Nonalcoholic Steatosis Research Articles

Hepatic fibrosis as an additional risk factor for the development of cardiovascular disorders in patients with type 2 diabetes mellitus with non-alcoholic fatty liver disease

The aim of the study was to determine the relationship between the degree of progression of liver fibrosis and the risk of cardiovascular complications in patients with Type 2 diabetes mellitus (DM) with non-alcoholic fatty liver disease (NAFLD). The study included 110 patients with Type 2 diabetes (62 men and 48 women), the average age of the subjects was 52.07±1.11 years. All patients were divided into 2 groups: the main group included 72 patients with Type 2 diabetes with concomitant NAFLD (38 men and 34 women); the control group included 38 patients with Type 2 diabetes without clinical manifestations of NAFLD (24 men and 14 women). Patients of the main group were divided into 3 subgroups, taking into account the predominant pathological processes in the clinical picture. The division into subgroups was carried out in 2 stages: at the first stage, those with predominant manifestations of liver fibrosis (F2 or more) were selected from the general population of patients with Type 2 diabetes with NAFLD according to the results of liver elastography and the use of Bonacini and Metavir scales. The number of such patients was 29, which accounted for 40.3% of the total number of patients in the main group. The remaining patients were divided into 2 subgroups: 11 patients (15.3%) had non-alcoholic liver steatosis, and 32 patients (44.4%) had signs of non-alcoholic steatohepatitis (NASH). As a result of the study, it was found that the presence of liver fibrosis in patients with Type 2 diabetes with NAFLD is significantly more often associated with cardiovascular complications, such as arterial hypertension, coronary heart disease, myocardial infarction, stroke, diabetic retinopathy and nephropathy. A significant decrease in the ejection fraction (EF) was found in patients with Type 2 diabetes with concomitant NAFLD. At the same time, the number of patients with EF disorders of varying degrees in the main group significantly exceeded that in the comparison group (33.3% and 6.7%, respectively, p<0.001). The average values of left ventricular myocardial mass are significantly lower in patients with NASH and fibrosis formation compared to patients with NAFLD at the stage of fatty hepatosis. There was also a significant decrease in the size of the left and right atria in patients with NASH compared to both patients with steatosis and patients with fibrotic liver changes. Patients with predominant fibrotic changes in the liver are characterized by a relative decrease in myocardial mass, a decrease in final diastolic and systolic volumes and EF, which may indicate the development of diastolic dysfunction in them. It is shown that it is necessary to take into account in clinical practice not only the generally accepted stages of NAFLD, but also the predominant pathological process in the liver in patients with Type 2 diabetes, namely steatosis, manifestations of inflammation and fibrotic disorders. It is proved that fibrotic changes in the liver can develop at all stages of liver tissue damage.

Does Nonalcoholic Pancreatic Steatosis Always Correlate with Nonalcoholic Fatty Liver Disease?

PurposeTo identify the correlation of nonalcoholic pancreatic steatosis (NAPS) with nonalcoholic fatty liver disease (NAFLD) in an outpatient group. Based on its metabolic and imaging properties, NAPS has been increasingly recognized in recent years; however, its interaction with NAFLD is still not clear.Patients and MethodsIn this cross-sectional observational study, 345 consecutive patients without any chronic illness who were referred to the senior radiologist for abdominal ultrasound (US) were included. The US report showed hepatic and pancreatic echogenicity. The patients’ demographic, anthropometric, and laboratory data were collected from medical records.ResultsOverall, NAPS and NAFLD were seen in 227 (65.8%) and 219 (63.5%) patients, respectively. Normal echogenicity was noted in 74 (21.4%) patients. Forty-four patients (12.8%) had steatotic liver without NAPS, 52 (15.1%) had steatotic pancreas without NAFLD, and 175 (50.7%) had steatosis in both organs. The discordance in steatosis grading between NAPS and NAFLD was 55.1%. Insulin resistance was present in 8.7, 26.7, 19, and 61.3% of patients with no steatosis, only NAFLD, only NAPS, and steatosis in both organs, respectively. Evident NAFLD and NAPS having grade 2 and 3 steatosis were present in 15.3% and 29.0% of the study group, respectively. Cholecystolithiasis was present in 6.8, 13.6, and 28.8% of patients with normal echogenic pancreas, only NAFLD, and only NAPS, respectively (p=0.01).ConclusionBased on the ultrasonographic, clinical, demographic, and anthropometric features of the included patients, we found that NAPS did not fully accompany nonalcoholic fatty liver. Despite severe pancreatic steatosis, more than a quarter of cases had normal liver echogenicity. Insulin resistance frequency was insignificantly higher in NAFLD than NAPS (p=0.694). The significantly higher frequency of cholecystolithiasis in NAPS needs further large-scale studies. The inconsistency of steatosis degree in NAPS and NAFLD in >50% cases may reflect differences in the pathophysiology of these two clinical entities.

