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Objective: To investigate the effect of mi R-206 on the non alcoholic fatty liver (NAFLD) cell model induced by long chain free fatty acids (FFA) in HepG2 cells and its relationship with silent information regulatory factor 1 (SIRT1）/AMPK pathway.Methods: HepG2 cells were treated with 1mM FFA for 24 hours to construct a NAFLD cell model. According to the different transfected substances, they were divided into 6 groups: Control group (without any treatment), FFA group (NAFLD model), FFA+mimics NC group (transfect mimics NC plasmid), FFA+mi R-206 mimics group (transfect mi R-206 mimics plasmid), FFA+Vector group (transfect Vector plasmid), and FFA+OE-SIRT1 group (transfect OE-SIRT1 plasmid). Oil red O staining was used to detect lipid accumulation in cells. Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and triglycerides (TG). Fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of mi R-206 and SIRT1 m RNA. Western blot was used to detect SIRT1, sterol regulatory element binding protein 1 (SREBP1), fatty acid synthase (FAS), stearoyl coenzyme Al (SCD1), acetyl CoA carboxylase 1 (ACC1), leukocyte differentiation antigen 36 (CD36), AMP activated protein kinase (AMPK), and p-AMPK protein levels. TargetScan was used to predict the binding site of mi R-206 to SIRT1. Dual luciferase reporter gene experiments was used to validate the targeting relationship between mi R-206 and SIRT1. Results: Compared with the Control group, the FFA group showed a significant increase in AST, ALT, and TG content, an increase in TG content, a significant decrease in mi R-206, SIRT1 protein and gene m RNA content, an increase in SREBP1, FAS, SCD1, ACC1, and CD36 protein content,and a decrease in p-AMPK/AMPK ratio (P＜0.01). Compared with the FFA+mimics NC group cells, the FFA+mi R-206 mimics group cells showed a decrease in intracellular TG content, a decrease in SREBP1, FAS, SCD1, ACC1, and CD36 protein levels, an increase in SIRT1 protein and gene m RNA levels, and an increase in p-AMPK/AMPK ratio, with statistically significant differences (P＜0.01). Compared with the FFA+Vector group cells, the FFA+OE-SIRT1 group cells showed a decrease in TG content, a decrease in SREBP1, FAS,SCD1, ACC1, and CD36 protein levels, and an increase in p-AMPK/AMPK ratio (P＜0.01). There was a binding site between mi R-206and the SIRT1 wild-type. The cell luciferase activity in the SIRT1 WT+mi R-206 mimics group was higher than that in the SIRT1WT+mimics NC group (P＜0.01). Conclusion: Upregulation of mi R-206 can alleviate NAFLD induced lipid metabolism in liver cells through the SIRT1/AMPK pathway. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance is common in people with NAFLD, although not always overt glucose intolerance. Present study was done to describe the frequency of undiagnosed diabetes mellitus in patients of non alcoholic fatty liver disease at a tertiary care centre. Material & Methods: This was a hospital based observational cross-sectional study conducted in the Department of Medicine, Surgery and Biochemistry at Dr. Vithalrao Vikhe Patil Foundation's Medical College. Patients fulfilling the inclusion criteria were selected. A detailed informed consent was taken from all the participants. Demographic profile recorded and detailed history with examination was done in all the patients as per the proforma attached. Analysis of symptoms was done along with underlying co- morbid conditions and drugs used. Anthropometric data, such as body mass index (BMI) and blood pressure were measured. Results: Mean age of the cases was 53.62±10.69 years. Mean age in males was 55.33±10.19 years while in female it was 51.04±10.92 years. Maximum number of patients was in 5th and 6th decades. Out of 120 total patients, total males were 29 and females were 91. Out of 18 total diabetic patients, 12 were females and 6 were males. Impaired fasting glucose were found in 55(45.83%) of patients. Increased serum Cholesterol level were seen in 56(46.66%) patients. Increased serum triglyceride level was seen in 68(56.67%) patients. Low serum HDL level was seen in 78(65%) patients. Increased serum LDL levels were 37(30.83%) of patients. ALT and AST levels were elevated in 63(52.5%) and 61(50.83%) of patients. Total of 120 cases, 64(53.33%), 52(43.33%) and 4(3.33%) of cases had grade I, II, and III fatty liver respectively. Conclusion: The prevalence of several components of metabolic syndrome is higher in NAFLD patients, according to our findings. [ABSTRACT FROM AUTHOR]

Background and Aim: This is a cross‐sectional observational study conducted on living liver donors focusing on "long‐term remnant liver health" specifically looking at steatosis, inflammation, and fibrosis using multiparametric ultra sonological evaluation and noninvasive blood tests. Methods: Multiparametric ultrasound evaluation included assessment of shear wave elastography (fibrosis), sound speed plane wave ultrasound, attenuation plane wave ultrasound (steatosis), and viscosity plane wave ultrasound (inflammation). Blood test based APRI and FIB‐4 were calculated. Liver biopsy was performed if noninvasive evaluation pointed toward clinically relevant fibro progression (F4). Results: Out of 36 donors, significant fibrosis (>F2) was found in 11 donors (30.5%), seven donors (19.4%) had severe fibrosis (>F3), and two donors had shear wave elastography values suggestive of cirrhosis(F4). Of these two, one donor was extensively evaluated and was found to have biopsy proven cirrhosis with endoscopic evidence of portal hypertension. The prevalence of fatty liver disease in our study group was 50%. Conclusion: We report the first liver donor cohort with fibroprogression and cirrhosis occurring in the remnant liver. Our donor cohort with a significant proportion having steatosis and fibroprogression underscores the importance of regular follow‐up of liver donors and evaluation of remnant liver. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy and accuracy of the Fibrosis-4 (FIB-4) index with FibroScan in assessing liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Methods: This cross-sectional study was conducted at Patel Hospital, Karachi, Pakistan, from October 2023 to April 2024. All known cases of NAFLD or non-alcoholic steatohepatitis (NASH) aged ≥18 years, regardless of gender, were included. FIB-4 scores were measured using age, platelet level, aspartate transaminase (AST), and alanine transaminase (ALT). FibroScan categorized liver fibrosis into stages F0 to F4 with specific stiffness ranges: F0 (1-6 kPa), F1 (6.1-7 kPa), F2 (7.1-9 kPa), F3 (9.1-10.3 kPa), and F4 (≥10.4 kPa). Results: Of the 146 patients, the median age was 52.00 (IQR: 47.00-54.00) years. Based on FibroScan results, 61 (41.8%) patients were classified as F1, 35 (24.0%) as F2, 30 (20.5%) as F3, and 20 (13.7%) as F4. The diagnostic performance of FIB-4 showed an area under the curve of 0.83 (95% CI: 0.76-0.90). The optimal cut-off for FIB-4 was 1.28 with sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy of 98.0%, 65.6%, 59.7%, 98.4%, and 76.7%, respectively. Spearman's correlation test (ρ) was applied and a significantly moderate correlation was found between FibroScan and FIB-4 (ρ = 0.50, p < 0.001). Conclusion: FIB-4 demonstrated higher accuracy and diagnostic performance in determining liver fibrosis in NAFLD patients compared to FibroScan. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim This is a cross‐sectional observational study conducted on living liver donors focusing on “long‐term remnant liver health” specifically looking at steatosis, inflammation, and fibrosis using multiparametric ultra sonological evaluation and noninvasive blood tests. Methods Multiparametric ultrasound evaluation included assessment of shear wave elastography (fibrosis), sound speed plane wave ultrasound, attenuation plane wave ultrasound (steatosis), and viscosity plane wave ultrasound (inflammation). Blood test based APRI and FIB‐4 were calculated. Liver biopsy was performed if noninvasive evaluation pointed toward clinically relevant fibro progression (F4). Results Out of 36 donors, significant fibrosis (>F2) was found in 11 donors (30.5%), seven donors (19.4%) had severe fibrosis (>F3), and two donors had shear wave elastography values suggestive of cirrhosis(F4). Of these two, one donor was extensively evaluated and was found to have biopsy proven cirrhosis with endoscopic evidence of portal hypertension. The prevalence of fatty liver disease in our study group was 50%. Conclusion We report the first liver donor cohort with fibroprogression and cirrhosis occurring in the remnant liver. Our donor cohort with a significant proportion having steatosis and fibroprogression underscores the importance of regular follow‐up of liver donors and evaluation of remnant liver.

