Markers Of Nonalcoholic Fatty Liver Disease Research Articles

Hepatic microRNA modulation might be an early event to non-alcoholic fatty liver disease development driven by high-fat diet in male mice

Metabolic alterations caused by an imbalance of macronutrient consumption are often related to the modulation of microRNAs (miRNAs), which could alter mRNAs expression profile and accelerate the development of non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the contribution of miRNAs in modulating early stages of NAFLD in mice submitted to a high-fat diet (HFD). Male Swiss mice, fed either a control diet or an HFD for 1, 3, 7, 15, 30, 56days, were assessed for metabolic alterations, gene expression and NAFLD markers. A hepatocyte cell line was used to investigate the effects of miR-370 modulation on enzymes involved in β-oxidation. Body weight and adiposity were higher after 7days of HFD. Fasting glucose and insulin increased after 3 and 7days of HFD, respectively. While hepatic lipid content increased from the first day on, hepatic glycogen had a decrease after 3days of HFD consumption. miR-370 and Let-7 expression increased with acute and chronic exposure to HFD, accompanied by carnitine palmitoyltransferase 1A (Cpt1a), acyl-CoA dehydrogenase very long chain (Acadvl) and protein kinase AMP-activated Catalytic Subunit 2 (Prkaa2) downregulation, while decreased miR-122 expression was accompanied by 1-acylglycerol-3-phosphate-O-acyltransferase (Agpat) upregulation after 56days of HFD consumption, some of them confirmed by in vitro experiments. Despite fluctuations in TNFa and IL6 mRNA levels, molecular modulation was consistent with hepatic TG and NAFLD development. Hepatic miR-370-122-Let7 miRNA modulation could be the first insult to NAFLD development, preceding changes in glycemic homeostasis and adiposity.

The Association of Alanine Aminotransferase Levels With Myocardial Perfusion Imaging and Cardiovascular Morbidity.

Studies suggest that non-alcoholic fatty liver disease (NAFLD) is associated with an independent risk of cardiovascular disease (CVD). We utilized a large cohort of patients undergoing myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) to determine the association between alanine aminotransferase (ALT) as a surrogate marker for presumed NAFLD, and the presence of myocardial ischemia and mortality. We retrospectively assessed SPECT-MPI results and medical records of individuals evaluated between 1997 and 2008. We excluded patients with known non-NAFLD liver diseases, ALT values <17 or >340 U/L and absent liver tests. Elevated ALT cases were classified as presumed NAFLD. The primary endpoint was abnormal SPECT-MPI. Secondary endpoints included cardiac death, acute myocardial infarction and all-cause mortality. Of 26,034 patients who underwent SPECT-MPI, 11,324 met inclusion criteria. 1635 (14.4%) patients had elevated ALT. SPECT-MPI results did not differ significantly between subjects with elevated ALT and controls. Elevated ALT was associated with increased risk for the composite endpoint of cardiac death or acute myocardial infarction at 5-year follow-up (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.01-1.67) and in all-cause mortality (HR 1.27, CI 1.02-1.58) but only in patients with normal SPECT-MPI. The long-term mortality of patients with abnormal SPECT-MPI is not modulated by ALT, likely reflecting an already high risk and established CVD. However, patients with normal SPECT-MPI are at increased risk for a future cardiac event if they have an elevated ALT level, suggesting an important role for NAFLD in earlier stages of CVD.

Bariatric surgery improves metabolic and nonalcoholic fatty liver disease markers in metabolically healthy patients with morbid obesity at 5 years

