Liver Fibrosis In Nonalcoholic Fatty Liver Disease Patients Research Articles

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

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

Effects of sodium-glucose co-transporter 2 inhibitors on liver fibrosis in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: An updated meta-analysis of randomized controlled trials

Background and aimSodium-glucose co-transporter 2 inhibitors (SGLT2i) has been verified to improve Non-alcoholic fatty liver disease (NAFLD) in previous clinical practice. We mainly aim to investigate the effects of SGLT2i on liver fibrosis in NAFLD patients with type 2 diabetes mellitus (T2DM). MethodsWe conducted a comprehensive literature search utilizing the databases PubMed, Embase, Web of Science, and Cochrane Library, and extracted continuous data in the form of mean and standard deviation of the difference before and after treatment. RevMan 5.3 software was used to chart the pooled forest plot and perform heterogeneity, sensitivity and subgroup analysis. This study is conducted under the protocol registered with the Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY protocol 4946, INPLASY202360058). ResultsA total of 16 articles involving 699 patients were included. Indicators of liver fibrosis, containing Liver Stiffness Measurement (LSM), Controlled Attenuation Parameter (CAP), Serum ferritin, Serum type 4 collagen 7s, and FIB-4 index, were found to be considerably reduced by SGLT2i medication and subgroup analysis manifested pronounced dose-dependence. Additionally, SGLT2i therapy decreased BMI, lipid buildup and insulin resistance. ConclusionsSGLT2 inhibitors significantly ameliorated liver fibrosis and liver fat content, improved body conditions and insulin resistance, demonstrating that SGLT2i might reduce the risk of the progression of liver fibrosis and have a positive effect on NAFLD patients with T2DM.

Liver Ultrasound Elastography in Non-Alcoholic Fatty Liver Disease: A State-of-the-Art Summary.

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease which is currently the most common hepatic disorder affecting up to 38% of the general population with differences according to age, country, ethnicity and sex. Both genetic and acquired risk factors such as a high-calorie diet or high intake of saturated fats have been associated with obesity, diabetes and, finally, NAFLD. A liver biopsy has always been considered essential for the diagnosis of NAFLD; however, due to several limitations such as the potential occurrence of major complications, sampling variability and the poor repeatability in clinical practice, it is considered an imperfect option for the evaluation of liver fibrosis over time. For these reasons, a non-invasive assessment by serum biomarkers and the quantification of liver stiffness is becoming the new frontier in the management of patients with NAFLD and liver fibrosis. We present a state-of-the-art summary addressing the methods for the non-invasive evaluation of liver fibrosis in NAFLD patients, particularly the ultrasound-based techniques (transient elastography, ARFI techniques and strain elastography) and their optimal cut-off values for the staging of liver fibrosis.

Artificial Intelligence for Detecting and Quantifying Fatty Liver in Ultrasound Images: A Systematic Review.

Non-alcoholic Fatty Liver Disease (NAFLD) is growing more prevalent worldwide. Although non-invasive diagnostic approaches such as conventional ultrasonography and clinical scoring systems have been proposed as alternatives to liver biopsy, their efficacy has been called into doubt. Artificial Intelligence (AI) is now combined with traditional diagnostic processes to improve the performance of non-invasive approaches. This study explores how well various AI methods function and perform on ultrasound (US) images to diagnose and quantify non-alcoholic fatty liver disease. A systematic review was conducted to achieve this objective. Five science bibliographic databases were searched, including PubMed, Association for Computing Machinery ACM Digital Library, Institute of Electrical and Electronics Engineers IEEE Xplore, Scopus, and Google Scholar. Only peer-reviewed English articles, conferences, theses, and book chapters were included. Data from studies were synthesized using narrative methodologies per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Forty-nine studies were included in the systematic review. According to the qualitative analysis, AI significantly enhanced the diagnosis of NAFLD, Non-Alcoholic Steatohepatitis (NASH), and liver fibrosis. In addition, modalities, image acquisition, feature extraction and selection, data management, and classifiers were assessed and compared in terms of performance measures (i.e., accuracy, sensitivity, and specificity). AI-supported systems show potential performance increases in detecting and quantifying steatosis, NASH, and liver fibrosis in NAFLD patients. Before real-world implementation, prospective studies with direct comparisons of AI-assisted modalities and conventional techniques are necessary.

