Markers Of Nonalcoholic Fatty Liver Disease Research Articles

Association of systemic inflammatory indices with anthropometric measures, metabolic factors, and liver function in non-alcoholic fatty liver disease

The present cross-sectional study aimed to explore the relationship between systemic inflammatory indices (SIIs) and anthropometric measures, metabolic, and liver function biomarkers in patients with non-alcoholic fatty liver disease (NAFLD). This study was carried out on 238 NAFLD patients with overweight or obesity, aged 18–55 years. Anthropometric measurements were done and body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were estimated. Metabolic factors including serum glucose, lipid profile, liver function biomarkers, and complete blood cell count were assessed after a 24-h fasting state. SIIs including the ratios of neutrophil to lymphocyte (NLR), monocytes to lymphocyte (MLR), platelet to lymphocyte (PLR), and monocytes to high-density lipoprotein cholesterol (MHR) were calculated. Results indicate that apart from PLR, all of the SIIs significantly changed by increasing steatosis severity (all p < 0.05). Moreover, changes in NLR showed a significant association with anthropometric indices including waist circumference (p = 0.032), BMI (p = 0.047), and WHtR (p = 0.002), as well as levels of fasting blood sugar (p = 0.045), triglycerides, (p = 0.025) and low-density lipoprotein cholesterol (p = 0.006). The findings also indicate the relations between lipid profile and all studied SIIs, notably MHR and MLR. All of the SIIs exhibited associations with some liver function indices as well. MHR was positively correlated with the metabolic risk factors of NAFLD while, oppositely, PLR was considered as a preventive marker of NAFLD.

Effect of sustained decreases in sedentary time and increases in physical activity on liver enzymes and indices in type 2 diabetes.

Current guidelines for nonalcoholic fatty liver disease (NAFLD) recommend high volumes and/or intensities of physical activity (PA), the achievement of which generally requires participation in supervised exercise training programs that however are difficult to implement in routine clinical practice. Conversely, counselling interventions may be more suitable, but result in only modest increases in moderate-to-vigorous-intensity PA (MVPA). This study assessed whether a counseling intervention for increasing PA and decreasing sedentary time (SED-time) is effective in improving NAFLD markers in people with type 2 diabetes. Three-hundred physically inactive and sedentary patients were randomized 1:1 to receive one-month theoretical and practical counseling once-a-year (intervention group) or standard care (control group) for 3 years. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltranspeptidase (γGT) levels were measured and fatty liver index (FLI), hepatic steatosis index (HSI), and visceral adiposity index (VAI) were calculated. Total PA volume, light-intensity PA (LPA), moderate-to-vigorous-intensity PA (MVPA), and SED-time were objectively measured by an accelerometer. Throughout the 3-year period, NAFLD markers did not change in the control group, whereas ALT, γGT, FLI, and HSI decreased in the intervention group, with significant between-group differences, despite modest MVPA increases, which however were associated with larger decrements in SED-time and reciprocal increments in LPA. Mean changes in NAFLD markers varied according to quartiles of (and correlated with) changes in MVPA (all markers) and SED-time, LPA, and PA volume (ALT, γGT, and HSI). Mean changes in MVPA or PA volume were independent predictors of changes in NAFLD markers. When included in the models, change in cardiorespiratory fitness and lower body muscle strength were independently associated with some NAFLD markers. A behavior change involving all domains of PA lifestyle, even if insufficient to achieve the recommended MVPA target, may provide beneficial effects on NAFLD markers in people with type 2 diabetes.

Potential diagnostic markers shared between non-alcoholic fatty liver disease and atherosclerosis determined by machine learning and bioinformatic analysis.

