Nonalcoholic Steatohepatitis Patients Research Articles

Diagnostic accuracy of FibroScan-AST (FAST) score, non-alcoholic fatty liver fibrosis score (NFS), FibroScan, and liver fibrosis index (FIB-4) for identifying fibrotic non-alcoholic steatohepatitis in patients with chronic hepatitis B with metabolic dysfunction-associated fatty liver disease

Objective To evaluate the diagnostic value of the FibroScan-AST (FAST) score, non-alcoholic fatty liver fibrosis score (NFS), FibroScan, and liver fibrosis index (FIB-4) for identifying fibrotic non-alcoholic steatohepatitis (NASH) in patients with chronic hepatitis B (CHB) with metabolic dysfunction-associated fatty liver disease (MAFLD). Methods All patients with CHB and MAFLD who underwent liver biopsy at the Zhenjiang Third Hospital affiliated with Jiangsu University between August 2010 and December 2022 were included in the analysis. The diagnostic accuracy of FAST, NFS, FibroScan, and FIB-4 for diagnosing NASH and liver fibrosis were evaluated based on the area under the receiver-operating characteristic curve (AUC). Results A total of 156 patients with CHB combined with MAFLD were included, including 69 with NASH and fibrosis stage 2 or higher (NASH+F ≥ 2), and 16 with NASH and cirrhosis (NASH+F4). The AUC of FAST, NFS, liver stiffness measurement (LSM), and FIB-4 for diagnosing NASH+F ≥ 2 was 0.739 (p < 0.001), 0.643 (p = 0.006), 0.754 (p < 0.001), and 0.665 (p = 0.003), respectively. The specificity of FAST, NFS, LSM, and FIB-4 was 67%, 51.8%, 78.6% and 76.8%, respectively, and the sensitivity was 75%, 78.6%, 67.9%, and 53.6%, respectively. No significant differences were found between groups. The AUC of FAST, NFS, LSM, and FIB-4 for diagnosing NASH+F4 was 0.650 (p = 0.038), 0.725 (p = 0.001), 0.851 (p < 0.001), and 0.560 (p = 0.533), respectively. The specificity of the FAST, NFS, LSM, and FIB-4 was 55.9%, 50.0%, 71.6%, and 75.5%, respectively and the sensitivity was 80.0%, 100%, 100%, and 50.0%, respectively. The differences between AUCs of FIB-4 and FAST compared with LSM were 0.291 and 0.201, respectively (p < 0.05). Conclusion In patients with CHB combined with MAFLD, FAST did not have better accuracy than NFS and FIB-4 for predicting fibrotic NASH, whereas LSM had better accuracy than FAST and FIB-4.

Efficacy and safety of the FGF19 analog aldafermin for the treatment of nonalcoholic steatohepatitis (NASH): A GRADE assessed systematic review and Meta-Analysis

Background: Non-alcoholic fatty liver disease (NAFLD) is increasingly concerning due to its rising prevalence. It encompasses conditions from simple steatosis to severe non-alcoholic steatohepatitis (NASH), posing risks such as fibrosis, cirrhosis, or hepatocellular carcinoma if untreated. This systematic review and meta-analysis aims to assess aldafermin, an FGF-19 analog, for efficacy and safety in NASH patients. Methods: Eligible studies were identified by searching PubMed, Cochrane Library, and Google Scholar, resulting in 1115 studies. Three RCTs were included. Risk of bias was assessed using the Cochrane Risk of Bias tool, and data synthesis utilized Review Manager software. Certainty of evidence was evaluated with the GRADE approach. Results: In the 3 mg dose group, aldafermin significantly improved various parameters. The ELF score decreased notably (pooled MD: -0.46, 95% CI -0.64 to -0.28; P&lt;0.00001). Additionally, fibrosis improvement without NASH worsening showed a pooled MD of 8.15 (95% CI -3.62 to 19.93; P&lt;0.17), and fibrosis improvement with NASH resolution displayed a pooled MD of 10.16 (95% CI 1.68 to 18.64; P=0.02). Furthermore, significant reductions were noted in absolute AST levels (pooled MD: -13.40, 95% CI -18.66 to -8.14; P&lt;0.00001) and absolute ALT levels (pooled MD: -19.92, 95% CI -27.08 to -12.75; P&lt;0.00001), suggesting improved liver function. Conclusion: The meta-analysis indicates that aldafermin, particularly, the 3 mg dose, shows significant efficacy in improving liver histology and biochemical markers in NASH patients compared to placebo along with a satisfactory safety profile.