A retrospective study to find out the correlation between NAFLD, diabetes, and obesity in Indian patients.

Nonalcoholic fatty liver disease (NAFLD) is present in the body with metabolic disorders such as Type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease. However, no significant evidence has been found till date exhibiting their association epidemiologically in Indian patients. To assess the association among NAFLD, T2DM, and obesity, and to validate the scoring system with grades of fatty liver (severity of liver disease) estimated by ultrasound vs. NAFLD fibrosis score, BARD score, and aspartate aminotransferase to platelet ratio index (APRI) score. A retrospective, observational study was conducted out in patients with NAFLD (n = 316) where diagnosis and grades of fatty liver were established via ultrasound reports. The patients were divided into two groups, Group A (n = 114, NAFLD with T2DM) and Group B (n = 202, NAFLD without T2DM). R 4.0.0 was used for statistical analysis. The mean age (in years) of the patients was 54.08 ± 10.78 in Group A and 48.10 ± 15.36 in Group B. The mean BMI in Group A was found to be slightly higher as compared to Group B, 27.49 ± 4.94 and 26.56 ± 4.68, respectively, and the difference was found to be statistically significant (p-value <0.05). The overall predictive ability of the NAFLD scoring system matched that to ultrasonography liver grading fibrosis report for approximately 53% of patients. The BARD scoring system was found to be matched with ultrasonography reported Grade 1 fatty liver (198/316). In the case of the APRI scoring system, the association was not observed with ultrasonography reports in any grades of fatty liver. Body mass index might be an independent risk factor for NAFLD. NAFLD fibrosis score appears to be a reliable non-invasive tool to determine the severity of liver fibrosis in NAFLD patients. BARD score may predict Grade 1 liver fibrosis. However, APRI scores do not correlate with imaging evidence of fibrosis like NAFLD and BARD scores.

Liver stiffness accuracy by magnetic resonance elastography in histologically proven non-alcoholic fatty liver disease patients: a Spanish cohort.

to evaluate the performance of magnetic resonance elastography (MRE) to stage liver fibrosis in patients with histologically confirmed nonalcoholic fatty liver disease (NAFLD) and to assess the impact of potential confounding factors in MRE diagnostic accuracy. The secondary objective was to compare MRE with other non-invasive methods for staging fibrosis such as transient elastography (TE) and non-invasive scores (APRI and FIB-4). sixty-five histologically confirmed NAFLD patients were prospectively enrolled at the Hospital Universitario Virgen del Rocío (Seville, Spain). Liver stiffness was measured by MRE, TE and non-invasive scores (APRI and FIB-4). Fibrosis was assessed by liver biopsy using the steatosis, activity and fibrosis (SAF) score. Patients were classified into three groups according to the consistency between MRE and histopathological findings: underestimation, concordance and overestimation groups. Areas under the ROC curve (AUROC) and diagnostic performance were evaluated. the area under the ROC curve (AUROC) of MRE in advanced fibrosis (≥ F3) was 0.90 (0.82-0.97), while TE AUROC was 0.82 (0.72-0.93) (p = 0.22) and lower for the non-invasive test (FIB-4 0.67 and APRI 0.62). Inflammatory activity, steatosis grade and higher levels of liver biochemistry appeared to overestimate MRE results in the univariate analysis, but only gamma-glutamyl transferase (GGT) was statistically significant in the multivariate analysis (p < 0.01). Age, sex, body mass index (BMI), weight, diabetes mellitus (DM), high blood pressure (HBP), platelets or lipidic profile did not affect MRE accuracy. MRE is an effective and non-invasive method for detecting and staging liver fibrosis in NAFLD patients. MRE is more accurate than TE and allows the study of liver anatomy. Histological inflammation and surrogate biomarkers of inflammation can overestimate liver stiffness, but only GGT was statistically significant in the multivariate analysis. Important features of NAFLD patients such as obesity, DM, or lipidic profile did not affect MRE accuracy.