Evidence indicates that chronic non-alcoholic fatty liver disease (NAFLD) can increase the risk of atherosclerosis (AS), but the underlying mechanism remains unclear. This study is intended for confirming key genes shared between NAFLD and AS, and their clinical diagnostic value to establish a foundation for searching novel therapeutic targets. We downloaded the Gene Expression Omnibus (GEO) datasets, GSE48452 and GSE89632 for NAFLD and GSE100927, GSE40231 and GSE28829 for AS. The progression of NAFLD co-expression gene modules were recognized via weighted gene co-expression network analysis (WGCNA). We screened for differentially expressed genes (DEGs) associated with AS and identified common genes associated with NAFLD and AS using Venn diagrams. We investigated the most significant core genes between NAFLD and AS using machine learning algorithms. We then constructed a diagnostic model by creating a nomogram and evaluating its performance using ROC curves. Furthermore, the CIBERSORT algorithm was utilized to explore the immune cell infiltration between the two diseases, and evaluate the relationship between diagnostic genes and immune cells. The WGCNA findings associated 1,129 key genes with NAFLD, and the difference analysis results identified 625 DEGs in AS, and 47 genes that were common to both diseases. We screened the core RPS6KA1 and SERPINA3 genes associated with NAFLD and AS using three machine learning algorithms. A nomogram and ROC curves demonstrated that these genes had great clinical meaning. We found differential expression of RPS6KA1 in patients with steatosis and NASH, and of SERPINA3 only in those with NASH compared with normal individuals. Immune infiltration findings revealed that macrophage and mast cell infiltration play important roles in the development of NAFLD and AS. Notably, SERPINA3 correlated negatively, whereas RPS6KA1 correlated positively with macrophages and mast cells. We identified RPS6KA1 and SERPINA3 as potential diagnostic markers for NAFLD and AS. The most promising marker for a diagnosis of NAFLD and AS might be RPS6KA1, whereas SERPINA3 is the most closely related gene for NASH and AS. We believe that further exploration of these core genes will reveal the etiology and a pathological relationship between NAFLD and AS.

Regeneration of Non-Alcoholic Fatty Liver Cells Using Chimeric FGF21/HGFR: A Novel Therapeutic Approach.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant liver ailment attributed to factors like obesity and diabetes. While ongoing research explores treatments for NAFLD, further investigation is imperative to address this escalating health concern. NAFLD manifests as hepatic steatosis, precipitating insulin resistance and metabolic syndrome. This study aims to validate the regenerative potential of chimeric fibroblast growth factor 21 (FGF21) and Hepatocyte Growth Factor Receptor (HGFR) in NAFLD-afflicted liver cells. AML12, a murine hepatocyte cell line, was utilized to gauge the regenerative effects of chimeric FGF21/HGFR expression. Polysaccharide accumulation was affirmed through Periodic acid-Schiff (PAS) staining, while LDL uptake was microscopically observed with labeled LDL. The expression of FGF21/HGFR and NAFLD markers was analyzed by mRNA analysis with RT-PCR, which showed a decreased expression in acetyl-CoA carboxylase 1 (ACC1) and sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) with increased expression of hepatocellular growth factor (HGF), hepatocellular nuclear factor 4 alpha (HNF4A), and albumin (ALB). These findings affirm the hepato-regenerative properties of chimeric FGF21/HGFR within AML12 cells, opening novel avenues for therapeutic exploration in NAFLD.

Association between TyG index trajectory and new-onset lean NAFLD: a longitudinal study.

The purpose of this manuscript is to identify longitudinal trajectories of changes in triglyceride glucose (TyG) index and investigate the association of TyG index trajectories with risk of lean nonalcoholic fatty liver disease (NAFLD). Using data from 1,109 participants in the Health Management Cohort longitudinal study, we used Latent Class Growth Modeling (LCGM) to develop TyG index trajectories. Using a Cox proportional hazard model, the relationship between TyG index trajectories and incident lean NAFLD was analyzed. Restricted cubic splines (RCS) were used to visually display the dose-response association between TyG index and lean NAFLD. We also deployed machine learning (ML) via Light Gradient Boosting Machine (LightGBM) to predict lean NAFLD, validated by receiver operating characteristic curves (ROCs). The LightGBM model was used to create an online tool for medical use. In addition, NAFLD was assessed by abdominal ultrasound after excluding other liver fat causes. The median age of the population was 46.6 years, and 440 (39.68%) of the participants were men. Three distinct TyG index trajectories were identified: "low stable" (TyG index ranged from 7.66 to 7.71, n=206, 18.5%), "moderate stable" (TyG index ranged from 8.11 to 8.15, n=542, 48.8%), and "high stable" (TyG index ranged from 8.61 to 8.67, n=363, 32.7%). Using a "low stable" trajectory as a reference, a "high stable" trajectory was associated with an increased risk of lean-NAFLD (HR: 2.668, 95% CI: 1.098-6.484). After adjusting for baseline age, WC, SBP, BMI, and ALT, HR increased slightly in "moderate stable" and "high stable" trajectories to 1.767 (95% CI:0.730-4.275) and 2.668 (95% CI:1.098-6.484), respectively. RCS analysis showed a significant nonlinear dose-response relationship between TyG index and lean NAFLD risk (χ2=11.5, P=0.003). The LightGBM model demonstrated high accuracy (Train AUC 0.870, Test AUC 0.766). An online tool based on our model was developed to assist clinicians in assessing lean NAFLD risk. The TyG index serves as a promising noninvasive marker for lean NAFLD, with significant implications for clinical practice and public health policy.

