both high and low selenium intake increased the risk of all-cause and cardiovascular death in adults younger than 60 years of age with NAFLD, which may help guide dietary adjustments and improve outcomes in adults with NAFLD.

Mortality outcomes in diabetic metabolic dysfunction-associated fatty liver disease: non-obese versus obese individuals.

The difference in the survival of obese patients and normal-weight/lean patients with diabetic MAFLD remains unclear. Therefore, we aimed to describe the long-term survival of individuals with diabetic MAFLD and overweight/obesity (OT2M), diabetic MAFLD with lean/normal weight (LT2M), MAFLD with overweight/obesity and without T2DM (OM), and MAFLD with lean/normal weight and without T2DM (LM). Using the NHANESIII database, participants with MAFLD were divided into four groups. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease (CVD)-related, and cancer-related mortalities for different MAFLD subtypes were evaluated using Cox proportional hazards models. Of the 3539 participants, 1618 participants (42.61%) died during a mean follow-up period of 274.41 ± 2.35 months. LT2M and OT2M had higher risks of all-cause mortality (adjusted HR, 2.14; 95% CI 1.82-2.51; p < 0.0001; adjusted HR, 2.24; 95% CI 1.32-3.81; p = 0.003) and CVD-related mortality (adjusted HR, 3.25; 95% CI 1.72-6.14; p < 0.0001; adjusted HR, 3.36; 95% CI 2.52-4.47; p < 0.0001) than did OM. All-cause and CVD mortality rates in LT2M and OT2M patients were higher than those in OM patients. Patients with concurrent T2DM and MAFLD should be screened, regardless of the presence of obesity.

Lipid-based insulin-resistance markers predict cardiovascular events in metabolic dysfunction associated steatotic liver disease.

BACKGROUND: Insulin resistance (IR) is the cornerstone of Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD), pathophysiologically being the key link between MASLD, metabolic disorders, and cardiovascular (CV) diseases. There are no prospective studies comparing the predictive values of different markers of insulin resistance (IR) in identifying the presence of MASLD and the associated risk of cardiovascular events (CVEs). METHODS: Post hoc analysis of the prospective Plinio Study, involving dysmetabolic patients evaluated for the presence of MASLD. The IR markers considered were Homeostatic Model Assessment for IR (HOMA-IR), Triglycerides-Glycemia (TyG) index, Triglycerides to High-Density Lipoprotein Cholesterol ratio (TG/HDL-C), Lipid Accumulation Product (LAP) and Visceral Adiposity Index (VAI). Receiver operative characteristic (ROC) analyses were performed to find the optimal cut-offs of each IR marker for detecting MASLD and predicting CVEs in MASLD patients. Logistic and Cox multivariable regression analyses were performed, after dichotomizing the IR markers based on the optimal cut-offs, to assess the factors independently associated with MASLD and the risk of CVEs. RESULTS: The study included 772 patients (age 55.6 ± 12.1 years, 39.4% women), of whom 82.8% had MASLD. VAI (Area Under the Curve [AUC] 0.731), TyG Index (AUC 0.723), and TG/HDL-C ratio (AUC: 0.721) predicted MASLD but was greater with HOMA-IR (AUC: 0.792) and LAP (AUC: 0.787). After a median follow-up of 48.7 (25.4-75.8) months, 53 MASLD patients experienced CVEs (1.8%/year). TyG index (AUC: 0.630), LAP (AUC: 0.626), TG/HDL-C (AUC: 0.614), and VAI (AUC: 0.590) demonstrated comparable, modest predictive values in assessing the CVEs risk in MASLD patients. CONCLUSION: In dysmetabolic patients HOMA-IR and LAP showed the best accuracy in detecting MASLD. The possible use of lipid-based IR markers in stratifying the CV risk in patients with MASLD needs further validation in larger cohorts.