PECULIARITIES OF THE CLINICAL COURSE OF NON-ALCOHOLIC STEATOHEPATITIS AND STEATOSIS OF THE LIVER AT COMORBID WITH CHRONIC KIDNEY DISEASE I-III STAGE

Purpose - to establish clinical peculiarities of the clinical course of the liver nonalcoholic steatosis (NALS) and steatohepatitis (NASH) at comorbidity with chronickidney disease (CKD) (chronic pyelonephritis) I-III stage.Material and methods. We have examined 444 patients: 84 patients with non-alcoholicadipose liver disease (NAALD) with obesity I degree (I group), containing 2 subgroups -32 patients with NALS and 52 patients with NASH; 270 NAALD patients with comorbidobesity I degree and CKD I-III stages (group 2), including 110 patients with NALS and160 patients with NASH. The control group consisted of 90 patients with CKD I-III stagewith normal body weight.Results. Clinical peculiarities of the liver non-alcoholic steatosis at comorbidity withCKD are a significant prevalence, in comparison with the clinical course without kidneypathology, of the frequency of manifestation of astheno-vegetative (70,9% to 40,6%),dyspeptic (33,6% to 18,8%), cholestatic (30,9% to 15,6%) syndromes, hepatomegaly(97,3% - 71,8%), predominance of steatosis II and III degree (47,2% and 31,8% to 25,0% and 15, 6% at NALS without kidney pathology). High frequency of asthenovegetative(98,1% to 61,5%) syndrome, dyspepsia (79,4% to 59,6%), discomfort in the rightsubcostal area (84,4% to 32,7%), cholestasis (37,5% to 17,3%), hepatomegaly (100,0%to 86,5%), prevalence of steatosis II and III degree (58,1% and 26,3% to 32,7% and11,5% at NASH without kidney pathology) is peculiar for non-alcoholic steatohepatitisclinical course at comorbidity with CKD as compared to the course without kidneypathology.Conclusions. Thus, the clinical course of nonalcoholic steatosis and steatohepatitis atcomorbidity with obesity and chronic kidney disease (CKD) is characterized by higherfrequency and intensity of the clinical and biochemical syndromes.

The Role of Lipid Profile as an Independent Predictor of Non-alcoholic Steatosis and Steatohepatitis in Morbidly Obese Patients.

Background and Aims: Obesity is one of the major health problems worldwide. Morbid obesity (body mass index >40 kg/m2 or over 35 with a comorbidity) is associated, apart from other diseases, with an increased risk of non-alcoholic fatty liver disease (NAFLD). Moreover, dyslipidemia is an important comorbidity that is frequently found in NAFLD patients. The aim of this study was to analyze whether serum lipids in morbidly obese patients are associated with the spectrum of NAFLD.Methods: Total serum cholesterol, LDL cholesterol, HDL cholesterol, non-HDL cholesterol, VLDL, and triglycerides were analyzed in 90 morbidly obese patients. The association of lipid profile parameters with histopathological, elastographic, and sonographic indices of NAFLD, non-alcoholic steatohepatitis (NASH), and liver fibrosis were explored.Results: The mean levels of serum total cholesterol, LDL-C, and non-HDL cholesterol in patients with positive histology for liver steatosis and NASH were significantly higher than those in patients with negative histology. None of the indices showed a strong association with NAFLD, NASH, or liver fibrosis after adjustment for potential confounders.Conclusion: A slight predictive value of lipid profile is not sufficiently enough to use solely as a non-invasive test in predicting NASH or liver fibrosis.