Effect of Statins for Primary Prevention of Cardiovascular Disease According to the Fatty Liver Index.

Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease (CVD). We investigated the primary preventive effect of statins on CVD according to the level of fatty liver index (FLI), which is a marker of NAFLD. We conducted a nested case-control study on the basis of a nationwide health screening cohort in Korea. The participants were divided into tertiles (T1, T2, and T3) according to their FLI score. Cases were defined as individuals who developed CVD (composite of myocardial infarction and stroke). Three controls were matched to each case and multivariable conditional logistic regression analysis was performed. Within a cohort of 206,263 participants without prior CVD, 7044 individuals suffered the primary outcome. For the nested case-control study, we selected these 7044 cases along with their corresponding 20,641 matched controls. Individuals in the T3 tertiles of FLI had a higher risk of CVD than those in the T1 tertile [adjusted odds ratio (OR) 1.30; 95% confidence interval (CI) 1.20-1.40, P < 0.001]. In sub-analyses based on FLI tertiles, statin therapy was associated with a lower risk of CVD (adjusted OR 0.72; 95% CI 0.61-0.85, P < 0.001) in the T3 tertile but not in the T1 and T2 tertiles. Statin therapy was associated with a reduced risk of CVD in individuals with high FLI but not in those with low FLI. Further research is needed to determine the pathophysiologic mechanism between statin and NAFLD.

Molecular Insights of Nonalcoholic Fatty Liver Disease Pathogenesis.

Nonalcoholic fatty liver disease (NAFLD) is now the most prevalent chronic liver disease. Many hepatic abnormalities are associated with NAFLD such as nonalcoholic steatohepatitis, progressive fibrosis, cirrhosis, and liver failure. Moreover, the pathogenesis of NAFLD has numerous etiologies and can be explained due to the existence of several of stimulus that act simultaneously on genetically susceptible patients. These stimuli include obesity, diabetes, and insulin resistance. In addition, identifying the role of gut microbiota on NAFLD progression has been illustrated. In this review, we clarified the several factors that lead to the development of NAFLD and identify those who are most at risk of developing liver end-stage disease. Highlighting the noninvasive diagnostic NAFLD markers could be helpful in the disease prevention and treatment approaches.

DIAGNOSTIC ACCURACY OF THE NON-INVASIVE MARKERS NFLS, NI-NASH-DS, AND FIB-4 FOR ASSESSMENT OF DIFFERENT ASPECTS OF NON-ALCOHOLIC FATTY LIVER DISEASE IN INDIVIDUALS WITH OBESITY: CROSS-SECTIONAL STUDY.

