Nonalcoholic Fatty Liver Disease Group Research Articles

Serum bile acid and unsaturated fatty acid profiles of non-alcoholic fatty liver disease in type 2 diabetic patients

BACKGROUND The understanding of bile acid (BA) and unsaturated fatty acid (UFA) profiles, as well as their dysregulation, remains elusive in individuals with type 2 diabetes mellitus (T2DM) coexisting with non-alcoholic fatty liver disease (NAFLD). Investigating these metabolites could offer valuable insights into the pathophysiology of NAFLD in T2DM. AIM To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM. METHODS A training model was developed involving 399 participants, comprising 113 healthy controls (HCs), 134 individuals with T2DM without NAFLD, and 152 individuals with T2DM and NAFLD. External validation encompassed 172 participants. NAFLD patients were divided based on liver fibrosis scores. The analytical approach employed univariate testing, orthogonal partial least squares-discriminant analysis, logistic regression, receiver operating characteristic curve analysis, and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers. RESULTS Compared to HCs, both T2DM and NAFLD groups exhibited diminished levels of specific BAs. In UFAs, particular acids exhibited a positive correlation with NAFLD risk in T2DM, while the ω-6:ω-3 UFA ratio demonstrated a negative correlation. Levels of α-linolenic acid and γ-linolenic acid were linked to significant liver fibrosis in NAFLD. The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients. CONCLUSION This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM, proposing their potential as biomarkers in the pathogenesis of NAFLD.

Cultivated Enterococcus faecium B6 from children with obesity promotes nonalcoholic fatty liver disease by the bioactive metabolite tyramine

ABSTRACT Gut microbiota plays an essential role in nonalcoholic fatty liver disease (NAFLD). However, the contribution of individual bacterial strains and their metabolites to childhood NAFLD pathogenesis remains poorly understood. Herein, the critical bacteria in children with obesity accompanied by NAFLD were identified by microbiome analysis. Bacteria abundant in the NAFLD group were systematically assessed for their lipogenic effects. The underlying mechanisms and microbial-derived metabolites in NAFLD pathogenesis were investigated using multi-omics and LC-MS/MS analysis. The roles of the crucial metabolite in NAFLD were validated in vitro and in vivo as well as in an additional cohort. The results showed that Enterococcus spp. was enriched in children with obesity and NAFLD. The patient-derived Enterococcus faecium B6 (E. faecium B6) significantly contributed to NAFLD symptoms in mice. E. faecium B6 produced a crucial bioactive metabolite, tyramine, which probably activated PPAR-γ, leading to lipid accumulation, inflammation, and fibrosis in the liver. Moreover, these findings were successfully validated in an additional cohort. This pioneering study elucidated the important functions of cultivated E. faecium B6 and its bioactive metabolite (tyramine) in exacerbating NAFLD. These findings advance the comprehensive understanding of NAFLD pathogenesis and provide new insights for the development of microbe/metabolite-based therapeutic strategies.

Diagnostic and prognostic value of NT-proBNP in patients with non-alcoholic fatty liver disease and acute decompensated heart failure