Abstract Due to the comprehensive hepatitis B virus vaccination program in Taiwan since 1986, the development of antiviral therapy for chronic hepatitis B and chronic hepatitis C infection and covered by National health insurance. Besides, the increased prevalence of nonalcoholic fatty liver disease (NAFLD) and currently, approved therapy for NAFLD remain developing. The etiology of liver-related diseases such as cirrhosis and hepatocellular carcinoma required reinterpretation. This study aimed to analyze the incidence and outcome of hepatocellular carcinoma (HCC) due to viral (hepatitis B and hepatitis C) infection compared to that of nonviral etiology. We retrospectively analyzed patients with HCC from January 2011 to December 2020 from the cancer registry at our institution. Viral-related hepatitis was defined as hepatitis B surface antigen positivity or anti-hepatitis C virus (HCV) antibody positivity. A total of 2748 patients with HCC were enrolled, of which 2188 had viral-related HCC and 560 had nonviral-related HCC. In viral HCC group, the median age at diagnosis was significantly lower (65 years versus 71 years, p

The intestinal microbiota is considered a "new virtual metabolic organ", widely involved in the digestion and absorption of nutrients in the body. The occurrence and development of digestive system dis- eases are closely related to the intestinal microbiota, and the intestinal microbiota and its metabolites play an important role in maintaining the dynamic balance between intestinal homeostasis and immune regulation. The article reviews the research progress on the intestinal microbiota and common digestive system diseases such as non-alcoholic fatty liver disease, irritable bowel syndrome, inflammatory bowel disease, and colorectal cancer. [ABSTRACT FROM AUTHOR]

Objective To observe the osteoprotective effect of equol (Eq) on postmenopausal rats with nonalcoholic fatty liver disease (NAFLD), and to explore its underlying mechanism. Methods Forty-eight 6-week-old female Sprague-Dawley (SD) rats were randomly divided into control group, model group, low-, middle- and high-dose Eq groups [20, 40 and 80 mg/(kg·d)], and estradiol intervention group [E2, 0.25 mg/(kg·d)], with 8 rats in each group. The control group was given sham operation and normal diet. The other groups were given ovariectomy (OVX) combined with high-fat diet. After 16 weeks, the body weight and length of rats were measured, BMI and Lee's index were calculated, and the changes of bone mineral density (BMD) and bone microstructure of rats were detected. After anesthesia, the rats were killed to detect the levels of serum estrogen, TNF-α and IL-6. The liver and femur tissues were observed for morphological changes, and the expression of insulin-like growth factor-1 (IGF-1) in the liver and bone was detected by Western blotting and qRT-PCR. Results In the model group, BMI and Lee's index were increased significantly, the liver tissue was obviously injured, the estrogen level and BMD were obvioiusly decreased, and the bone microstructure was seriously damaged, suggesting that postmenopausal NAFLD was complicated with obvious bone injury. The treatment of Eq or E2 increased the level of serum estrogen and BMD, decreased BMI, Lee's index and serum TNF-α and IL-6 levels, attenuated steatosis and lipid accumulation in bone microstructure, and enhanced the expression of IGF-1 at protein and mRNA level in the liver and bone. Conclusion Eq can improve the bone injury of postmenopausal NAFLD rats and shows a bone protective effect. The mechanism may partially be related to Eq promoting the expression of IGF-1 and reducing inflammation. x

Abstract Background Increasing incidence of non-alcoholic fatty liver disease (NAFLD) calls for improved understanding of how the disease affects metabolic liver function. Aims To investigate in vivo effects of different NAFLD stages on metabolic liver function, quantified as regional and total capacity for galactose metabolism in a NAFLD model. Methods Male Sprague Dawley rats were fed a high-fat, high-cholesterol diet for 1 or 12 weeks, modelling early or late NAFLD, respectively. Each NAFLD group (n = 8 each) had a control group on standard chow (n = 8 each). Metabolic liver function was assessed by 2-[18F]fluoro‐2‐deoxy‐D-galactose positron emission tomography; regional galactose metabolism was assessed as standardised uptake value (SUV). Liver tissue was harvested for histology and fat quantification. Results Early NAFLD had median 18% fat by liver volume. Late NAFLD had median 32% fat and varying features of non-alcoholic steatohepatitis (NASH). Median SUV reflecting regional galactose metabolism was reduced in early NAFLD (9.8) and more so in late NAFLD (7.4; p = 0.02), both significantly lower than in controls (12.5). In early NAFLD, lower SUV was quantitatively explained by fat infiltration. In late NAFLD, the SUV decrease was beyond that attributable to fat; probably related to structural NASH features. Total capacity for galactose elimination was intact in both groups, which in late NAFLD was attained by increased fat-free liver mass to 21 g, versus 15 g in early NAFLD and controls (both p ≤ 0.002). Conclusion Regional metabolic liver function was compromised in NAFLD by fat infiltration and structural changes. Still, whole liver metabolic function was preserved in late NAFLD by a marked increase in the fat-free liver mass.

Non-alcoholic fatty liver disease currently affects more than 30% of the population. Recent studies highlight the role of genetic polymorphisms in genes associated with fat catabolism and anabolism in the manifestation of this condition and its progression. The work analyzes foreign publications on the molecular and biochemical aspects of these polymorphisms, as well as works studying their effect on the state of the liver and markers of its pathology over the past 10 years. Thus, polymorphisms of the PNPLA3, MBOAT7, and TM6SF2, affecting the functionality of the proteins they express, lead to a change in the metabolism of fatty acids in the liver, which in turn leads to the development of NAFLD and its progression. Despite the fact that the contribution of the rs738409 polymorphism of the PNPLA3 gene is well described both in foreign and Russian articles, polymorphisms of the MBOAT7 and TM6SF2 genes and their effect on NAFLD, as well as the molecular biochemical mechanisms underlying it, have been studied much worse in foreign studies and are little mentioned in Russian ones. In addition, the issue of the severity of the influence of the above polymorphisms on populations of different ethnic and age groups requires additional research. This work attempts to systematize the available data on these issues.