Correlation between Non-Alcoholic Fatty Liver Disease (NAFLD) fibrosis score (NFS) with Left Ventricular Mass Index (LVMI) in patients with NAFLD

Background: Cardiovascular-related mortality is a major concern in NAFLD. Advanced fibrosis was known to be associated with cardiovascular diseases. NAFLD Fibrosis Score (NFS) is used to identify the development of liver fibrosis in NAFLD patients. Left ventricular mass index (LVMI) is a sign of subclinical cardiovascular complications in NAFLD. The correlation between NAFLD fibrosis score with LVMI in NAFLD patients is not fully established.Objective: To analyze the correlation between NAFLD fibrosis score with LVMI in NAFLD patients.Methods: A cross-sectional study of NAFLD patients in Kariadi Hospital Indonesia. NFS was done using a formula based on clinical and biochemical parameters. LVMI was measured with echocardiography. Pearson’s, Mann-Whitney, and logistic regression were used for analysis.Results: A total of 64 patients with primary NAFLD were enrolled, 54.7% males and 45.3% females. Mean age was 52,8 ± 10,5 years (30-77 years). Based on NFS criteria, high probability group was the highest (50%), followed by intermediate probability group (34,4%) and low probability group (15,6%). Highest increase in LVMI was obtained in the high probability group (93,8%), followed by intermediate probability (59,1%), and low probability group (10%) respectively. There was significant correlation between NFS and LVMI (P 0,002). Logistic regression showed that NFS has a more significant correlation with LVMI compared to gender (P=0,002).Conclusion: NFS is a non‐invasive liver fibrosis scores which independently corelated with Left ventricular mass index (LVMI), a marker of cardiovascular abnormality.

Serum Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Can Predict Mild or Significant Liver Fibrosis in Non-alcoholic Fatty Liver Disease

Background: The serum levels of M2BPGi increase with liver fibrosis progression in patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. However, the diagnostic performance of M2BPGi in non-alcoholic fatty liver disease (NAFLD) patients remains unclear. Objectives: To assess the severity of liver fibrosis in NAFLD patients and healthy controls by M2BPGi using acoustic radiation force impulse (ARFI) as the standard reference. Methods: Those suffering from NAFLD and healthy controls were recruited. NAFLD diagnosis was confirmed using fatty liver in imaging after excluding HCV, HBV, alcohol, drug, or other known causes of chronic liver disease. ARFI was used as the standard reference to determine the stage of liver fibrosis. Results: A total of 226 subjects were recruited, including 130 (57.5%) NAFLD patients who were divided into three groups according to the stage of liver fibrosis: F0, F1, and F ≥ 2. The serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST to platelet ratio index (APRI), M2BPGi, and the fatty liver grade were significantly different between the three groups. The levels of M2BPGi were correlated with median ARFI value (P &lt; 0.001), APRI (P = 0.011), and fibrosis 4 index (FIB-4) (P &lt; 0.001). The area under the curve (AUC) of M2BPGi test was 0.58 for F ≥ 1 and 0.68 for F ≥ 2, respectively (P = 0.039 and P = 0.024). Conclusions: The M2BPGi levels were correlated with ARFI, APRI, and FIB-4 scores in this study population. The level of M2BPGi could predict mild (F ≥ 1) and significant liver fibrosis (F ≥ 2) in NAFLD patients, suggesting a surrogate marker to differentiate between normal, mild, and significant fibrosis.

The Co-occurrence of Chronic Hepatitis B and Fibrosis Is Associated With a Decrease in Hepatic Global DNA Methylation Levels in Patients With Non-alcoholic Fatty Liver Disease.