Non-invasive markers have been developed to assess the presence and severity of liver abnormalities related to non-alcoholic fatty liver disease (NAFLD). To analyze the diagnostic accuracy of non-invasive NAFLD markers (NAFLD liver fat score [NLFS], non-invasive non-alcoholic steatohepatitis detection score [NI-NASH-DS] and fibrosis score based on four variables [FIB-4]) in individuals with obesity undergoing bariatric surgery. A descriptive retrospective cross-sectional study was carried out enrolling 91 individuals who underwent bariatric surgery at a tertiary-level public university hospital. Non-invasive NAFLD markers were calculated using laboratory tests, clinical and anthropometric variables and diagnostic accuracy tests were calculated comparing them in relation to the gold-standard test for this analysis (histopathological evaluation). A total of 85.7% of the participants were female and mean age was 39.1±9.8 years. The average body mass index was 38.4±3.6 kg/m2. At histopathological examination, 84 (92.3%) patients presented with steatosis, 82 (90.1%) with some type of fibrosis; 21 (23.1%) patients were diagnosed with NASH according to the NAFLD activity score criteria. The overall accuracy of NLFS score was 58.2% for general hepatic steatosis and 61.5% for moderate to severe steatosis. The overall accuracy of FIB-4 was 95.4% for advanced fibrosis. NI-NASH-DS had a 74.7% overall accuracy for NASH. In a population of individuals with obesity, the FIB-4 score had high overall accuracy in assessing the presence of advanced liver fibrosis, whereas the NFLS and NI-NASH-DS had moderate accuracies for the assessment of steatosis and NASH, respectively.

Endotoxin biomarkers, hepatic fat fraction, liver volume and liver stiffness among adolescents at high-risk for non-alcoholic fatty liver disease: The HEROES study.

Non-alcoholic fatty liver disease (NAFLD) is on the rise among youth. Identifying biomarkers of NAFLD progression/risk can aid in prevention efforts. This pilot study investigated associations of two endotoxin biomarkers-lipopolysaccharide-binding protein (LBP) and anti-endotoxin core immunoglobulin G (EndoCab)-with markers of NAFLD among 99 Latino/Latina adolescents (11-19 years) with obesity. We used linear regression to examine associations of each endotoxin biomarker (per 1-SD) with hepatic fat fraction (HFF), liver volume, and liver stiffness. We found positive associations of LBP with HFF and liver volume. Each 1-SD increment in LBP corresponded with 2.35% (95% CI: 0.46%, 4.23%) higher HFF and 0.14 (0.06, 0.23) L greater liver volume after adjusting for age, sex, and maternal education. Accounting for abdominal adiposity and Tanner stage did not change results. Excluding 72 participants with NAFLD attenuated associations of LBP with HFF but associations with liver volume persisted (0.11 [0.01, 0.21] L). EndoCab was not associated with any liver outcomes. Neither endotoxin biomarker predicted liver stiffness. While additional research is warranted, our results support LBP as a biomarker of NAFLD risk/progression in high-risk youth.

Duration of intermittent hypoxia impacts metabolic outcomes and severity of murine NAFLD.

Obstructive sleep apnea (OSA) is associated with metabolic dysfunction, including progression of nonalcoholic fatty liver disease (NAFLD). Chronic intermittent hypoxia (IH) as a model of OSA worsens hepatic steatosis and fibrosis in rodents with diet induced obesity. However, IH also causes weight loss, thus complicating attempts to co-model OSA and NAFLD. We sought to determine the effect of various durations of IH exposure on metabolic and liver-related outcomes in a murine NAFLD model. We hypothesized that longer IH duration would worsen the NAFLD phenotype. Male C57BL/6J mice (n = 32) were fed a high trans-fat diet for 24 weeks, to induce NAFLD with severe steatohepatitis. Mice were exposed to an IH profile modeling severe OSA, for variable durations (0, 6, 12, or 18 weeks). Intraperitoneal glucose tolerance test was measured at baseline and at six-week intervals. Liver triglycerides, collagen and other markers of NAFLD were measured at sacrifice. Mice exposed to IH for 12 weeks gained less weight (p = 0.023), and had lower liver weight (p = 0.008) relative to room air controls. These effects were not observed in the other IH groups. IH of longer duration transiently worsened glucose tolerance, but this effect was not seen in the groups exposed to shorter durations of IH. IH exposure for 12 or 18 weeks exacerbated liver fibrosis, with the largest increase in hepatic collagen observed in mice exposed to IH for 12 weeks. Duration of IH significantly impacts clinically relevant outcomes in a NAFLD model, including body weight, fasting glucose, glucose tolerance, and liver fibrosis.