Recurrent FAN1 p.W707X Pathogenic Variant Originating Before ad 1800 Underlies High Frequency of Karyomegalic Interstitial Nephritis in South Pacific Islands

Recurrent FAN1 p.W707X Pathogenic Variant Originating Before ad 1800 Underlies High Frequency of Karyomegalic Interstitial Nephritis in South Pacific Islands

Hepatocyte Nuclear Factor 4α Prevents the Steatosis-to-NASH Progression by Regulating p53 and Bile Acid Signaling (in mice).

Hepatocyte nuclear factor 4α (HNF4α) is highly enriched in the liver, but its role in the progression of nonalcoholic liver steatosis (NAFL) to NASH has not been elucidated. In this study, we investigated the effect of gain or loss of HNF4α function on the development and progression of NAFLD in mice. Overexpression of human HNF4α protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of Hnf4α had opposite effects. HNF4α prevented hepatic triglyceride accumulation by promoting hepatic triglyceride lipolysis, fatty acid oxidation, and VLDL secretion. Furthermore, HNF4α suppressed the progression of NAFL to NASH. Overexpression of human HNF4α inhibited HFCF diet-induced steatohepatitis in control mice but not in hepatocyte-specific p53-/- mice. In HFCF diet-fed mice lacking hepatic Hnf4α, recapitulation of hepatic expression of HNF4α targets cholesterol 7α-hydroxylase and sterol 12α-hydroxylase and normalized hepatic triglyceride levels and attenuated steatohepatitis. The current study indicates that HNF4α protects against diet-induced development and progression of NAFLD by coordinating the regulation of lipolytic, p53, and bile acid signaling pathways. Targeting hepatic HNF4α may be useful for treatment of NASH.

MicroRNA-29c Acting on FOS Plays a Significant Role in Nonalcoholic Steatohepatitis Through the Interleukin-17 Signaling Pathway.

Nonalcoholic fatty liver disease is the most common hepatic disease in western countries and is even more ubiquitous in Asian countries. Our study determined that TH17/Treg cells were imbalanced in animal models. Based on our interest in the mechanism underlying TH17/Treg cell imbalance in nonalcoholic fatty liver mice, we conducted a joint bioinformatics analysis to further investigate this process. Common gene sequencing analysis was based on one trial from one sequencing platform, where gene expression analysis and enrichment analysis were the only analyses performed. We compared different sequencing results from different trials performed using different sequencing platforms, and we utilized the intersection of these analytical results to perform joint analysis. We used a bioinformatics analysis method to perform enrichment analysis and map interaction network analysis and predict potential microRNA sites. Animal experiments were also designed to validate the results of the data analysis based on quantitative polymerase chain reaction (qPCR) and western blotting. Our results revealed 8 coexisting differentially expressed genes (DEGs) and 7 hinge genes. The identified DEGs may influence nonalcoholic steatosis hepatitis through the interleukin-17 pathway. We found that microRNA-29c interacts with FOS and IGFBP1. Polymerase chain reaction analyses revealed both FOS and microRNA-29c expression in NASH mice, and western blot analyses indicated the same trend with regard to FOS protein levels. Based on these results, we suggest that microRNA-29c acts on FOS via the interleukin-17 signaling pathway to regulate TH17/Treg cells in NASH patients.

Phosphonate inhibits steatosis and lobular inflammation of non-alcoholic steatohepatitis through depleting macrophages

Objective: To explore the role of macrophages in non-alcoholic steatohepatitis (NASH) in order to provide directions for the therapeutic target of metabolic liver disease. Methods: Twenty C57BL/6 wild-type male mice at 6-8 weeks were randomly divided into two groups: 5 in the control group, methionine-and choline-deficient diet (MCD); 15 in the experimental group, MCD diet + intraperitoneal injection of disodium chlorophosphonate liposomes (to clear macrophages). Mice were fed for 4 weeks to establish NASH model. Blood, liver and spleen were collected to analyze the body mass index, liver index, spleen index, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Non-alcoholic steatosis (NAS) activity score was evaluated by HE and Oil Red O staining. The relative expression level of F4/80 mRNA was compared by RT-PCR. Data comparison between groups was analyzed by t-test. Results: NASH model was successfully established by feeding the mice with MCD for four week. The expression of F4/80 mRNA (t = 4.167, P < 0.01), hepatic steatosis (t = 10.70, P < 0.05), interlobular inflammatory infiltration (t = 3.08, P < 0.05), and NAS score were decreased (t = 8.06, P < 0.05) in the experimental group. At the same time, ALT level [(817.00 ± 128.90) U/L vs. (231.20 ± 36.28) U/L, t = 5.71, P < 0.01], AST level [(1 211.00 ± 248.90) U/L vs. (505.30 ± 88.20) U/L, t = 3.32, P < 0.01] was decreased significantly. However, the spleen volume and spleen index of the experimental group were larger (0.24 ± 0.01 and 0.32 ± 0.02, t = 2.41, P < 0.05), and there was no significant effect on liver ballooning, body mass index and liver index. Conclusion: In NASH, phosphonate can consume macrophages to inhibit liver inflammation and protect the damaged liver.

