Non-alcoholic Fat Liver Disease Research Articles

Alpha lipoic acid administration improved both peripheral sensitivity to insulin and liver clearance of insulin reducing potential risk of diabetes and nonalcoholic fatty liver disease in overweight/obese PCOS patients

Objective To evaluate the effects of alpha lipoic acid (ALA) on hormonal and metabolic parameters in a group of overweight/obese Polycystic Ovary Syndrome (PCOS) patients. Methods This was a retrospective study in which thirty-two overweight/obese patients with PCOS (n = 32) not requiring hormonal treatment were selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of complementary treatment with ALA (400 mg/day). Hepatic Insulin Extraction (HIE) index was also calculated. Results ALA administration significantly improved insulin sensitivity and decreased ALT and AST plasma levels in all subjects, though no changes were observed on reproductive hormones. When PCOS patients were subdivided according to the presence or absence of familial diabetes background, the higher effects of ALA were observed in the former group that showed AST and ALT reduction and greater HIE index decrease. Conclusion ALA administration improved insulin sensitivity in overweight/obese PCOS patients, especially in those with familial predisposition to diabetes. ALA administration improved both peripheral sensitivity to insulin and liver clearance of insulin. Such effects potentially decrease the risk of nonalcoholic fat liver disease and diabetes in PCOS patients.

Identification of m6A-associated autophagy genes in non-alcoholic fatty liver.

Studies had shown that autophagy was closely related to nonalcoholic fat liver disease (NAFLD), while N6-methyladenosine (m6A) was involved in the regulation of autophagy. However, the mechanism of m6A related autophagy in NAFLD was unclear. The NAFLD related datasets were gained via the Gene Expression Omnibus (GEO) database, and we also extracted 232 autophagy-related genes (ARGs) and 37 m6A. First, differentially expressed ARGs (DE-ARGs) and differentially expressed m6A (DE-m6A) were screened out by differential expression analysis. DE-ARGs associated with m6A were sifted out by Pearson correlation analysis, and the m6A-ARGs relationship pairs were acquired. Then, autophagic genes in m6A-ARGs pairs were analyzed for machine learning algorithms to obtain feature genes. Further, we validated the relationship between feature genes and NAFLD through quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB). Finally, the immuno-infiltration analysis was implement, and we also constructed the TF-mRNA and drug-gene networks. There were 19 DE-ARGs and four DE-m6A between NAFLD and normal samples. The three m6A genes and five AGRs formed the m6A-ARGs relationship pairs. Afterwards, genes obtained from machine learning algorithms were intersected to yield three feature genes (TBK1, RAB1A, and GOPC), which showed significant positive correlation with astrocytes, macrophages, smooth muscle, and showed significant negative correlation with epithelial cells, and endothelial cells. Besides, qRT-PCR and WB indicate that TBK1, RAB1A and GOPC significantly upregulated in NAFLD. Ultimately, we found that the TF-mRNA network included FOXP1-GOPC, ATF1-RAB1A and other relationship pairs, and eight therapeutic agents such as R-406 and adavosertib were predicted based on the TBK1. The study investigated the potential molecular mechanisms of m6A related autophagy feature genes (TBK1, RAB1A, and GOPC) in NAFLD through bioinformatic analyses and animal model validation. However, it is critical to note that these findings, although consequential, demonstrate correlations rather than cause-and-effect relationships. As such, more research is required to fully elucidate the underlying mechanisms and validate the clinical relevance of these feature genes.

THERE IS NO CORRELATION BETWEEN STAGES OF NAFLD ASSESSED BY LIVER BIOPSY AND THE DIAGNOSTIC CRITERIA FOR SARCOPENIA IN ACTIVE POPULATIONS: A CROSS-SECTIONAL STUDY