No studies have evaluated the effect of metabolic and bariatric surgery (MBS) on nonalcoholic fatty liver disease (NAFLD) and cardiometabolic markers in metabolically healthy patients with morbid obesity (MHMO) at midterm.To assess the effect of MBS on NAFLD and cardiometabolic markers in MHMO patients and ascertain whether metabolically unhealthy patients with morbid obesity (MUMO) remain metabolically healthy at 5 years after MBS.University hospital.A total of 191 patients with a body mass index >40 kg/m2 and at least 5 years of follow-up were retrospectively analyzed. Lost to follow-up were 37.6% (151 of 401 patients). Patients were classified as MHMO if 1 or 0 of the cardiometabolic markers were present using the Wildman criteria. The degree of liver fibrosis was assessed using the NAFLD fibrosis score (NFS).Forty-one patients (21.5%) fulfilled the criteria for MHMO. They showed significant improvements in blood pressure (from 135.1 ± 22.1 and 84.2 ± 14.3 mm Hg to 117.7 ± 19.2 and 73.0 ± 10.9 mm Hg), plasma glucose (from 91.0 ± 5.6 mg/dL to 87.2 ± 5.2 mg/dL), homeostatic model assessment for insulin resistance (from 2.2 ± .9 to 1.0 ± .8), triglycerides (from 88.0 [range, 79.5-103.5] mg/dL to 61.0 [range, 2.0-76.5] mg/dL), alanine aminotransferase, gamma-glutamyl transpeptidase NFS (from -1.0 ± 1.0 to -1.9 ± 1.2), and high-density lipoprotein cholesterol (from 56.9 ± 10.5 mg/dL to 77.9 ± 17.4 mg/dL) at 5 years after surgery. A total of 108 MUMO patients (84.4%) who became metabolically healthy after 1 year stayed healthy at 5 years.MBS induced a midterm improvement in cardiometabolic and NAFLD markers in MHMO patients. Seventy-six percent of MUMO patients became metabolically healthy at 5 years after MBS.

Fetuin-A in newly detected type 2 diabetes mellitus as a marker of non-alcoholic fatty liver disease.

Fetuin-A has been implicated in the causation of metabolic disorders such as obesity, diabetes, and hepatic steatosis. Numerous studies have shown the association between levels of fetuin-A in type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). The levels of fetuin-A in newly detected type 2 diabetic (NDD)patients and its relationship with the presence of NAFLD have not been studied. To study the fetuin-A levels in patients with NDD and its relationship with NAFLD. A total of 60 NDD patientswere studied. The diagnosis of NAFLD was made on the basis of transient elastography. Serum fetuin-A and serum fasting insulin were measured along with other investigations. The percentage of patients with NAFLD in NDD was 53.33%. Fetuin-A levels were significantly higher in NDD with NAFLD compared to those without NAFLD. There was no association of fetuin-A with age, systolic and diastolic blood pressure, fasting blood sugar (FBS), hemoglobin (Hb)A1c, fasting insulin, homeostatic model assessment-insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and markers of advanced fibrosis. Fetuin-A levels beyond 1166.5 mcg/mL could predict the development of NAFLD with odds ratio (OR) of 4.33 (95%CI: 1.364-13.77), which remained significant after adjustment for various confounding factors. Fetuin-A is a reliable marker of NAFLD in NDD and is positively associated with insulin resistance (IR). The observation in this study suggests that high serum fetuin-A levels in patients with NAFLD do not merely reflect the effects of insulin resistance, but also a more extensive distortion of liver architecture.

The effects of resveratrol supplementation in patients with type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease: an umbrella review of meta-analyses of randomized controlled trials

Uncertainty remains about the estimates of the effects for resveratrol supplementation, including the certainty of the evidence for each estimate and the magnitude of the observed impact based on the minimal important difference. We aimed to provide an overview of the effects of resveratrol supplementation, in comparison to control groups, for the management of cardiometabolic risk factors in patients with type 2 diabetes (T2D), metabolic syndrome (MetS), and nonalcoholic fatty liver disease (NAFLD). PubMed, Scopus, and ISI Web of Science were searched from inception to May 2021. For each meta-analysis, the mean difference and its 95% CI were recalculated using a random-effects model. The certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. We identified 11 meta-analyses corresponding to 29 outcomes in 1476 individuals with T2D, 17 meta-analyses reporting 26 outcomes in 727 participants with the MetS, and 10 meta-analyses reporting 24 outcomes in 271 patients with NAFLD. Resveratrol supplementation had beneficial effects on some outcomes such as blood pressure, lipid profile, glycemic control, and insulin resistance in T2D, waist circumference in MetS, and body-weight and inflammation markers in NAFLD; however, for almost all outcomes, the magnitude of the effect was trivial, the certainty of evidence was very low to low, or the number of trials was too few. In the case of glycated hemoglobin (HbA1c), there was evidence that resveratrol can exert favorable and clinically important effects in the short term (<12 wk; mean difference: -1.05%, 95% CI: -2.09%, -0.02%; n=6; GRADE=moderate). Current evidence does not support supplementation with resveratrol for the management of cardiometabolic risk factors in patients with T2D, MetS, and NAFLD. In the case of HbA1c, subject to the limitations such as short-term follow-up and small sample size, there was a clinically important effect. The protocol of the present systematic review was registered in Open Science Framework (https://osf.io/ake85; registration doi: 10.17605/OSF.IO/AKE85).