CONSTRUCTION OF COMPUTER MODEL FOR DIAGNOSTICS AND MONITORING OF NON-ALCOHOLIC FATTY LIVER DISEASE

Timely diagnosis and treatment of non-alcoholic fatty liver disease (NAFLD) are essential to prevent the development of steatohepatitis and liver cirrhosis. This is especially true for patients with type 2 diabetes. The aim of our workwas to build a computer model for the diagnosis and monitoring of NAFLD treatment. Materials and methods. The study included more than 55 clinical and laboratory parameters of 233 patients with non-alcoholic steatosis (NAS) and 60 patients with steatohepatitis (NASH). Results. The calculations were based on the levels of systolic blood pressure, erythrocytes, ALT, AST, glutamate dehydrogenase and platelets in persons with type 2 diabetes mellitus with NAS and NASH. The model allows to differentiate NAS andNASH with a sensitivity of 82% and a specificity of 88%

Hepatic connective tissue growth factor expression and regulation differ between non-steatotic and non-alcoholic steatotic livers from brain-dead donor

Accurate evaluation of liver steatosis is required from brain-dead donors (BDDs) with nonalcoholic fatty liver disease (NAFLD). Our purposes were to investigate expression and regulation of connective tissue growth factor (CTGF) expression in livers from human and rat after brain death, and further evaluate its potential application. NAFLD and brain death models were established in rats. LX2 cells were cultured under hypoxia/reoxygenation. CTGF protein and mRNA levels were measured in liver samples from BDDs of human and rat by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. YAP-regulated CTGF expression was investigated in LX2 cells via YAP small interfering RNA and Verteporfin treatment. Blood CTGF level from BDDs was measured by enzyme-linked immunosorbent assay. After brain death, CTGF, transforming growth factor-β and YAP were overexpressed in non-alcoholic steatotic liver, whereas CTGF was downregulated in non-steatotic liver. Time-series analysis revealed that CTGF and YAP expression was comparable, as confirmed by inhibited YAP expression in LX2 cells. CTGF level and NAFLD activity were linearly correlated. CTGF expression and regulation differ between non-steatosis and nonalcoholic steatosis livers from BDDs. CTGF may be an important factor to evaluate graft quality from BDDs with NAFLD.

Prevalence of advanced liver fibrosis and steatosis in type-2 diabetics with normal transaminases: A prospective cohort study.

BACKGROUNDNonalcoholic fatty liver disease (NAFLD) and type-2 diabetes mellitus (T2DM) have an intricate bidirectional relationship. Individuals with T2DM, not only have a higher prevalence of non-alcoholic steatosis, but also carry a higher risk of progression to nonalcoholic steatohepatitis. Experts still differ in their recommendations of screening for NAFLD among patients with T2DM.AIMTo study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM.METHODSDuring the study period (November 2018 to January 2020), 59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively. Patients with known significant liver disease and alcohol use were excluded. Demographic data and lab parameters were recorded. Liver elastography was performed in all patients.RESULTSIn the study group comprised of patients with T2DM and normal alanine aminotransferase levels (mean 17.8 ± 7 U/L), 81% had hepatic steatosis as diagnosed by elastography. Advanced hepatic fibrosis (stage F3 or F4) was present in 12% of patients with T2DM as compared to none in the control group. Patients with T2DM also had higher number of individuals with grade 3 steatosis [45.8% vs 11.5%, (P < 0.00001) and metabolic syndrome (84.7% vs 11.5%, P < 0.00001)].CONCLUSIONA significant number of patients with T2DM, despite having normal transaminase levels, have NAFLD, grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.