Correlation of alanine aminotransferase levels and a histological diagnosis of steatohepatitis with ultrasound-diagnosed metabolic-associated fatty liver disease in patients from a centre in Nigeria.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is defined as the occurrence of hepatic fat accumulation in patients with negligible alcohol consumption or any other cause of hepatic steatosis. This study aimed to correlate the ultrasound-based diagnosis of MAFLD with the histological diagnosis of nonalcoholic steatohepatitis (NASH) and alanine aminotransferase (ALT) levels in patients with MAFLD. METHODS: This was a hospital-based cross-sectional study of 71 patients with MAFLD diagnosed by ultrasound. Percutaneous liver biopsy was performed for histological evidence of NASH in all patients, regardless of liver function test (LFT) values, provided that they had no contraindications. Liver histology was graded using the NASH Clinical Research Network MAFLD Activity Score. The data obtained were entered into SPSS version 21 and analysed using descriptive and inferential statistics. The significance level was set at < 0.05. RESULTS: A total of 71 patients (26 males and 45 females) with MAFLD were included. Thirty-nine (76.5%) patients with MAFLD and normal ALT levels had NASH, while 14 (82.4%) had elevated ALT levels. There was no statistically significant difference in the histological grade of NASH between patients with normal and elevated ALT levels. A weak correlation was found between the severity of steatosis on ultrasound scan and NASH incidence (p = 0.026). The sensitivity and specificity of ALT levels for predicting NASH according to the area under the receiver operating characteristics (AUROC 0.590) at an ALT cut-off value of 27.5 IU/L were 55.8% and 64.7%, respectively. CONCLUSION: NASH can occur in patients with MAFLD, irrespective of alanine transaminase (ALT) levels, and ultrasound grading of the severity of steatosis cannot accurately predict NASH. Liver biopsy remains the investigation of choice.

Liver histology is associated with long-term clinical outcomes in patients with metabolic dysfunction-associated steatohepatitis.

BACKGROUND: Few studies have examined the risk of long-term clinical outcomes in patients with metabolic dysfunction-associated steatohepatitis in relation to liver histology. We aimed to study this using a real-world cohort. METHODS: Adults (N = 702) recorded on Vanderbilt University Medical Center's Synthetic Derivative database (1984-2021) with evidence of metabolic dysfunction-associated steatohepatitis on liver biopsy were followed from the first biopsy until the first clinical event or last database entry (median: 4.7 y). Risks of cirrhosis (N = 650), other noncirrhotic liver-related (N = 702) and cardiovascular-related outcomes (N = 660), and mortality due to liver, cardiovascular, or cancer events (N = 660) were determined as a function of baseline histology (fibrosis stage [F], lobular inflammation grade [LI], hepatocyte ballooning grade [HB], and steatosis score) adjusting for sex, age, diabetes, and weight-loss surgery. RESULTS: Cirrhosis risk was reduced for lower versus higher fibrosis stage (HR: F0-1 vs. F3: 0.22 [95% CI: 0.12-0.42]), LI1 versus LI2-3 (0.42 [0.19-0.97]), and HB1 versus HB2 (0.20 [0.08-0.50]). Lower fibrosis stage was associated with significantly lower risks of liver-related outcomes versus F4 cirrhosis (eg, F0-1: 0.12 [0.05-0.25]), whereas no differences were seen across baseline lobular inflammation, hepatocyte ballooning, and steatosis grades/scores. Lower versus higher lobular inflammation grade was associated with lower risks for liver-related outcomes in patients with weight-loss surgery. There was a trend for lower risks for cardiovascular-related and any long-term outcomes with lower versus higher fibrosis stage. CONCLUSIONS: Fibrosis stage and lobular inflammation and hepatocyte ballooning grades predict the risk of long-term outcomes, supporting the use of these histological features as potential surrogate markers of disease progression or clinical outcomes.

Features of exocrine pancreatic insufficiency in patients with non-alcoholic fatty liver disease in combination with type 2 diabetes and COVID-19.