Background: "Non Alcoholic Fatty Liver Disease" is one of the most quotidian liver diseases in the entire world. The risk factors for developing "Non Alcoholic Steato-Hepatitis" or (NASH) include - 1) Obesity, especially Central Adiposity, 2) Impaired Glucose tolerance,3) „Type 2 diabetes mellitus? (T2DM), and 4) Dyslipidemia. Material And Methods: A total of 65 NAFLD patients, both male and female, were included in the research study. „Type 2 diabetes mellitus? diagnosis was made according to ADA criteria which includes - (1) symptoms of diabetes mellitus plus random blood glucose concentration more than equal to 11.1mmol/L(200mg/dl); (2) Fasting blood(plasma) glucose more than 7.0mmol/L(126mg/dl); (3) Two hour plasma glucose more than equal to 11.1 mmol/L(200mg/dl) on oral glucose tolerance test (OGTT). Results: This study shows Association of and PP blood sugar levels with hypertension and obesity. It shows mean ± SD (175.57±72.50) of fasting blood sugar in NAFLD hypertensive subgroup was found to be higher as compared to NAFLD without hypertension mean±SD (133.43±68.06). This was statistically significant(p=.020). Mean±SD(292±107.62) of Post Prandial blood sugar in NAFLD-hypertension subgroup was found to be higher than the Post Parandial blood sugar of NAFLD without hypertension & this was statistically significant(p=.04). The mean±SD(175.12±77.50) of fasting blood sugar of Obesity fasting subgroup of NAFLD were higher as compared to mean±SD of those without obesity(138.0±63.78). This was found to be statistically significant. Conclusion: The present study concludes that higher fasting and postprandial glucose level were significantly associated to NAFLD in hypertensive patients compared to non hypertensive NAFLD patients. Also significant higher fasting glucose levels were associated with obese patients having NAFLD compared to non obese patients having NAFLD. Timely assessment and analysis of NAFLD at a mild stage or at a moderate stage with appropriate and adequate lifestyle changes of the patients such as (1) physical activities and (2) proper diet could thus indirectly prevent the occurrence of pathological states including „type 2 diabetes mellitus?, obesity and metabolic syndrome. Future research with bigger study sample are needed for more concrete and decisive outcomes. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is accepted as a counterpart to alcohol-related liver disease because it is defined as hepatic steatosis without excessive use of alcohol. However, the definition of moderate alcohol consumption, as well as whether moderate alcohol consumption is beneficial or detrimental, remains controversial. In this review, the findings of clinical studies to date with high-quality evidence regarding the effects of moderate alcohol consumption in NAFLD patients were compared and summarized.

Background: Increasing incidence of non-alcoholic fatty liver disease (NAFLD) calls for improved understanding of how the disease affects metabolic liver function. Aims: To investigate in vivo effects of different NAFLD stages on metabolic liver function, quantified as regional and total capacity for galactose metabolism in a NAFLD model. Methods: Male Sprague Dawley rats were fed a high-fat, high-cholesterol diet for 1 or 12 weeks, modelling early or late NAFLD, respectively. Each NAFLD group (n = 8 each) had a control group on standard chow (n = 8 each). Metabolic liver function was assessed by 2-[18F]fluoro‐2‐deoxy‐D-galactose positron emission tomography; regional galactose metabolism was assessed as standardised uptake value (SUV). Liver tissue was harvested for histology and fat quantification. Results: Early NAFLD had median 18% fat by liver volume. Late NAFLD had median 32% fat and varying features of non-alcoholic steatohepatitis (NASH). Median SUV reflecting regional galactose metabolism was reduced in early NAFLD (9.8) and more so in late NAFLD (7.4; p = 0.02), both significantly lower than in controls (12.5). In early NAFLD, lower SUV was quantitatively explained by fat infiltration. In late NAFLD, the SUV decrease was beyond that attributable to fat; probably related to structural NASH features. Total capacity for galactose elimination was intact in both groups, which in late NAFLD was attained by increased fat-free liver mass to 21 g, versus 15 g in early NAFLD and controls (both p ≤ 0.002). Conclusion: Regional metabolic liver function was compromised in NAFLD by fat infiltration and structural changes. Still, whole liver metabolic function was preserved in late NAFLD by a marked increase in the fat-free liver mass. [ABSTRACT FROM AUTHOR]

As an endocrine hormone, fibroblast growth factor 21 (FGF21) plays a crucial role in regulating lipid, glucose, and energy metabolism. Endogenous FGF21 is generated by multiple cell types but acts on restricted effector tissues, including the brain, adipose tissue, liver, heart, and skeletal muscle. Intervention with FGF21 in rodents or non-human primates has shown significant pharmacological effects on a range of metabolic dysfunctions, including weight loss and improvement of hyperglycemia, hyperlipidemia, insulin resistance, cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD). Due to the poor pharmacokinetic and biophysical characteristics of native FGF21, long-acting FGF21 analogs and FGF21 receptor agonists have been developed for the treatment of metabolic dysfunction. Clinical trials of several FGF21-based drugs have been performed and shown good safety, tolerance, and efficacy. Here we review the actions of FGF21 and summarize the associated clinical trials in obesity, type 2 diabetes mellitus (T2DM), and NAFLD, to help understand and promote the development of efficient treatment for metabolic diseases via targeting FGF21. [ABSTRACT FROM AUTHOR]

Background: Controlled attenuation parameter (CAP) has been suggested as a new non-invasive measurement performed during transient elastography (TE) to assess liver steatosis. The aim of this study was to evaluate CAP values head to head with ultrasound (US) as reference standard. Methods: A consecutive cohort of patients attending abdominal US in an outpatient liver unit was included in this study with simultaneous CAP determination using the FibroScan® M probe and fibrosis scored by TE. Patients were subdivided in four groups on the basis of risk factors for Metabolically Associated Fatty Liver Disease (MAFLD). Results: Four hundred thirty-five patients were included in the analysis: 221 (51%) were male; 117 (26.9%) were in control group, 144 (33.1%) in group 2 with inactive HCV or HBV infection and at low-risk for MAFLD, 134 (30.8%) in group 3 at high-risk of MAFLD, 40 (9.2%) in group 4 at high-risk of MAFLD and concomitant inactive HCV or HBV infection. Liver steatosis detected with US evaluation was observed in the 41% of the entire cohort; in particular in the 3.4%, 20.1%, 83.6% and 87.4% of the group 1, 2, 3 and 4, respectively (p < 0.001). In patients at high-risk factor for MAFLD (group 3 and 4), CAP median levels were found statistically different among the severity-grading groups for US steatosis (S0 [n.27], ≥S1 [n.59], ≥S2 + S3 [n.89]), observing higher CAP levels in patients with a higher steatosis grade (≥S2 + S3 327.5 [±40.6] vs ≥S1 277.7 [±45.6] vs S0 245.1 [±47.4]; p < 0.001 for the whole cohort analysis) (p < 0.001 between ≥S2 + S3 and ≥S1) (p < 0.001 between ≥S2 + S3 and S0) (p = 0.004 between ≥S1 and S0). ROC analysis showed that the global performance of the CAP median level ≥ 258 to predict liver steatosis (S0 vs S1–3), was excellent with an Area Under the Curve (AUC) value of 0.87 [CI 95% 0. 835–0.904] with an 84% of sensitivity and a 78% of specificity, and a positive predictive value (PPV) of 73% and negative predictive value (NPV) of 88%. A TE-kPa median value <8.0 was detected in the 100%, 84%, 83.6% and 60% of patients in group 1, 2, 3 and 4, respectively. A TE-kPa median value >13.0 was detected in the 0%, 4.2%, 5.2% and 17.5% of patients in group 1, 2, 3 and 4, respectively. Conclusions: CAP values are strongly associated with the standard US criteria for different degree of steatosis. Integrating TE up to 5% of patients may be identified at risk for advanced fibrosis. [ABSTRACT FROM AUTHOR]

