Microbial Signatures in COVID-19: Distinguishing Mild and Severe Disease via Gut Microbiota.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has significantly impacted global healthcare, underscoring the importance of exploring the virus's effects on infected individuals beyond treatments and vaccines. Notably, recent findings suggest that SARS-CoV-2 can infect the gut, thereby altering the gut microbiota. This study aimed to analyze the gut microbiota composition differences between COVID-19 patients experiencing mild and severe symptoms. We conducted 16S rRNA metagenomic sequencing on fecal samples from 49 mild and 43 severe COVID-19 cases upon hospital admission. Our analysis identified a differential abundance of specific bacterial species associated with the severity of the disease. Severely affected patients showed an association with Enterococcus faecium, Akkermansia muciniphila, and others, while milder cases were linked to Faecalibacterium prausnitzii, Alistipes putredinis, Blautia faecis, and additional species. Furthermore, a network analysis using SPIEC-EASI indicated keystone taxa and highlighted structural differences in bacterial connectivity, with a notable disruption in the severe group. Our study highlights the diverse impacts of SARS-CoV-2 on the gut microbiome among both mild and severe COVID-19 patients, showcasing a spectrum of microbial responses to the virus. Importantly, these findings align, to some extent, with observations from other studies on COVID-19 gut microbiomes, despite variations in methodologies. The findings from this study, based on retrospective data, establish a foundation for future prospective research to confirm the role of the gut microbiome as a predictive biomarker for the severity of COVID-19.

Effect of the consumption of brazzein and monellin, two recombinant sweet-tasting proteins, on rat gut microbiota.

Sweet-tasting proteins (SPs) are proteins of plant origin initially isolated from tropical fruits. They are thousands of times sweeter than sucrose and most artificial sweeteners. SPs are a class of proteins capable of causing a sweet taste sensation in humans when interacting with the T1R2/T1R3 receptor. SP thaumatin has already been introduced in the food industry in some countries. Other SPs, such as monellin and brazzein, are promising products. An important stage in researching SPs, in addition to confirming the absence of toxicity, mutagenicity, oncogenicity, and allergenic effects, is studying their influence on gut microbiota. In this paper we describe changes in the composition of rat gut microbiota after six months of consuming one of two recombinant SPs-brazzein or monellin. A full length 16S gene sequencing method was used for DNA library barcoding. The MaAsLin2 analysis results showed noticeable fluctuations in the relative abundances of Anaerocella delicata in brazzein-fed rat microbiota, and of Anaerutruncus rubiinfantis in monellin-fed rat microbiota, which, however, did not exceed the standard deviation. The sucrose-fed group was associated with an increase in the relative abundance of Faecalibaculum rodentium, which may contribute to obesity. Overall, prolonged consumption of the sweet proteins brazzein and monellin did not significantly change rat microbiota and did not result in the appearance of opportunistic microbiota. This provides additional evidence for the safety of these potential sweeteners.

Evaluation of serum and urine biomarkers for severe COVID-19.

Introduction: The new coronavirus disease, COVID-19, poses complex challenges exacerbated by several factors, with respiratory tissue lesions being notably significant among them. Consequently, there is a pressing need to identify informative biological markers that can indicate the severity of the disease. Several studies have highlighted the involvement of proteins such as APOA1, XPNPEP2, ORP150, CUBN, HCII, and CREB3L3 in these respiratory tissue lesions. However, there is a lack of information regarding antibodies to these proteins in the human body, which could potentially serve as valuable diagnostic markers for COVID-19. Simultaneously, it is relevant to select biological fluids that can be obtained without invasive procedures. Urine is one such fluid, but its effect on clinical laboratory analysis is not yet fully understood due to lack of study on its composition. Methods: Methods used in this study are as follows: total serum protein analysis; ELISA on moderate and severe COVID-19 patients' serum and urine; bioinformatic methods: ROC analysis, PCA, SVM. Results and discussion: The levels of antiAPOA1, antiXPNPEP2, antiORP150, antiCUBN, antiHCII, and antiCREB3L3 exhibit gradual fluctuations ranging from moderate to severe in both the serum and urine of COVID-19 patients. However, the diagnostic value of individual anti-protein antibodies is low, in both blood serum and urine. On the contrary, joint detection of these antibodies in patients' serum significantly increases the diagnostic value as demonstrated by the results of principal component analysis (PCA) and support vector machine (SVM). The non-linear regression model achieved an accuracy of 0.833. Furthermore, PCA aided in identifying serum protein markers that have the greatest impact on patient group discrimination. The study revealed that serum serves as a superior analyte for describing protein quantification due to its consistent composition and lack of organic salts and drug residues, which can otherwise affect protein stability.