Global DNA hypomethylation has been reported in patients with chronic hepatitis B (CHB) and non-alcoholic fatty-liver disease (NAFLD). However, the global DNA methylation profile of patients with concurrent NAFLD and CHB (NAFLD + CHB) is still unclear. We aimed to detect the hepatic global DNA methylation levels of NAFLD + CHB patients and assess the associated risk factors. Liver biopsies were collected from 55 NAFLD patients with or without CHB. The histological characteristics of the biopsy were then assessed. Hepatic global DNA methylation levels were quantified by fluorometric method. The hepatic global DNA methylation levels in NAFLD + CHB group were significantly lower than that in NAFLD group. Participants with fibrosis showed lower levels of hepatic global DNA methylation than those without fibrosis. Participants with both CHB and fibrosis had lower levels of hepatic global DNA methylation than those without either CHB or fibrosis. The co-occurrence of CHB and fibrosis was significantly associated with a reduction in global DNA methylation levels compared to the absence of both CHB and fibrosis. Our study suggests that patients with NAFLD + CHB exhibited lower levels of global DNA methylation than patients who had NAFLD alone. The co-occurrence of CHB and liver fibrosis in NAFLD patients was associated with a decrease in global DNA methylation levels.

1285-PUB: A Retrospective Observational Study to Find Out the Association between NAFLD, Diabetes, and Obesity in Indian Patients

Background: Nonalcoholic fatty liver disease (NAFLD) is present in the body with metabolic disorders such as type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease. However, no significant evidence has been found till date exhibiting their association epidemiologically in Indian patients. Objective: To assess the association among NAFLD, T2DM, and obesity, and to validate the scoring system with grades of fatty liver (severity of liver disease) estimated by ultrasound vs. NAFLD fibrosis score, BARD score, and APRI score. Methodology: A retrospective, observational study was conducted out in patients with NAFLD (n=316) where diagnosis and grades of fatty liver were established via ultrasound reports. The patients were divided into two groups, Group A (n=114, NAFLD with T2DM) and Group B (n=202, NAFLD without T2DM). R 4.0.0 was used for statistical analysis. Results: The mean age (in years) of the patients was 54.08 ± 10.78 in Group A and 48.10 ± 15.36 in Group B. The mean BMI in Group A was found to be slightly higher as compared to Group B, 27.49 ± 4.94 and 26.56 ± 4.68 respectively, and the difference was found to be statistically significant (p-value &amp;lt;0.05). The overall predictive ability of the NAFLD scoring system matched that to ultrasonography liver grading fibrosis report for approximately 53% of patients. The BARD scoring system was found to be matched with ultrasonography reported Grade-1 fatty liver (198/316). In the case of the APRI scoring system, the association was not observed with ultrasonography reports in any grades of fatty liver. Conclusion: BMI might be an independent risk factor for NAFLD. NAFLD fibrosis score appears to be a reliable non-invasive tool to determine the severity of liver fibrosis in NAFLD patients. BARD score may predict Grade 1 liver fibrosis. However, APRI scores do not correlate with imaging evidence of fibrosis like NAFLD and BARD scores. Disclosure M. Saran: None. J. K. Sharma: None. A. Ranjan: None. S. Deka: None. M. Sabharwal: Employee; Self; Health Arx Technologies Pvt. Ltd. S. Palukuri: None. B. Chandolia: None.

Performance of liver stiffness measurements obtained with FibroScan is affected by glucose metabolism in patients with nonalcoholic fatty liver disease

BackgroundThe performance of liver stiffness measurements (LSMs) obtained using FibroScan can be affected by several factors, and cut-off values are different for fibrosis caused by various aetiologies. The study aims to evaluate the diagnostic accuracy of LSM in nonalcoholic fatty liver disease (NAFLD) patients with abnormal glucose metabolism and investigate whether the LSM value would be affected by metabolic indicators.MethodsThe study involved 91 NAFLD patients with abnormal glucose metabolism who underwent liver biopsy. The diagnostic accuracy of LSM value was evaluated by the receiver operator characteristic (ROC) curves, with the biopsy results taken as the gold standard. Multivariate linear regression and subgroup analysis were performed to determine the correlated indicators.ResultsThe areas under the ROC curves (AUROCs) of LSM values for detecting fibrosis stage ≥1, 2, 3 and 4 were 0.793 (95% confidence interval [CI]: 0.695–0.871), 0.764 (95% CI: 0.663–0.846), 0.837 (95% CI: 0.744–0.906) and 0.902 (95% CI: 0.822–0.955), with cut-off values of 6.3, 7.6, 8.3 and 13.8 kPa, respectively. Multivariate linear regression demonstrated that haemoglobin A1c (HbA1c, β = 0.205, P = 0.026) and alanine aminotransferase (ALT, β = 0.192, P = 0.047) were independently associated with the LSM value after adjustment for fibrosis stage, ballooning and inflammation grade from liver biopsy. Subgroup analysis demonstrated that LSM values were slightly higher in patients with HbA1c ≥7% than in those with HbA1c < 7% and in patients with body mass index (BMI) ≥30 kg/m2 than in those with BMI < 30 kg/m2.ConclusionsFibroScan was valuable for the evaluation of liver fibrosis in NAFLD patients with abnormal glucose metabolism. FibroScan is recommended to evaluate severe fibrosis, especially to exclude advanced fibrosis. Glucose metabolism state may affect LSM values.