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.

Assessment of Left Ventricular Diastolic Function in Young Adults with Nonalcoholic Fatty Liver Disease.

There is strong evidence that, in addition to increasing the risk of cirrhosis as well as hepatocellular carcinoma, nonalcoholic liver disease represents an independent risk factor for different diseases including cardiovascular and chronic kidney disease and also type 2 diabetes. Objective: to assess whether nonalcoholic fatty liver disease is associated with diastolic dysfunction of the left ventricle, independent of other classic risk factors. Methods: we included 79 patients aged 15-45, diagnosed with non-alcoholic liver disease, and a group of 80 healthy people in the same age group. We assessed left ventricular diastolic function using Doppler pulsed wave transmitral flow and Tissue Doppler Imaging methods. Results: there were lower velocities of E and e’ wave, a decrease in E/A ratio and an increase in E/e’ ratio in the group of patients with hepatic steatosis and in those with associated diabetes compared to the control group, but not the same was observed when comparing patients with steatosis alone vs. hepatic steatosis and associated diabetes mellitus. Conclusion: nonalcoholic steatosis is linked to echocardiographic features of early diastolic dysfunction that are present in patients suffering from diabetes.

THE COURSE OF CHRONIC KIDNEY DISEASE (CHRONIC PYELONEPHRITIS) IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE AND OBESITY

The aim of the research: to investigate the features of the comorbid course of chronic kidney disease (CKD) (chronic pyelonephritis), non-alcoholic fatty liver disease and obesity, depending on the stage of CKD. To achieve this goal, 250 patients with chronic kidney disease (CKD) (chronic bilateral pyelonephritis) stage I–III were examined, of which 160 patients had concomitant NASH and class 1 obesity (1 group) and 90 people had CKD stage I–III without NASH and obesity (group 2). Depending on the stage of CKD, patients of group 1 were divided into 3 subgroups: with CKD stage I – 63 patients, with CKD stage II – 52 patients, with CKD stage III – 45 patients. Patients of group 2 were also divided into 3 subgroups: with CKD stage I – 32 patients, with CKD stage II – 31 patients, with CKD stage III – 27 patients. The control group included 30 apparently healthy individuals (AHIs). The average age of patients was 49.8 ± 5.8 years. The study did not include patients with CKD stage I–III with nephrotic syndrome and patients with chronic uncomplicated pyelonephritis in the phase of exacerbation. According to the results of our study, we noted a probable effect of nonalcoholic steatosis and steatohepatitis on the functional state of the kidneys in patients with stage I–III CKD: significant changes in glomerular filtration rate, nitrogen excretory function, increased hypoalbuminemia, increased protein in the urine, erythrocytes, leukocytes, the presence of bacteria, compared with patients with CKD without comorbidity. There was a significant correlation between a decrease in glomerular filtration rate (GFR), an increase in the intensity of oxidative stress, a decrease in blood glutathione, hydrogen sulfide, hyperproduction of homocysteine, cytokeratin-18, connective tissue components (collagen, sialic acids). In patients with CKD stage I–II without comorbid NASH and obesity, we found a significantly higher renal functional reserve in response to water-electrolyte stimulation, which is sufficient in both groups of patients (increase in GFR by 28–37% vs. 19–31% for comorbidity with NASH). In patients with CKD stage III with nonalcoholic steatohepatitis we found a significantly reduced functional reserve of the kidneys (increase in GFR by 8.9% vs. 17.5% in patients without NASH), and in 4.9% of patients with comorbidity ­– no functional reserve of the kidneys (p &gt; 0.05), indicating irreversible changes in the functional state of the kidneys.

Role of mitochondria in liver metabolic health and diseases

The liver is a major organ that coordinates the metabolic flexibility of the whole body, which is characterized by the ability to adapt dynamically in response to fluctuations in energy needs and supplies. In this context, hepatocyte mitochondria are key partners in fine-tuning metabolic flexibility. Here we review the metabolic and signalling pathways carried by mitochondria in the liver, the major pathways that regulate mitochondrial function and how they function in health and metabolic disorders associated to obesity, i.e. insulin resistance, non-alcoholic steatosis and steatohepatitis and hepatocellular carcinoma. Finally, strategies targeting mitochondria to counteract liver disorders are discussed.