Abstract Funding Acknowledgements None. Aim To study N-terminal propeptide natriuretic hormone (NT-proBNP) values in patients with non-alcoholic fatty liver disease (NAFLD) with acute decompensated heart failure (ADHF) at admission and discharge to evaluate its impact on clinical outcomes. Material and methods Included were 566 patients hospitalized with ADHF, functional classes II–IV (NYHA) [49,3% men, mean age 72,4 ± 11.4 years, left ventricular ejection fraction (LVEF) - 45 (33; 55) %. Patients were divided into 2 groups: 1 – ADHF and NAFLD (n=168), 2 – ADHF without NAFLD (n=398). All patients had NT-proBNP levels determined upon admission and discharge. The degree of liver steatosis was determined using a sensor device using the CAP (Controlled Attenuation Parameter) ultrasound option. Threshold CAP values corresponded to the degree of hepatic steatosis - S0 (<294 dB/m), S1 (295-309 dB/m), S2 (310-330 dB/m), S3 (≥331 dB/m). Results NAFLD was diagnosed in 29.7% of all patients. The incidence of NAFLD was higher in patients with preserved LVEF - 43% vs 25% - reduced LVEF. Patients with severe steatosis (S3) had significantly lower NT-proBNP values than patients with moderate steatosis (S1,S2) and no steatosis (S0) at admission [926 (256;1870) pg/ml, 1246 (298; 2000) pg/ml, 1850 (798;3515) pg/ml, respectively, p<0.001] and at discharge [480 (107;1406) pg/ml, 1077 (250;1649) pg/ml, 1685 (628;2733) ) pg/ml, respectively, p<0.001]. In patients with NAFLD and ADHF, according to multivariate Cox regression analysis, NTproBNP level >1593 pg/ml at discharge (hazard ratio (HR) 3.14; 95% confidence interval (CI) 1.52– 6.43; p<0.001) and LVEF<40% (HR 2.90; 95% CI 1.46–5.76; p=0.002) were independently associated with a higher likelihood of all-cause death during the 3-year follow-up period. Conclusions NAFLD and ADHF group was characterized by lower NT-proBNP values, with an inverse correlation with the degree of steatosis, which may complicate timely diagnosis and prescription of adequate therapy. At the same time, assessment of NTproBNP and LVEF values in patients with ADHF and NAFLD at discharge had an important prognostic role for stratifying by risk of death from all causes during the observed period, despite lower NTproBNP threshold values.

Association between non-alcoholic fatty liver disease and risk of sarcopenia: a systematic review and meta-analysis

ObjectivesTo determine the association of non-alcoholic fatty liver disease (NAFLD) with the incidence of sarcopenia.DesignSystematic review and meta-analysis of observational clinical studies.Setting and participantsAdults with NAFLD.MethodsDatabases such as PubMed, Embase,...

Therapeutic potential of Lactobacillus casei and Chlorella vulgaris in high-fat diet-induced non-alcoholic fatty liver disease (NAFLD)-associated kidney damages: a stereological study.

The non-alcoholic fatty liver disease (NAFLD) is prevalent in as many as 25% of adults who are afflicted with metabolic syndrome. Oxidative stress plays a significant role in the pathophysiology of hepatic and renal injury associated with NAFLD. Therefore, probiotics such as Lactobacillus casei (LBC) and the microalga Chlorella vulgaris (CV) may be beneficial in alleviating kidney injury related to NAFLD. This animal study utilized 30 C57BL/6 mice, which were evenly distributed into five groups: the control group, the NAFLD group, the NAFLD + CV group, the NAFLD + LBC group, and the NAFLD + CV + LBC group. A high-fat diet (HFD) was administered to induce NAFLD for six weeks. The treatments with CV and LBC were continued for an additional 35 days. Biochemical parameters, total antioxidant capacity (TAC), and the expression of kidney damage marker genes (KIM 1 and NGAL) in serum and kidney tissue were determined, respectively. A stereological analysis was conducted to observe the structural changes in kidney tissues. A liver histopathological examination confirmed the successful induction of NAFLD. Biochemical investigations revealed that the NAFLD group exhibited increased ALT and AST levels, significantly reduced in the therapy groups (p < 0.001). The gene expression levels of KIM-1 and NGAL were elevated in NAFLD but were significantly reduced by CV and LBC therapies (p < 0.001). Stereological examinations revealed reduced kidney size, volume, and tissue composition in the NAFLD group, with significant improvements observed in the treated groups (p < 0.001). This study highlights the potential therapeutic efficacy of C. vulgaris and L. casei in mitigating kidney damage caused by NAFLD. These findings provide valuable insights for developing novel treatment approaches for managing NAFLD and its associated complications.

Diagnostic performances of Fibrosis-4 index and nonalcoholic fatty liver disease fibrosis score in metabolic dysfunction-associated steatotic liver disease in Asian primary care clinics.