OBJECTIVE: Aim: The aim of the research was to study the features of pancreatic exocrine insufficiency (EPI) in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (DM) at COVID-19. PATIENTS AND METHODS: Materials and Methods: 72 patients with NAFLD and COVID-19 were examined. The patients have been divided into two groups: group 1 included 42 patients with NAFLD and insulin resistance (IR); group 2 consisted of 30 patients with NAFLD in the combination with type 2 DM. EPI was detected by 13С-mixed triglyceride breath test (13С-MTBT) in all the patients. RESULTS: Results: The result of 13С-MTBT indicates EPI in the examined subjects of the 2 group. A significant decrease in the maximum concentration of 13СО2 between 150 and 210 min was also diagnosed in group 1 patients. research (up to 8.2 ± 0.9% - p < 0.05), however, the total concentration of 13СО2 at the end of 360 min. the study reached only 27.7 ± 1.1% (p < 0.05). CONCLUSION: Conclusions: Based on the results of laboratory-instrumental methods of research, patients with NAFLD and type 2 diabetes with COVID-19 were diagnosed with severe EPI. The results of 13С-MTBT in NAFLD and IR with COVID-19 indicate a decrease in the functional reserves of the pancreas and the formation of its EPI.

Exploration of the core pathway of inflammatory bowel disease complicated with metabolic fatty liver and two-sample Mendelian randomization study of the causal relationships behind the disease.

Background: Inflammatory bowel disease (IBD) is often associated with complex extraintestinal manifestations. The incidence of nonalcoholic fatty liver disease (NAFLD) in IBD populations is increasing yearly. However, the mechanism of interaction between NAFLD and IBD is not clear. Consequently, this study aimed to explore the common genetic characteristics of IBD and NAFLD and identify potential therapeutic targets. Materials and methods: Gene chip datasets for IBD and NAFLD were obtained from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to identify modules in those datasets related to IBD and NAFLD. ClueGO was used for biological analysis of the shared genes between IBD and NAFLD. Based on the Human MicroRNA Disease Database (HMDD), microRNAs (miRNAs) common to NAFLD and IBD were obtained. Potential target genes for the miRNAs were predicted using the miRTarbase, miRDB, and TargetScan databases. Two-sample Mendelian randomization (MR) and two-way MR were used to explore the causal relationship between Interleukin-17 (IL-17) and the risk of IBD and NAFLD using data from GWAS retrieved from an open database. Results: Through WGCNA, gene modules of interest were identified. GO enrichment analysis using ClueGO suggested that the abnormal secretion of chemokines may be a common pathophysiological feature of IBD and NAFLD, and that the IL-17-related pathway may be a common key pathway for the pathological changes that occur in IBD and NAFLD. The core differentially expressed genes (DEGs) in IBD and NAFLD were identified and included COL1A1, LUM, CCL22, CCL2, THBS2, COL1A2, MMP9, and CXCL8. Another cohort was used for validation. Finally, analysis of the miRNAs identified potential therapeutic targets. The MR results suggested that although there was no causal relationship between IBD and NAFLD, there were causal relationships between IL-17 and IBD and NAFLD. Conclusion: We established a comorbid model to explain the potential mechanism of IBD with NAFLD and identified the chemokine-related pathway mediated by cytokine IL-17 as the core pathway in IBD with NAFLD, in which miRNA also plays a role and thus provides potential therapeutic targets.

Mesenteric panniculitis associated with non-alcoholic fatty liver disease: A case series.

Mesenter ic p anniculitis (MP) is a b enign infla mmatory condi tion of the abdomin al mesentery, whi ch presents with a wid e variety of symptoms. I t is diagnosed non - invasively through com puted to mography (CT ) scan, whereas biopsy is still co nside red th e gold standa rd. Steroids are the first line of treatment. Here, we report four cases who presented with abdominal pain. These patients were overweight and the CT scan findings were suggestive of mese nte ric panniculitis. Three cases had concomitant non- alcoholic steatohep atitis w ith el evated alanine transaminase levels, dyslipidaemia, and insulin resistance. FibroSca n showed moderate to severe steatosis. PNPLA3 rs738409 genotype was homozygous positive (GG) in one patient, whereas two patients were heterozygous positive (CG ). This a ssociat io n has not been well-described so far and w arrants f ur ther inve s tigation. There may be some common predisposing factors.

Assessing Causal Relationships Between Periodontitis and Non-alcoholic Fatty Liver Disease: A Two-Sample Bidirectional Mendelian Randomisation Study.