Involvement of G protein-coupled receptor kinase 2 (GRK2) in the development of non-alcoholic steatosis and steatohepatitis in mice and humans

Involvement of G protein-coupled receptor kinase 2 (GRK2) in the development of non-alcoholic steatosis and steatohepatitis in mice and humans

The ratio of the main phylotypes of the intestinal microbiota in patients with non-alcoholic fatty liver disease against the background of obesity and its correlation with the stage of hepatic steatosis

Objective — to study the ratio of the main phylotypes of the gut microbiota (GM) in patients with non‑alcoholic fatty liver disease (NAFLD) depending on the body mass index and its correlation with the stage of hepatic steatosis.Materials and methods. The study included 140 individuals. The main group consisted of 120 patients with NAFLD, who were divided into two subgroups depending on body mass index: I — 85 (70.83 %) patients with concomitant obesity (OB) I — III degree, II — 35 (29.17 %) overweight patients. Each subgroup was divided into two groups depending on the stage of NAFLD: A — non‑alcoholic steatosis (NAS), B — non‑alcoholic steatohepatitis (NASH). The control group consisted of 20 apparently healthy individuals. In the main group there were 59 (49.2 %) men and 61 (50.8 %) women, in the control group — 8 (40.0 %) and 12 (60.0 %), respectively. The median and interquartile range of the age of patients in the study group was 48.75 [40.5; 60.0] years, in the control group — 46.30 [35.00; 56.00] years. All patients underwent ultrasound examination of the liver, general clinical and laboratory examinations with measurement of the level of the main phylotypes (Bacteroidetes, Firmicutes and Actinobacteria) in the fecal contents by the polymerase chain reaction method in real time and calculating the Firmicutes/Bacteroidetes ratio.Results. As the result of investigation of the ratio of the main phylotypes of GM it has been revealed that in subgroup ІА (n = 34) the value of Firmicutes/Bacteroidetes ratio was 6.96 [1.57; 8.39], in subgroup IB (n = 51) — 8.68 [1.77; 10.40], in subgroup IIA (n = 26) — 5.25 [1.14; 7.37], in subgroup II B (n = 9) — 3.30 [1.17; 6.17]. Indicators in the subgroups did not differ significantly, though significantly differed from the indicator of the control group (0.64 [0.52; 1.47]). The increase in Firmicutes/Bacteroidetes ratio in the studied subgroups was associated with the enrichment of GM with bacteria of Firmicutes type: 51.91 [42.6; 64.96] %, 53.65 [41.85; 69.66] %, 48.35 [37.47; 62.99] % and 44.31 [37.43; 62.80] % in subgroups ІА, ІB, ІІА, IIB, respectively. The relative content of Firmicutes was almost the same in the subgroups, but significantly different from the indicator of the control group (34.65 [24.58; 43.53] %), and the relative content of Bacteroidetes was less and was 18.77 in subgroup IA — 18.77 [8.10; 26.09] %, in subgroup IB — 18.79 [5.78; 25.76] %, in subgroup IIA — 24.69 [8.38; 34.04] %, in subgroup II B — 25.19 [12.93; 37.44] %. According to this indicator, there was no significant difference between the subgroups, and in subgroups IIA and II B — also with the indicator of the control group (29.97 [22.52; 41.75] %). The relative number of Actinobacteria almost did not differ in the subgroups and the control group (8.66 [3.81; 9.61] %, 8.95 [2.63; 9.00] %, 5.05 [1.37; 6, 85] %, 10.80 [2.75; 17.95] % and 4.92 [2.63; 9.00] %, respectively).Conclusions. The results of the study showed that the GM composition in terms of the content of the main phylotypes was significantly different in patients with NAFLD, depending on the body mass index and the stage of steatosis, compared with the control group. There was a significant increase in Firmicutes/Bacteroidetes ratio in the subgroups compared with the control group: in NAS patients with concomitant OB — by 13.56 times, in patients with NAS with concomitant OB — by 10.87 times, in overweight patients with NASH — 8.2 times, in patients with NASH with overweight — 5.16 times. The relative content of Actinobacteria in the subgroups and the control group did not significantly differ. Analysis of the relative composition of GM did not reveal significant differences between the subgroups. In NAFLD patients with OB or overweight, the relationship between the stage of hepatic steatosis and the ratio of the main GM phylotypes was not found.