We aimed to explore the extent to which individuals previously diagnosed with nonalcoholic fatty liver disease (NAFLD) meet the criteria fulfilled with the new nomenclature, metabolic dysfunction-associated steatotic liver disease (MASLD), within an Asian primary clinic cohort. Additionally, we assessed the reliability of the diagnostic performance of FIB-4 and NAFLD fibrosis score (NFS) for MASLD within the primary clinic cohort. This retrospective cross-sectional study included participants who underwent magnetic resonance elastography and abdominal ultrasonography during their health checkups at nationwide health promotion centers (n=6740). The prevalence rates of NAFLD and MASLD diagnosed based on ultrasonography results were 36.7% and 38.0%, respectively. Notably, 96.8% of patients in the NAFLD cohort fulfilled the new criteria for MASLD. A small proportion of patients with NAFLD (n=80, 3.2%) did not meet the MASLD criteria. Additionally, 168 patients (6.6%) were newly added to the MASLD group. The areas under the receiver operating characteristic curves for diagnosing advanced hepatic fibrosis for FIB-4 (0.824 in NAFLD vs. 0.818 in MASLD, p=0.891) and NFS (0.803 in NAFLD vs. 0.781 in MASLD, p=0.618) were comparable between the MASLD and NAFLD groups. Furthermore, the sensitivity, specificity, positive predictive value, and negative predictive value of FIB-4 and NFS for advanced fibrosis in MASLD were also comparable to those in NAFLD. Most patients (96.8%) previously diagnosed with NAFLD fulfilled the new criteria for MASLD in an Asian primary clinic cohort. Diagnostic performance of FIB-4 in the MASLD cohort demonstrated satisfactory results.

Serum Vitamin D Level in Overweight Individuals and Its Correlation With the Incidence of Non-alcoholic Fatty Liver Disease

In this study, we investigated the serum vitamin D level in overweight individuals and its correlation with the incidence of nonalcoholic fatty liver disease (NAFLD). Between May 2020 and May 2021, the Department of Gastroenterology at the People’s Hospital of Henan University of Traditional Chinese Medicine treated a total of 321 outpatients and inpatients with NAFLD, who were included in the NAFLD group, while 245 healthy age- and gender-matched individuals were included in the control group. All the data were collected for the relevant indices, including fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine transaminase, and 25-hydroxy vitamin D (25[OH]D. The patients with NAFLD were divided into the normal BMI group, the overweight group, and the obese group, according to the body mass index, and the 25(OH)D levels were compared between the different groups. Spearman’s correlation analysis was performed to analyze the correlation between the serum 25(OH)D level and NAFLD. Regarding the serum 25 (OH)D level, it was lower in the NAFLD group than in the control group ([18.36 + 1.41] µg/L vs [22.33 + 2.59] µg/L, t = −5.15, P&lt;0.001), and was lower in the overweight group than in the normal group ([18.09 ± 5.81] µg/L vs [20.60 ± 4.16] µg/L, t = 0.26, P = 0.041). The serum 25(OH)D level was thus negatively correlated with the incidence of NAFLD in overweight individuals (r = 0.625, P&lt;0.05). In conclusion, the level of 25(OH)D decreased in patients with NAFLD with increasing BMI (normal, overweight, obese). Keywords: Nonalcoholic fatty liver disease • Vitamin D

Non–small cell lung cancer and immune checkpoint inhibitor therapy: does non-alcoholic fatty liver disease have an effect?

BackgroundImmunotherapy based on the application of immune checkpoint inhibitors (ICIs) is one of the standard treatments for advanced non-small cell lung cancer (NSCLC). Non-alcoholic fatty liver Disease (NAFLD) has demonstrated predictive value for response to immunotherapy in non-lung cancer types. Our study investigated the effect of NAFLD on the efficacy of real-life use of ICIs for patients with stage III / IV NSCLC.MethodsThe clinical and imaging data of patients with stage III / IV NSCLC who were first admitted to Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 2020 to July 2022 were retrospectively collected to ensure that they underwent at least one CT scan before treatment. A total of 479 patients were divided into the NAFLD group (Liver/Spleen density ratio ≤ 1) and the non-NAFLD group (Liver/Spleen density ratio > 1) by measuring the baseline liver and spleen CT value. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) of the patients were obtained.ResultsA total of 118 patients with NAFLD and 361 patients without NAFLD were included in the study. Patients with NAFLD tended to have higher BMI and higher total bilirubin compared to patients without NAFLD. The median duration of follow-up in the study was 22 m (IQR, 17–29 m). Both of 2 groups had a higher DCR (94% vs. 92%, p = 0.199) and ORR (38.1% vs. 44.9%, p = 0.452) respectively. There was no difference in efficacy between the two groups. In univariate analysis, NAFLD had no significant effect on PFS (p = 0.785) and OS (p = 0.851). Surprisingly, the presence of hypertension was observed to be associated with a higher OS (HR 1.471 95%CI 1.018–2.127, p = 0.040). Besides, based on multivariate analysis, lactic dehydrogenase was associated with PFS (HR 1.001 95%CI 1.000,1.002, p = 0.037) and OS (HR 1.002, 95%CI 1.001–1.003, p < 0.001).ConclusionsAmong patients with NSCLC, NAFLD did not result in changes in survival or disease progression after immune checkpoint inhibitor therapy.