The Effect of Eight Weeks Endurance Training, Somatropin Injection, and Its Lipolytic Fragment (AOD9604) on Cytokeratin-18 and Liver Enzymes of Mice Induced Liver Damage Due to a High-Fat Diet

Aims: Fatty liver and its treatment are among the concerns of today’s society. So this study aimed to investigate the effect of endurance training, Somatropin injection, and its lipolytic fragment (AOD9604) on cytokeratin-18 (CK18) levels and liver enzymes of mice with fatty liver. Methods &amp; Materials: In this experimental study, 28 male mice were randomly divided into four groups (7 mice in every group): control (C), exercise (E), exercise + fragment (EA), and exercise + growth hormone (EGH). A medium-intensity endurance training program was performed for 8 weeks, 5 sessions per week with an intensity of 50% VO2max. The somatropin and fragment injection protocols were 1 mg and 250 mc/kg of body weight, respectively. The mice were evaluated 48 hours after the last training session. The obtained data were analyzed using 1-way ANOVA and post hoc Tukey tests at the significant level of P&lt;0.05 in SPSS version 26. Findings: CK18 showed a significant decrease in group E compared to the control group only (P=0.00). CK18 values were significantly higher in the EGH group compared to the E (P=0.00) and EA (P=0.04) groups. HOMA-IR (homeostatic model assessment for insulin resistance) index had a significant decrease in the E (P=0.00) and EA (P=0.03) groups, but no significant changes were seen in the EGH group. Changes in aspartate transaminase were not significant in any of the groups. Alanine transaminase levels in all three groups of E (P=0.00), EGH (P=0.03), and EA (P=0.00) were significantly lower than those in the control group, but the inter-group changes were not significant. Conclusion: Endurance training has produced a more effective response in improving nonalcoholic fatty liver disease markers than GH and fragment peptides. Growth hormone injection can have negative consequences on some indicators of this abnormality.

Association of Urinary and Dietary Selenium and of Serum Selenium Species with Serum Alanine Aminotransferase in a Healthy Italian Population.

The trace element selenium is of considerable interest due to its toxic and nutritional properties, which markedly differ according to the dose and the chemical form. It has been shown that excess selenium intake increases the risk of type 2 diabetes and, possibly, other metabolic diseases like hyperlipidemia and non-alcoholic fatty liver disease (NAFLD). For the latter, however, epidemiologic evidence is still limited. We carried out a cross-sectional study recruiting 137 healthy blood donors living in Northern Italy and assessed their exposure to selenium through different methods and measuring serum selenium species. We performed linear and spline regression analyses to assess the relation of selenium and its forms with serum alanine aminotransferase (ALT) levels, a marker of NAFLD. Urinary selenium levels were positively and somewhat linearly correlated with ALT (beta regression coefficient (β) 0.11). Conversely, the association of dietary selenium intake with ALT was positive up to 100 µg/day and null above that amount (β 0.03). Total serum selenium was inversely associated with ALT up to 120 µg/L, and slightly positive above that amount. Concerning the different serum selenium species, ALT positively correlated with two organic forms, selenocysteine (β 0.27) and glutathione peroxidase-bound selenium (β 0.09), showed a U-shaped relation with the inorganic tetravalent form, selenite, and an inverse association with human serum albumin-bound selenium (β −0.56). Our results suggest that overall exposure to selenium, and more specifically to some of its chemical forms, is positively associated with ALT, even at levels so far generally considered to be safe. Our findings add to the evidence suggesting that low-dose selenium overexposure is associated with NAFLD.

Elevated Serum Cyclophilin D Level is Associated with Nonalcoholic Fatty Liver Disease and Higher Fibrosis Scores in Patients with Diabetes Mellitus.

