Presence Of Nonalcoholic Fatty Liver Disease Research Articles

Association between higher duodenal levels of the fructose carrier glucose transporter-5 and nonalcoholic fatty liver disease and liver fibrosis.

An increased dietary fructose intake has been shown to exert several detrimental metabolic effects and contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). An augmented intestinal abundance of the fructose carriers glucose transporter-5 (GLUT-5) and glucose transporter-2 (GLUT-2) has been found in subjects with obesity and type 2 diabetes. Herein, we investigated whether elevated intestinal levels of GLUT-5 and GLUT-2, resulting in a higher dietary fructose uptake, are associated with NAFLD and its severity. GLUT-5 and GLUT-2 protein levels were assessed on duodenal mucosa biopsies of 31 subjects divided into 2 groups based on ultrasound-defined NAFLD presence who underwent an upper gastrointestinal endoscopy. Individuals with NAFLD exhibited increased duodenal GLUT-5 protein levels in comparison to those without NAFLD, independently of demographic and anthropometric confounders. Conversely, no difference in duodenal GLUT-2 abundance was observed amongst the two groups. Univariate correlation analyses showed that GLUT-5 protein levels were positively related with body mass index, waist circumference, fasting and 2h post-load insulin concentrations, and insulin resistance (IR) degree estimated by homeostatic model assessment of IR (r=0.44; p=0.02) and liver IR (r=0.46; p=0.03) indexes. Furthermore, a positive relationship was observed between duodenal GLUT-5 abundance and serum uric acid concentrations (r=0.40; p=0.05), a product of fructose metabolism implicated in NAFLD progression. Importantly, duodenal levels of GLUT-5 were positively associated with liver fibrosis risk estimated by NAFLD fibrosis score. Increased duodenal GLUT-5 levels are associated with NAFLD and liver fibrosis. Inhibition of intestinal GLUT-5-mediated fructose uptake may represent a strategy for prevention and treatment of NAFLD.

Association of single nucleotide polymorphism in patatin like phopholipase domain containing 3 (PNPLA3) gene with paediatric non-alcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is the most unabating cause of chronic liver disease in children and adolescents. This study aimed to examine the association of single nucleotide polymorphism in patatin-like phospholipase domain containing 3 (PNPLA3) gene with paediatric non-alcoholic fatty liver disease. Methods: This case-control study was conducted from June 2021 to December 2022. Fifty-one overweight children aged 6–17 years were recruited in this study and divided into NAFLD (cases) and non-NAFLD (controls) groups based on hepatic steatosis detected by liver ultrasonography. We analysed the rs738409 polymorphism by TaqMan assay and examined its association with NAFLD. Results: Thirty-one (60.8%) children were in the case group and 20 (39.2%) children were in the control group. Alanine aminotransferase (P<0.001) and triglycerides (P=0.02) were found to be significantly higher in cases. However, no significant association was found between the PNPLA3 rs738409 single nucleotide polymorphism (SNP) and the presence of NAFLD in children. Conclusion: Our study didn't find any association between PNPLA3 rs 738409 single nucleotide polymorphisms and presence of NAFLD in children, but we discovered that high alanine aminotransferase and triglycerides level can be useful in screening overweight children for NAFLD. Bangabandhu Sheikh Mujib Medical University Journal 2023;16(3): 139-143

Association between Dietary Niacin Intake and Nonalcoholic Fatty Liver Disease: NHANES 2003-2018.

Evidence regarding the association between dietary niacin intake and nonalcoholic fatty liver disease (NAFLD) is limited. The objective of this study was to examine the association of dietary niacin intake with NAFLD. Subjects aged 20 years and older who participated in the National Health and Nutrition Examination Survey (NHANES) 2003-2018 were included in this study. Dietary niacin intake was assessed by two 24-h dietary recalls. NAFLD was defined using the United States fatty liver index (US-FLI). Weighted logistic regression models and restricted cubic splines were used to examine the association between dietary niacin and NAFLD. Of the 12,355 participants in this study, 4378 had NAFLD. There is no evident nonlinear relationship between dietary niacin intake and the presence of NAFLD in the restricted cubic spline regression (poverall < 0.001; pnon-linearity = 0.068). The multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were 0.84 (0.68-1.03), 0.80 (0.65-0.97), and 0.69 (0.55-0.85), respectively, when comparing the second, third, and fourth quartiles of niacin intake levels to the lowest quartile (ptrend = 0.001). Stratified analysis revealed that the effect of niacin intake on NAFLD varied in the group with or without hypertension (pinteraction = 0.033). In conclusion, our results indicate that higher dietary niacin intake may be associated with a lower likelihood of NAFLD.