Synthesis and biological evaluation of a novel 68Ga-labeled GalNAc-PET probe for asialoglycoprotein receptor imaging

PurposeThe asialoglycoprotein receptor (ASGPR), expressed exclusively on mammalian hepatocyte membranes, recognizes ligands terminated with β-D-galactose (Gal) and N-acetylglucosamine (GalNAc). This study aims to develop a 68Ga-labeled monovalent GalNAc derivative that particularly interacts with ASGPR. It also aims to assess the potential utility of this derivative in visualizing ASGPR-related liver dysfunction using positron emission tomography (PET)/ computed tomography (CT) imaging. MethodsThe PET imaging probe 68Ga-NOTA-GalNAc was developed and characterized with regard to radiochemical purity, biocompatibility, biodistribution patterns, and specific ASGPR-targeting ability. Groups of normal mice, mice with acute liver injury (ALI) induced by CCl4, mice with early-stage liver fibrosis induced by CCl4, mice with nonalcoholic fatty liver disease (NAFLD), and orthotopic HepG2 hepatoma-bearing mice were imaged with 68Ga-NOTA-GalNAc PET to evaluate the potential of this technique in monitoring ASGPR-related liver dysfunction. Results68Ga-NOTA-GalNAc, a hydrophilic compound with high radiochemical purity (>99 %) and good liver targeting ability, particularly binds ASGPR on the surface of hepatocytes with moderate affinity (KD = 6.82 μM). Compared with control, ASGPR-related liver dysfunction groups, even the group of mice with ALI (P <0.0001), revealed sensitive distinctions in the liver uptake value of 68Ga-NOTA-GalNAc. The 68Ga-NOTA-GalNAc absorbed in the livers of mice with early-stage liver fibrosis and NAFLD group is significantly less than that absorbed in the livers of mice in the normal group (P <0.0001). Hepatoma can be visualized in orthotopic HepG2 hepatoma-bearing mice because of different radioactivity accumulated in the nontumor region and lesion region, corresponding to the ASGPR expression confirmed with immunohistochemical staining. Conclusion68Ga-NOTA-GalNAc has the potential to be a specific, noninvasive, and sensitive PET imaging agent for ASGPR-related liver dysfunction.

Neutrophil to albumin ratio: a biomarker in non-alcoholic fatty liver disease and with liver fibrosis.

Given the high prevalence of non-alcoholic fatty liver disease (NAFLD) and its potential to progress to liver fibrosis, it is crucial to identify the presence of NAFLD in patients to guide their subsequent management. However, the current availability of non-invasive biomarkers for NAFLD remains limited. Therefore, further investigation is needed to identify and develop non-invasive biomarkers for NAFLD. A retrospective analysis was conducted on 11,883 patients admitted to the Healthcare Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2016 to December 2019 and divided into NAFLD and non-NAFLD groups. Anthropometric and laboratory examination data were collected. The correlations between variables and NAFLD were evaluated using the student's t-test or Mann-Whitney U test and binary logistic regression analysis. The predictive ability of these variables for NAFLD was assessed using the areas under the curves (AUCs) of receiver operating characteristics. Among the included patients, 3,872 (32.58%) were diagnosed with NAFLD, with 386 (9.97%) individuals having liver fibrosis. Patients with NAFLD exhibited a higher proportion of males, elevated body mass index (BMI), and increased likelihood of hypertension, diabetes mellitus, and atherosclerosis. Logistic regression analysis identified the neutrophil to albumin ratio (NAR) as the most promising novel inflammation biomarkers, with the highest AUC value of 0.701, a cut-off value of 0.797, sensitivity of 69.40%, and specificity of 66.00% in identifying the risk of NAFLD. Moreover, NAR demonstrated superior predictive value in identifying NAFLD patients at risk of liver fibrosis, with an AUC value of 0.795, sensitivity of 71.30%, and specificity of 73.60% when NAR reached 1.285. These findings highlight that the novel inflammatory biomarker, NAR, is a convenient and easily accessible non-invasive predictor for NAFLD and NAFLD with liver fibrosis.