Pu-erh tea belongs to the six tea categories of black tea, according to the processing technology and quality characteristics, is divided into two types of raw tea and ripe tea. Raw tea is made from fresh leaves of tea as raw materials, through the process of greening, kneading, sun drying, steam molding and other processes made of tightly pressed tea. Ripe tea is made from Yunnan large-leafed sun green tea, using a specific process, post-fermentation (rapid post-fermentation or slow post-fermentation) processing of loose tea and tightly pressed tea. TAETEA Prebiotea is Puerh Ripe Tea, TAETEA Prebiotea has the effect of increasing insulin level and improving hyperglycemia in mice, and it also has the effect of regulating blood lipids, which can reduce the level of serum total cholesterol (TC) and triglycerides (TG), increase the level of high-density lipoprotein cholesterol (HDL-C), and improve the metabolism of lipids. Therefore, further experiments were conducted by us, and TAETEA Prebiotea was formulated into a suitable dose for the intervention of non alcoholic fatty liver disease (NAFLD) model rats, and at the end of the experiments, the samples of each group of experiments were analyzed and detected by the method of UHPLC-Q-Exactive LC-MS liquid-mass spectrometry methodology, and the relevant metabolites as well as metabolic pathways were analyzed by the method of Non targeted metabolomics analysis. As a result, 71 differential metabolites could be screened, of which 35 differential metabolites were up-regulated after intervention and 36 differential metabolites were down-regulated after intervention. Based on the KEGG pathway enrichment and Pathway Impact bubble diagram analysis, glycine, serine, threonine metabolism, arginine and proline metabolism, protein digestion and absorption, and central carbon metabolism in cancer may be the main metabolic pathways in which TAETEA Prebiotea exerted preventive effects on NAFLD rats, C00148 (Proline), C00300 (Creatine) and C00719 (Betaine) are the differential metabolites that play important regulatory roles. • A pioneering study of the preventive effect of TAETEA probiotics on non-alcoholic fatty liver. • The samples were analyzed using a UHPLC-Q-Exactive LC-MS liquid-mass spectrometer. • Metabolites and metabolic pathways were screened by metabolomics analysis. • Mechanisms of action of metabolites and metabolic pathways are discussed. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are known to play crucial roles in nonalcoholic fatty liver disease (NAFLD). This research sought to explore mechanisms by which lncRNA MALAT1 regulates the progression of NAFLD. Thus, in order to detect the function of MALAT1 in NAFLD, in vitro and in vivo model of NAFLD were established. Then, fatty acid uptake and triglyceride level were investigated by BODIPY labeled-fatty acid uptake assay and Oil red O staining, respectively. The expressions of MALAT1, miR-206, ARNT, PPARα and CD36 were detected by western blotting and qPCR. Dual luciferase, RIP and ChIP assay were used to validate the relation among MALAT1, miR-206, ARNT and PPARα. The data revealed expression of MALAT1 was up-regulated in vitro and in vivo in NAFLD, and knockdown of MALAT1 suppressed FFA-induced lipid accumulation in hepatocytes. Meanwhile, MALAT1 upregulated the expression of ARNT through binding with miR-206. Moreover, miR-206 inhibitor reversed MALAT1 knockdown effects in decreased lipid accumulation in FFA-treated hepatocytes. Furthermore, ARNT could inhibit the expression of PPARα via binding with PPARα promoter. Knockdown of MALAT1 significantly upregulated the level of PPARα and downregulated the expression of CD36, while PPARα knockdown reversed these phenomena. MALAT1 regulated PPARα/CD36 -mediated hepatic lipid accumulation in NAFLD through regulation of miR-206/ARNT axis. Thus, MALAT1/miR-206/ARNT might serve as a therapeutic target against NAFLD.

Background: Obesity had become a global problem today. Obesity is a significant risk factor of cardiovascular and other metabolic diseases such as non-alcoholic fatty liver disease (NAFLD). It remains unclear if the increased mean platelet volume (MPV) at the steatosis state is practicable as early detection of the occurrence of fatty liver in individuals with central obesity. This study aims to determine the association of interleukin-6 (IL-6) and MPV levels in central obesity with or without NAFLD. Method: This study was descriptive-analytic with a cross-sectional approach conducted in Prof. dr. R. D. Kandou Manado general hospital from May to July 2018. Consecutive sampling was performed based on inclusion criteria, then IL-6, MPV, and abdominal ultrasound examinations were performed. Results: This study included 40 samples of men with central obesity, 28 people (70%) among them were diagnosed with NAFLD. The Fisher exact test showed an association between NAFLD and an increase in IL-6 (p = 0.039), also between MPV and NAFLD (p=0.015). Pearson correlation test showed there was no significant correlation between IL-6 and MPV in the NAFLD sample group (p = 0.084; r -0.332) and in the non-NAFLD sample group (p = 0.564; r -0.186). Conclusion: Elevated MPV and IL-6 values may be used as marker for NAFLD presence among central obesity patients.

A B S T R A C T Alternative splicing produces complex and dynamic changes in the protein isoforms that are necessary for the proper biological functioning of the metabolic pathways involved in liver development and hepatocyte homeostasis. Changes in the physiological state of alternatively spliced forms are increasingly linked to liver pathologies. This may occur when the expression or function of the set of proteins controlling the alternative splicing processes are altered by external effectors such as oxidative stress and other environmental variations. Studies addressing these modifications reveal a complex interplay between the expression levels of different proteins that regulate the alternative splicing process as well as the changes in alternative splicing. This interplay results in a cascade of different protein isoforms that correlate with the progression of nonalcoholic fatty liver disease, hepatocellular carcinoma, and alcoholic liver disease. However, research on the detailed molecular mechanism underlying the production of these isoforms is needed. It is imperative to identify the physiological processes affected by the differentially spliced isoforms and confirm their role on the onset and maintenance of the pathology. This is required to design potential therapeutic approaches targeting the key splicing changes to revert the pathological condition as well as identify prognostic markers. In this review, we describe the complexity of the splicing process through an example to encourage researchers to go down this path. Subsequently, rather than a catalog of splicing events we have hand-picked and discuss a few selected studies of specific liver pathologies and suggested ways to focus research on these areas. [ABSTRACT FROM AUTHOR]