A machine learning-based predictive model discriminates nonalcoholic steatohepatitis from nonalcoholic fatty liver disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a leading cause of liver-related morbidity and mortality. The diagnosis of non-alcoholic steatohepatitis (NASH) plays a crucial role in the management of NAFLD patients. ObjectiveThe aim of our observational study was to build a machine learning model to identify NASH in NAFLD patients. MethodsThe clinical characteristics of 259 NAFLD patients and their initial laboratory data (Cohort 1) were collected to train the model and carry out internal validation. We compared the models built by five machine learning algorithms and screened out the best models. Receiver operating characteristic (ROC) curves, sensitivity, specificity, and accuracy were used to evaluate the performance of the model. In addition, the NAFLD patients in Cohort 2 (n = 181) were externally verified. ResultsWe finally identified six independent risk factors for predicting NASH, including neutrophil percentage (NEU%), aspartate aminotransferase/alanine aminotransferase (AST/ALT), hematocrit (HCT), creatinine (CREA), uric acid (UA), and prealbumin (PA). The NASH-XGB6 model built using the XGBoost algorithm showed sufficient prediction accuracy, with ROC values of 0.95 (95 % CI, 0.91–0.98) and 0.90 (95 % CI, 0.88–0.93) in Cohort 1 and Cohort 2, respectively. ConclusionsNASH-XGB6 can serve as an effective tool for distinguishing NASH patients from NAFLD patients.

Effectiveness of Resmetirom in Reducing Cholesterol Levels in Patients With Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) associated with metabolic syndrome and increased cardiovascular risk. Resmetirom, a novel liver-directed selective thyroid hormone receptor-β (THR-β) agonist, has shown promise in addressing both hepatic and systemic lipid metabolism. This systematic review and meta-analysis aimed to evaluate the efficacy of resmetirom in improving cholesterol levels in NASH patients. A systematic literature search was conducted across multiple databases including PubMed, Embase, Cochrane Library, andClinicalTrials.gov, identifying three randomized controlled trials for inclusion. The meta-analysis revealed that resmetirom significantly reduced low-density lipoprotein cholesterol (LDL-C) levels compared to placebo (MD: -23.62; 95% CI: -37.32 to -9.93; p < 0.001). Similarly, triglyceride (TG) levels showed a significant reduction in the resmetirom group (MD: -33.86; 95% CI: -47.79 to -19.92; p < 0.001). Importantly, there was no significant difference in the risk of serious adverse events between resmetirom and placebo groups (RR: 1.09; 95% CI: 0.73 to 1.63; p = 0.67). These findings suggest that resmetirom effectively improves lipid profiles in NASH patients without compromising safety. However, the analysis was limited by the small number of studies, all from the same research group, and high heterogeneity in results. Future research should include more diverse studies, longer follow-up periods, and cost-effectiveness evaluations. Despite these limitations, resmetirom shows promise as a potential treatment for managing dyslipidemia and cardiovascular risk in NASH patients, potentially influencing future treatment guidelines for both liver and cardiovascular health in this population.