BackgroundCyclophilin D (CypD) is a mitochondrial matrix protein involved in liver steatosis and fibrosis in vitro. However, the role of CypD in the development of fatty liver and liver fibrosis in humans has not been determined.PurposeTo measure the serum level of CypD in patients with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD) and to assess its relation to the presence of hepatic steatosis and fibrosis in this group of patients.Patients and MethodsIn this cross-sectional study, 30 patients with diabetes and NAFLD were compared to 30 patients with diabetes without NAFLD and 30 age- and sex-matched healthy subjects. Abdominal ultrasound was used to diagnose NAFLD. Serum CypD was measured using ELISA. Fibrosis-4 (FIB-4) index, AST to platelet ratio index (APRI), and NAFLD fibrosis score (NFS) were used as markers of liver fibrosis in patients with NAFLD. Patients with NAFLD were divided into two subgroups based on FIB-4 index: patients with liver fibrosis (FIB-4 >1.45) and patients without liver fibrosis (FIB-4 <1.45). CypD and other clinical and biochemical parameters were validated as predictors of NAFLD and liver fibrosis in diabetic patients in multivariate logistic regression analysis.ResultsDiabetic patients with NAFLD had higher serum CypD levels than those without NAFLD (11.65±2.96 vs 6.58±1.90 ng/mL, respectively, P <0.001). Correlation analysis revealed a significant positive correlation between CypD and FIB-4 index (P=0.001), APRI (P=0.013) and NFS (P<0.001). GGT and CypD were the only predictors of NAFLD. For the prediction of significant fibrosis, AUROC of CypD was 0.835 with a cutoff >14.05 ng/mL provides specificity of 81.8% and sensitivity of 75%.ConclusionSerum CypD is related to hepatic steatosis and fibrosis in diabetic patients. Serum CypD may thus provide a novel marker and therapeutic target of NAFLD and liver fibrosis.

The Relationship between Resistin Level and the Degree of Non-Alcoholic Fatty Liver Disease (NAFLD)

Background: NAFLD is a metabolic syndrome that manifests in the liver and is associated with type 2 diabetes mellitus (type 2 DM), insulin resistance, obesity and hyperlipidemia. The number of sufferers continues to increase worldwide in line with the increasing prevalence of obesity and diabetes. Resistin is a potential marker for NAFLD, which also have an important relationship with obesity and insulin resistance. Purpose: to analyze the relationship between resistin level and the degree of NAFLD. Methods: This cross sectional study was conducted at the Gastroentero-hepatology Department of Haji Adam Malik General Hospital, Medan, from January to March 2020. Patients with NAFLD diagnosed with abdominal ultrasound underwent measurement of body mass index (BMI), examination of resistin levels, fasting blood glucose, platelet count, albumin, AST and ALT, and the degree of NAFLD Fibrosis Score (NFS) was determined. Results: From 67 samples, based on abdominal ultrasound, the largest proportion was grade I NAFLD (40.4%). There was a statistically significant relationship between resistin levels and the degree of NAFLD (p value &lt;0.01), NAFLD comorbid in both type 2 DM and BMI ≥ 23 kg/m2 (p value &lt;0.001), NFS with the degree of NAFLD (p value &lt;0.001), and also resistin levels with the degree of NFS (p value &lt;0.001). Conclusion: Significant relationship was found between resistin level and the degree of NAFLD (p value &lt;0.001) and also between resistin levels and the degree of NAFLD Fibrosis Score (NFS) (p value &lt;0.001). Keywords: resistin, NAFLD, NFS, diabetes

The effect of (Cornus mas L.) fruit extract on liver function among patients with nonalcoholic fatty liver: A double-blind randomized clinical trial.

This double-blind randomized clinical trial aimed to investigate impact of Cornus mas L. fruit extract (CMFE) on liver function in nonalcoholic fatty liver disease (NAFLD). Fifty patients were randomly assigned into the CMFE and placebo groups to receive 20 ml of the extract or placebo for 12 weeks, respectively. Serum alanine aminotransferase, aspartate aminotransferase, cytokeratin 18 (CK-18) levels, and steatosis and fibrosis scores were examined before and after the intervention. Although, a significant decrease was observed in CK-18 levels among the CMFE group (288.80 ± 85.40 vs. 235.66 ± 60.38; p=.001) after 12 weeks, no significant difference was found between the two groups. Moreover, a significant increase in fibrosis score in the placebo group (8.20 (6.35-9.40) vs. 8.40 (7.70-13.00); p= .03) as well as a significant difference in this marker (CMEF: 7.64 (6.30-8.25); placebo: 8.40 (7.70-13.00); p= .02) and its changes (CMEF: 0.60 (-1.00-1.07); placebo: 0.80 (-0.25-3.95); p= .02) were found between the groups after 12 weeks. No significant effect was noted on other variables. Therefore, consuming CMFE might have some beneficial effects on liver function markers in NAFLD. However, more studies are required in this area.