The association of non-alcoholic fatty liver disease (NAFLD) with several other diseases has gained increased interest during the recent years. Among them, the association with chronic kidney disease (CKD) has emerged as an important one regarding both its prevalence and significance. The early recognition of this association is important for the prognosis of patients with NAFLD and CKD. Apart from early diagnosis, the accurate assessment of renal function is also crucial in the clinical practice of hepatologists. Several methods have been used in the literature for the evaluation of kidney function in patients with NAFLD up to now. In this respect, calculators (or formulas) for the estimation of Glomerular Filtration Rate (eGFR) and Albumin to Creatinine Ratio (ACR) are simple, practical and easily available methods for this purpose. The aim of this review is to report on the epidemiology and pathophysiology of the relationship between NAFLD and CKD and to describe the different methods of kidney function assessment in patients with NAFLD. The collection of all relevant data regarding this association will provide hepatologists with pertinent knowledge on this topic and allow them to use the most accurate methods for the assessment of kidney function in these patients in their clinical practice.

Aim. The purpose of the study is to assess the characteristics of heart risk variability in patients with non - alcoholic fatty liver disease (NAFLD). Materials and methods. The study included 103 patients. All patients were divided into three groups. The first group is 34 healthy patients. The second group - 34 patients with a diagnosis of coronary artery disease; exertional angina II-III FC. The third group - 35 patients diagnosed with NAFLD and type 2 diabetes. An assessment of abdominal circumference, body mass index, ALT, AST, XC, HDL, LDL, TG, glucose and the level of glycated hemoglobin (HbA1c), liver ultrasound and daily ECG monitoring with the determination of HRV were evaluated. Evaluated HRV using statistical analysis: avNN, ms; pNN 50%; SDNNidx, ms; SDNN, ms; SDNNidx, ms; RMSSD, ms. HRV characteristics were evaluated: VLF, LF, HF, LF/HF. Results. Compared with the first group, the increase in cholesterol in patients in the second group was noted by 38.8%, in the third group - by 43.7%, TG - by 34.6 and 41.95%. In patients with NAFLD + DM of the second type, SDNN and SDNNidx decreased in comparison with the healthy patients by 15% (p

The article reflects current literature data on the epidemiology and risk factors of non - alcoholic fatty liver disease. An important aspect is the description of the modern views of combined lesions of the hepatobiliary tract and small intestine. Disorders of the intestinal microbiota play a special role in the development of non - alcoholic fatty liver disease. The value of enterohepatic circulation of bile acids in the development of intestinal and liver diseases was shown. It seems relevant to further study the comorbidity of the development of non - alcoholic fatty liver disease and enteropathy for the development of pathogenetically substantiated therapy.

Alternative splicing produces complex and dynamic changes in the protein isoforms that are necessary for the proper biological functioning of the metabolic pathways involved in liver development and hepatocyte homeostasis. Changes in the physiological state of alternatively spliced forms are increasingly linked to liver pathologies. This may occur when the expression or function of the set of proteins controlling the alternative splicing processes are altered by external effectors such as oxidative stress and other environmental variations. Studies addressing these modifications reveal a complex interplay between the expression levels of different proteins that regulate the alternative splicing process as well as the changes in alternative splicing. This interplay results in a cascade of different protein isoforms that correlate with the progression of non-alcoholic fatty liver disease, hepatocellular carcinoma, and alcoholic liver disease. However, research on the detailed molecular mechanism underlying the production of these isoforms is needed. It is imperative to identify the physiological processes affected by the differentially spliced isoforms and confirm their role on the onset and maintenance of the pathology. This is required to design potential therapeutic approaches targeting the key splicing changes to revert the pathological condition as well as identify prognostic markers. In this review, we describe the complexity of the splicing process through an example to encourage researchers to go down this path. Subsequently, rather than a catalog of splicing events we have hand-picked and discuss a few selected studies of specific liver pathologies and suggested ways to focus research on these areas.

Background: Non-alcoholic fatty liver disease (NAFLD), characterized by the excessive accumulation of hepatic triglycerides (TGs), has become a worldwide chronic liver disease. But efficient therapy keeps unsettled. Our previous works show that geniposide and chlorogenic acid combination (namely the GC combination), two active chemical components combined with a unique ratio (67.16:1), presents beneficial effects on high-fat diet-induced NAFLD rodent models. Notably, microarray highlighted the more than 5-fold down-regulated SCD-1 gene in the GC combination group. SCD-1 is an essential lipogenic protein for monounsaturated fatty acids’ biosynthesis and serves as a key regulatory enzyme in the last stage of hepatic de novo lipogenesis (DNL).Methods: NAFLD mice model was fed with 16 weeks high-fat diet (HFD). The pharmacological effects, primarily on hepatic TG, TC, FFA, and liver enzymes, et al. of the GC combination and two individual components were evaluated. Furthermore, hepatic SCD-1 expression was quantified with qRT-PCR, immunoblotting, and immunohistochemistry. Finally, the lentivirus-mediated over-expressed cell was carried out to confirm the GC combination’s influence on SCD-1.Results: The GC combination could significantly reduce hepatic TG, TC, and FFA in NAFLD rodents. Notably, the GC combination presented synergetic therapeutic effects, compared with two components, on normalizing murine hepatic lipid deposition and disordered liver enzymes (ALT and AST). Meanwhile, the robust SCD-1 induction induced by HFD and FFA in rodents and ALM-12 cells was profoundly blunted, and this potent suppression was recapitulated in lentivirus-mediated SCD-1 over-expressed cells.Conclusion: Taken together, our data prove that the GC combination shows a substantial and synergetic anti-lipogenesis effect in treating NAFLD, and these amelioration effects are highly associated with the potent suppressed hepatic SCD-1 and a blunted DNL process.

The association of Non-alcoholic steatohepatitis (NASH) with type 2 Diabetes Mellitus (DM) is common. NASH in type 2 DM has not been well studied and in type 2 DM, there is an epidemic rise in advanced and advancing countries. Its coalition with chronic liver disease in the form of NASH makes it an important health problem. The world-wide commonness of non-alcoholic fatty liver disease (FLD) is estimated to have more in adults. Non Alcoholic Fatty Liver Disease (NAFLD) is often associated with insulin resistance and is strongly associated with type 2 diabetes mellitus and corpulence. NAFLD patients are at risk of progressing to NASH and ultimately cirrhosis; they are also at higher risk of cardiovascular diseases (CVD), including coronary heart disease and stroke. In this paper we are trying to analyse the risk of new CVD event in child-bearing women with diabetic and non-diabetic issues. Our attempt is to derive a statistical model for estimating the association of many such components with blood sugar, with baseline characteristics like age, obesity, diabetic level, hypertension, cholesterol level etc. Finally the significance of the model is statistically tested. We also propose to amplify our study to prove whether NASH is an independent risk factor for CVD later. [ABSTRACT FROM AUTHOR]

In recent years there has been an active discussion about the relationship between diabetes mellitus (DM) and chronic liver diseases (CLD). On the one hand, patients with diabetes have an increased risk of developing CLD. On the other hand, patients with CLD very often identify abnormal glucose metabolism which ultimately leads to impaired glucose tolerance and the development of diabetes. This review outlines potential causal relationships between some CLD and DM. Common mechanisms that provoke metabolic and autoimmune disorders in the development of various nosologies of the CKD group, leading to steatosis, insulin resistance, impaired glucose tolerance and the development of diabetes are described. Certain features of the assessment of carbohydrate metabolism compensation in patients with hepatic dysfunction, anemia and protein metabolism disorders are described.