Plasma Amino Acids in NAFLD Patients with Obesity Are Associated with Steatosis and Fibrosis: Results from the MAST4HEALTH Study.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been linked to changes in amino acid (AA) levels. The objective of the current study was to examine the relationship between MRI parameters that reflect inflammation and fibrosis and plasma AA concentrations in NAFLD patients. Plasma AA levels of 97 NAFLD patients from the MAST4HEALTH study were quantified with liquid chromatography. Medical, anthropometric and lifestyle characteristics were collected and biochemical parameters, as well as inflammatory and oxidative stress biomarkers, were measured. In total, subjects with a higher MRI-proton density fat fraction (MRI-PDFF) exhibited higher plasma AA levels compared to subjects with lower PDFF. The concentrations of BCAAs (p-Value: 0.03), AAAs (p-Value: 0.039), L-valine (p-Value: 0.029), L-tyrosine (p-Value: 0.039) and L-isoleucine (p-Value: 0.032) were found to be significantly higher in the higher PDFF group compared to lower group. Plasma AA levels varied according to MRI-PDFF. Significant associations were also demonstrated between AAs and MRI-PDFF and MRI-cT1, showing the potential utility of circulating AAs as diagnostic markers of NAFLD.

Association between the platelet/high-density lipoprotein cholesterol ratio and nonalcoholic fatty liver disease: results from NHANES 2017–2020

The platelet/high-density lipoprotein cholesterol ratio (PHR) is a novel inflammatory and hypercoagulability marker that represents the severity of metabolic syndrome. Liver metabolic syndrome is manifested by nonalcoholic fatty liver disease (NAFLD), which is associated with inflammation and hypercoagulability. This cross-sectional investigation aimed to identify the relationship between PHR and NAFLD. Participants in the National Health and Nutrition Examination Survey (NHANES) 2017–2020 were evaluated for hepatic steatosis and fibrosis using vibration-controlled transient elastography. The PHR was calculated as the ratio of platelets to high-density lipoprotein cholesterol. Increased PHR was associated with an increased incidence of NAFLD and hepatic fibrosis. Compared with patients in the first PHR quartile, after adjustment for clinical variables, the corresponding odds ratio (OR) for NAFLD in the fourth quartile was 2.36 (95% CI, 1.76 to 3.18) (p < 0.05); however, the OR for hepatic fibrosis was not statistically significant (p > 0.05). Furthermore, restricted cubic spline analyses showed an S-shaped association between PHR and NAFLD and an L-shaped relationship between PHR and hepatic fibrosis. The results support the effectiveness of PHR as a marker for NAFLD and hepatic fibrosis. Therefore, interventions to improve the PHR may be of benefit in reducing the incidence of both hepatic steatosis and fibrosis.

Disease Progression-Related Markers for Aged Non-Alcoholic Fatty Liver Disease Patients.

Liver fibrosis is an important phenomenon in non-alcoholic fatty liver disease (NAFLD) progression. Standard markers reflecting liver fibrosis, including the FIB-4 index, increase with age. This study aimed to identify fibrosis progression-related markers that are diagnostically beneficial even in aged individuals. Serum levels of pro- and anti-inflammatory cytokines were measured by multiple enzyme-linked immunosorbent assay. Two standard NAFLD or fibrosis progression-related markers - the FIB-4 index and APRI score - were analyzed along with cytokine levels to define the best approach to discriminate advanced fibrosis. Ninety-eight NAFLD patients were enrolled: 59 and 39 patients with fibrosis stages 1-2 and 3-4 respectively. In addition to the FIB-4 index and APRI score, the following factors showed significant differences between stages 1-2 and stages 3-4 in a multivariate analysis: platelet counts, IP-10, and RANTES. The fibrosis stage, FIB-4, APRI, PDGF-BB, and RANTES were related to the prognosis. In aged patients, IP-10, GM-CSF, and RANTES differed between stages 1-2 and stages 3-4. FIB-4 and APRI were beneficial for their correlation with fibrosis. However, to stratify either young or elderly advanced fibrosis patients, and to identify patients likely to have a bad outcome, RANTES was the best marker.