Lactobacillus attenuates progression of nonalcoholic fatty liver disease by lowering cholesterol and steatosis.

Background/AimsNonalcoholic fatty liver disease (NAFLD) is closely related to gut-microbiome. There is a paucity of research on which strains of gut microbiota affect the progression of NAFLD. This study explored the NAFLD-associated microbiome in humans and the role of Lactobacillus in the progression of NAFLD in mice.MethodsThe gut microbiome was analyzed via next-generation sequencing in healthy people (n=37) and NAFLD patients with elevated liver enzymes (n=57). Six-week-old male C57BL/6J mice were separated into six groups (n=10 per group; normal, Western, and four Western diet + strains [109 colony-forming units/g for 8 weeks; L. acidophilus, L. fermentum, L. paracasei, and L. plantarum]). Liver/body weight ratio, liver pathology, serum analysis, and metagenomics in the mice were examined.ResultsCompared to healthy subjects (1.6±4.3), NAFLD patients showed an elevated Firmicutes/Bacteroidetes ratio (25.0±29.0) and a reduced composition of Akkermansia and L. murinus (P<0.05). In the animal experiment, L. acidophilus group was associated with a significant reduction in liver/body weight ratio (5.5±0.4) compared to the Western group (6.2±0.6) (P<0.05). L. acidophilus (41.0±8.6), L. fermentum (44.3±12.6), and L. plantarum (39.0±7.6) groups showed decreased cholesterol levels compared to the Western group (85.7±8.6) (P<0.05). In comparison of steatosis, L. acidophilus (1.9±0.6), L. plantarum (2.4±0.7), and L. paracasei (2.0±0.9) groups showed significant improvement of steatosis compared to the Western group (2.6±0.5) (P<0.05).ConclusionsIngestion of Lactobacillus, such as L. acidophilus, L. fermentum, and L. plantarum, ameliorates the progression of nonalcoholic steatosis by lowering cholesterol. The use of Lactobacillus can be considered as a useful strategy for the treatment of NAFLD.

Effect of omega-3 polyunsaturated fatty acids on insulinresistance, endothelial function, triglycerides level in patients with chronic coronary syndrome in combination with non-alcoholic steatosis

Effect of omega-3 polyunsaturated fatty acids on insulinresistance, endothelial function, triglycerides level in patients with chronic coronary syndrome in combination with non-alcoholic steatosis

Comparative Effects of Pterostilbene and Its Parent Compound Resveratrol on Oxidative Stress and Inflammation in Steatohepatitis Induced by High-Fat High-Fructose Feeding.

Different studies have revealed that oxidative stress and inflammation are crucial in NAFLD (Non-alcoholic fatty liver disease). The aim of this study is to analyze whether pterostilbene and resveratrol are able to either avoid or delay the progression of non-alcoholic liver steatosis towards steatohepatitis. This has been performed by examining their effects on oxidative stress, inflammation, fibrosis and pre-carcinogenic stages. Rats were distributed into five experimental groups and were fed with either a standard diet or a high-fat high-fructose diet, supplemented or not with pterostilbene (15 or 30 mg/kg/d) or resveratrol (30 mg/kg/d), for 8 weeks. Liver histological analysis was carried out by haematoxylin–eosin staining. Serum and hepatic oxidative stress-related parameters were assessed using spectrophotometry, and the expression of genes related to inflammation, fibrosis and cancer by qRT-PCR. The dietary model used in this study led to the development of steatohepatitis, where rats displayed oxidative stress, inflammation and ballooning, although not fibrosis. It also modified the expression of hepatocarcinoma-related genes. The results show, for the first time, that pterostilbene was able to partially prevent these alterations, with the exception of changes in hepatocarcinoma-related genes, mainly at 30 mg/kg/d. Pterostilbene was more effective than its parent compound resveratrol, probably due to its high bioavailability and higher anti-oxidant and anti-inflammatory activities, attributable to its different chemical structure.