Patients with inflammatory liver diseases, particularly alcohol-associated liver disease and metabolic dysfunction-associated fatty liver disease (MAFLD), have higher incidence of infections and mortality rate due to sepsis. The current focus in the development of drugs for MAFLD is the resolution of non-alcoholic steatohepatitis and prevention of progression to cirrhosis. In patients with cirrhosis or alcoholic hepatitis, sepsis is a major cause of death. As the metabolic center and a key immune tissue, liver is the guardian, modifier, and target of sepsis. Septic patients with liver dysfunction have the highest mortality rate compared with other organ dysfunctions. In addition to maintaining metabolic homeostasis, the liver produces and secretes hepatokines and acute phase proteins (APPs) essential in tissue protection, immunomodulation, and coagulation. Inflammatory liver diseases cause profound metabolic disorder and impairment of energy metabolism, liver regeneration, and production/secretion of APPs and hepatokines. Herein, the author reviews the roles of (1) disorders in the metabolism of glucose, fatty acids, ketone bodies, and amino acids as well as the clearance of ammonia and lactate in the pathogenesis of inflammatory liver diseases and sepsis; (2) cytokines/chemokines in inflammatory liver diseases and sepsis; (3) APPs and hepatokines in the protection against tissue injury and infections; and (4) major nuclear receptors/signaling pathways underlying the metabolic disorders and tissue injuries as well as the major drug targets for inflammatory liver diseases and sepsis. Approaches that focus on the liver dysfunction and regeneration will not only treat inflammatory liver diseases but also prevent the development of severe infections and sepsis., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Background: Obesity had become a global problem today. Obesity is a significant risk factor of cardiovascular and other metabolic diseases such as non-alcoholic fatty liver disease (NAFLD). It remains unclear if the increased mean platelet volume (MPV) at the steatosis state is practicable as early detection of the occurrence of fatty liver in individuals with central obesity. This study aims to determine the association of interleukin-6 (IL-6) and MPV levels in central obesity with or without NAFLD. Method: This study was descriptive-analytic with a cross-sectional approach conducted in Prof. dr. R. D. Kandou Manado general hospital from May to July 2018. Consecutive sampling was performed based on inclusion criteria, then IL-6, MPV, and abdominal ultrasound examinations were performed. Results: This study included 40 samples of men with central obesity, 28 people (70%) among them were diagnosed with NAFLD. The Fisher exact test showed an association between NAFLD and an increase in IL-6 (p = 0.039), also between MPV and NAFLD (p = 0.015). Pearson correlation test showed there was no significant correlation between IL-6 and MPV in the NAFLD sample group (p = 0.084; r: -0.332) and in the non-NAFLD sample group (p = 0.564; r: -0.186). Conclusion: Elevated MPV and IL-6 values may be used as marker for NAFLD presence among central obesity patients. [ABSTRACT FROM AUTHOR]

The incidence rate of nonalcoholic fatty liver disease(NAFLD) is continuously increasing in the world, and NAFLD is a major cause of chronic liver disease in developed countries such as the United States and may become the most common chronic liver disease in China in the future. NAFLD is often observed in the obese population; however, it is also commonly seen in lean individuals. This article summarizes the latest studies on lean NAFLD and elaborates on the following pathogeneses of this disease: the change in single nucleotide polymorphism is one of the predisposing factors for NAFLD in the lean population; the change of gut microbiota and sarcopenia may induce a variety of metabolic disorders including hyperlipidemia, hyperuricemia, insulin resistance, and iron metabolic disorders, and such metabolic disorders may promote the development of NAFLD; in addition, unhealthy dietary habits and lifestyle may contribute to the accumulation of fat and increase the burden of the liver. The combined effect of these factors eventually lead to the development of NAFLD, but further studies are still needed to clarify the pathogenesis of lean NAFLD. [ABSTRACT FROM AUTHOR]

The association of non-alcoholic fatty liver disease (NAFLD) with several other diseases has gained increased interest during the recent years. Among them, the association with chronic kidney disease (CKD) has emerged as an important one regarding both its prevalence and significance. The early recognition of this association is important for the prognosis of patients with NAFLD and CKD. Apart from early diagnosis, the accurate assessment of renal function is also crucial in the clinical practice of hepatologists. Several methods have been used in the literature for the evaluation of kidney function in patients with NAFLD up to now. In this respect, calculators (or formulas) for the estimation of Glomerular Filtration Rate (eGFR) and Albumin to Creatinine Ratio (ACR) are simple, practical and easily available methods for this purpose. The aim of this review is to report on the epidemiology and pathophysiology of the relationship between NAFLD and CKD and to describe the different methods of kidney function assessment in patients with NAFLD. The collection of all relevant data regarding this association will provide hepatologists with pertinent knowledge on this topic and allow them to use the most accurate methods for the assessment of kidney function in these patients in their clinical practice. [ABSTRACT FROM AUTHOR]

Abstract Background Secreted frizzled-related protein 5 (SFRP5) is an anti-inflammatory adipokine modulating metabolism dysfunction. This study aims to observe the effect of recombinant SFRP5 protein on nonalcoholic steatohepatitis (NASH). Methods We set up a prokaryotic expression system and purified the recombinant SFRP5 protein. Recombinant SFRP5 protein was further identified by SDS-PAGE, western blot, high performance liquid chromatography (HPLC), protein mass spectrometry and in vitro Wnt5a-binding test. NASH mouse model was induced by methionine and choline deficient diet (MCDD) for 2 weeks. SFRP5 treatment group received intraperitoneal injection with a dosage of 10μg/kg SFRP5 twice a day for 2 weeks. Saline was used as control. Inflammation and fatty lesion score of liver tissue pathology and serum transaminase level were compared. Results The purity of recombinant SFRP5 protein is 90% identified by HPLC. Its molecule size is 36,096.08 tested by mass spectrometry. Recombinant SFRP5 can specifically bind with Wnt5a which verifies its activity in vitro. The endotoxin level of this recombinant protein is 0.01EU/μg-0.1EU/μg and is suitable for animal experiment. SFRP5 can significantly improve liver inflammation (SFRP5 vs. control, 1.40 ± 0.70 vs. 2.00 ± 0.47, P

Non-alcoholic fatty liver disease (NAFLD) has been defined as a spectrum of histological abnormalities and is characterized by significant and excessive accumulation of triglycerides in the hepatocytes in patients without alcohol consumption or other diseases. Current studies are targeting new molecular mechanisms that underlie NAFLD and associated metabolic disorders. Many therapeutic targets have been found and used in clinical studies. Peroxisome proliferator-activated receptors (PPARs) are among the potential targets and have been demonstrated to exert a pivotal role in modulation of NAFLD. Many drugs developed so far are targeted at PPARs. Thus, the aim of this paper is to summarize the roles of PPARs in the treatment of NAFLD.