Non-alcoholic fatty liver disease: from understanding risk factors to finding optimal treatment regimens: A review

Non-alcoholic fatty liver disease (NAFLD) is now a major risk factor for death among patients with liver disease. Currently, drugs that primarily affect surrogate markers of NAFLD are available. However, none of these drugs showed a significant effect on the course of steatohepatitis and fibrogenesis. The search for the most relevant lifestyle modification programs is still a priority in comprehensive treatment. A clinical case of follow-up of a comorbid patient is presented. Despite comprehensive treatment, disease regression was not achieved. NAFLD therapy remains a relevant issue. Finding new ways to affect the NAFLD course and individualize treatment approaches is necessary.

Predictive value of the Framingham steatosis index for cardiovascular risk: a nationwide population-based cohort study.

Non-alcoholic fatty liver disease (NAFLD) is common and is associated with cardiovascular (CV) disease and mortality. The Framingham steatosis index (FSI) was recently proposed as a diagnostic marker of NAFLD and was calculated from age, body mass index, triglyceride, aspartate aminotransferase, alanine aminotransferase, diabetes history, and hypertension status. We aimed to evaluate the predictive ability of FSI for CV risk using a large-scale population dataset from the Korean National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). Among 514,866 individuals in the NHIS-HEALS, we excluded those who died, had a history of admission due to a CV event, and were heavy drinkers. The final study cohort comprised 283,427 participants. We employed both unadjusted and covariate-adjusted models in Cox proportional hazards regression analyses to determine the association between FSI and major adverse cardiovascular events (MACEs), CV events, and CV mortality. During a median follow-up of 5.9 years, we documented 9,674, 8,798, and 1,602 cases of MACEs, CV events, and CV mortality, respectively. The incidence of MACEs was 1.28%, 2.99%, 3.94%, and 4.82% in the first to fourth quartiles of FSI, respectively. The adjusted hazard ratios (95% confidence interval) for MACEs gradually and significantly increased with the FSI quartiles [1.302 (1.215-1.395) in Q2, 1.487 (1.390-1.590) in Q3, and 1.792 (1.680-1.911) in Q4], following an adjustment for conventional CV risk factors, including age, sex, smoking, drinking, physical activities, low-density lipoprotein cholesterol, estimated glomerular filtration rate, and waist circumference. Participants in the higher quartiles of FSI exhibited a noteworthy increase in the occurrence of CV event. However, upon adjusting for relevant risk factors, the association between FSI and CV mortality did not reach statistical significance. Our study suggests that the FSI, which is a surrogate marker of NAFLD, has a prognostic value for detecting individuals at higher risk of CV events.

High parathyroid hormone level as a marker of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: A systematic review and meta-analysis

Background and aimsStudies have suggested that high parathyroid hormone (PTH) was associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), although the results from existing studies are inconsistent. Using systematic review and meta-analysis, we aimed to determine the association of PTH with NAFLD and NASH. MethodsPotentially eligible studies were identified from Embase and Medline databases from using search strategy consisting of terms for “NAFLD/NASH”, and “PTH”. Eligible study must consist of one group of patients with NAFLD/NASH and another group without NAFLD/NASH. The study must provide mean ± SD PTH in both groups. We extracted such data to calculate mean difference (MD). Pooled MD was then calculated by combining MDs of each study using random-effects model. Funnel plot was used to assess for the presence of publication bias. ResultsA total of 388 articles were identified. After systematic review, 12 studies fulfilled the eligibility criteria and were included into the meta-analysis. The meta-analysis of 10 studies revealed the significant association between high PTH and NAFLD, with the pooled MD of 5.479 (95%CI 0.947–10.011, I2 82.4%). The funnel plot was symmetric and did not suggest publication bias. The meta-analysis of 4 studies revealed the non-significant association between high PTH and NASH, with the pooled MD of 11.955 (95%CI -4.703 – 28.614, I2 81.0%). ConclusionsHigh PTH level is significantly associated with NAFLD and can be used as a marker of NAFLD. However, high PTH level is non-significantly associated with NASH. Further studies are needed to increase the sample size and eliminate the confounding factors.