Identification of necroptosis genes and characterization of immune infiltration in non-alcoholic steatohepatitis

BackgroundThe most common progressive form of non-alcoholic fatty liver disease (NAFLD) is non-alcoholic steatohepatitis (NASH), which is characterized by the development of cirrhosis, and requires liver transplantation. We screened for the differentially expressed necroptosis-related genes in NASH in this study, and analyzed immune infiltration through microarray and bioinformatics analysis to identify potential biomarkers, and explore the molecular mechanisms involved in NASH.MethodsThe GSE24807 microarray dataset of NASH patients and healthy controls was downloaded, and we identified the differentially expressed genes (DEGs). Necroptosis-related differential genes (NRDEGs) were extracted from these DEGs, and functionally annotated by enrichment analyses. The core genes were obtained by constructing gene co-expression networks using weighted gene co-expression network analysis (WGCNA). Finally, the transcription factor (TF) regulatory network and the mRNA-miRNA network were constructed, and the infiltrating immune cell populations were analyzed with CIBERSORT.ResultsWe identified six necroptosis-related genes (CASP1, GLUL, PYCARD, IL33, SHARPIN, and IRF9), and they are potential diagnostic biomarkers for NASH. In particular, PYCARD is a potential biomarker for NAFLD progression. Analyses of immune infiltration showed that M2 macrophages, γδ T cells, and T follicular helper cells were associated with the immune microenvironment of NASH, which is possibly regulated by CASP1, IL33, and IRF9.ConclusionsWe identified six necroptosis-related genes in NASH, which are also potential diagnostic biomarkers. Our study provides new insights into the molecular mechanisms and immune microenvironment of NASH.

PDCD4 deficiency in hepatocytes exacerbates nonalcoholic steatohepatitis through enhanced MHC class II transactivator expression

Nonalcoholic steatohepatitis (NASH) is a primary cause of liver cirrhosis and hepatocellular carcinoma, presenting a significant and unmet medical challenge. The necessity to investigate the molecular mechanisms underlying NASH is highlighted by the observed decrease in programmed cell death 4 (PDCD4) expression in NASH patients, suggesting that PDCD4 may play a protective role in maintaining liver health. In this study, we identify PDCD4 as a natural inhibitor of NASH development in mice. The absence of PDCD4 leads to the spontaneous progression of NASH. Notably, PDCD4-deficient hepatocytes display elevated major histocompatibility complex class II (MHCII) expression due to CIITA activation, indicating that PCDC4 prevents the abnormal transformation of hepatocytes into antigen-presenting cells (APCs). Cell co-culture experiments reveal that hepatocytes lacking PDCD4, which resemble APCs, can directly activate CD4+ T cells by presenting multiple peptides, resulting in the release of inflammatory factors. Additionally, both cellular and animal studies show that CIITA promotes lipid accumulation in hepatocytes and exacerbates NASH progression. In summary, our findings reveal a novel role of PDCD4 in regulating CIITA and MHCII expression during NASH development, offering new therapeutic approaches for NASH treatment.

MiR-378a-3p and miR-181b-5p as nonalcoholic steatohepatitis non-invasive diagnostic biomarkers and their correlations with liver fibrosis

Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases that is diagnosed by biopsy and, therefore, requires the development of non-invasive tests for diagnosis. Serum levels of microRNAs were shown to correlate with the severity of various liver diseases, but the role of miR-378a and miR-181b-5p in NASH remains unclear. The current study aims to assess the serum expression level of miR-378a-3p and miR-181b-5p in patients with NASH and to find out the correlation of these indices with liver fibrosis. The case-control research was carried out on 60 patients with confirmed NASH relative to 50 healthy subjects. Extraction and reverse transcription of micro RNAs was performed using miRCURY LNA RT Kit (Qiagen, Maryland, USA) Detection of miR-378a-3p and miR-181b-5p was done using qPCR. It was shown that serum expression level of miR-378a-3p in NASH patients was downregulated with a median range fold change 0.29, while that of miR-181b-5p was upregulated with a median range fold change 13.08. The ROC curve was constructed to discriminate the NASH group from the healthy group. The optimal cut-off value of miR-378a-3p was ≤0.031 with a sensitivity of 65%, the optimal cut-off value of miR-181b-5p was ≥ 0.063 with a sensitivity of 93.3%. Statistically significant positive correlation between miR-181b-5p level and fibroscan data was demonstrated. The present study showed that serum miR-378a-3p and miR-181b-5p could be used as biomarkers of NASH. Keywords: liver fibrosis, miR-181b-5p, miR-378a-3p, nonalcoholic steatohepatitis (NASH)