Objective: To demonstrate the correlations of the diagnostic criteria for sarcopenia and the levels of Non-alcoholic Fat Liver Disease (NAFLD) assessed by liver biopsy in a physically active population. Methods: Cross-sectional study. Individuals aged >18 years, with NAFLD confirmed by liver biopsy, physically active. Sarcopenia assessment followed EWGSOP2: muscle strength by handgrip, Skeletal Muscle Mass by Bioimpedance, and physical performance by usual gait speed. Statistical Analysis: To test differences between groups in continuous variables, Student's T or Mann-Whitney U Test for independent samples. Pearson and Spearman tests were used for correlations. A 5% significance was considered (p<0.05). Results: 52 patients with NAFLD included, consisting of 35 women and 15 men. There was no difference in age or anthropometric variables.  Were found difference statically significant in platelets (higher in women), basal insulin, HOMA-IR and Quick (higher in men). In sarcopenia, the handgrip strength showed difference in favors of men. There was no statistically significant correlation between the sarcopenia and NAFLD levels. Discussion: sarcopenia has been reported as an independent risk factor for NAFLD and its progressions. The physical exercise is one of the most recommended and more effective treatment for both conditions, so is expected that a non-sedentary individual can reduce both indicators. However, there is no consensus about the best method. Also, the both conditions share heterogeneity in diagnosis, prognosis, reason for develop and risk factors across the literature. Conclusion: For populations where most individuals are physically active, it is not possible to find correlation between sarcopenia diagnostic criteria and the stages of NAFLD.

Adipocytes-derived exosomal miR-122 promotes non-alcoholic fat liver disease progression via targeting Sirt1

Adipocytes-derived exosomal miR-122 promotes non-alcoholic fat liver disease progression via targeting Sirt1

The Role of Interferon Receptors α/β/γ Ablation During Western Diet-Induced Obesity and Insulin Resistance in the Inflectional Model AG129 Mice Strain.

Diet-induced obesity triggers elevation of circulating pro-inflammatory cytokines and acute-phase proteins, including interferons (IFNs). IFNs strongly contribute to low-grade inflammation associated with obesity-related complications, such as nonalcoholic fat liver disease and diabetes. In this study, AG129 mice model (double-knockout strain for IFN α/β/γ receptors) was fed with a high-fat high-sucrose (HFHS) diet (Western diet) for 20 weeks aiming to understand the impact of IFN receptor ablation on diet-induced obesity, insulin resistance, and nonalcoholic fat liver disease. Mice were responsive to the diet, becoming obese after 20 weeks of HFHS diet which was accompanied by 2-fold increase of white adipose tissues. Moreover, animals developed glucose and insulin intolerance, as well as dysregulation of insulin signaling mediators such as Insulin Receptor Substrate 1 (IRS1), protein kinase B (AKT), and S6 ribosomal protein. Liver increased interstitial cells, and lipid accumulation was also found, presenting augmented fibrotic markers (transforming growth factor beta 1 [Tgfb1], Keratin 18 [Krt18], Vimentin [Vim]), yet lower expression on IFN receptor downstream proteins (Toll-like receptor [TLR] 4, nuclear factor kappa-light-chain-enhancer of activated B cells [NFκB], and cAMP response element-binding protein [CREB]). Thus, IFN receptor ablation promoted effects on NFκB and CREB pathways, with no positive effects on systemic homeostasis in diet-induced obese mice. Therefore, we conclude that IFN receptor signaling is not essential for promoting the complications of diet-induced obesity and thus cannot be correlated with metabolic diseases in a noninfectious condition.

Once a week consumption of Western diet over twelve weeks promotes sustained insulin resistance and non-alcoholic fat liver disease in C57BL/6 J mice

The Western diet (high in fat and sucrose) consumption is a highly prevalent feature in the whole world, mainly due to the increasing consumption of ultra-processed foods (UPF), which are cheaper and easier-to-eat, as compared to fresh and highly nutritive meals. Epidemiological studies have associated UPF consumption with development of obesity, non-alcoholic fat liver disease (NAFLD) and insulin resistance. For molecular studies, mice fed with Western diets have been used to characterize signaling pathways involved in these diet-induced pathologies. However, these studies fed mice continuously with the diets, which is not compatible with what occurs in real life, when consumption is occasional. Here, we fed mice once-a-week with a high fat, high sucrose (HFHS) diet and compared these animals with those fed continuously with HFHS diet or with a standard diet. Our results show that after a single day of consuming HFHS, animals presented impaired oral glucose tolerance test (oGTT) as compared to control group. Although this impairment was reversed after 24 h consuming regular diet, repetition of HFHS consumption once-a-week aggravated the picture such as after 12-weeks, oGTT impairment was not reversed after 6 days under control diet. Liver steatosis, inflammation, impaired insulin signaling pathway and endoplasmic reticulum stress are similar comparing animals that consumed HFHS once-a-week with those that continuously consumed HFHS, though weekly-fed animals did not gain as much weight. Therefore, we conclude that regimen of one day HFHS plus 6 days normal diet over 12 weeks is sufficient to induce insulin resistance and NAFLD in mice.