PROGRESSION OF HYPERTENSION-MEDIATED ORGAN DAMAGE IN PATIENTS WITH AND WITHOUT NONALCOHOLIC FATTY LIVER DISEASE

Objective: Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease and is associated with an increased risk of cardiovascular death. Fatty liver index (FLI) is a validated marker of NAFLD and can be used as a screening measure of hepatic steatosis. The purpose of the study was to compare the progression of hypertension-mediated organ damage (HMOD) in hypertensive patients with and without NAFLD. Design and method: Hypertensive patients (n = 60) without a history of cardiovascular disease participated in the study (mean age, 52 years; males, 55%; baseline clinic BP, 145/92 mmHg) and were followed for one year. In the baseline visit, FLI was calculated, and patients were divided into two groups by FLI below 60 or 60 or above (i.e., high-risk of NAFLD). All patients underwent clinic and 24-hour ambulatory BP measurements, echocardiographic examination, nailfold capillaroscopy, pulse wave velocity, and urinary albumin excretion assessment (albumin to creatinine ratio, [ACR]). Left ventricular mass index (LVMI) was also calculated using the Devereux formula. Results: In baseline visit, patients with FLI &gt; or = 60 (n = 32) compared to the control group had higher values of ACR (26.5±57mg/g vs. 9.6±6.3 mg/g, p = 0.02) and lower values of capillary densities (75±18cap/mm2 vs. 86±12cap/mm2, p = 0.002), whereas there was no relative difference in PWV and LVMI. At the end of follow-up, patients with FLI &gt; or = 60 had higher values of ACR (12.6±11.9 mg/g vs. 6.8±5.3 mg/g p = 0.025), PWV (9.9±2m/sec vs. 8.8±1.3 m/sec, p = 0.02), LVMI (81.4±13.2 g/m2 vs. 72.5±13.2 g/m2, p = 0.02) but lower number of capillaries (65.1±8.8 cap/mm2 vs. 79.6±7.5 cap/mm2, p&lt;0.001). Linear regression analysis revealed that FLI &gt; or = 60 was an independent determinant of follow-up ACR, PWV, LVMI, and the number of capillaries. Conclusions: Increased FLI may adversely modify the progression of HMOD in hypertension.

Hyperglycemia, pregnancy outcomes and maternal metabolic disease risk during pregnancy and lactation in a lean gestational diabetes mouse model.

Hyperglycemia in pregnancy (HIP) is a pregnancy complication characterized by mild to moderate hyperglycemia that negatively impacts short- and long-term health of mother and child. However, relationships between severity and timing of pregnancy hyperglycemia and postpartum outcomes have not been systemically investigated. We investigated the impact of hyperglycemia developing during pregnancy (gestational diabetes mellitus, GDM) or already present pre-mating (pre-gestational diabetes mellitus, PDM) on maternal health and pregnancy outcomes. GDM and PDM were induced in C57BL/6NTac mice by combined 60% high fat diet (HF) and low dose streptozotocin (STZ). Animals were screened for PDM prior to mating, all underwent an OGTT on gestational day (GD)15. Tissues were collected at GD18 or at postnatal day (PN)15. Among HFSTZ-treated dams, 34% developed PDM and 66% developed GDM, characterized by impaired glucose-induced insulin release and inadequate suppression of endogenous glucose production. No increased adiposity or overt insulin resistance was observed. Furthermore, markers of non-alcoholic fatty liver disease (NAFLD) were significantly increased in PDM at GD18 and were positively correlated with basal glucose levels at GD18 in GDM dams. By PN15, NAFLD markers were also increased in GDM dams. Only PDM affected pregnancy outcomes such as litter size. Our findings indicate that GDM and PDM, resulting in disturbances of maternal glucose homeostasis, increase the risk of postpartum NAFLD development, related to the onset and severity of pregnancy hyperglycemia. These findings signal a need for earlier monitoring of maternal glycemia and more rigorous follow-up of maternal health after GDM and PDM pregnancy in humans. KEY POINTS: We studied the impact of high-fat diet/streptozotocin induced hyperglycemia in pregnancy (HIP) in mice and found that this impaired glucose tolerance and insulin release. Litter size and embryo survival were compromised by pre-gestational, but not by gestational diabetes. Despite postpartum recovery from hyperglycemia in a majority of dams, liver disease markers were further elevated by PN15. Maternal liver disease markers were associated with the severity of hyperglycemia at GD18. The association between hyperglycemic exposure and NAFLD signal a need for more rigorous monitoring and follow-up of maternal glycemia and health in diabetic pregnancy in humans. Abstract figure legend Streptozotocin and high fat diet were used to induce GDM in female BL6/NTac mice. Pregnant dams underwent an OGTT at GD15 to confirm GDM diagnosis. By GD18, dams were hyperglycemic and showed a reduction in pancreatic beta cells. By PN15, dams additionally had developed an increase in NAFLD markers, despite the majority of the dams having recovered from hyperglycemia. This article is protected by copyright. All rights reserved.