The Effect of Non-Alcoholic Fatty Liver Disease on Weight Loss and Resolution of Obesity-Related Disorders After Bariatric Surgery

BackgroundPatients undergoing bariatric surgery have a high incidence of non-alcoholic fatty liver disease (NAFLD). However, the effect of NAFLD or non-alcoholic steatohepatitis (NASH) on the weight loss and resolution of obesity-related disorders is a matter of debate.MethodsIn this study, we compare the long-term outcomes after bariatric with the presence of NAFLD in the liver biopsy at the time of surgery.ResultsThe follow-up was available for 226 out of 288 patients. The mean follow-up time was 24.9 (± 13.6) months. The baseline histology showed that 112 patients (38.9%) had no NASH, 70 (24.3%) were borderline, and 106 (36.8%) had NASH. At follow-up, the mean BMI dropped from (52 ± 10.2) to (36.6 ± 8) kg/m 2. Excess weight loss (EWL) was similar in all NAFLD groups. Type 2 diabetes mellitus dropped from 35.7 to 11.4%, hypertension from 65.6 to 36.7%, hyperlipidemia from 62.3 to 33%, and obstructive sleep apnea from 37.5 to 14.9%. Only hyperlipidemia was significantly associated with NASH compared to the groups with no NASH or borderline NASH (p value = 0.002 and p value = 0.04, respectively) during the first two years of follow-up.ConclusionThe beneficial effects of bariatric surgery are evident across all patients with NAFLD. Patients with NASH have comparable outcomes regarding weight loss and resolution of obesity-related comorbidities.

NAFLD is associated with less severe liver fibrosis in chronic hepatitis B: A multi-center, retrospective study

Introduction and ObjectivesChronic hepatitis B (CHB) may progress to more serious liver diseases and it is often accompanied by non-alcoholic fatty liver disease (NAFLD). NAFLD and CHB share risk factors for liver fibrosis and cirrhosis, but the influence of NAFLD on fibrosis progression is controversial. This retrospective study evaluated the prevalence of NAFLD in patients with CHB and investigated associations between NAFLD and liver fibrosis in a large multi-center cohort of hepatitis B patients submitted to liver biopsy. Patients and MethodsTreatment-naïve patients with CHB who underwent liver biopsy were analyzed. Propensity score matching (PSM) was performed to adjust the confounders between patients with and without NAFLD. ResultsA total of 1496 CHB patients were included. Two hundred and ninety (19.4%) patients were diagnosed with NAFLD by liver biopsy. The proportions of significant liver fibrosis (52.8% vs. 63.9%, P<0.001), advanced liver fibrosis (27.2% vs. 36.5%, P=0.003), and cirrhosis (13.4% vs. 19.7%, P=0.013) was considerably lower in CHB patients with NAFLD compared to those without NAFLD. 273 patients were included in each group after PSM adjusted for age, sex, hepatitis B envelope antigen status, and hepatitis B virus DNA. Liver fibrosis remained less severe in CHB patients with NAFLD than those without NAFLD (P<0.05) after PSM. The presence of NAFLD was considered an independent negative factor of significant liver fibrosis (odds ratio (OR) 0.692, P=0.013) and advanced liver fibrosis (OR 0.533, P = 0.002) in CHB patients. ConclusionsNAFLD is not uncommon in CHB patients with the prevalence of 19.4%. The presence of NAFLD is associated with less severe liver fibrosis in CHB patients. Registration No. of the study/trialNCT03097952.

Level of IL-6 and IL-8 and their associations with non-alcoholic fatty liver disease in patients with type 2 diabetes