Adipocytes-derived exosomal miR-122 promotes non-alcoholic fat liver disease progression via targeting Sirt1

AimsNonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects adipose function. This study aimed to explore the function of adipocytes-derived exosomal (ADEs) miR-122 in NAFLD. MethodsA high-fat and high-fructose diet-induced rat model and a palmitic acid (PA)-induced in vitro model were established. The RNA level of miR-122 and Sirt1 was measured using qRT-PCR. The protein levels of exosome biomarkers, and lipogenesis, inflammation and fibrosis biomarkers were determined by western blotting. Cell viability and apoptosis were assessed using cell counting kit-8 and flow cytometry, respectively. Serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride levels were measured. Liver tissue damage was assessed using haematoxylin and eosin staining. The interaction between miR-122 and Sirt1 3′UTR was assessed using a luciferase reporter gene assay. ResultsADEs exhibited abundant level of miR-122 and promoted lipogenesis, impaired hepatocyte survival, enhanced liver damage and increased serum lipid levels in vivo and in vitro. Inhibition of miR-122 in ADEs alleviated NAFLD progression, lipid and glucose metabolism, liver inflammation and fibrosis both in vivo and in vitro. miR-122 binds directly to the 3′UTR of Sirt1 to suppress its expression. Moreover, Sirt1 overexpression reversed the increase in cell apoptosis, glucose and lipid metabolism, liver inflammation and fibrosis induced by ADEs in vivo and in vitro. ConclusionsThe ADEs miR-122 promotes the progression of NAFLD via modulating Sirt1 signalling in vivo and in vitro. The ADEs miR-122 may be a promising diagnostic biomarker and therapeutic target for NAFLD.

Liver cirrhosis

The liver cirrhosis (LC) is a severe disease, the 11th by the cause of death in the world, 50 % of patients die during 5 years. The most frequent etiological factors are alcoholic disease of the liver and chronic viral hepatitis. The following general pathological mechanisms are involved in LC pathogenesis: hepatocyte damage, endothelial dysfunction, oxidant stress, fibrosis activation, pathological regeneration, neoangiogenesis, architectonic impairment of the organ with the development of portal hypertension. Genetic factors contribute to the progression of the liver pathology. Depending on the LC etiology, there are the features of pathogenesis, clinical picture, morphology, diagnostics, treatment and prognosis for alcoholic liver disease, chronic viral hepatitis, nonalcoholic fat liver disease, autoimmune hepatitis, primary biliary LC, hemochromatosis, Wilson-Konovalov disease, A1-antitripcin deficiency disease. Among rare causes of LC, there are noted Budd-Chiari syndrome, cardiac cirrhosis, Indian childhood cirrhosis.

Serum interleukin-38 levels correlated with insulin resistance, liver injury and lipids in non-alcoholic fatty liver disease

BackgroundInsulin resistance, liver injury and dyslipidemia are reported in non-alcoholic fat liver disease (NAFLD) patients. Interleukin (IL)-38 may take part in the pathophysiology of insulin resistance. Nevertheless, the function of IL-38 in NAFLD is unknown. Herein, we determined whether serum IL-38 level might be utilised as a biochemical marker for diagnosing NAFLD.MethodsNAFLD patients and healthy participants (n = 91 each) were enrolled. Circulating serum IL-38 levels were detected using enzyme-linked immunosorbent assay. Other metabolic and inflammatory indices related to NAFLD were also assessed.ResultsPatients with NAFLD had higher serum IL-38 levels than healthy individuals. Significantly higher serum IL-38 levels were found in patients with severe and moderate NAFLD than in patients with mild NAFLD. IL-38 showed a significant correlation with parameters of insulin resistance, inflammation, and liver enzyme in NAFLD cases. Anthropometric, insulin resistance, inflammatory parameters, lipids and frequency of NAFLD showed significant differences among the serum IL-38 level tertiles. Participants in the 2nd and 3rd tertiles of serum IL-38 levels had a greater risk of NAFLD than those in the 1st tertile. Furthermore, IL-38 ROC curve showed a high area under ROC with 0.861.ConclusionsIt is possible for serum IL-38 to be a biomarker for NAFLD.