Is mean platelet volume a simple marker of non-alcoholic fatty liver disease?

Due to the increasing prevalence of non-alcoholic fatty liver disease (NAFLD), there was a need to establish non-invasive tests for its detection. Mean platelet volume (MPV) is an inexpensive, practical and easily accessible marker of inflammation in many disorders. Our study was aimed at investigating the relationship between MPV and both NAFLD and liver histology. Total 290 patients with biopsy-proven NAFLD (n = 124) and 108 control patients were included in the study. To exclude the effect of other diseases on MPV, we included 156 patient controls in our study.Those whohave liver-related diseases and those who use drugs that may cause fatty liver were not included in the study. Liverbiopsywas performed for those whose alanine aminotransferase level persisted for >6 months above the upper limits. We found that MPV was significantly higher in the NAFLD group compared with the control group, and MPV had an independent predictive value for the development of NAFLD. We determined that the number of platelets was significantly lower in the NAFLD group compared with that in the control group. We compared MPV values histologically with both stage and grade in all patients with biopsy-proven NAFLD and found that MPV had a significant positive correlation with stage. We observed a positive correlation between MPV and non-alcoholic steatohepatitis grade, but this was not statistically significant. MPV can be useful because it is simple, easy to measure, cost-effective, and routinely tested in daily practice. MPV can be used as a simple marker of NAFLD and an indicator of fibrosis-stage in NAFLD.

Transcriptome Sequencing Reveals Autophagy Networks in Rat Livers during the Development of NAFLD and Identifies Autophagy Hub Genes

(1) Autophagy is an important biological process in cells and is closely associated with the development and progression of non-alcoholic fatty liver disease (NAFLD). Therefore, this study aims to investigate the biological function of the autophagy hub genes, which could be used as a potential therapeutic target and diagnostic markers for NAFLD. (2) Male C57BL/6J mice were sacrificed after 16 and 38 weeks of a high-fat diet, serum biochemical indexes were detected, and liver lobules were collected for pathological observation and transcriptome sequencing. The R software was used to identify differentially expressed autophagy genes (DEGs) from the transcriptome sequencing data of mice fed with a normal diet for 38 weeks (ND38) and a high-fat diet for 38 weeks (HFD38). Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on the DEGs, a protein-protein interaction (PPI) network of the DEGs was established using the STRING data website, and the results were visualized through Cytoscape. (3) After 16 weeks and 38 weeks of a high-fat diet, there was a significant increase in body weight, serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and triglycerides (TG) in mice, along with lipid accumulation in the liver, which was more severe at 38 weeks than at 16 weeks. The transcriptome data showed significant changes in the expression profile of autophagy genes in the livers of NAFLD mice following a long-term high-fat diet. Among the 31 differentially expressed autophagy-related genes, 13 were upregulated and 18 were downregulated. GO and KEGG pathway analysis revealed that these DEGs were primarily involved in autophagy, cholesterol transport, triglyceride metabolism, apoptosis, the FoxO signaling pathway, the p53 signaling pathway and the IL-17 signaling pathway. Four hub genes were identified by the PPI network analysis, of which Irs2, Pnpla2 and Plin2 were significantly downregulated, while Srebf2 was significantly upregulated by the 38-week high-fat diet. (4) The hub genes Irs2, Pnpla2, Srebf2 and Plin2 may serve as key therapeutic targets and early diagnostic markers in the progression of NAFLD.