Value of constructing a non-invasive diagnostic model based on serum heme oxygenase-1 and glucose regulatory protein 78 for non-alcoholic fatty liver disease

Objective: To analyze the clinical application value of serum heme oxygenase (HO)-1expression level in non-alcoholic fatty liver disease (NAFLD) and, based on that, establish a diagnostic model combined with glucose regulatory protein 78 (GRP78) so as to clarify its diagnostic effectiveness and application value. Methods: A total of 210 NAFLD patients diagnosed by abdominal B-ultrasound and liver elastography were included, and at the same time, 170 healthy controls were enrolled. The general clinical data, peripheral blood cell counts, and biochemical indicators of the research subjects were collected. The expression levels of HO-1 and GRP78 were detected using an enzyme-linked immunosorbent assay. Multivariate analysis was used to screen independent risk factors for NAFLD. Visual output was performed through nomogram diagrams, and the diagnostic model was constructed. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA) were used to evaluate the diagnostic effectiveness of NAFLD. Measurement data were analyzed using a t-test or Mann-Whitney U rank sum test to detect data differences between groups. Enumeration data were analyzed using the Fisher's exact probability test or the Pearson χ(2) test. Results: Compared with the healthy control group, the white blood cell count, aspartate aminotransferase (AST), alanine aminotransferase, gamma-glutamyl transferase (GTT), fasting blood glucose (Glu), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), serum HO-1, and GRP78 levels were significantly increased in the NAFLD group patients (P < 0.05). Binary logistic analysis results showed that AST, TG, LDL-C, serum HO-1, and GRP78 were independent risk factors for NAFLD (P < 0.05). A nomogram clinical predictive model HGATL was established using HO-1 (H), GRP78 (G) combined with AST (A), TG (T), and LDL-C (L), with the formula P=-21.469+3.621×HO-1+0.116 ×GRP78+0.674×AST+6.250×TG+4.122 ×LDL-C. The results confirmed that the area under the ROC curve of the HGATL model was 0.965 8, with an optimal cutoff value of 81.69, a sensitivity of 87.06%, a specificity of 92.82%, a P < 0.05, and the diagnostic effectiveness significantly higher than that of a single indicator. The calibration curve and DCA both showed that the model had good diagnostic performance. Conclusion: The HGATL model can be used as a novel, non-invasive diagnosis model for NAFLD and has a positive application value in NAFLD diagnosis and therapeutic effect evaluation. Therefore, it should be explored and promoted in clinical applications.

Non-Alcoholic Fatty Liver Disease May Be a Risk Factor for Liver Metastasis After Radical Surgery for Colorectal Cancer: A Retrospective Study.

Distant metastasis develops in approximately one-third of patients with colorectal cancer (CRC) who undergo radical surgery, and colorectal liver metastasis (CRLM) is the most common form of distant metastasis in CRC. Hepatectomy is the only potentially curative treatment for CRLM, but few patients with metastatic CRC meet the criteria for this radical resection, and the 5-year survival rate is poor. Identifying risk factors for CRLM is critical. Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for CRC. However, the effect of NAFLD on CRC liver metastasis after radical surgery remains unclear. Therefore, we examined the impact of NAFLD-associated hepatic fibrosis on liver metastasis after radical surgery for CRC. We retrospectively analyzed data from 388 patients who underwent curative surgery for CRC at our hospital between April 2008 and March 2015. The patients' clinical results, surgical procedures, postoperative course, and pathological and survival data were collected from the hospital records. The NAFLD fibrosis score was calculated and used to divide the patients into two groups (NAFLD and non-NAFLD). Recurrence was observed in 83/388 (21.4%) patients after a mean follow-up of 65.6 ± 15.1months. Twenty-five patients had liver metastasis: 8 in the NAFLD group (8/45; 17.8%) and 17 in the non-NALFD group (17/343; 5.0%) (p = 0.004). Liver metastasis-free survival was significantly worse in the NAFLD than non-NAFLD group (p < 0.001). NAFLD and cancer stage were independent risk factors for liver metastasis recurrence. NAFLD may be a risk factor for liver metastasis in patients with CRC who undergo curative surgery.