The Effects of Probiotics, Prebiotics and Synbiotics in Non-Alcoholic Fat Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH): A Systematic Review

Modifications in the microbiota caused by environmental and genetic reasons can unbalance the intestinal homeostasis, deregulating the host’s metabolism and immune system, intensifying the risk factors for the development and aggravation of non-alcoholic fat liver disease (NAFLD). The use of probiotics, prebiotics and synbiotics have been considered a potential and promising strategy to regulate the gut microbiota and produce beneficial effects in patients with liver conditions. For this reason, this review aimed to evaluate the effectiveness of probiotics, prebiotics, and symbiotics in patients with NAFLD and NASH. Pubmed, Embase, and Cochrane databases were consulted, and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines were followed. The clinical trials used in this study demonstrated that gut microbiota interventions could improve a wide range of markers of inflammation, glycemia, insulin resistance, dyslipidemia, obesity, liver injury (decrease of hepatic enzymes and steatosis and fibrosis). Although microbiota modulators do not play a healing role, they can work as an important adjunct therapy in pathological processes involving NAFLD and its spectrums, either by improving the intestinal barrier or by preventing the formation of toxic metabolites for the liver or by acting on the immune system.

Considering Intestinal Hyperpermeability and Immune-Inflammatory Metabolism in the Treatment of Food Allergy

Food Allergy is a chronic systemic immuno-inflammatory condition that depends on several factors, but, above all, the gastrointestinal epithelial barrier. The rupture of this intestinal barrier results in a deleterious increase in intestinal permeability allowing the paracellular permeation of molecules greater than 150 Da into the bloodstream, producing an equivalent immune response, decreasing the immune tolerance. Intestinal Hyperpermeability has been linked not only to food allergy but also to Metabolic Syndrome and Non-Alcoholic Fat Liver Disease. Here we review the factors that contribute to producing Intestinal Hyperpermeability, as well the factors that contribute to the restoration of the epithelial barrier, improving the clinical outcome of food-allergic patients. The main factors that increase the Intestinal Hyperpermeability are A) Immune-Inflammatory (food allergy itself and autoimmune conditions); B) Iatrogenic (steroids, non-steroidal anti-inflammatories, antacids, antibiotics, and gastric-bypass surgeries); C) Infectious (rotavirus, HIV, SARS-CO2, Helicobacter pylori, Candida albicans, etc.); and D) Lifestyle-related (alcoholic beverages, food addiction, food overconsumption, consumption of industrialized food with high-fructose content and emulsifiers). The main factors that restore the intestinal barrier and immune tolerances are the intestinal microbiota and functional nutrients such as Vitamin A and vegetal fibers. Mucoprotectants agents, such as gelatin tannate and xyloglucan, are in study to become part of the medical arsenal to treat Intestinal Hyperpermeability conditions.

Modification of a model of non-alcoholic fat liver disease in rats with a сombination of a hypercaloric diet and hypodynamia

Introduction. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world, and non-alcoholic steatohepatitis is the second most common cause of liver transplantation in the adult population. An urgent task is to find and develop an optimal model of NAFLD in laboratory animals, which would reproduce all the features of this disease in the clinic.Aim. Modification of the NAFLD model in laboratory animals (rats), which allows the obtained data to be transmitted to humans as fully as possible.Materials and methods. The study was conducted on 52 outbred white male rats of the same age. As the basis of the model, a hypercaloric high-fat diet was used with the addition of food appeal enhancers (sodium glutamate and liquid shrimp extract) and for the first-time conditions of hypodynamia were used – restriction of the motor activity of animals using specially designed cells, in which an individual 11 × 18 cm cell was allocated for each individual. The duration of the study was 12 months. In the course of the experiment, body weight, physical performance, biochemical parameters of blood serum and urine in dynamics were assessed, and lethality was recorded. After the end of the study, the mass of internal organs, visceral and epididymal fat was analyzed, and a histological examination of the liver was performed.Results and discussion. In the course of the experimental study, the development of NAFLD in rats of the control group of animals was histologically confirmed. A high mortality rate was revealed in the group of animals with pathology. Compared with animals of the intact group, a statistically significant increase in their body weight, liver weight, visceral and epididymal fat, a decrease in physical performance, disturbances in lipid, carbohydrate and protein metabolism were revealed, as well as signs of deterioration of the protein synthesis and excretory functions of the liver.Conclusion. A number of advantages of the NAFLD model with a combination of a hypercaloric diet and hypodynamic conditions were revealed, including the similarity of the conditions for the formation and pathogenesis of the disease in experimental animals and humans, which ensures the adequacy of data translation from preclinical practice to clinical practice.