Collagen-targeted protein nanomicelles for the imaging of non-alcoholic steatohepatitis

In vivo molecular imaging tools hold immense potential to drive transformative breakthroughs by enabling researchers to visualize cellular and molecular interactions in real-time and/or at high resolution. These advancements will facilitate a deeper understanding of fundamental biological processes and their dysregulation in disease states. Here, we develop and characterize a self-assembling protein nanomicelle called collagen type I binding – thermoresponsive assembled protein (Col1-TRAP) that binds tightly to type I collagen in vitro with nanomolar affinity. For ex vivo visualization, Col1-TRAP is labeled with a near-infrared fluorescent dye (NIR-Col1-TRAP). Both Col1-TRAP and NIR-Col1-TRAP display approximately a 3.8-fold greater binding to type I collagen compared to TRAP when measured by surface plasmon resonance (SPR). We present a proof-of-concept study using NIR-Col1-TRAP to detect fibrotic type I collagen deposition ex vivo in the livers of mice with non-alcoholic steatohepatitis (NASH). We show that NIR-Col1-TRAP demonstrates significantly decreased plasma recirculation time as well as increased liver accumulation in the NASH mice compared to mice without disease over 4 hours. As a result, NIR-Col1-TRAP shows potential as an imaging probe for NASH with in vivo targeting performance after injection in mice. Statement of significanceDirect molecular imaging of fibrosis in NASH patients enables the diagnosis and monitoring of disease progression with greater specificity and resolution than do elastography-based methods or blood tests. In addition, protein-based imaging probes are more advantageous than alternatives due to their biodegradability and scalable biosynthesis. With the aid of computational modeling, we have designed a self-assembled protein micelle that binds to fibrillar and monomeric collagen in vitro. After the protein was labeled with near-infrared fluorescent dye, we injected the compound into mice fed on a NASH diet. NIR-Col1-TRAP clears from the serum faster in these mice compared to control mice, and accumulates significantly more in fibrotic livers.This work advances the development of targeted protein probes for in vivo fibrosis imaging.

Cardiovascular risk in US adults with nonalcoholic steatohepatitis (NASH) vs. matched non-NASH controls, National Health and Nutrition Examination Survey, 2017-2020.

NASH is considered a contributor to atherosclerotic cardiovascular disease (ASCVD) risk; however, its contribution beyond traditional risk factors for CVD, particularly diabetes, is less clearly understood. This study aimed to quantify the cardiovascular-event risk associated with NASH, independent of diabetes status. A cross-sectional analysis was conducted using the 2017-2020 NHANES pre-pandemic cycle. NASH was defined based on presence of steatosis without other causes of liver disease, and FibroScan+AST score from vibration-controlled transient elastography (VCTE). Significant fibrosis (stages F2-F4) was identified by liver stiffness measurement from VCTE. Predicted primary CV-event risk was estimated using both the Pooled Cohort Equations (PCE) and the Framingham Risk Score (FRS). NASH patients were matched with non-NASH controls on age, sex, race/ethnicity, and diabetes status. Weighted logistic regression was conducted, modeling elevated predicted CV risk (binary) as the dependent variable and indicators for NASH / fibrosis stages as independent variables. A sample of 125 NASH patients was matched with 2585 controls. NASH with significant fibrosis was associated with elevated predicted 10-year CV risk, although this association was only statistically significant in PCE analyses (odds ratio and 95% CI 2.34 [1.25, 4.36]). Analyses restricting to ages <65 years showed similar results, with associations of greater magnitude. Independent of diabetes, a significant association was observed between NASH with significant liver fibrosis and predicted primary CV-event risk in US adults, particularly for those <65. These findings suggest the importance of accounting for NASH and liver-fibrosis stage in predicting CV-event risk.