non-alcoholic fatty liver disease (NAFLD) is indicated by the accumulation of lipids within the hepatocytes exceeding 5% of liver weight without excessive alcohol intake and secondary liver diseases. The efforts of many scientists worldwide are focused on improving the understanding of pathogenic processes and triggers of NAFLD progression, with an emphasis on the simultaneous study of several pathophysiological pathways to identify disorders throughout the disease spectrum. The aim was to examine the serum levels of IL-6 and IL-8 and its associative relationships with anthropometric parameters and metabolic profiles in patients with T2D, depending on the presence of NAFLD. This cross-sectional study involved 375 patients aged 40–80 with type 2 diabetes. They were divided into 3 groups. The control group included 98 T2D patients without NAFLD. The main group included T2D patients with NAFLD, which was separated into two subgroups depending on the level of transaminases: normal (group 2A, n=150) and increased (group 2B, n=127) transaminases group. In order to identify predictors of rapid progression of liver fibrosis in patients with T2D, a sub-analysis was conducted, which included 82 patients from group 2. We found significant relationships between the level of studied interleukins and the components of the metabolic syndrome. Both IL-6 and Il-8 levels are significantly associated with gender, duration and severity of T2D, BMI, ALT, AST and total bilirubin level in a simple logistic regression analysis. However, step-by-step multiple logistic regression analysis revealed no reliable link between both cytokines and NAFLD development. From the other hand elevated IL-8 and decreased IL-6 had a significant effect on the fibrosis progression in patients with NAFLD associated with T2D. Our study has demonstrated significant links between the level of IL-6 and IL-8 and the components of the metabolic syndrome such as obesity or transaminase activity, but not with NAFLD itself.

Detection of Non-Alcoholic Fatty Liver Disease with Non-invasive Tools in Turkish People Living with HIV and with Apparently Normal Liver Function.

Non-alcoholic fatty liver disease (NAFLD) has become a significant cause of mortality and morbidity in people living with HIV. We aimed to investigate NAFLD presence by magnetic resonance imaging (MRI) methods, including MRI-derived proton density fat fraction (MRI-PDFF) and MRE, and ultrasound elastography among Turkish people living with HIV (PLWH), and identify factors correlated with fatty liver. We included 57 PLWH attending outpatient clinics on antiretroviral therapy (ART) for more than six months, without HBV/HCV co-infection, significant alcohol consumption, active opportunistic infection, previously diagnosed hepatobiliary disease, T2DM, and hyperlipidemia. We performed MRI, MRE, and US elastography on all participants. The mean age of the participants (M/F, 47/10) was 41.7± 12 years. The median duration of HIV infection was 3 (0.5-19 years) years. The mean MRI-PDFF was 4.4 ± 3.8 %, and 11 had fatty liver. The mean MRE value was 2.27 ± 0.6 kPa, inflammation was present in 16, and 4 participants had values consistent with fibrosis. The mean US elastography of the study population was 4.1±2.4 kPa. The mean right and left CCA intima-media of the study population was 0.65± 0.23 mm and 0.66± 0.25 mm; 16 had increased intima-media thickness. In patients with fatty liver, a significant positive correlation was present between MRE and CCA intima-media thickness (rs=0.82, p:0.006 for MRE-left CCA; r=0.68, p=0.042 for MRE-right CCA). We demonstrated that even a significant proportion of PLWH individuals with normal transaminase levels have fatty liver. Future prospective trials are warranted to understand and mitigate the risk factors, course of NAFLD, and accurate non-invasive tests, predicting fibrosis in people living with HIV.

Combined Effect of Body Mass Index and Waist Circumference in Predicting Nonalcoholic Fatty Liver Disease.

Background: Body mass index (BMI) and waist circumference (WC) are the most widely used anthropometric indices for identifying obesity. This study aimed to compare and clarify the usefulness of BMI, WC, and the combination of these two indicators in predicting nonalcoholic fatty liver disease (NAFLD). Methods: This cross-sectional study included 15,267 Korean adults. We defined four obesity categories using BMI and WC as follows: BMI nonobese and WC nonobese (BNWN); BMI obese and WC nonobese (BOWN); BMI nonobese and WC obese (BNWO); and BMI obese and WC obese (BOWO). Analysis of variance was used to compare fatty liver severity across each category. The odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were calculated using multiple logistic regression. Results: Compared with BNWN, participants with BNWO were 3.235 (95% CI: 2.774-3.773) times more likely and participants with BOWN were 2.344 (95% CI: 2.045-2.687) times more likely to have NAFLD. Participants with BNWO had higher OR for NAFLD than those with BOWN. Moreover, BOWO participants had the highest OR of 4.788 (95% CI: 4.350-5.270) for NAFLD among all obesity categories. Conclusion: Combined obesity classification by BOWO is the most reliable indicator for NAFLD presence in Korean adults.

The newly proposed alanine aminotransferase to high-density lipoprotein cholesterol ratio has shown effectiveness in identifying non-alcoholic fatty liver disease.

Alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDL-C) are important predictive factors for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to analyze the association between the ALT/HDL-C ratio and NAFLD. We conducted a retrospective analysis of data from 14,251 individuals participating in the NAGALA project's health screening program. The presence of NAFLD was diagnosed based on the participants' alcohol consumption status and liver ultrasonography images. Multivariable logistic regression models were used to assess the association between the ALT/HDL-C ratio and NAFLD. Receiver operating characteristic (ROC) analysis was performed to determine and compare the effectiveness of ALT, HDL-C, the aspartate aminotransferase to HDL-C (AST/HDL-C) ratio, the gamma-glutamyl transferase to HDL-C (GGT/HDL-C) ratio and the ALT/HDL-C ratio in identifying NAFLD. We observed a significant positive association between the ALT/HDL-C ratio and the prevalence of NAFLD. For each standard deviation (SD) increase in the ALT/HDL-C ratio, the adjusted odds ratio (OR) for NAFLD among the participants was 3.05 [95% confidence interval (CI): 2.63, 3.53], with the highest quartile of ALT/HDL-C ratio having a 9.96-fold increased risk compared to the lowest quartile. In further subgroup analyses stratified by gender, age, and waist circumference (WC), we observed a significantly higher risk of NAFLD associated with the ALT/HDL-C ratio among individuals aged ≥45 years, males, and those who were abdominal obesity. Furthermore, based on the results of ROC analysis, we found that the ALT/HDL-C ratio [area under the curves (AUC): 0.8553] was significantly superior to ALT, HDL-C, AST/HDL-C ratio and GGT/HDL-C ratio in identifying NAFLD (All Delong P<0.05); the threshold of suggested ALT/HDL-C ratio for identifying NAFLD was 15.97. This population-based study demonstrates a positive association between the ALT/HDL-C ratio and NAFLD. The ALT/HDL-C ratio can effectively identify individuals with NAFLD.

Cardiac Structure and Function in Patients With Obesity and Non-alcoholic Fatty Liver Disease.

Introduction Non-alcoholic fatty liver disease (NAFLD) has emerged as a leading cause of chronic liver disease worldwide. The global prevalence of NAFLD is expected to increase dramatically with the increasing prevalence of obesity and type 2 diabetes mellitus (T2DM). The role of NAFLD as a cardiometabolic risk factor or component of metabolic syndrome on the heart remains unclear. Thus, the independent effect of NAFLD on structural and functional heart parameters warrants validation. Our goal was to study cardiac structure and function in subjects with obesity and NAFLD. Methods A total of 164 patients were examined in this cross-sectional study. Participants were grouped based on BMIand the presence or absence of abdominal obesity (AO) and/or NAFLD. The subjects were divided into four groups:group 1: normal BMI without AO and NAFLD; group 2: BMI ≥ 25 kg/m2or AO without NAFLD; group 3: BMI ≥ 25 kg/m2and AO without NAFLD;group 4: patients with BMI ≥ 25 kg/m2,AO, and NAFLD. We performed a thorough clinical examination, a biochemical blood analysis, and echocardiography. Indices of liver steatosis and fibrosis were calculated. A study of liver assessment of the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) was conducted. Statistical analysis was performed using IBM SPSS Statistics version 26 (IBM Corp., Armonk, NY). Results The mean age of the participants was 35.0 (31.0-38.5) years. We found a higher frequency of multiple cardiometabolic risk factors in the general cohort. However, on comparing groups 3 and 4, we found a higher frequency of hyperinsulinemia, homeostatic model assessment of insulin resistance (HOMA-IR), and obesity (p < 0.05). To assess the role of NAFLD independent of obesity, we conducted further analyses after adjusting for BMI. Among patients with NAFLD, we observed a similar trend for parameters of carbohydrate metabolism (p < 0.005).In individuals with NAFLD, an increase in left atrial (LA) volume, interventricular septal (IVS) thickness, and left ventricular (LV) myocardial mass, and a decrease in LV ejection fraction and LV stroke volume index were found (p < 0.005). The hepatic steatosis index (HSI) correlated with LA volume, LV end-systolic volume (ESV) and LV end-diastolic volume (EDV), stroke volume, and LV myocardial mass. An association between an increase in CAP score and an increase in the LA volume, stroke volume index, IVS thickness, LV myocardial mass, and the values of LSM with an increase in the LA volume was established. Conclusion The presence of NAFLD without cardiovascular disease and diabetes mellitus revealed an association with the structural and functional parameters of the heart.The results of this study can also be used to improve the effectiveness of a comprehensive assessment of patients and to develop strategies for the primary and secondary prevention of heart failure with preserved ejection fraction in NAFLD.

Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis

Non-alcoholic fatty liver disease (NAFLD) is regarded as a pandemic that affects about a quarter of the global population. Recently, host-gut microbiota metabolic interactions have emerged as distinct mechanistic pathways implicated in the development of NAFLD. Here, we report that a group of gut microbiota-modified bile acids (BAs), hyodeoxycholic acid (HDCA) species, are negatively correlated with the presence and severity of NAFLD. HDCA treatment has been shown to alleviate NAFLD in multiple mouse models by inhibiting intestinal farnesoid X receptor (FXR) and upregulating hepatic CYP7B1. Additionally, HDCA significantly increased abundances of probiotic species such as Parabacteroides distasonis, which enhances lipid catabolism through fatty acid-hepatic peroxisome proliferator-activated receptor alpha (PPARα) signaling, which in turn upregulates hepatic FXR. These findings suggest that HDCA has therapeutic potential for treating NAFLD, with a unique mechanism of simultaneously activating hepatic CYP7B1 and PPARα.

The first external validation of the Dallas steatosis index in biopsy-proven Non-alcoholic fatty liver Disease: A multicenter study

AimsA new non-invasive tool (NIT) for non-alcoholic fatty liver disease (NAFLD) proposed in 2022 by the multi-ethnic Dallas Heart Study, i.e. the Dallas Steatosis Index (DSI), was validated herein using for the first time the gold standard i.e. liver biopsy-proven NAFLD. MethodsThis is a multicenter study based on samples and data from two Gastroenterology-Hepatology Clinics (Greece and Australia) and one Bariatric-Metabolic Surgery Clinic (Italy). Overall, n = 455 patients with biopsy-proven NAFLD (n = 374) and biopsy-proven controls (n = 81) were recruited. ResultsThe ability of DSI to correctly classify participants as NAFLD or controls was very good, reaching an Area Under the Curve (AUC) = 0.887. The cut-off point that could best differentiate the presence vs. absence of NAFLD corresponded to DSI = 0.0 (risk threshold: 50% | Sensitivity: 0.88; Positive Predictive Value (PPV): 93.0%; F1-score = 0.91). DSI demonstrated significantly better performance characteristics than other liver steatosis indexes. Decision curve analysis revealed that the benefit of DSI as a marker to indicate the need for invasive liver assessment was confirmed only when higher DSI values, i.e. ≥ 1.4, were used as risk thresholds. DSI performance to differentiate disease progression was inadequate (all AUCs < 0.700). ConclusionsDSI is more useful for disease screening (NAFLD vs. controls) than to differentiate diseases stages or progression. The value of any inclusion of DSI to guidelines needs to be further studied.

Novel approach using [18F]FTHA-PET and de novo synthesized VLDL for assessment of FFA metabolism in a rat model of diet induced NAFLD

The worldwide prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) raises concerns about associated risk factors, such as obesity and type 2 Diabetes Mellitus, for leading causes of disability and death. Besides Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS), functional imaging with Positron Emission Tomography (PET) could contribute to a deeper understanding of the pathophysiology of NAFLD. Here we describe a novel approach using the PET tracer [18F]FTHA, which is an analog of long-chain free fatty acids (FFA) and is taken up by tissues to enter mitochondria or to be incorporated into complex lipids for further export as very-low-density lipoprotein (VLDL). Male Sprague Dawley rats, after 6 weeks on a high-fat diet (HFD), were used as a model of diet induced NAFLD, while a standard diet (SD) served as a control group. Liver fat was estimated by MR spectroscopy at a 9.4T system for phenotyping. To measure hepatic FFA uptake, rats underwent 60min dynamic [18F]FTHA-PET scans after unrestricted access to food (HFD: n=6; SD: n=6) or overnight (≤16h) fasting (HFD: n=6; SD: n=5). FFA removal was assessed from incorporated 18F-residual in de novo synthesized VLDL out of plasma. MRS of the liver confirmed the presence of NAFLD (>5.6% fat). Under non-fasting conditions, hepatic [18F]FTHA uptake was significantly increased in NAFLD: SUVmean (p=0.03) within [0; 60] min interval, SUVmean (p=0.01) and SUVmax (p=0.03) within [30; 60] min interval. SUVs for hepatic uptake under fasting conditions were not significantly different between the groups. Analysis of FFA removal demonstrated elevated values of 18F-residue in the VLDL plasma fraction of the healthy group compared to the NAFLD (p=0.0569). Our novel approach for assessing FFA metabolism using [18F]FTHA demonstrated differences in the hepatic FFA uptake and FFA incorporation into VLDL between healthy and NAFLD rats. [18F]FTHA-PET could be used to study metabolic disturbances involved in the progression of NAFLD.