Validation of Fatty Liver Index as a Marker for Non-Alcoholic Fatty Liver Disease

Background: Many studies have been conducted to validate fatty liver index (FLI) as a marker for non-alcoholic fatty liver disease (NAFLD). However, there are insufficient data in Korea to verify the usefulness of FLI, and the results of these studies are contradictory. This study aimed to validate FLI as a marker for NAFLD in Korea. For better accuracy, computed tomography (CT) scan was used instead of ultrasound scan.Methods: A cross-sectional analysis was performed in 785 subjects who participated in a health examination. The participants were divided according to presence of NAFLD, which was determined by abdominal CT. Frequency analysis was performed on all results. The chi-square test and independent t-test were used to compare the differences between the non-NAFLD group and the NAFLD group in terms of general characteristics and blood tests. The ability of the FLI to detect (nonalcoholic) fatty liver was assessed using area under the receiver operator characteristic (AUROC) curve analysis.Results: FLI was significantly higher in the NAFLD group (42.48±27.63) than in the non-NAFLD group (22.59±20.05) (P&lt;0.0001). The algorithm for FLI had a better AUROC of 0.696 (95% confidence interval, 0.649-0.742) than any other variable in the prediction of NAFLD.Conclusions: FLI is a marker that can be used as a simple and cost-effective tool to screen for NAFLD.

Alterations in bile acid metabolizing gut microbiota and specific bile acid genes as a precision medicine to subclassify NAFLD.

Multiple mechanisms for the gut microbiome contributing to the pathogenesis of nonalcoholic fatty liver disease (NAFLD) have been implicated. Here, we aim to investigate the contribution and potential application for altered bile acids (BA) metabolizing microbes in NAFLD by post hoc analysis of whole metagenome sequencing (WMS) data. The discovery cohort consisted of 86 well-characterized patients with biopsy-proven NAFLD and 38 healthy controls. Assembly-based analysis was performed to identify BA-metabolizing microbes. Statistical tests, feature selection, and microbial coabundance analysis were integrated to identify microbial alterations and markers in NAFLD. An independent validation cohort was subjected to similar analyses. NAFLD microbiota exhibited decreased diversity and microbial associations. We established a classifier model with 53 differential species exhibiting a robust diagnostic accuracy [area under the receiver-operator curve (AUC) = 0.97] for detecting NAFLD. Next, eight important differential pathway markers including secondary BA biosynthesis were identified. Specifically, increased abundance of 7α-hydroxysteroid dehydrogenase (7α-HSDH), 3α-hydroxysteroid dehydrogenase (baiA), and bile acid-coenzyme A ligase (baiB) was detected in NAFLD. Furthermore, 10 of 50 BA-metabolizing metagenome-assembled genomes (MAGs) from Bacteroides ovatus and Eubacterium biforme were dominant in NAFLD and interplayed as a synergetic ecological guild. Importantly, two subtypes of patients with NAFLD were observed according to secondary BA metabolism potentials. Elevated capability for secondary BA biosynthesis was also observed in the validation cohort. These bacterial BA-metabolizing genes and microbes identified in this study may serve as disease markers. Microbial differences in BA-metabolism and strain-specific differences among patients highlight the potential for precision medicine in NAFLD treatment.

Effect of Important Food Sources of Fructose-Containing Sugars on Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Controlled Trials

ObjectivesFructose as a source of excess calories increases non-alcoholic fatty liver disease (NAFLD) markers. Whether this effect is mediated by the food matrix is unknown. We thus conducted a systematic review and meta-analysis of controlled feeding trials assessing the effect of important food sources of fructose-containing sugars at different energy control levels on NAFLD markers. MethodsMEDLINE, Embase, and Cochrane Library were searched through January 18, 2021 for controlled trials ≥7-days. Four trial designs were prespecified based on energy control: substitution (energy-matched replacement of sugars by other macronutrients); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients). The primary outcome was intrahepatocellular lipid (IHCL). Secondary outcomes were alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Independent reviewers extracted data and assessed risk of bias. Certainty of evidence was assessed by GRADE. ResultsWe included 44 trials (65 trial comparisons, n = 1941) assessing the effect of 8 food sources (sugar-sweetened beverages [SSBs]; sweetened dairy alternative [soy]; fruit juice; fruit; dried fruit; baked goods, desserts and sweets; added nutritive sweetener; and mixed sources) across 4 energy levels. Total fructose-containing sugars increased IHCL in addition trials (standardized mean difference = 1.69 [95% CI, 1.00–2.37], P < 0.001), but no effect in substitution, subtraction and ad libitum trials. There was evidence of interaction by food source in addition trials with SSBs increasing IHCL and ALT, and mixed sources increasing AST. The overall certainty of evidence was high for SSBs on IHCL and ALT in addition trials and high to very low for all other comparisons. ConclusionsEnergy control and food source appear to mediate the effect of fructose-containing sugars on NAFLD markers. High certainty evidence suggests that SSBs providing excess energy increase NAFLD markers, while the evidence is less certain that mixed sources share the same effect and other food sources do not. More high-quality randomized trials of different food sources are needed to improve our estimates (ClinicalTrials.gov identifier, NCT02716870). Funding SourcesPrimary funding: Diabetes Canada.