PURPOSE: To investigate the causality between periodontitis and non-alcoholic fatty liver disease (NAFLD) using a two-sample bidirectional Mendelian randomisation (MR) analysis. MATERIALS AND METHODS: Genetic variations in periodontitis and NAFLD were acquired from genome-wide association studies (GWAS) using the Gene-Lifestyle Interaction in Dental Endpoints, a large-scale meta-analysis, and FinnGen consortia. Data from the first two databases were used to explore the causal relationship between periodontitis and NAFLD ("discovery stage"), and the data from FinnGen was used to validate our results ("validation stage"). We initially performed MR analysis using 5 single nucleotide polymorphisms (SNPs) in the discovery samples and 18 in the replicate samples as genetic instruments for periodontitis to investigate the causative impact of periodontitis on NAFLD. We then conducted a reverse MR analysis using 6 SNPs in the discovery samples and 4 in the replicate samples as genetic instruments for NAFLD to assess the causative impact of NAFLD on periodontitis. We further implemented heterogeneity and sensitivity analyses to assess the reliability of the MR results. RESULTS: Periodontitis was not causally related to NAFLD (odds ratio [OR] = 1.036, 95% CI: 0.914-1.175, p = 0.578 in the discovery stage; OR = 1.070, 95% CI: 0.935-1.224, p = 0.327 in the validation stage), and NAFLD was not causally linked with periodontitis (OR = 1.059, 95% CI: 0.916-1.225, p = 0.439 in the discovery stage; OR = 0.993, 95% CI: 0.896-1.102, p = 0.901 in the validation stage). No heterogeneity was observed among the selected SNPs. Sensitivity analyses demonstrated the absence of pleiotropy and the reliability of our MR results. CONCLUSION: The present MR analysis showed no genetic evidence for a cause-and-effect relationship between periodontitis and NAFLD. Periodontitis may not directly influence the development of NAFLD and vice versa.

Reply to the Letter to the Editor on "Prolactin is a Key Factor for Nonalcoholic Fatty Liver Disease in Obese Children".

Dear Editor,The authors thank the writers 1 of the letter for reviewing and assessing our article 2, "Prolactin is a Key Factor for Nonalcoholic Fatty Liver Disease in Obese Children". Overall, we agree that possible selection bias must be considered. However, in clinical studies, we found that hyperprolactinemia is mainly caused by pathological and idiopathic hyperprolactinemia. The former includes hypothalamic pituitary lesions (pituitary prolactinoma and empty sella syndrome, etc.), systemic diseases (hypothyroidism, etc.), tumor secretion (ovarian teratoma, etc.), trauma (chest wall trauma, etc.), surgery (artificial abortion, etc.), and drug side effects (antipsychotics, antidepressants, etc.).

Association between severity of nonalcoholic fatty liver disease and major adverse cardiovascular events in patients assessed by coronary computed tomography angiography.

BACKGROUND: The effect of nonalcoholic fatty liver disease (NAFLD) on major adverse cardiovascular events (MACEs) can be influenced by the degree of coronary artery stenosis. However, the association between the severity of NAFLD and MACEs in patients who underwent coronary computed tomography angiography (CCTA) is unclear. METHODS: A total of 341 NAFLD patients who underwent CCTA were enrolled. The severity of NAFLD was divided into mild NAFLD and moderate-severe NAFLD by abdominal CT results. The degree of coronary artery stenosis was evaluated by using Coronary Artery Disease Reporting and Data System (CAD-RADS) category. Cox regression analysis and Kaplan-Meier analysis were used to assess poor prognosis. RESULTS: During the follow-up period, 45 of 341 NAFLD patients (13.20%) who underwent CCTA occurred MACEs. The severity of NAFLD (hazard ratio [HR] = 2.95[1.54-5.66]; p = 0.001) and CAD-RADS categories 3-5 (HR = 16.31[6.34-41.92]; p < 0.001) were independent risk factors for MACEs. The Kaplan-Meier analysis showed that moderate to severe NAFLD patients had a worsen prognosis than mild NAFLD patients (log-rank p < 0.001). Moreover, the combined receiver operating characteristic curve of the severity of NAFLD and CAD-RADS category showed a good predicting performance for the risk of MACEs, with an area under the curve of 0.849 (95% CI = 0.786-0.911). CONCLUSION: The severity of NAFLD was independent risk factor for MACEs in patients with obstructive CAD, having CAD-RADS 3-5 categories on CCTA.