Introduction: Metabolically Healthy Obesity/Metabolic Healthy Obesity (MHO) is an enigma in scientific medical literature. Debate is still on regarding the safety status of MHO phenotype. The general consensus states that it is a condition with obesity but lacking metabolic abnormalities such as dyslipidemia, impaired glucose tolerance, or Metabolic Syndrome (MS). MHO population has less visceral adipose tissue, and a decreased inflammatory profile as compared to MS. Aim: To assess subclinical cardiovascular risk markers like Carotid Intima-Media Thickness (CIMT), Non Alcoholic Fatty Liver Disease (NAFLD) and high sensitivity C-reactive Protein (hs-CRP) level in MHO subjects. Materials and Methods: This cross-sectional study was done in a tertiary care hospital conducted for a period of three years from January 2016 to January 2019. After obtaining institutional ethical clearance, this cross-sectional study was conducted on 222 MHO subjects, 65 MS and 81 Metabolic Healthy Non Obese (MHNO) subjects. Anthropometric data was obtained. Metabolic parameters like hs-CRP, CIMT and NAFLD status were estimated and compared with MS and MHNO group. The data was analysed using appropriate statistical significance tests. Results: In one way Analysis of Variance (ANOVA), anthropometric determinants and metabolic variables differed significantly across the groups (p

Introduction: Metabolically Healthy Obesity/Metabolic Healthy Obesity (MHO) is an enigma in scientific medical literature. Debate is still on regarding the safety status of MHO phenotype. The general consensus states that it is a condition with obesity but lacking metabolic abnormalities such as dyslipidemia, impaired glucose tolerance, or Metabolic Syndrome (MS). MHO population has less visceral adipose tissue, and a decreased inflammatory profile as compared to MS. Aim: To assess subclinical cardiovascular risk markers like Carotid Intima-Media Thickness (CIMT), Non Alcoholic Fatty Liver Disease (NAFLD) and high sensitivity C-reactive Protein (hs-CRP) level in MHO subjects. Materials and Methods: This cross-sectional study was done in a tertiary care hospital conducted for a period of three years from January 2016 to January 2019. After obtaining institutional ethical clearance, this cross-sectional study was conducted on 222 MHO subjects, 65 MS and 81 Metabolic Healthy Non Obese (MHNO) subjects. Anthropometric data was obtained. Metabolic parameters like hs-CRP, CIMT and NAFLD status were estimated and compared with MS and MHNO group. The data was analysed using appropriate statistical significance tests. Results: In one way Analysis of Variance (ANOVA), anthropometric determinants and metabolic variables differed significantly across the groups (p<0.0001). The mean hs-CRP in MHO was; 4.01 ±1.68 versus control group; 2.16±0.56 (p<0.0001). Using Pearson's correlation coefficient, significant positive correlation was found between the sub clinical CVD risk markers with other anthropometric and metabolic parameters. In multiple regression analysis body mass index Waist Circumference (WC), NAFLD and abnormal CIMT were significantly associated with elevated hs-CRP. The mean CIMT in MHO was; 0.74±0.17 versus control group; 0.65±0.14 (p<0.0001). In multiple regression analysis NAFLD and hs-CRP were significantly associated with CIMT values. Prevalence of NAFLD in MHO was 59.01%. In multiple regression analysis WC, CIMT and hsCRP were significantly associated with NAFLD. Adjusted Odd's Ratio (AOR) for high hs-CRP, NAFLD, and abnormal CIMT in MHO as compared to MHNO was 1.98, 1.81, 1.61 respectively. Conclusion: MHO phenotype is associated with higher prevalence of fatty liver, increased hs-CRP levels and abnormal CIMT as compared to MHNO phenotype. This indicates that obesity even if associated with a healthy metabolic profile, still harbour subclinical inflammation. So subjects with MHO should be targeted for appropriate preventive strategies in form of health education, life style modifications to avoid future cardiovascular morbidities. MHO phenotype with evidence of subclinical vascular inflammation should not be considered a benign condition. [ABSTRACT FROM AUTHOR]

Aim: This study aims to determine the prevalence of non-alcoholic fatty liver in diabetic patients. Materials and Methods: A total of 100 case reports of diabetic patients were collected. A pro forma was created with details such as the name, age, fasting blood sugar, postprandial blood sugar, hemoglobin A1c, liver function test, renal function test, diabetic foot ulcer, electrolyte levels, and ultrasound sonography abdomen. Diabetic patients with the habit of alcohol consumption were excluded from the study. The data were collected and compared. Results: About 23% of diabetic patients had non-alcoholic fatty liver disease. Conclusion: From this study, we can conclude that diabetic patients are at the risk of getting fatty liver disease along with other systemic problems like cardiovascular disease. [ABSTRACT FROM AUTHOR]

Perlemakan Hati Non Alkoholik (Non Alcoholic Fatty Liver Disease/NAFLD) merupakan salah satu penyebab utama dari penyakit hati kronis di negara berkembang. NAFLD dapat berkembang menjadi menjadi penyakit hati yang lebih berat seperti Non Alcoholic Steatohepatis (NASH), sirosis hepatis, dan karsinoma hati. Tatalaksana NAFLD terus berkembang, dan saat ini klinisi dihadapkan dengan berbagai pilihan alternatif baik dari segi nonfarmakoterapi maupun farmakoterapi. Tulisan ini akan membahas berbagai pilihan terapi NAFLD terkini tersebut berdasarkan bukti terbaru.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manife-station of metabolic syndrome. The increased prevalence of obesity, diabetes, hypertension, hypertriglyceridaemia and hypercholesterolemia are considered to be the potential causative factors for NAFLD. NAFLD is emerging as a major clinical problem worldwide. Recently much attention has been focused in India as the prevalence of obesity and diabetes is rising. NAFLD is responsible for unexplained raise in transaminases, and an important cause of cryptogenic cirrhosis and cryptogenic hepatocellular carcinoma in India. NAFLD is a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), potentially leading to fibrosis and cirrhosis. Studies have suggested that the adipokines are involved in the pathogenesis of NAFLD and its progression to NASH, through their metabolic and pro- or anti-inflammatory activity. Adipokines in particular tumor necrosis factor-α and interleukin-6 are believed to mediate the shift in pathology from steatosis to steatohepatitis. In addition, other adipokines such as adiponectin, leptin and resistin also play a crucial role in the development and progression of NAFLD through their metabolic and pro–or anti-inflammatory activity. This suggests that imbalance between pro-inflammatory and anti-inflammatory cytokines may have a role in the development of liver damage in NAFLD. Understanding the relationship between adipokines and NAFLD may play an important role in the early identification /diagnosis, treatment and also help in preventing disease progression.