Elevation of plasma tRNA fragments as a promising biomarker for liver fibrosis in nonalcoholic fatty liver disease

Fibrotic tissue remodelling in nonalcoholic fatty liver disease (NAFLD) will probably emerge as the leading cause of end-stage liver disease in the coming decades, but the ability to diagnose liver fibrosis in NAFLD patients noninvasively is limited. The abnormal expression of tRNA-derived small RNA (tsRNA) in plasma provides a novel idea for noninvasive diagnosis of various diseases, however, the relationship between tsRNAs and NAFLD is still unknown. Here, we took advantage of small RNA-Seq technology to profile tsRNAs in NAFLD patients and found the ubiquitous presence of hepatic tsRNAs secreted into circulating blood. Verification in a cohort of 114 patients with NAFLD and 42 patients without NAFLD revealed that three tsRNAs (tRF-Val-CAC-005, tiRNA-His-GTG-001, and tRF-Ala-CGC-006) were significantly elevated in the plasma of NAFLD patients, and the expression level are associated with NAFLD activity score (calculated from 0 to 8) and fibrosis stage (scored from 0 to 4). In mouse models, we further found that increased plasma levels of these three tsRNAs were positively correlated with the degree of liver fibrosis. Our study potentially identifies a new class of NAFLD biomarkers and reveal the possible existence of tsRNAs in the blood that can be used to predict fibrogenesis risk in patients diagnosed with NAFLD.

Fucoidan and Fucoxanthin Attenuate Hepatic Steatosis and Inflammation of NAFLD through Modulation of Leptin/Adiponectin Axis.

Non-alcoholic fatty liver disease (NAFLD) is the emerging cause of chronic liver disease globally and lack of approved therapies. Here, we investigated the feasibility of combinatorial effects of low molecular weight fucoidan and high stability fucoxanthin (LMF-HSFx) as a therapeutic approach against NAFLD. We evaluated the inhibitory effects of LMF-HSFx or placebo in 42 NAFLD patients for 24 weeks and related mechanism in high fat diet (HFD) mice model and HepaRGTM cell line. We found that LMF-HSFx reduces the relative values of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, fasting blood glucose and hemoglobin A1c in NAFLD patients. For lipid metabolism, LMF-HSFx reduces the scores of controlled attenuation parameter (CAP) and increases adiponectin and leptin expression. Interestingly, it reduces liver fibrosis in NAFLD patients, either. The proinflammatory cytokines interleukin (IL)-6 and interferon-γ are reduced in LMF-HSFx group. In HFD mice, LMF-HSFx attenuates hepatic lipotoxicity and modulates adipogenesis. Additionally, LMF-HSFx modulates SIRI-PGC-1 pathway in HepaRG cells under palmitic acid-induced lipotoxicity environment. Here, we describe that LMF-HSFx ameliorated hepatic steatosis, inflammation, fibrosis and insulin resistance in NAFLD patients. LMF-HSFx may modulate leptin-adiponectin axis in adipocytes and hepatocytes, then regulate lipid and glycogen metabolism, decrease insulin resistance and is against NAFLD.