Nonalcoholic fatty liver disease is an independent risk factor for ischemic stroke after revascularization in patients with Moyamoya disease: a prospective cohort study

BackgroundThe study aimed to investigate the association between nonalcoholic fatty liver disease (NAFLD) and ischemic stroke events after revascularization in patients with Moyamoya disease (MMD).MethodsThis study prospectively enrolled 275 MMD patients from September 2020 to December 2021. Patients with alcoholism and other liver diseases were excluded. NAFLD was confirmed by CT imaging or abdominal ultrasonography. Stroke events and modified Rankin Scale (mRS) scores at the latest follow-up were compared between the two groups.ResultsA total of 275 patients were enrolled in the study, among which 65 were diagnosed with NAFLD. Univariate logistic regression analysis showed that NAFLD (P = 0.029) was related to stroke events. Multivariate logistic regression analysis showed that NAFLD is a predictor of postoperative stroke in MMD patients (OR = 27.145, 95% CI = 2.031–362.81, P = 0.013). Kaplan-Meier analysis showed that compared with MMD patients with NAFLD, patients in the control group had a longer stroke-free time (P = 0.004). Univariate Cox analysis showed that NAFLD (P = 0.016) was associated with ischemic stroke during follow-up in patients with MMD. Multivariate Cox analysis showed that NAFLD was an independent risk factor for stroke in patients with MMD (HR = 10.815, 95% CI = 1.259–92.881, P = 0.030). Furthermore, fewer patients in the NAFLD group had good neurologic status (mRS score ≤ 2) than the control group (P = 0.005).ConclusionNAFLD was an independent risk factor for stroke in patients with MMD after revascularization and worse neurological function outcomes.

Influence of MAFLD and NAFLD on arterial stiffness: A longitudinal cohort study

Background and aimsThis cohort study investigated associations of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction–associated fatty liver disease (MAFLD) with risk of increase in arterial stiffness (AS), measured as brachial-ankle pulse wave velocity (baPWV). Methods and resultsParticipants who had health examinations between 2006 and 2019 were analyzed for fatty liver and increased baPWV using liver ultrasonography and automatic volume plethysmography device. Participants were classified based on presence of MAFLD or NAFLD and further divided into subgroups: no fatty liver disease (reference), NAFLD-only, MAFLD-only, and both NAFLD and MAFLD. Subgroups were additionally stratified by sex. Cox proportional hazard model was utilized to analyze the risk of developing baPWV ≥1400 cm/s in participants without baseline elevation of the baPWV. The NAFLD and MAFLD groups exhibited higher risks of increased baPWV (NAFLD: adjusted hazard ratio (aHR), 1.35 [95% CI, 1.29–1.42]; MAFLD: aHR, 1.37 [95% CI, 1.31–1.43]) compared to group without the conditions. Incidence of NAFLD or MAFLD were higher in men than in women but aHR of developing the increase in AS was higher in women. In subgroup analysis, the MAFLD-only group presented the strongest associations with increase in AS (aHR, 1.53 [95% CI, 1.43–1.64]), with the trend more pronounced in women than in men (Women, aHR, 1.63 [95% CI, 1.08–2.46]; Men, aHR 1.45 [95% CI, 1.35–1.56]). ConclusionsBoth NAFLD and MAFLD are significantly associated with elevated AS. These associations tended to be stronger in MAFLD than in NAFLD, in women than in men.