Non-alcoholic fatty liver disease and heart failure: A comprehensive bioinformatics and Mendelian randomization analysis.

Heart failure (HF) and non-alcoholic fatty liver disease (NAFLD) are significant global health issues with a complex interrelationship. This study investigates their shared biomarkers and causal relationships using bioinformatics and Mendelian randomization (MR) approaches. We analysed NAFLD and HF datasets from the Gene Expression Omnibus (GEO). The GSE126848 dataset included 57 liver biopsy samples [14 healthy individuals, 12 obese subjects, 15 NAFL patients and 16 non-alcoholic steatohepatitis (NASH) patients]. The GSE24807 dataset comprised 12 NASH samples and 5 healthy controls. The GSE57338 dataset included 313 cardiac muscle samples [177 HF patients (95 ischaemic heart disease patients and 82 idiopathic dilated cardiomyopathy patients) and 136 healthy controls]. The GSE84796 dataset consisted of 10 end-stage HF patients and 7 healthy hearts procured from organ donors. We identified differentially expressed genes (DEGs) and constructed a protein-protein interaction (PPI) network. Functional pathways were elucidated through enrichment analyses using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneMANIA annotation. Single nucleotide polymorphism (SNP) data for HF and NAFLD were sourced from genome-wide association studies (GWAS). The HF dataset included 486160 samples (14262 experimental and 471898 control), and the NAFLD dataset comprised 377988 samples (4761 experimental and 373227 control). MR analysis investigates the causal interrelations. Our analysis revealed 4032 DEGs from GSE126848 and 286 DEGs from GSE57338. The top 10 hub genes (CD163, VSIG4, CXCL10, FCER1G, FPR1, C1QB, CCR1, C1orf162, MRC1 and CD38) were significantly enriched in immune response, calcium ion concentration regulation and positive regulation of monocyte chemotaxis. CIBERSORT analysis indicated associations between these hub genes and natural killer (NK) cells and macrophages. Transcription factor (TF) target prediction for CD38, CXCL10 and CCR1 highlighted related TFs. A two-sample MR analysis confirmed a bidirectional causal relationship between NAFLD and HF. The main method [inverse variance weighted (IVW)] demonstrated a significant positive causal relationship between NAFLD and HF [P=0.037; odds ratio (OR)=1.024; 95% confidence interval (CI): 1.001 to 1.048]. Similarly, HF was associated with an increase in the risk of NAFLD (P<0.001; OR=1.117; 95% CI: 1.053 to 1.185). Our findings reveal novel molecular signatures common to NAFLD and HF and confirm their bidirectional causality, highlighting the potential for targeted therapeutic interventions and prompting further investigation into their intricate relationship.

The role of C5aR1-mediated hepatic macrophage efferocytosis in NASH

Non-alcoholic fatty liver disease (NAFLD) has become the first major chronic liver disease in developed countries. 10–20% of NAFLD patients will progress to non-alcoholic steatohepatitis (NASH), and up to 25% of NASH patients may develop cirrhosis within 10 years. Therefore, it is critical to find key targets that may treat this disease. Here, we identified C5aR1 as a highly-expressed gene in NASH mouse model through analyzing Gene Expression Omnibus (GEO) database and confirmed its higher expression in livers of NASH patients than that of NAFL patients. Meanwhile, we verified its positive correlation with patients’ serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. In vivo and in vitro experiments revealed that knocking down C5aR1 in liver significantly reduced liver weight ratio and serum ALT and AST levels and attenuated inflammatory cell infiltration and cell apoptosis in the liver of NASH mice as well as enhanced the efferocytotic ability of liver macrophages, suggesting that C5aR1 may play a crucial role in the efferocytosis of liver macrophages. Furthermore, we also found that the expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3), caspase-1, IL-1β and other inflammation-related factors in the liver were significantly reduced. Our work demonstrates a potential mechanism of how C5aR1 deficiency protects against diet-induced NASH by coordinating the regulation of inflammatory factors and affecting hepatic macrophage efferocytosis.