How Good Is Trans Abdominal Ultrasound for Evaluating NAFLD in the General Population? A Cross-Sectional Study

Nonalcoholic fatty liver disease (NAFLD) is one of the most common cause of liver test abnormality and chronic liver disease in the world and can increase liver related mortality. Association of NAFLD with metabolic syndrome increase mortality due to cardiovascular disease too. NAFLD is categorized histologically into the nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). Liver biopsy has been known as gold standard of evaluating NAFLD, but this procedure is invasive. It is time to replace available and easier way to diagnose, and predict the prognosis for better management of NAFLD. This study was comparing the result of transabdominal ultrasonography with Fibroscan as a new and accurate method for evaluating severity of fatty liver disease. This was a cross-sectional study that was conducted using 101 patients with NAFLD. All patients who had TUS by one experienced radiologist and fibro scan at the same time were included. Visual liver echogenicity was basis of grading in TUS. Fibro scans results are based on controlled attenuation parameters (CAP) which is not operator dependent. Other information, such as age, waist, and BMI, were also gathered. TUS has a low value for the diagnosis of liver fibrosis in NAFLD patients and predicting prognosis. TUS has a good correlation with fibroscan in grade 0 and 1of fatty liver, but in grade 2 and 3 of fatty liver, we can not rely on TUS for accurate grading.

Diagnostic value of liver stiffness measurement for the evaluation of liver fibrosis in nonalcoholic fatty liver

Objective: To investigate the clinical and diagnostic value of liver stiffness measurement (LSM) for the evaluation and comparison of aspartate aminotransferas/platelet ratio index (APRI), fibrosis 4 indexes (FIB-4) and NAFLD fibrosis score (NFS) with liver fibrosis staging in relation to nonalcoholic fatty liver disease (NAFLD). Methods: 103 cases with NAFLD who met the inclusion criteria confirmed by liver biopsy were selected for retrospective analysis. The results of serological tests and LSM were recorded. The APRI, FIB-4 and NFS were calculated. The accuracy and applicability of four liver fibrosis models in the diagnosis of liver fibrosis in NAFLD patients were compared with the receiver operating characteristic curve (ROC), and the diagnostic cut-off value of LSM was established. Results: Varying degrees of LSM, APRI, FIB-4 and NFS had shown positive correlations with the increasing degree of liver fibrosis. Among them, LSM was positively correlated with the degree of liver fibrosis, and the correlation coefficient was r = 0.727, P < 0.0001. Consistent with this, the area under the receiver operating characteristic curve, sensitivity, and specificity of LSM diagnosis of liver fibrosis in different stages was significantly higher than APRI, FIB-4 and NFS. Area under receiver operating characteristic curve of LSM was 0.862 and 0.928 for significant liver fibrosis (f ≥ 2), and advanced liver fibrosis (f ≥ 3). Conclusion: LSM has a good diagnostic exclusion value for NAFLD-induced fibrosis, and its sensitivity and specificity are better than APRI, FIB-4 and NFS.

Fatty acid-driven modifications in T-cell profiles in non-alcoholic fatty liver disease patients.

The interaction between T-cells/fatty acids involved in non-alcoholic fatty liver disease (NAFLD) and liver fibrosis progression is poorly understood. In this study, we conducted a comprehensive analysis of T-cell profiles of NAFLD patients to better understand their relationship with fatty acids and relevance to liver fibrosis. We analyzed the differences in T-cell profiles of peripheral blood mononuclear cells (PBMCs) between 40 NAFLD patients and 5 healthy volunteers (HVs), and their relationship with liver fibrosis stage or progression. Moreover, we analyzed the relationship between T-cell profiles and fatty acid compositions in vivo, and changes in T-cell profiles after treatment with fatty acids in vitro. T-cell profiles of NAFLD patients were different from those of HVs. The CD25+CD45+CD4+ T-cell frequency was increased in NAFLD patients with high liver fibrosis stage and progression, and this indicated immune activation. Despite such a state of immune activation, the PD1+CD4+ T-cell frequency was decreased in the same patients group. The PD1+CD4+ T-cell frequency had a significantly negative correlation with the serum fatty acid composition ratio C16:1n7/C16:0. Moreover, the PD1+CD4+ T-cell frequency was significantly decreased by in vitro treatment with fatty acids. In addition, its rate of frequency change was significantly different between C16:0 and C16:1n7 and decreased by artificially increasing the C16:1n7/C16:0 ratio. The analysis of PBMCs in NAFLD patients showed that T-cell profiles were different from those of HVs. And, it suggested that fatty acids modified T-cell profiles and were involved in liver fibrosis in NAFLD patients.