Comparative analysis of perioperative and long-term outcomes of patients with hepatocellular carcinoma: Nonalcoholic fatty liver disease versus viral hepatitis.

Despite the accumulating evidence regarding the oncological differences between nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) and viral infection-related HCC, the short- and long-term outcomes of surgical resection of NAFLD-related HCC remain unclear. While some reports indicate improved postoperative survival in NAFLD-related HCC, other studies suggest higher postoperative complications in these patients. Patients with NAFLD and those with hepatitis viral infection who underwent hepatectomy for HCC at our department were retrospectively analyzed. The clinical, surgical, pathological, and survival outcomes were compared between the two groups. Among the 1047 consecutive patients who underwent hepatectomy for HCC, 57 had NAFLD-related HCC (NAFLD group), and 727 had virus-related HCC (VH group). The body mass index and serum glycated hemoglobin levels were significantly higher in the NAFLD group than in the VH group. There were no significant differences in operative time and bleeding amount. Moreover, the morbidity and the length of postoperative hospital stays were similar across both groups. The pathological results showed that the tumor size was significantly larger in the NAFLD group than in the VH group. No significant differences between the groups in overall or recurrence-free survival were found. In a subgroup analysis with matched tumor diameters, patients in the NAFLD group had a better prognosis after hepatectomy than those in the VH group. Surgical outcomes after hepatectomy were comparable between the groups. Subgroup analysis reveals early detection and surgical intervention in NAFLD-HCC may improve prognosis.

Relation between non-alcoholic fatty liver disease and carotid artery intimal media thickness as a surrogate for atherosclerosis: a systematic review and meta-analysis.

Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis without heavy alcohol consumption or other chronic conditions, encompasses a spectrum from non-alcoholic fatty liver to non-alcoholic steatohepatitis leading to cirrhosis. This analysis aimed to investigate the correlation between NAFLD and carotid intimal media thickness (C-IMT), a non-invasive surrogate for atherosclerosis. Database searches, including PubMed, EMBASE and Cochrane Library, yielded studies up to April 2023. Included were studies exploring the NAFLD-C-IMT relationship in populations aged >18 years. Exclusions comprised non-English papers, those involving animals or pediatric populations and studies lacking control groups. No statistical significance was noted between mild and moderate NAFLD compared to the control group regarding C-IMT [95% confidence intervals (CI): -0.03, 0.12] and (95% CI: -0.03, 0.21), respectively. There was a statistically significant difference only in the Severe NAFLD group ( P value 0.03). NAFLD with and without metabolic syndrome showed statistically significant differences compared to control regarding C-IMT (95% CI: 0.04, 0.12) and (95% CI: 0.01, 0.07), respectively. Fifty-nine studies were mentioned without classification of NAFLD severity and revealed a high statistically significant difference between NAFLD and controls regarding C-IMT with (95% CI: 0.09, 0.12, P < 0.00001). Stratified analysis according to sex was done in two studies and revealed statistical differences between NAFLD and control regarding C-IMT in both groups. This meta-analysis underscores a significant association between NAFLD and increased C-IMT, emphasizing the importance of assessing C-IMT in NAFLD patients to identify cardiovascular risk and tailor therapeutic interventions for improved patient outcomes.

CCN3/NOV Serum Levels in Non-Alcoholic Fatty Liver Disease (NAFLD) Patients in Comparison with the Healthy Group and their Correlation with TNF-α and IL-6.

Adipokine irregularity leads to inflammation, endothelial dysfunction, insulin resistance (IR), and Non-Alcoholic Fatty Liver Disease (NAFLD). Previous studies linked NOV/CCN3 to obesity, IR, and inflammation, but no research has explored the connection between CCN3 serum levels and NAFLD. This case-control study assessed CCN3, IL-6, adiponectin, and TNF-α serum levels in 80 NAFLD patients and 80 controls using ELISA kits. Biochemical parameters were measured with commercial kits and an auto analyzer. NAFLD patients exhibited significantly higher CCN3 (2399.85 ± 744.53 vs. 1712.84 ± 478.19 ng/ml), TNF-α, and IL-6 levels, and lower adiponectin levels compared to controls (P<0.0001). In the NAFLD group, CCN3 showed positive correlations with FBG, insulin, HOMA-IR, and TNF-α. Binary logistic regression analysis revealed increased NAFLD risk in the adjusted model (OR [95% CI] = 1.220 [1.315 -1.131]). A CCN3 cut-off value of 1898.0050 pg/mL differentiated NAFLD patients from controls with 78.8% sensitivity and 73.2% specificity. It was found that elevated CCN3 serum levels directly correlate with NAFLD incidence and inflammation markers (IL-6 and TNF-α). CCN3 could serve as a potential biomarker for NAFLD, but further research is needed to validate this finding and assess its clinical utility.