Genotypic variation in CYP2E1, GCKR, and PNPLA3 among nonalcoholic steatohepatitis patients of Turkish origin.

This study examines genetic variations in CYP2E1 (rs6413432, rs3813867), GCKR (rs780094, rs1260326), and PNPLA3 (rs738409) among Turkish patients to assess their influence on nonalcoholic steatohepatitis. Allele and genotype frequencies were compared between 245 NASH patients and 120 healthy controls using SNP genotyping via polymerase chain reaction-restriction fragment length polymorphism. Additionally, the deviation of the observed genotype frequencies from Hardy-Weinberg proportion was examined. No significant differences were found in the allelic and genotypic distributions of rs6413432, rs3813867, and rs780094 between NASH patients and healthy controls. However, significant disparities were noted for rs1260326 and rs738409. Gender and age-specific distributions showed no notable differences. The only observed deviation from Hardy-Weinberg proportion was in the genotype frequency of rs738409. Variants in GCKR (rs1260326) and PNPLA3 (rs738409) are significantly associated with increased NASH risk in the Turkish population, with the rs738409 variant potentially playing a more prominent role in NASH development.

Diagnostic Role of Non-Invasive Risk Scores in Prediction of Simple Steatosis versus Non-Alcoholic Steatohepatitis

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is currently considered one of the most common liver diseases in the Western world. NAFLD includes a spectrum of diseases from simple fatty liver disease, to non-alcoholic steatohepatitis (NASH), liver cirrhosis and hepatocellular carcinoma (HCC). NASH, the critical stage in NAFLD progression, is the only bridge between NAFLD and liver cirrhosis, and its persistent existence has become one of the leading causes of liver cirrhosis and even HCC. Aim of the Work To assess the value of non-invasive risk scores in differentiation between simple steatosis and NASH Patients and Methods This was prospective cohort study, conducted Internal Medicine and Gastroenterology outpatient clinics and ward in Ain Shams University Hospitals, on 60 patients with NAFLD divided into 2 groups: (Group I): Patients with normal liver enzymes, (Group II): Patients with persistant elevation of liver enzymes, during a period of 6 months. Results There was statistically insignificant difference between the two studied groups and sex and age. There were 12 (40%) of the group I were males and 18 (60.0%) were females. There were 16(53.3%) of the group II were males and 14(46.7%) were females. The mean age of group I was 40.63 ± 10.53 SD with range (25.0 – 59.0). The mean age of group II was 40.83 ± 9.06SD with range (27.0 – 54.0). There was statistically significant difference between the two studied groups and weight, BMI and waist circumference. There was statistically insignificant difference between the two studied groups and height, DM and HTN. There was statistically significant difference between the two studied groups and ALT, AST, GGT, ALP, ALB and Platelets. There was statistically significant difference between the two studied groups and TC, HDL, LDL, TG and AST/ALT ratio. There was statistically insignificant difference between the two studied groups and FBG. There was statistically significant difference between the two studied groups and FLI, NFS, BARD, APRI, FIB-4 and Fibrosis score. There was statistically significant difference between the two studied groups and Ultrasound (Size, Findings and Fibrosis score). The mean size in group I was 10.03 ± 1.56 SD with range (8.0 – 12.0). The mean size in group II was 13.63 ± 1.22SD with range (12.0 – 16.0). Conclusion A combination of Fibroscan, Fib-4, NFS, BARD and APRI provides a valuable non- invasive method in diagnosis of NASH patients, and this can eliminate the need for liver biopsy in patients without clear indication, BMI, platelet count, HDL cholesterol level, ALT level, and the AST/ALT ratio were independent predictors of NAFLD.