Circulating microRNA‑135a‑3p in serum extracellular vesicles as a potential biological marker of non‑alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a widespread threat to human health. However, the present screening methods for NAFLD are time-consuming or invasive. The present study aimed to assess the potential of microRNAs (miRNAs/miRs) in serum extracellular vesicles (EVs) as a biomarker of NAFLD. C57BL/6J mice were fed either a 12-week high-fat diet (HFD) or standard chow to establish NAFLD and control groups, respectively. Serum samples were obtained from the mouse model of NAFLD, as well as 50 patients with NAFLD and 50 healthy individuals, and EVs were extracted and verified. Using reverse transcription-quantitative PCR, the mRNA expression level of selected miRNAs in the serum and EVs was analyzed. In order to determine the diagnostic value, receiver operating characteristic (ROC) curves were used. The mice treated with HFD showed notable hepatic steatosis and higher concentrations of serum alanine aminotransferase (ALT). There was also a significant decrease in the expression levels of miR-135a-3p, miR-129b-5p and miR-504-3p, and an increase in miR-122-5p expression levels in circulating EVs in mice treated with HFD and patients with NAFLD. There were also similar miR-135a-3p and miR-122-5p expression patterns in the serum. ROC analysis demonstrated that miR-135a-3p in circulating EVs was highly accurate in diagnosing NAFLD, with the area under the curve value being 0.849 (95% CI, 0.777–0.921; P<0.0001). Bioinformatics analysis indicated that dysregulated miR-135a-3p was associated with ‘platelet-derived growth factor receptor signaling pathway’ and ‘AMP-activated protein kinase signaling pathway’. In summary, circulating miR-135a-3p in EVs may serve as a potential non-invasive biomarker to diagnose NAFLD. This miRNA was a more sensitive and specific biological marker for NAFLD compared with ALT.

Effect of l-carnitine supplementation on children and adolescents with nonalcoholic fatty liver disease (NAFLD): a randomized, triple-blind, placebo-controlled clinical trial.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in the pediatric population at global level. Present study aims to assess the effect of l-carnitine supplementation on the NAFLD in children and adolescents. This randomized, triple-blind, placebo-controlled clinical trial was conducted in 2018-2019. Study was carried out in NAFLD participants (5-15 years). They were randomly assigned to receive either 50mg/kg/day l-carnitine twice a day or identical placebo per day for three months. Liver enzymes and liver ultrasonography were assessed before and after the intervention. Both groups received similar consultation for lifestyle changes. Overall, 55 participants completed the study, 30 patients in the l-carnitine group and 25 patients in placebo group. Mean changes of anthropometric measurements did not have significant differences between groups (p>0.05). No significant differences in the mean changes of aspartate aminotransferase (AST) (p=0.82) and alanine aminotransferase (ALT) (p=0.76) levels were documented between two groups. Based on within-group analysis, there were significant changes in AST and ALT levels before and after the intervention in both groups. The sonographic grades of fatty liver were not significantly different between two groups before (p=0.94) and after intervention (p=0.93). In the present clinical trial, L-carnitine did not have significant effect on improving biochemical and sonographic markers of NAFLD in children and adolescents. Future studies are necessary to evaluate the applicability and efficacy of long-term l-carnitine supplementation to treatment of NAFLD in pediatric population. IRCT20170628034786N2.