Semaglutide combined with empagliflozin vs. monotherapy for non-alcoholic fatty liver disease in type 2 diabetes: Study protocol for a randomized clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM. METHODS: This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed. DISCUSSION: This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).

Monitoring disease progression in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease. Its prevalence is increasing with the epidemic of obesity and metabolic syndrome. MASLD progression into metabolic dysfunction-associated steatohepatitis (MASH) and advanced fibrosis may lead to decompensated cirrhosis and development of liver-related events, hepatocellular carcinoma and death. Monitoring disease progression is critical in decreasing morbidity, mortality, need for transplant and economic burden. Assessing for treatment response once FDA-approved medications are available is still an unmet clinical need. AIMS: To explore the most up-to-date literature on testing used for monitoring disease progression and treatment response METHODS: We searched PubMed from inception to 15 August 2023, using the following MeSH terms: 'MASLD', 'Metabolic dysfunction-associated steatotic liver disease', 'MASH', 'metabolic dysfunction-associated steatohepatitis', 'Non-Alcoholic Fatty Liver Disease', 'NAFLD', 'non-alcoholic steatohepatitis', 'NASH', 'Biomarkers', 'clinical trial'. Articles were also identified through searches of the authors' files. The final reference list was generated based on originality and relevance to this review's broad scope, considering only papers published in English. RESULTS: We have cited 101 references in this review detailing methods to monitor MASLD disease progression and treatment response. CONCLUSION: Various biomarkers can be used in different care settings to monitor disease progression. Further research is needed to validate noninvasive tests more effectively.

Non-alcoholic fatty liver disease and coexisting depression, anxiety and/or stress in adults: a systematic review and meta-analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease, affecting 25-30% of the general population globally. The condition is even more prevalent in individuals with obesity and is frequently linked to the metabolic syndrome. Given the known associations between the metabolic syndrome and common mental health issues, it is likely that such a relationship also exists between NAFLD and mental health problems. However, studies in this field remain limited. Accordingly, the aim of this systematic review and meta-analysis was to explore the prevalence of one or more common mental health conditions (i.e., depression, anxiety, and/or stress) in adults with NAFLD. Methods: PubMed, EBSCOhost, ProQuest, Ovid, Web of Science, and Scopus were searched in order to identify studies reporting the prevalence of depression, anxiety, and/or stress among adults with NAFLD. A random-effects model was utilized to calculate the pooled prevalence and confidence intervals for depression, anxiety and stress. Results: In total, 31 studies were eligible for inclusion, involving 2,126,593 adults with NAFLD. Meta-analyses yielded a pooled prevalence of 26.3% (95% CI: 19.2 to 34) for depression, 37.2% (95% CI: 21.6 to 54.3%) for anxiety, and 51.4% (95% CI: 5.5 to 95.8%) for stress among adults with NAFLD. Conclusion: The present findings suggest a high prevalence of mental health morbidity among adults with NAFLD. Given the related public health impact, this finding should prompt further research to investigate such associations and elucidate potential associations between NAFLD and mental health morbidity, exploring potential shared underlying pathophysiologic mechanisms. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021288934.

Serum stromal cell-derived factor-1 concentrations are increased and associated with nonalcoholic fatty liver disease in children with obesity.

INTRODUCTION: Stromal cell-derived factor-1 (SDF-1) is a newly discovered small molecule adipocytokine, and research has shown that it is closely related to the occurrence and development of obesity. However, there are currently few research reports on SDF-1 in childhood obesity and nonalcoholic fatty liver disease (NAFLD), and this study aims to explore the relationship between SDF-1 and obesity related indicators in obese children. METHODS: Serum SDF-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Clinical and biochemical data were collected, such as body mass index (BMI), waist and hip circumference, blood pressure, liver enzymes, cholesterol, and fasting insulin. Children with NAFLD or not were evaluated through Color Doppler Ultrasound. RESULTS: Serum SDF-1 concentrations were significantly higher in obese subjects than in non-obese subjects (P < 0.05), and were elevated in the NAFLD obese subjects than in the non-NAFLD obese subjects (P < 0.05). SDF-1 was positively correlated with BMI, waist-to-hip ratio, systolic blood pressure, body fat percentage (BFP), basal metabolic rate (BMR), alanine transaminase (ALT), aspartate transaminase (AST), glutyltranspeptidase (GT), and homoeostasis model of HOMA-IR, independent of their uric acid (UA), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), gender and age. BFP and BMR were associated with the serum SDF-1 concentrations in multivariable linear regression analysis. CONCLUSION: These results suggest that SDF-1 levels are elevated in obese children and are associated with NAFLD, indicating that SDF-1 may play a role in the development of childhood obesity and metabolic disorders.