Insight to the association among fibroblast growth factor 21, non-alcoholic fatty liver disease and cardiovascular outcomes: A population-based study

ObjectiveWe aimed to investigate whether there was a joint effect of fibroblast growth factor 21 (FGF21) and non-alcoholic fatty liver disease (NAFLD) or interaction on the incidence of cardiovascular diseases based on a community-dwelling population. MethodsSerum FGF21 levels were determined using an enzyme-linked immunosorbent method. NAFLD was diagnosed via ultrasonography. Multivariable-adjusted cox proportional hazards models were used to assess the joint effects of FGF21 and NAFLD on the major adverse cardiovascular events (MACE). ResultsA total of 1194 participants were enrolled in the final analysis. The multivariable-adjusted hazard ratio (HR) of MACE was 1.84 (95% confidence interval (CI) 1.18–2.86) in participants with diagnosed NAFLD at baseline, compared with those without NAFLD at baseline. The multivariable-adjusted HRs of MACE across quintiles of serum FGF21 levels at baseline were 1.00, 1.48 (95%CI 0.68–3.21), 2.01 (95%CI 0.98–4.13), 1.94 (95%CI 0.94–4.02) and 2.14 (95%CI 1.03–4.44) respectively. Participants with high FGF21 levels and NAFLD at baseline showed the highest risk of MACE with a significant interaction between the presence of NAFLD and serum FGF21 levels. ConclusionsBoth FGF21 and NAFLD were associated with MACE, while the association between FGF21 and MACE may be interacted by the presence of NAFLD at baseline.

Dietary inflammatory index (DII) is correlated with the incidence of non-alcoholic fatty liver disease (NAFLD): Fasa PERSIAN cohort study

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease predisposing patients to life-threatening conditions, including cirrhosis. There is evidence that the incidence of NAFLD is related to the individuals’ dietary patterns; however, it is still remaining unknown whether the inflammatory potential of various foods/dietary patterns can directly predict a higher incidence of NAFLD.MethodsIn this cross-sectional cohort study, we investigated the relationship between the inflammatory potential of various food items and the incidence/odds of NAFLD. We used data from Fasa PERSIAN Cohort Study comprising 10,035 individuals. To measure the inflammatory potential of diet, we used the dietary inflammatory index (DII®). Fatty liver index (FLI) was also calculated for each individual to identify the presence of NAFLD (cut-off = 60).ResultsOur findings showed that higher DII is significantly associated with increased incidence/odds of NAFLD (OR = 1.254, 95% CI: 1.178—1.334). Additionally, we found out that higher age, female gender, diabetes mellitus, hypertriglyceridemia, hypercholesterolemia, and hypertension are other predictors of developing NAFLD.ConclusionsIt can be concluded that consuming foods with a higher inflammatory potential is associated with a greater risk of developing NAFLD. Additionally, metabolic diseases, including dyslipidemia, diabetes mellitus, and hypertension, can also predict the incidence of NAFLD.

Assessment of the diagnostic accuracy of noninvasive scoring tools in predicting moderate-to-severe steatohepatitis via ultrasonography in asymptomatic healthy subjects admitted to family medicine outpatient clinics.

Efficacies of the noninvasive scoring tools in screening and diagnosing nonalcoholic fatty liver disease (NAFLD) remain controversial. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, AST-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) index are the most frequently used parameters for differentiating moderate and severe steatohepatitis. In this context, the objective of this study is to evaluate the diagnostic accuracy of noninvasive tools in predicting moderate-to-severe steatohepatitis via ultrasonography in asymptomatic healthy subjects admitted to family medicine outpatient clinics. The population of this retrospective study consisted of healthy individuals tested within the scope of a medical check-up program between January and July 2021. All participants included in the study underwent relevant laboratory tests and liver ultrasonography (US). Steatohepatitis was graded using the US images as normal (grade 0), mild (grade 1), moderate (grade 2), and severe (grade 3). The participants with grade 0 and 1 steatohepatitis were categorized as Group 1, whereas those with grade 2 and 3 steatohepatitis (NAFLD) were categorized as Group 2. Any relationship between the aminotransferase/alanine aminotransferase (AST/ALT), AST-to-platelet ratio index (APRI), and fibrosis-4 index (FIB-4) parameters and the diagnostic powers thereof were analyzed based on the collected data. The mean age of the study sample (n=408) was 46.1±12.7 years. There were 352 (86.3%) and 56 individuals in Groups 1 and 2, respectively. Platelet-to-lymphocyte ratio (PLR) and AST/ALT values were significantly higher, whereas APRI values were significantly lower in Group 1 than in Group 2 (p=0.004, p<0.001, and p<0.001, respectively). There were significant correlations between the presence of NAFLD and PLR values of ≤90.78 [area under the curve (AUC)=0.619, 95% confidence interval (CI): 0.570-0.666, p=0.007], AST/ALT values of ≤0.91 (AUC=0.802, 95% CI: 0.760-0.840, p<0.001), and APRI values of >0.22 (AUC=0.687, 95% CI: 0.640-0.732, p<0.001). The composite noninvasive indices, including PLR, AST/ALT, and APRI, can be beneficial in predicting NAFLD in healthy individuals.