Genetic predictors and pathophysiological features of non-alcoholic fat liver disease

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in highly developed countries. The risk of developing NAFLD and associated complications varies greatly among people of different nationalities and is determined by environmental and genetic factors. Genome-wide studies have revealed strong and reproducible associations between gene variations such as PNPLA3, TM6SF2, MBOAT7, GCKR, HSD17B1, and NAFLD. In this article, we consider the influence of genes and environmental factors on the pathophysiological features of NAFLD. The use of a sufficient population sample with the analysis of SNP arrays and the use of sequencing methods (exome and genome as a whole) will lead to the discovery of additional genetic variants, will inevitably improve the understanding of the pathogenesis of NAFLD, and will allow the development of a technology for personalized risk in assessing the disease in a patient. The aim of our study was to study the genetic predictors of NAFLD based on literature data with the interpretation of the studies. There is now strong evidence that specific variants of genetic risk have a large effect on NAFLD, and their effect is comparable to that of major metabolic risk factors such as obesity and type 2 diabetes. The increased risk extends to the onset and progression of the entire spectrum of NAFLD manifestations, including overall mortality due to liver disease. Currently, individual genetic variants do not allow the creation of a personalized risk profile; therefore, the most expedient approach today is the development of polygenic risk assessments. The number of genetic loci associated with the prevalence and outcome of NAFLD remains limited. The use of a sufficient population sample with the analysis of SNP arrays and the use of sequencing methods (exome and genome as a whole) will lead to the discovery of additional genetic variants and will inevitably improve the understanding of the pathogenesis of NAFLD and will allow the development of a technology for personalized risk in the assessment of the disease.

What Is the Effect of Physical Exercise on Nafld/Nash

Non-alcoholic fat liver disease (NAFLD) is a pathologic entity characterized by an excessive accumulation of hepatic lipid without alcohol consumption. Both endurance and strength exercise have shown to be beneficial in NAFLD. PubMed database has been searched for randomized trials and prospective cohort studies in adults aged ≥ 18, rats and mice that have investigated the effects of at least 4 weeks of exercise only or combination with diet on NAFLD from 2014 to 2019. The review selected have been those in which exercise was clearly described by type, duration, intensity, and frequency, and that the NAFLD diagnosis, as well as the outcome measures, were confirmed through, at least, one of the following methods: biopsy, anthropometric measures, blood testing, ultrasonography imaging, biochemical analysis and Image Resonance Magnetic (MRI). Lifestyle has shown to greatly influence human behavior and health, however, a major factor impacting studies results is the difficulty in controlling people`s compliance with a healthier lifestyle, unlike animals that are forced to exercise over time, frequency and intensity, according to the researchers` wish. Therefore, animal studies have shown better results of the effect of exercise on the disease. However, both human and animal studies have reached a positive change in the following parameters: weight, fat percentage, blood glucose, insulin and ALT and AST levels. Physical exercise improves non-alcoholic fat liver disease (NAFLD), however, an optimum approach is still unclear. A regular and long-term systematic practice of exercise leads to better general health, body weight control, and life quality improvement.