Fetuin-A as a Marker of NAFLD

Fetuin-A has been implicated in the causation of metabolic disorders such as obesity, diabetes, and hepatic steatosis. There are numerous studies which have shown the association between levels of fetuin-A in Type 2 diabetes mellitus (T2DM) and Nonalcoholic fatty liver disease (NAFLD). The levels of fetuin-A in newly detected type 2 diabetic patients (NDD) and its correlation with presence of NAFLD has not been studied. Objective: To study the fetuin-A levels in patients with NDD and its correlation with NAFLD. Methods: A total of 60 newly diagnosed type 2 diabetes (NDD) were studied. Diagnosis of NAFLD was made on the basis of transient elastography. Serum fetuin-A and serum fasting insulin were measured along with other investigations. Results: Percentage of patients with NAFLD in NDD was 53.33%. Fetuin-A levels were significantly higher in NDD with NAFLD compared to those without NAFLD. There was no association of fetuin-A with age, both systolic and diastolic blood pressure, FBS, HbA1c, fasting insulin, HOMA-IR, QUICKI and markers of advanced fibrosis. Fetuin-A levels beyond 1166.5 mcg/ml could predict the development of NAFLD with OR of 4.33 (95%CI:1.364–13.77) which remained significant after adjustment for various confounding factors. Conclusion: Fetuin-A is a reliable marker of NAFLD in NDD and is positively associated with IR. The observation in this study suggests that high serum fetuin-A levels in patients with NAFLD do not merely reflect the effects of insulin resistance, but also a more extensive distortion of liver architecture.

Diagnostic Efficacy of Serum Mac-2 Binding Protein Glycosylation Isomer and Other Markers for Liver Fibrosis in Non-Alcoholic Fatty Liver Diseases.

BackgroundMac-2 binding protein glycosylation isomer (M2BPGi) has been established as a non-invasive biomarker for liver fibrosis. We evaluated the diagnostic efficacy of M2BPGi compared with those of other liver fibrosis markers in liver fibrosis in non-alcoholic fatty liver disease (NAFLD).MethodsWe analyzed serum M2BPGi levels in 113 NAFLD patients. A pathologist graded liver fibrosis histopathologically. The diagnostic efficacies of serum M2BPGi and other liver fibrosis markers (aspartate aminotransferase to platelet ratio index, fibrosis index based on four factors, and NAFLD fibrosis score [NFS]) were evaluated using correlation, area under the ROC curve (AUC), logistic regression, and C-statistics.ResultsSerum M2BPGi level and other liver fibrosis markers showed a moderate correlation with fibrosis grade. The AUC values of M2BPGi were 0.761, 0.819, 0.866, and 0.900 for diagnosing fibrosis (F)>0, F>1, F>2, and F>3, respectively. Logistic regression analysis showed M2BPGi as the only independent factor associated with F>2 and F>3. Although C-statistics showed that NFS was the best diagnostic factor for F>2 and F>3, M2BPGi with NFS had an increased C-statistics value, indicating that it is a better diagnostic model.ConclusionsThe serum M2BPGi level increased with liver fibrosis severity and could be a good biomarker for diagnosing advanced fibrosis and cirrhosis in NAFLD patients. A well-controlled, prospective study with a larger sample size is needed to validate the diagnostic power of M2BPGi and other fibrosis markers in NAFLD.

Consumption of High-Fructose Corn Syrup Compared with Sucrose Promotes Adiposity and Increased Triglyceridemia but Comparable NAFLD Severity in Juvenile Iberian Pigs

BackgroundFructose consumption has been linked to nonalcoholic fatty liver disease (NAFLD) in children. However, the effect of high-fructose corn syrup (HFCS) compared with sucrose in pediatric NAFLD has not been investigated. ObjectivesWe tested whether the isocaloric substitution of dietary sucrose by HFCS would increase the severity of NAFLD in juvenile pigs, and whether this effect would be associated with changes in gut histology, SCFA production, and microbial diversity. MethodsIberian pigs, 53-d-old and pair-housed in pens balanced for weight and sex, were randomly assigned to receive a mash diet top-dressed with increasing amounts of sucrose (SUC; n = 3 pens; 281.6–486.8 g/kg diet) or HFCS (n = 4; 444.3–724.8 g/kg diet) during 16 wk. Diets exceeded the animal’s energy requirements by providing sugars in excess, but met the requirements for all other nutrients. Animals were killed at 165 d of age after blood sampling, and liver, muscle, and gut were collected for histology, metabolome, and microbiome analyses. Data were analyzed by multivariate and univariate statistics. ResultsCompared with SUC, HFCS increased subcutaneous fat, triacylglycerides in plasma, and butyrate in colon (P ≤ 0.05). In addition, HFCS decreased UMP and short-chain acyl carnitines in liver, and urea nitrogen and creatinine in serum (P ≤ 0.05). Microbiome analysis showed a 24.8% average dissimilarity between HFCS and SUC associated with changes in SCFA-producing bacteria. Body weight gain, intramuscular fat, histological and serum markers of liver injury, and circulating hormones, glucose, and proinflammatory cytokines did not differ between diets. ConclusionsFructose consumption derived from HFCS promoted butyrate synthesis, triglyceridemia, and subcutaneous lipid deposition in juvenile Iberian pigs, but did not increase serum and histological markers of NAFLD compared with a sucrose-enriched diet. Longer studies could be needed to observe differences in liver injury among sugar types.