Background and aims Obesity is frequently associated with non-alcoholic fatty liver disease (NAFLD), insulin resistance (IR), inflammation and metabolic syndrome (MetS), all of which increase the risk of type 2 diabetes (T2DM). However, the role of these risk factors in mediating the effect of obesity remains unclear. We investigated the association between obesity and T2DM in the absence and presence of NAFLD, IR, inflammation and MetS components. Methods 29,836 obese subjects without diabetes were studied in a Korean health screening program. Obesity was defined by the appropriate ethnic-specific body mass index (BMI) threshold ≥25 kg/m 2 . Hazard ratios (HRs and 95% confidence intervals, CIs) for incident T2DM were estimated for the group with no hypertension, dyslipidemia, impaired fasting glucose, fatty liver, IR, or inflammation ( n  = 1717), compared to the reference group, with one or more of these factors ( n  = 19,757). Results Mean (SD) age at baseline was 37 (7) years and 1200 incident cases of diabetes occurred. Crude T2D incidence was 12.6/10,000 person-years in the group without metabolic abnormality and 143/10,000 person-years in the reference group. HR (95% CIs) for incident diabetes was 0.13 (0.06, 0.33) in the group without metabolic abnormality. Conclusions Obese subjects without components of the metabolic syndrome, IR, fatty liver and inflammation have an approximately 11-fold lower risk of incident type 2 diabetes than obese subjects who have these risk factors. These simple factors could be used to target limited resources in high risk obese subjects in the prevention of diabetes. [ABSTRACT FROM AUTHOR]

Abstract: The estimated prevalence of non‐alcoholic fatty liver disease (NAFLD) worldwide is approximately 25%. However, the real prevalence of NAFLD and the associated disorders is unknown mainly because reliable and applicable diagnostic tests are lacking. This is further complicated by the lack of consensus on the terminology of different entities such as NAFLD or nonalcoholic steatohepatitis (NASH). Although assessing fatty infiltration in the liver is simple by ultrasound, the gold standard for the assessment of fibrosis, the only marker of progression towards more severe liver disease is still liver biopsy. Although other non‐invasive tests have been proposed, they must still be validated in large series. Because NAFL/NAFLD/NASH and related metabolic diseases represent an economic burden, finding an inexpensive method to diagnose and stage fatty liver is a priority. A translational approach with the use of cell and/or animal models could help to reach this goal. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between non alcoholic fatty liver disease and coronary artery disease. Methodology: This cross sectional study was conducted from July to December 2016, in Cardiology Unit, Lady Reading Hospital. By using non probability consecutive sampling, patients of all age groups and either gender, presenting to cath lab for coronary angiography, indicated for angina CCS III, were included in the study. All patients fulfilling inclusion and exclusion criteria were subjected to screening for NAFLD by using ultrasonography. Patients were classified into having no, mild, moderate and sever NAFLD. Correlation between NAFLD and CAD, confirmed on cath was done using chi square test. Results: Total of 370 patients with mean age of 55.36 ± 10.07 years were enrolled in the study, of which 44.6% were females. Known risk factors for CAD like diabetes mellitus, hypertension, and smoking were present in 63.5%, 64.9% and 23% respectively. About 28.4% of patients had no NAFLD, 28.4% had mild, 28.4% had moderate and 14.4% had sever NAFLD, 12.2% had no CAD while mild, moderate and sever disease was present in 36.5%, 31.1% and 2.3% respectively. By using Chi square test relation between NAFLD and CAD was calculated and came out to be 285.5 (p<0.000). NAFLD also increased the POR of having by 2.9times with p<0.000. Conclusion: NAFLD can be considered as an independent risk factor with CAD and increases the odds of having CAD. [ABSTRACT FROM AUTHOR]

Background & aims. In our country prospective studies to establish the prevalence of obesity and non-alcoholic fatty liver disease (NAFLD) are lacking. We prospectively assessed the prevalence and severity of NAFLD in a cohort of asymptomatic patients attending the national screening programme for colorectal cancer. Methods. Screening for NAFLD was performed using abdominal ultrasound and Fibroscan with CAP module. Also antropometric parameters, comorbidities like diabetes and arterial hypertension, and risk behaviours like smoking and alcohol consumption were evaluated Results. We screened 70 patients with FIT positive tests, attending for colonoscopy. The mean age was 60 ± 7.0 years, 48.5% were male, the mean BMI was 28.46 ± 4.54 kg/m2, and 37,1% were obese. The prevalence of NAFLD as evaluated as any degree of steatosis on Fibroscan with CAP module was 79.7% and the prevalence of severe steatosis was 26.6%. Significant fibrosis (F =2) was present in 13.8%. In a multivariable logistic analysis, the only factor associated with the presence of NAFLD was waist cirumference at high risk (>102 cm in men and >88 cm in women) Conclusion. The obesity and NAFLD incidence rate in asymptomatic general population is high and worrying. Abdominal obesity seems to be more predictable than BMI for the diagnosis of fatty liver. [ABSTRACT FROM AUTHOR]

The clustering of cardio-metabolic risk factors, either when called metabolic syndrome (MetS) or not, substantially increases the risk of cardiovascular disease (CVD) and causes mortality. One of the possible mechanisms for this clustering's adverse effect is an increase in arterial stiffness (AS), and in high central aortic blood pressure (CABP), which are significant and independent CVD risk factors. Arterial hypertension was connected to AS long ago; however, other MetS components (obesity, dyslipidaemia, dysglycaemia) or MetS associated abnormalities not included in MetS diagnostic criteria (renal dysfunction, hyperuricaemia, hypercoaglutability, menopause, non alcoholic fatty liver disease, and obstructive sleep apnea) have been implicated too. We discuss the evidence connecting these cardio-metabolic risk factors, which negatively affect AS and finally increase CVD risk. Furthermore, we discuss the impact of possible lifestyle and pharmacological interventions on all these cardio-metabolic risk factors, in an effort to reduce CVD risk and identify features that should be taken into consideration when treating MetS patients with or without arterial hypertension.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is emerging as an independent cardiovascular risk factor. Recently, Endocan has been studied as an early marker of endothelial dysfunction. Our aim was to evaluate Endocan serum levels in patients with NAFLD with or without type 2 diabetes mellitus. Method: We enrolled 56 patients: 19 with NAFLD and 37 with type 2 diabetes mellitus with or without NAFLD, and compared them to 25 healthy controls. Endocan serum level was measured by using the ELISA EndoMark assay. Results: Endocan level was significantly higher in NAFLD subjects, compared to controls (1.23±1.51 vs 0.68±0.4 ng/mL; p=0.016). It was higher in patients with non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH) (1.12±1.11, 1.49±2.16 and 0.68±0.4 ng/ml vs controls, respectively), independently from presence of type 2 diabetes mellitus. The increase was more marked in patients with NASH and in those with NAFL versus controls (p=0.001 and p=0.004, respectively), but not statistically different between the two groups (p=0.448). Finally, we found a statistically relevant increase of this marker in diabetic NAFLD patients compared to those non diabetic (1.56±0.81 vs 0.72±0.58 ng/ml; p=0.01). Conclusion: We demonstrated an increased Endocan serum level in NAFLD patients, higher in those with type 2 diabetes mellitus and/or NASH because of an endothelial dysfunction in these pathologies. [ABSTRACT FROM AUTHOR]