Vitex agnus castus and Some Female Disorders: A Review

Vitex agnus castus L., is a deciduous tree which has been utilized in ancient Greece, Iran, Egypt and Rome for over 2500 years for a large variety of female reproductive system health difficulties. In Saudi Arabia, many women have menstrual cycle disturbances and menopausal dysfunction and many have polycystic ovary syndrome at young age. Using Vitex is not in Saudi tradition like other Arab countries. Recently, just few people used this herb for treating some infertility problems. A variety of beneficial effects of this curative herb have been reported in clinical studies, including antioxidant, anti-inflammatory, hypolipidemic, anti-diabetic, hormonal modulatory, anti-nociceptive and opioidergic activities, preventing oxidative stress and nonalcoholic fat liver disease. Adverse effects of the plant are mild and reversible. The advantages of this herb as natural medicine attract the people and make it one of best choose and utilize widely in women disorders specially that related with menopauses. Its constituents could interact with dopaminergic antagonists and exhibited progesteronic and estrogenic activities. This brief review introduces this plant to Saudi society and others to expand it usage and discusses the potential effect of the plant to cure some of the women disorders displaying its main ingredients and the side effects.

Hepatic steatosis integrated approach: nutritional guidelines and joined nutraceutical administration.

The nonalcoholic fat liver disease (NAFLD) progresses in 30% of the patients to not alcoholic steatohepatitis (NASH) and subsequently in liver fibrosis and even primary cancer and death. Due to the complex physiopathology of the liver steatosis, NASH is an area orphan of specific drugs, but many authors suggest an integrated treatment based upon diet, lifestyle change, and pharmacology. Our clinical study selected from a wider patient cohort, 13 subjects, appealing to the Second Opinion Medical Consulting Network, for liver and nutritional problems. The diet was integrated with regular prescription of an herbal derivative based on Chrysanthellum americanum and Pistacia lentiscus L. extracts. Clinical data of the recruited patients including body weight, Body Mass Index, were recorded before and after treatment. Each patient underwent pre-post accurate clinical examination and lab exams. The liver stiffness and liver steatosis were evaluated by a trained hepatologist with FibroScan®. A significant reduction of anthropometric parameters was detected in all the patients at the end of the study; liver fibrosis and steatosis were instrumentally decreased in 8 subjects, but not significant changes in lab exams and no adverse effects were reported. Chrysanthellum americanum and Pistacia lentiscus L. extracts were absolutely safe and effective and gave a substantial contribution to the life quality benefit, metabolic balance and gut function in patients with hepatic steatosis.

Possibilities of ultrasonic methods of research in the diagnosis of non-alcoholic fat liver disease in children

The prevalence of non-alcohol fatty liver disease in a pediatric population over the past few decades is constantly increasing. The aim of the study - to describe the possibilities of ultrasound methods of research in the diagnosis of non-alcoholic fat liver disease in children. Materials and methods. 47 children with non-alcohol fatty liver disease, aged from 9 to 18 years were investigated: 25 boys (53.19 %) and 22 girls (46.81%). 19 children of prepubertal age (9-12 years old), which accounted for 40.43 % and 28 of puberty age (13-17 years) – 59.57 %. According to the index of body weight in 34 (72.34 %) of investigated children, an excessive body weight (85-95 percentile), and in 13 (27.66 %) children an alimentary-constitutional type of obesity (≥ 95 percentile) were registered. All patients had a laboratory-instrumental examination. Ultrasound examination of abdominal organs according to a generally accepted method, ultrasonic steatometry and ultrasound elastography for determining the signs of fibrous damage were carried out. 26 patients had the diagnosis of liver steatosis and 21 – steatohepatitis. Results of the research. Grayscale ultrasound recorded 2 degrees of echographic changes: with non-alcoholic fatty steatosis in 46.15 %, with non-alcoholic steatohepatitis in 85.71 % of cases. According to the results of steatometry, the greatest deviations were in children with excessive body weight and obesity in groups: S-1 (38.46 % – with steatosis and 33.3 % – with steatohepatitis) and S-2 (50 % – with steatosis and 52.38 % with steatohepatitis). A slight increase in the stiffness of the liver parenchyma, according to elastography, has been registered in 2 children with liver steatosis and in 3 patients with steatohepatitis. Conclusion. Ultrasonic methods are an important tool not only in screening diagnosis of the non-alcohol fatty liver disease, but in objective measurements of the fat damage degree and in determining the fibrotic changes in the liver as well.