Sweet-Tasting Natural Proteins Brazzein and Monellin: Safe Sugar Substitutes for the Food Industry.

This article presents the results of a comprehensive toxicity assessment of brazzein and monellin, yeast-produced recombinant sweet-tasting proteins. Excessive sugar consumption is one of the leading dietary and nutritional problems in the world, resulting in health complications such as obesity, high blood pressure, and cardiovascular disease. Although artificial small-molecule sweeteners widely replace sugar in food, their safety and long-term health effects remain debatable. Many sweet-tasting proteins, including thaumatin, miraculin, pentadin, curculin, mabinlin, brazzein, and monellin have been found in tropical plants. These proteins, such as brazzein and monellin, are thousands-fold sweeter than sucrose. Multiple reports have presented preparations of recombinant sweet-tasting proteins. A thorough and comprehensive assessment of their toxicity and safety is necessary to introduce and apply sweet-tasting proteins in the food industry. We experimentally assessed acute, subchronic, and chronic toxicity effects, as well as allergenic and mutagenic properties of recombinant brazzein and monellin. Our study was performed on three mammalian species (mice, rats, and guinea pigs). Assessment of animals' physiological, biochemical, hematological, morphological, and behavioral indices allows us to assert that monellin and brazzein are safe and nontoxic for the mammalian organism, which opens vast opportunities for their application in the food industry as sugar alternatives.

Esophageal Mucosal Resistance in Reflux Esophagitis: What We Have Learned So Far and What Remains to Be Learned.

Gastroesophageal reflux disease (GERD) has the highest prevalence among diseases of the digestive system and is characterized by a significant decrease in patients' quality of life, comparable to arterial hypertension and coronary heart disease. One in every ten cases of reflux esophagitis leads to the formation of Barrett's esophagus, which is associated with a high risk of esophagus adenocarcinoma. The key factors determining the progression of the disease are the frequency and duration of the reflux of the stomach's contents. As a result, refluxate, which includes hydrochloric acid, pepsin, and, in the case of concomitant duodeno-gastric reflux, bile acids and lysolecithin, is thrown into the overlying sections of the digestive tract. At the same time, in addition to aggression factors, it is necessary to take into account the state of resistance in the esophageal mucosa to the effects of aggressive refluxate molecules. This review was prepared using systematized data on the protective properties of the esophageal mucosa and modern methods to assess the mucosal barrier in reflux esophagitis. Lesions of the epithelial barrier structure in the esophagus are recognized as the main pathogenetic factor in the development of reflux esophagitis and are a potentially significant therapeutic target in the treatment of GERD and Barrett's esophagus. This article presents the characteristics of the esophageal mucosal barrier and the protective mechanisms of the esophagus's mucous membrane in conditions of gastroesophageal reflux. Diagnostic approaches for assessing the course of reflux esophagitis are described for both histological criteria and the possibility of a comprehensive assessment of the state of mucins, tight-junction proteins, and the proliferative activity of the mucosa, including under the conditions of ongoing therapy.

Features of Lipid Metabolism Disorders in Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune liver disease that mostly affects women. A progressive disorder in the processes of bile secretion and enterohepatic bile salts circulation in patients with PBC already in its early stages, leading to an insufficient release of bile acids into the bowel and their entry into the systemic circulation. Insufficient bile acids released into the duodenum contributes to the development of malabsorption, energy malnutrition, and slowly progressive weight loss. The pathophysiological mechanisms of weight loss and its slow progression are associated with the deterioration of the fat emulsification processes and with the reduced absorption of hydrolyzed products, such as fatty acids and monoglycerides, with steatorrhea in patients with PBC, as well as in those with gut dysbiosis. Just in the early stages of the disease, this results in accelerated fatty acid ß-oxidation that is aimed at compensating for progressive energy malnutrition. The entry of bile acids into the systemic circulation in PBC is accompanied by dyslipidemia. The mechanism of hyperlipidemia in patients with PBC differs from that in other conditions because along with an increase in total cholesterol (TC), there are elevated high-density lipoprotein levels and the appearance of unusual lipoprotein X (Lp-X). The appearance of Lp-X is most likely to be the body's protective reaction to inactivate the detergent effect of bile acids on the membrane structures of blood corpuscles and vascular endothelial cells. It is bile acids, rather than TC levels, that correlate with the content of Lp-X and determine its formation. Concomitant hypercholesterolemia in patients with PBC is also aimed at neutralizing the detergent effect of bile acids that have entered the systemic circulation and is most likely a compensatory reaction of the body. "Anomalous" hypercholesterolemia in PBC can serve as a model system for the search and development of new methods for the treatment of dyslipidemia since it occurs without an increase in the incidence of cardiovascular events.