The promising role of probiotic and synbiotic therapy in aminotransferase levels and inflammatory markers in patients with nonalcoholic fatty liver disease - a systematic review and meta-analysis.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. The pathogenesis of NAFLD is complex and multifactorial. There is growing evidence that altered gut microbiota plays a key role in NAFLD progression. Probiotics/synbiotics, by modifying gut microbiota, may be a promising treatment choice for NAFLD management. The aim of this study was to study the effect of probiotics/synbiotics on various laboratory and radiographic parameters in NAFLD management. A systematic review and meta-analysis were carried out according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We searched PubMed, Medline, and Google Scholar for randomized-controlled trials that studied the role of probiotics/synbiotics in NAFLD. The primary outcome was change in baseline alanine aminotransferase and aspartate aminotransferase in the treatment arm. We used a random-effects model and inverse variance for the continuous data to estimate the mean difference (MD) and the standard mean difference (SMD) in RevMan Version 5.3. We included 12 randomized-controlled trials for analysis. The intervention arm, which comprised of the probiotic and/or the synbiotic arm, showed a significant improvement in alanine aminotransferase levels, MD=-13.93, confidence interval (CI)=-20.20 to -7.66, P value of less than 0.0001, I=92% and aspartate aminotransferase levels MD=-11.45, CI=-15.15 to -7.74, P value of less than 0.00001, I=91%. There was a reduction in high-sensitivity C-reactive protein levels in the intervention arm, SMD=-0.68, CI=-1.10 to -0.26, P value of 0.001, I=0%. The liver fibrosis score improved in the intervention arm, MD=-0.71, CI=-0.81 to -0.61, P value less than 0.00001, I=0%. Probiotic/synbiotic use improves aminotransaminase levels and reduces proinflammatory marker high-sensitivity C-reactive protein and liver fibrosis in NAFLD patients.

Relationship between the Triglyceride Glucose Index and the Presence and Fibrosis of Nonalcoholic Fatty Liver Disease in Korean Adults

Background: Recently, the triglyceride glucose (TyG) index has been considered a surrogate marker of insulin resistance. Insulin resistance is a well known pathogenic factor in nonalcoholic fatty liver disease (NAFLD). However, few studies have investigated the relationship between the TyG index and liver fibrosis in subjects with NAFLD. Thus, we investigated the relationship between the TyG index and liver fibrosis in Korean adults. Methods: In total, 5158 participants who underwent ultrasonography in a health promotion center were enrolled. Anthropometric profiles and multiple metabolic risk factors were measured. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated. NAFLD was diagnosed by ultrasonography, and degree of liver fibrosis was assessed by NAFLD fibrosis score (NFS). Significant liver fibrosis was defined as NFS ≥ -1.5. Results: All subjects were stratified into four groups based on their TyG indices. Significant differences were observed in metabolic parameters among the groups, and the prevalence of NAFLD and liver fibrosis by NFS significantly increased with increasing TyG index. When classifying the severity of NAFLD into three groups, there was a significant correlation between the severity of NAFLD and the TyG index. In the logistic regression analysis after adjustment for multiple risk factors, the odds ratio for the prevalence of liver fibrosis, when comparing the highest and lowest quartiles of the TyG index was 1.92 (95% CI: 1.46-2.53; P for trend &amp;lt; 0.01); the odds ratio for the prevalence of liver fibrosis, when comparing the highest and lowest quartiles of HOMA-IR was 2.92 (95% CI: 1.12-2.40; P for trend &amp;lt;0.01). Conclusion: There is a significant association between the TyG index and liver fibrosis of NAFLD, but HOMA-IR was superior to TyG index for predicting liver fibrosis in NAFLD patients. Disclosure M. Kim: None. J. Kim: None. K. Park: None. S. Lee: None. J. Nam: None. S. Kang: None. J. Park: None. C. Ahn: None. Y. Kim: None.