Prognostic value of metabolic dysfunction-associated steatotic liver disease over coronary computed tomography angiography findings: comparison with no-alcoholic fatty liver disease.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the proposed name change for non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the association of cardiovascular disease risk with MASLD and NAFLD in patients who underwent clinically indicated coronary computed tomography angiography (CCTA). METHODS: This retrospective study included 2289 patients (60% men; mean age: 68 years) with no history of coronary artery disease who underwent CCTA. The steatotic liver was defined as a hepatic-to-spleen attenuation ratio of < 1.0 on CT just before CCTA. MASLD is defined as the presence of hepatic steatosis along with at least one of the five cardiometabolic risk factors. Adverse CCTA findings were defined as obstructive and/or high-risk plaques. Major adverse cardiac events (MACE) encompassed composite coronary events, including cardiovascular death, acute coronary syndrome, and late coronary revascularization. RESULTS: MASLD and NAFLD were identified in 415 (18%) and 368 (16%) patients, respectively. Adverse CCTA findings were observed in 40% and 38% of the patients with MASLD and with NAFLD, respectively. Adverse CCTA findings were significantly associated with MASLD (p = 0.007) but not NAFLD (p = 0.253). During a median follow-up of 4.4 years, 102 (4.4%) MACE were observed. MASLD was significantly associated with MACE (hazard ratio 1.82, 95% CI 1.18-2.83, p = 0.007), while its association with NAFLD was not significant (p = 0.070). By incorporating MASLD into a prediction model of MACE, including the risk score and adverse CCTA findings, global chi-squared values significantly increased from 87.0 to 94.1 (p = 0.008). CONCLUSIONS: Patients with MASLD are likely to have a higher risk of cardiovascular disease than those with NAFLD. Concurrent assessment of MASLD during CCTA improves the identification of patients at a higher risk of cardiovascular disease among those with clinically indicated CCTA.

Low ankle-brachial index is associated with higher cardiovascular mortality in individuals with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Ankle brachial index (ABI) is a risk factor for cardiovascular mortality, but it is unclear whether ABI is associated with cardiovascular mortality in patients with nonalcoholic fatty liver disease (NAFLD). The current study aimed to evaluate the association between ABI with cardiovascular and all-cause mortality in patients with NAFLD. METHODS: We performed a cohort study using the data of the1999-2004 National Health and Nutrition Examination Survey data of adults. Mortality data were followed up to December 2015. NAFLD was defined by the hepatic steatosis index or the US fatty liver index. ABI was classified into three groups: ABI ≤ 0.9 (low value); 0.9 < ABI ≤ 1.1 (borderline value); ABI greater than 1.1 (normal value). RESULTS: We found that low ABI was associated with an increased risk of cardiovascular mortality in patients with NAFLD (HR: 2.42, 95% CI 1.10-5.33 for low value ABI vs normal value ABI, P for trend = 0.04), and the relationship was linearly and negatively correlated in the range of ABI < 1.4. However, low ABI was not associated with all-cause mortality in patients with NAFLD. Stratified by cardiovascular disease, ABI remains inversely correlated with cardiovascular mortality in NAFLD patients without cardiovascular disease. Stratified by diabetes, ABI is inversely correlated with cardiovascular mortality in NAFLD patients regardless of diabetes status. CONCLUSIONS: Low ABI is independently associated with higher cardiovascular mortality in NAFLD cases. This correlation remains significant even in the absence of pre-existing cardiovascular disease or diabetes.