Study of Plasma Pentraxin Levels as a Novel Marker versus Liver Stiffness for Nonalcoholic Steatohepatitis (NASH) in Egyptian Patients

Abstract Background Nonalcoholic fatty liver disease (NAFLD) includes a variety of histopathological findings ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which can only be differentiated by liver biopsy. There is yet no unique biomarker found to discriminate NASH from simple steatosis. We aimed to investigate the relationship of plasma pentraxin 3 (PTX3) and liver elasticity measured by fibroscan both with the degree of liver damage in NAFLD. Methods Plasma PTX3 levels &amp; fibroscan measurements were estimated in 60 patients with NAFLD (30 with NASH, 30 with non-NASH) and 20 controls Results PTX3 levels were found significantly higher in the NAFLD group than in the control group (3.59 ± 1.77 vs. 1.16 + –0.29 ng/mL, P &amp;lt; 0.001), and in NASH subgroup than non-NASH subgroup (4.97 + –1.36 vs. 21 + –.75 ng/mL, P = 0.001). To discriminate NASH from non-NASH PTX3 had 96.67% sensitivity and 93.33% specificity at the cutoff value of 3.1 ng/mL. Plasma PTX3 levels showed no significant correlation with NAFLD activity score, fibrosis stage and steatosis. Conclusion This study demonstrated markedly higher PTX3 levels in NAFLD patients compared with controls, and in NASH patients compared with non-NASH ones and no correlation wih fibroscan stages. Thus, in this cohort we showed that plasma PTX3 may be a promising biomarker for the presence of NASH.

Association between paravertebral muscle radiological parameter alterations and non-alcoholic fatty liver disease.

To assess changes in laboratory indices, paravertebral muscle (PVM) fat infiltration and multi b-value DWI parameters and their potential correlation with NAFLD. This retrospective analysis included 178 patients with histopathologically confirmed NAFLD, incluiding 76 with non-alcoholic steatohepatitis (NASH). Differences in PVM fat infiltration ratio (FIR), DWI parameters, and laboratory indices were compared between two groups. The correlation between FIR and NAFLD activity score (NAS) was also analysed. Binary logistic regression was used to identify the independent risk factors for NASH. The clinical utility of PVM fat infiltration, DWI parameters, and laboratory indices for diagnosing NASH in patients with NAFLD was evaluated using receiver operating characteristic (ROC) curves. The FIRs at the L2 and L3 levels were significantly higher in the with NASH group than those in the without NASH group. The heterogeneity index (α) and perfusion fraction (f) values at the L3 level of PVM were lower in the with NASH group. Moreover, the FIR at the L3 level was positively correlated with NAS. FIR at the L3 level was an independent risk factor for NASH along with alanine aminotransferase level. The area under the ROC curve (AUC) using L3 level PVM radiological parameters and laboratory indices for diagnosing NASH in patients with NAFLD was significantly higher than that using the degree of PVM fat infiltration, DWI parameters, or laboratory indices alone. Radiological parameters of the PVM were correlated with NAFLD. An integrated curve combining PVM radiological parameters may help distinguish NASH from NAFLD, thereby offering novel insights into the diagnosis of NASH.

EE462 Healthcare Utilization in Non-Alcoholic Steatohepatitis (NASH) Patients with Elevated Nafld Activity Score (NAS): Impact of Fibrosis Levels

EE462 Healthcare Utilization in Non-Alcoholic Steatohepatitis (NASH) Patients with Elevated Nafld Activity Score (NAS): Impact of Fibrosis Levels

Machine Learning Approach for Cardiovascular Death Prediction among Nonalcoholic Steatohepatitis (NASH) Liver Transplant Recipients.