Diagnostic Performance of Greyscale Ultrasound in Detecting Fatty Liver Disease in a Type 2 Diabetes Population Using FibroScan as the Reference Standard.

Introduction Brightness mode ultrasound (B-mode US) and FibroScan (Echosens, Paris, France) are the two ultrasound methods often recommended for screening non-alcoholic fatty liver disease (NAFLD) in persons with type 2 diabetes mellitus (T2DM). This study assessed the diagnostic performance of B-mode US using FibroScan as the reference standard. Methods Persons with a known history of T2DM were invited to screen for NAFLD using B-mode US and FibroScan on separate days within a one-month period. Assessors of B-mode US and FibroScan were blinded to each other's findings. Both B-mode US and FibroScan independently assessed and graded each participant for the presence of NAFLD. Using the diagnostic test findings of FibroScan as a reference standard, the sensitivity and specificity of B-mode US were analyzed.The area under the receiver operating characteristic curve (AUROC) was analyzed using Jamovi (version 2.3.21). A multinomial logistic regression of the B-mode US and FibroScan in predicting NAFLD grade was also analyzed. Results A total of 171 participants were assessed. B-mode US detected NAFLD in T2DM patients with 63.6% sensitivity, 65.6% specificity, and 0.646 AUROC. Sensitivity and specificity in overweight and obese participants were 36-43% and 76-85%, respectively. Multinomial logistic regression demonstrated an insignificant statistical relationship between FibroScan and B-mode US in predicting grade 1 steatosis (p-value = 0.397), which was significantly affected by a higher BMI (p-value = 0.034) rather than a higher liver fibrosis level (p-value = 0.941). The logistic regression further showed a significant relationship between B-mode US and FibroScan in predicting steatosis grade 2 (p-value = 0.045) and grade 3 (p-value < 0.001), which was not significantly affected by BMI (p-value = 0.091). Conclusion B-mode US can replace FibroScan for severe steatosis; however, it cannot be used to screen for NAFLD in T2DM patients due to lower sensitivity for early detection in the overweight.

THE POLYMORPHISM -308 G/A OF THE TNF GENE AND METABOLIC IMBALANCE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND NON-ALCOHOLIC FATTY LIVER DISEASE, TAKING INTO ACCOUNT CARDIOVASCULAR COMPLICATIONS

Non-alcoholic fatty liver disease (NAFLD), the most common form of liver disease, is now recognized as a major public health problem worldwide. Tumor necrosis factor alfa (TNF-α), a member of the TNF/TNFR cytokine family, is an intercellular transmission molecule that has been reported in a wide range of human noninfection diseases. The aim of the study was to determine the circulating levels of TNF-α and the nature of its relationships with the components of insulin resistance, both metabolic and hormonal, in patients with type 2 diabetes; and establishing the nature of cardiovascular complications (taking into account TNF-α gene polymorphism) in the presence and absence of NAFLD. Materials and methods. Case-control study included information about 50 practically healthy people from the city of Kharkiv and the region. The examined population (except control subjects) consisted exclusively of patients with type 2 diabetes mellitus with a long-term existence of the disease against the background of metabolic syndrome, with varying degrees of glycemic control and violations of liver homeostasis in the absence of renal failure. 117 people were selected for analysis: 63 of them with type 2 diabetes in the presence of NAFLD and 54 patients with type 2 diabetes without NAFLD. Genotyping for single nucleotide polymorphism -308 G&gt;A of the TNF-α was performed by the method of polymerase chain reaction with appropriate primers and NcoI endonuclease. Testing of statistical hypotheses was carried out using the odds ratio and χ2 criteria at the significance level of P≤0.05. Results. The contribution of the genetic component to the formation of the predisposition to the development of type 2 diabetes mellitus based on the single-nucleotide polymorphism -308 G&gt;A of the TNFα gene was determined, which makes it possible to consider the carrier of the A allele as a factor of increased risk for the development of type 2 diabetes mellitus. No association of the studied polymorphism with the risk of developing NAFLD was found. The obtained data make it possible to assume that the studied polymorphism -308 G&gt;A of the TNFα gene is more associated with the risk of developing type 2 diabetes, and the occurrence or progression of NAFLD primarily depends on metabolic imbalance, and not on the contribution of the studied polymorphism. Conclusions. Non-alcoholic fatty liver disease is closely related to hormonal and metabolic risk factors and markers of cardiovascular disease and type 2 diabetes and may increase the risk of developing and progressing cardiovascular complications. The contribution of the genetic component to the formation of the predisposition to the development of type 2 diabetes mellitus based on the single-nucleotide polymorphism -308 G&gt;A of the TNFα gene was determined, which makes it possible to consider the carrier of the A allele as a factor of increased risk for the development of type 2 diabetes mellitus.