NONINVASIVE METHODS IN THE DIAGNOSIS OF NON-ALCOHOLIC FATTY LIVER DISEASE

Non-alcoholic fatty liver disease (NAFLD) being increasingly diagnosed worldwide is considered as the most common liver disease in Western countries. The incidence is growing rapidly due to the continuing epidemic of the obesity and diabetes mellitus type 2. There is the extremely topical question of the affordable, effective and early diagnosis of NAFLD. Over the past few years, significant progress has been made in the understanding of its risk factors, pathogenesis, clinical course, methods of diagnosis and treatment of NAFLD. The article gives an overview of modern and promising methods for diagnosing NAFLD, useful for physicians of various specialties who have to deal with NAFLD patients. Key problems of diagnostics are formulated and directions for further research are determined. There is discussed the role of biomarkers as promising noninvasive diagnostic methods, that provides to assess the severity of necrotic inflammatory processes and liver fibrosis in NAFLD patients.

Gastric Bypass Surgery Impacts Cardiac and Liver Outcomes With Better Survival in Patients With Non-Alcoholic Fatty Liver Disease

Introduction: Non-alcoholic fatty liver disease (NAFLD) is increasing due to current obesity epidemic. NAFLD patients are also at higher risk for cardiac events. Gastric bypass surgery (GBP) is increasingly utilized as a treatment for morbid obesity and is shown to improve liver fibrosis in NAFLD patients. The aim our study is to assess the impact of GBP on development of cirrhosis, occurrence of cardiac events, and overall survival among NAFLD patients. Methods: This is a single-center retrospective study on NAFLD patients (2007-2011) with diagnosis based on histology with changes of steatohepatitis or imaging with findings of steatosis, excluding other liver diseases. All patients had documented alcohol use of <10 g/d. Medical charts were reviewed for a) demographics, comorbidities, history of GBP, and b) follow-up from first clinic encounter for diagnosis of cirrhosis or of cardiac event (arrhythmia, congestive heart failure, angina, myocardial infarction, stroke, or peripheral arterial disease), transplantation, and survival. Results: Of 230 NAFLD patients, 29 with GBP differed from the remaining 201 for age (54±11 vs. 48±8 years, p=0.002), females (83% vs. 61%, p=0.024), and BMI (35±8 vs. 40±9 kg/m2, p=0.002). Compared to patients without GBP, those with GBP had fewer cardiac events (3.5% vs. 15%, p=0.090) and cirrhosis (24% vs. 57%, p=0.001). None of GBP patients needed liver transplantation (LT) compared to 20 (10%) patients without GBP who underwent LT, p=0.070. Overall survival tended to be better among GBP patients (96.5% vs. 90%, p=0.230) with significantly better LT-free survival (96.5% vs. 80%, p=0.035). Controlling for age, sex, cirrhosis, diabetes, BMI, use of beta blockers, and use of statins, the risk of cardiac events and the LT-free mortality were reduced with GPB, although not statistically significant due to small sample size: HR 0.29, 95% CI 0.04-2.34, p=0.25 and HR 0.58, 95% CI 0.05-4.56, p=0.52, respectively. LT-free mortality was 43-fold higher in presence of cirrhosis: 43 (5.3-353) and was reduced by 76% (0.24; 0.07-0.81) with use of statin and by 60% in females (0.4; 0.17-0.92). Conclusion: GBP improves the natural history of NAFLD with reduced risk of end organ damage, cardiac or liver-related complications, and mortality. Given the protective effect of statins on LT-free mortality, physicians may be encouraged to continue use of these drugs in NAFLD patients when indicated for treatment of dyslipidemia or cardiac disease. Further larger studies are suggested to examine the impact of GBP on hard end points, including LT-free mortality. Studies are urgently needed to identify patients at risk for cirrhosis in NAFLD, as a basis for using GBP as a potential personalized treatment option to improve their survival.