Sex-Specific Association between Sodium Intake Estimated by 24-Hour Urinary Sodium Excretion and Nonalcoholic Fatty Liver Disease: The Community-Based Prospective Cohort Study.

Evidence for the association between high sodium intake and the onset of nonalcoholic fatty liver disease (NAFLD) is insufficient. This study examined the sex-specific association between sodium intake and the risk of NAFLD. This study included 2582 adults (aged 40-69 years; 1011 males and 1571 females). The total sodium excreted over 24 h was estimated from spot urine specimens using Tanaka's equation. Based on these estimates, participants were categorized into three groups according to their 24-h urinary sodium excretion levels: lowest (T1), middle (T2), and highest (T3). In addition, the participants were divided into non-NAFLD (≤36) and NAFLD (>36) groups based on the hepatic steatosis index. During the follow-up period (14 years), NAFLD was observed in 551 participants. The estimated 24-h urinary sodium excretion levels were positively associated with the incidence of NAFLD in all subjects. Upon sex stratification, females in the T2 and T3 groups exhibited adjusted hazard ratios of 1.35 and 1.51, respectively, compared with the T1 group. However, a significant relationship was not observed in males. High intake of sodium, especially among females, may be an important factor contributing to the development of NAFLD. Individuals with high sodium intake should be appropriately counselled and monitored for the risk of NAFLD.

Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study

ObjectiveTo investigate the risk of non-alcoholic fatty liver disease (NAFLD) for cardiovascular disease and all cause death in patients with type 2 diabetes mellitus (T2DM).DesignNationwide population based study.SettingLongitudinal cohort study...

Predictors of High Cardiovascular Risk Among Nonobese Patients with Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease in a Chinese Population.

This study aims to investigate cardiovascular risk factors in nonobese patients with type 2 diabetes (T2DM) and non-alcoholic fatty liver disease (NAFLD) and to determine whether they might be used to predict high-risk individuals effectively. This cross-sectional study included 245 nonobese patients with T2DM who underwent FibroTouch in the National Metabolic Management Center of the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from January 2021 to December 2022. All individuals were divided into NAFLD and non-NAFLD groups. Patients with NAFLD were further grouped by UAP tertiles (T1, T2 and T3). We created a Cardiovascular Score (total scale: 0-5 points; ≥3 points was defined as high-risk individual) based on baPWV, carotid ultrasound, and urinary microalbumin creatinine ratio (UA/CR) to assess the risk of cardiovascular disease in non-obese T2DM patients with NAFLD. Risk factors were evaluated using univariate and multivariate analysis. The performance of risk factors was compared according to the area under the receiver operating characteristic (ROC) curve. Atherogenic index of plasma (AIP), atherosclerosis index (AI), prevalence of hypertension, body mass index (BMI) and homeostatic model assessment of insulin resistance (HOMA-IR) were higher in the NAFLD group compared to the non-NAFLD group. In T3 group, AIP, AI, BMI and HOMA-IR were higher than those of T1 group. Multivariate logistic regression showed that age, systolic blood pressure, low-density lipoprotein-cholesterol (LDL-C) and AIP were risk factors for cardiovascular disease among nonobese patients with T2DM and NAFLD. The area under the ROC curve for age, systolic blood pressure, LDL-C and AIP were 0.705, 0.688, 0.738 and 0.642, respectively. The area under the ROC curve was 0.895 when combining them. Age, systolic blood pressure, AIP and LDL-C are all independent risk factors for cardiovascular disease in non-obese individuals with T2DM and NAFLD, which can be combined to identify high-risk populations and carry out intervention.