Cardiovascular disease is the leading cause of mortality among nonalcoholic steatohepatitis (NASH) patients who undergo liver transplants. In the present study, machine learning algorithms were used to identify important risk factors for cardiovascular death and to develop a prediction model. The Standard Transplant Analysis and Research data were gathered from the Organ Procurement and Transplantation Network. After cleaning and preprocessing, the dataset comprised 10,871 patients and 92 features. Recursive feature elimination (RFE) and select from model (SFM) were applied to select relevant features from the dataset and avoid overfitting. Multiple machine learning algorithms, including logistic regression, random forest, decision tree, and XGBoost, were used with RFE and SFM. Additionally, prediction models were developed using a support vector machine, Gaussian naïve Bayes, K-nearest neighbors, random forest, and XGBoost algorithms. Finally, SHapley Additive exPlanations (SHAP) were used to increase interpretability. The findings showed that the best feature selection method was RFE with a random forest estimator, and the most critical features were recipient and donor blood type, body mass index, recipient and donor state of residence, serum creatinine, and year of transplantation. Furthermore, among all the outcomes, the XGBoost model had the highest performance, with an accuracy value of 0.6909 and an area under the curve value of 0.86. The findings also revealed a predictive relationship between features and cardiovascular death after liver transplant among NASH patients. These insights may assist clinical decision-makers in devising strategies to prevent cardiovascular complications in post-liver transplant NASH patients.

Sphingosine d18:1 promotes nonalcoholic steatohepatitis by inhibiting macrophage HIF-2α

Non-alcoholic steatohepatitis (NASH) is a severe type of the non-alcoholic fatty liver disease (NAFLD). NASH is a growing global health concern due to its increasing morbidity, lack of well-defined biomarkers and lack of clinically effective treatments. Using metabolomic analysis, the most significantly changed active lipid sphingosine d18:1 [So(d18:1)] is selected from NASH patients. So(d18:1) inhibits macrophage HIF-2α as a direct inhibitor and promotes the inflammatory factors secretion. Male macrophage-specific HIF-2α knockout and overexpression mice verified the protective effect of HIF-2α on NASH progression. Importantly, the HIF-2α stabilizer FG-4592 alleviates liver inflammation and fibrosis in NASH, which indicated that macrophage HIF-2α is a potential drug target for NASH treatment. Overall, this study confirms that So(d18:1) promotes NASH and clarifies that So(d18:1) inhibits the transcriptional activity of HIF-2α in liver macrophages by suppressing the interaction of HIF-2α with ARNT, suggesting that macrophage HIF-2α may be a potential target for the treatment of NASH.

Impact of Pentoxifylline Therapy on the Quality of Life in Nonalcoholic Steatohepatitis Patients

Impact of Pentoxifylline Therapy on the Quality of Life in Nonalcoholic Steatohepatitis Patients

Predicting Non-Alcoholic Steatohepatitis: A Lipidomics-Driven Machine Learning Approach.

Nonalcoholic fatty liver disease (NAFLD), nowadays the most prevalent chronic liver disease in Western countries, is characterized by a variable phenotype ranging from steatosis to nonalcoholic steatohepatitis (NASH). Intracellular lipid accumulation is considered the hallmark of NAFLD and is associated with lipotoxicity and inflammation, as well as increased oxidative stress levels. In this study, a lipidomic approach was used to investigate the plasma lipidome of 12 NASH patients, 10 Nonalcoholic Fatty Liver (NAFL) patients, and 15 healthy controls, revealing significant alterations in lipid classes, such as glycerolipids and glycerophospholipids, as well as fatty acid compositions in the context of steatosis and steatohepatitis. A machine learning XGBoost algorithm identified a panel of 15 plasma biomarkers, including HOMA-IR, BMI, platelets count, LDL-c, ferritin, AST, FA 12:0, FA 18:3 ω3, FA 20:4 ω6/FA 20:5 ω3, CAR 4:0, LPC 20:4, LPC O-16:1, LPE 18:0, DG 18:1_18:2, and CE 20:4 for predicting steatohepatitis. This research offers insights into the connection between imbalanced lipid metabolism and the formation and progression of NAFL D, while also supporting previous research findings. Future studies on lipid metabolism could lead to new therapeutic approaches and enhanced risk assessment methods, as the shift from isolated steatosis to NASH is currently poorly understood.