Beneficial and deleterious effects of sitagliptin on a methionine/choline-deficient diet-induced steatohepatitis in rats

Non-alcoholic fat liver disease (NAFLD) is the most common chronic liver disease in the world. NAFLD is a spectrum of diseases ranging from simple steatosis to hepatic carcinoma. The complexity of pathomechanisms makes treatment difficult. The oral antidiabetic agents, dipeptidyl peptidase four inhibitors (DPP-4i) have been proposed as possible therapeutic agents. This study was performed using a well-established NAFLD model in rats to elucidate whether sitagliptin could prevent steatohepatitis. Rats were fed a methionine/choline-deficient (MCD) diet with or without sitagliptin treatment for six weeks. Liver tissue was examined to estimate sitagliptin’s effect on the development of NASH. The MCD diet decreased the SAM/SAH ratio, and increased plasma levels of homocysteine, free fatty acids, and long-chain acylcarnitines in the MCD rats. MMP2 and Col1A2 expression also increased under the MCD diet. Sitagliptin treatment did not reverse these effects and increased steatosis and long-chain acylcarnitines. In conclusion, sitagliptin was ineffective to prevent from NAFLD in the MCD rat model. This result challenges previous data reporting beneficial effects and is consistent with the clinical trials’ negative results.

The state of plasma hemostasis in patients with hypertonic disease and non-alcoholic fat-liver disease under conditions of hypercholesterinemia and associated statinotherapy

Background. Non-alcoholic fatty liver disease (NAFLD) is a marker of metabolic and dyslipidemic disorders. Given the prevalence of atherogenic dyslipidemias and their proven effect on the development of thrombotic cardiovascular complications in patients with NAFLD, it is important to understand the role of hemostatic blood activity.The objective: to increase the effectiveness of early diagnosis of thrombophilic blood changes in patients with hypertension (HT) combined with non-alcoholic fatty liver disease by determining the state of plasma hemostasis in conditions of hypercholesterolemia and concomitant statin therapy.Materials and methods. 152 patients were examined. Groups of patients: I - 46 patients with stage II HT, II - 54 patients with NAFLD without HT, group III - 52 patients with stage II HT with concomitant NAFLD.Results. The degree of spontaneous аggregаtion wаs significаntly higher in pаtients with hypercholesterolemiа - by 32.4% (p <0.05). The level of fibrinogen wаs higher by 13.5% (p <0.05) due to hypercholesterolemiа, аt the sаme time there wаs а decreаse in аntithrombin III by 8.7% (p <0.05) in pаtients with high cholesterol. Pаtients with comorbid HT аnd NАFLD on stаtin therаpy hаd а 16.5% (p <0.05) lower degree of spontаneous аggregаtion thаn pаtients who did not receive this treаtment. In the NАFLD group, pаtients receiving stаtins hаd а significаntly lower degree of АC-induced аggregаtion аgаinst pаtients without lipid-lowering therаpy (by 54.0%, p <0.001). However, the аnаlysis of the generаl populаtion of the exаmined reveаled а decreаse in the degree of collаgen-induced аggregаtion by 38.7% (p <0.05) in а subgroup of pаtients receiving treаtment. We observed а 23.4% (p <0.001) shortening of PTT in the NАFLD group аnd а 16.0% (p <0.05) shortening in the combined course of HT аnd NАFLD. In the аbsence of stаtin therаpy in the NАFLD group, there wаs а significаnt decreаse in INR - by 9.7% (p <0.05) - compаred with pаtients receiving lipid-lowering therаpy. А decreаse in TT by 12.2% (p <0.05) wаs observed in the subgroup receiving stаtins аmong pаtients with NАFLD. In the generаl cohort, the use of stаtins increаsed the аctivity of АT III by 10.7% (p <0.01), but in the NАFLD group this difference wаs more significаnt - by 14.3% (p <0.001) АT III wаs more аctive in pаtients who received lipid-lowering therаpy.Conclusion. The results of the аnаlysis proved thаt pаtients with hypercholesterolemiа hаve procoаgulаnt аnd prothrombogenic blood аctivity, but аgаinst the bаckground of stаtin treаtment there is а decreаse in plаtelet аggregаtion, blood coаgulаtion potentiаl аnd increаsed аctivity of аnticoаgulаnt hemostаsis.

Relative contribution of fat diet and physical inactivity to the development of metabolic syndrome and non-alcoholic fat liver disease in Wistar rats

Relative contribution of fat diet and physical inactivity to the development of metabolic syndrome and non-alcoholic fat liver disease in Wistar rats