Correlation of Serum Transaminase Levels with Liver Fibrosis Assessed by Transient Elastography in Vietnamese Patients with Nonalcoholic Fatty Liver Disease.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a cause of chronic liver disease, often resulting in liver cirrhosis, portal hypertension, and hepatocellular carcinoma damaging outcomes. Alanine transaminase (ALT) and aspartate aminotransferase (AST) are indicators of hepatocellular injury. Several studies have demonstrated that high ALT levels are correlated with higher nonalcoholic steatohepatitis (NASH) risk. The aim was to determine the correlation of serum alanine aminotransferase and aspartate transaminase with liver stiffness in Vietnamese patients with NAFLD.Patients and MethodsThe study included 18 to 80 years old patients diagnosed with fatty liver on ultrasound at the University of Medical Center (UMC) liver clinic. Liver stiffness was measured using transient elastography. The histopathological, demographic, and laboratory data of the participants were also collected. The baseline and clinical characteristics of NAFLD patients were stratified by serum ALT levels.ResultsThere were 138 NAFLD patients, including 82 men (59.4%) and 56 women (40.6%) (mean ± SD age of 41 ± 11 years). Liver fibrosis (F0) between the two groups showed no significant difference (p = 0.469). Similarly, no difference was found in the mild fibrosis level (F2) of the two groups of patients (p = 0.371). ALT level was significantly higher in NAFLD patients with advanced fibrosis (F3, F4) (3.2% vs 15.9%, p = 0.0013; 3.2% vs 13.2%, p = 0.0047, respectively). NAFLD patients with mild to moderate fibrosis (F1-F2) were detected at 59 U/L cut-off value with 67% sensitivity and 51% specificity. However, severe fibrosis and/or cirrhosis patients (F3-F4) had a cut-off value of 81 U/L with 53% sensitivity and 67% specificity in patients.ConclusionUsing ALT level as a marker for severe NAFLD would consider high-risk patients as mild cases, even though there is still the risk of progressive and severe hepatic disease. Our study underlines the small contribution of ALT as an independent factor for detecting NAFLD severity.

Evaluation of the Role of Hyaluronic Acid as A potential Biomarker for Diagnosis of Non-Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, ranging from simple steatosis and non-alcoholic steatohepatitis (NASH) to cirrhosis, with its complications including hepatocellular carcinoma (HCC). The non-invasive diagnostic markers of NAFLD are gaining interest due to the invasive nature and potential side effects of liver biopsy, and are the current gold standard of diagnosis. Objective: This study aimed to evaluate hyaluronic acid (HA) as a potential non-invasive biomarker for diagnosis and prognosis of NAFLD and to compare it with the traditional non-invasive techniques. Patients and methods: This study included 63 subjects divided into 3 groups; including 21 patients with fatty liver, 21 patients with NASH, in addition to 21 healthy controls. Non-invasive assessment of liver fibrosis was done to all study subjects using aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 score (FIB4), in addition to measurement of HA serum levels. Results: As regard assessment of liver fibrosis, there was a highly significant statistical difference between groups as regard APRI and Fib4 scores. As for HA there was a highly significant statistical difference between study groups. HA receiver operating characteristics curves (ROC) achieved excellent diagnostic performance for fatty liver with 100% sensitivity and specificity at cutoff of 25 ng/ml for fatty liver, versus a sensitivity of 95.2% and specificity of 85.7% for NASH at cutoff of 110 ng/ml. Conclusion: HA can be used as an accurate and specific non-invasive biomarker for the diagnosis of NAFLD and staging of the severity of disease compared with the traditional known non-invasive scores.