Relationship between nonalcoholic fatty liver disease and hyperandrogenemia in adolescents with polycystic ovary syndrome.

Nonalcoholic fatty liver disease (NAFLD) is common in adults with polycystic ovary syndrome (PCOS), and several studies on adults have investigated its influencing factors. However, factors associated with NAFLD in adolescents with PCOS remain unknown. This study aimed to investigate the presence of NAFLD in adolescents with PCOS using the noninvasive methods of vibration-controlled transient elastography (VCTE) and ultrasonography (USG), along with assessing NAFLD-related metabolic and hormonal risk factors. This study included patients aged 12-18 years who were diagnosed with PCOS according to the Rotterdam criteria. The control group included young women with similar age and body mass index (BMI) z scores, who had menstruated regularly for more than 2 years. Patients with PCOS were divided into hyperandrogenemia and nonhyperandrogenemia groups based on serum androgen level. USG was performed on all patients to evaluate the presence of hepatic steatosis. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were assessed using VCTE (Fibroscan). Clinical, laboratory, and radiological data were compared between groups. This study included 124 adolescent girls aged 12-18 years (61 with PCOS, 63 controls). BMI z scores were similar between groups. Waist circumference and total cholesterol, triglyceride, and alanine aminotransferase levels were higher in the PCOS versus the control group. The presence of hepatic steatosis on USG was similar between groups. However, the rate of hepatic steatosis on USG was higher in patients with hyperandrogenic PCOS (P=0.01). LSM and CAP measurements were similar between groups. No increase in prevalence of NAFLD was observed among adolescents with PCOS. However, hyperandrogenemia is a risk factor for NAFLD. Therefore, adolescents with PCOS and elevated androgen level should be screened for NAFLD.

The Presence and Severity of NAFLD are Associated With Cognitive Impairment and Hippocampal Damage.

Although cognitive impairment in nonalcoholic fatty liver disease (NAFLD) has received attention in recent years, little is known about detailed cognitive functions in histologically diagnosed individuals. This study aimed to investigate the association of liver pathological changes with cognitive features and further explore the underlying brain manifestations. We performed a cross-sectional study in 320 subjects who underwent liver biopsy. Among the enrolled participants, 225 underwent assessments of global cognition and cognitive subdomains. Furthermore, 70 individuals received functional magnetic resonance imaging scans for neuroimaging evaluations. The associations among liver histological features, brain alterations, and cognitive functions were evaluated using structural equation model. Compared with controls, patients with NAFLD had poorer immediate memory and delayed memory. Severe liver steatosis (odds ratio, 2.189; 95% CI, 1.020-4.699) and ballooning (OR, 3.655; 95% CI, 1.419-9.414) were related to a higher proportion of memory impairment. Structural magnetic resonance imaging showed that patients with nonalcoholic steatohepatitis exhibited volume loss in left hippocampus and its subregions of subiculum and presubiculum. Task-based magnetic resonance imaging showed that patients with nonalcoholic steatohepatitis had decreased left hippocampal activation. Path analysis demonstrated that higher NAFLD activity scores were associated with lower subiculum volume and reduced hippocampal activation, and such hippocampal damage contributed to lower delayed memory scores. We are the first to report the presence and severity of NAFLD to be associated with an increased risk of memory impairment and hippocampal structural and functional abnormalities. These findings stress the significance of early cognitive evaluation in patients with NAFLD.