Prevalence and Risk of Dental Erosion in Patients with Gastroesophageal Reflux Disease: A Meta-Analysis.

AIM: The present paper aims to systematize data concerning the prevalence and risk of dental erosion (DE) in adult patients with gastroesophageal reflux disease (GERD) compared to controls. MATERIALS AND METHODS: Core electronic databases, i.e., MEDLINE/PubMed, EMBASE, Cochrane, Google Scholar, and the Russian Science Citation Index (RSCI), were searched for studies assessing the prevalence and risk of DE in adult GERD patients with publication dates ranging from 1 January 1985 to 20 January 2022. Publications with detailed descriptive statistics (the total sample size of patients with GERD, the total sample size of controls (if available), the number of patients with DE in the sample of GERD patients, the number of patients with DE in the controls (if available)) were selected for the final analysis. RESULTS: The final analysis included 28 studies involving 4379 people (2309 GERD patients and 2070 control subjects). The pooled prevalence of DE was 51.524% (95 CI: 39.742-63.221) in GERD patients and 21.351% (95 CI: 9.234-36.807) in controls. An association was found between the presence of DE and GERD using the random-effects model (OR 5.000, 95% CI: 2.995-8.345; I2 = 79.78%) compared with controls. When analyzing studies that only used validated instrumental methods for diagnosing GERD, alongside validated DE criteria (studies that did not specify the methodologies used were excluded), a significant association between the presence of DE and GERD was revealed (OR 5.586, 95% CI: 2.311-13.503; I2 = 85.14%). CONCLUSION: The meta-analysis demonstrated that DE is quite often associated with GERD and is observed in about half of patients with this extremely common disease of the upper gastrointestinal tract.

Role of silymarin as antioxidant in clinical management of chronic liver diseases: a narrative review.

Chronic liver disease (CLD), manifested as hepatic injury, is a major cause of global morbidity and mortality. CLD progresses to fibrosis, cirrhosis, and-ultimately-hepatocellular carcinoma (HCC) if left untreated. The different phenotypes of CLD based on their respective clinical features and causative agents include alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD), and drug-induced liver injury (DILI). The preferred treatment modality for CLD includes lifestyle modification and diet, along with limited pharmacological agents for symptomatic treatment. Moreover, oxidative stress (OS) is an important pathological mechanism underlying all CLD phenotypes; hence, the use of antioxidants to manage the disease is justified. Based on available clinical evidence, silymarin can be utilized as a hepatoprotective agent, given its potent antioxidant, antifibrotic, and anti-inflammatory properties. The role of silymarin in suppressing OS has been well established, and therefore silymarin is recommended for use in ALD and NAFLD in the guidelines approved by the Russian Medical Scientific Society of Therapists and the Gastroenterology Scientific Society of Russia. However, to discuss the positioning of the original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies, an expert panel of international and Russian medical professionals was convened on 11 November 2020. The panel reviewed approaches for the prevention and treatment of OS, existing guidelines for patient management for CLD, and available evidence on the effectiveness of silymarin in reducing OS, fibrosis, and hepatic inflammation and presented in the form of a narrative review. Key messagesAn expert panel of international and Russian medical professionals reviewed existing guidelines for ALD, NAFLD, MAFLD, and DILI to establish consensus recommendations that oxidative stress is the common pathophysiological mechanism underlying these conditions.The panel also discussed the positioning of original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies.The panel reviewed the effectiveness of 140 mg original silymarin three times a day in reducing oxidative stress in chronic liver diseases such as ALD, NAFLD, MAFLD, and DILI.

Evaluation of photocytotoxicity liposomal form of furanocoumarins Sosnowsky's hogweed.

Sosnovsky's hogweed, Heracleum sosnowskyi has a high photosensitizing ability. Although Sosnovsky's hogweed is known as a poisonous plant, its chemical composition and phototoxicity are poorly studied. We analyzed the chemical composition of the Sosnovsky's hogweed juice that grew in natural conditions. It was found that the content of 8-methoxypsoralen in the juice is 1332.7 mg/L, and that of 5-methoxypsoralen is 34.2 mg/L. We have developed and analyzed liposomes containing furanocoumarins of Sosnovsky's hogweed juice and studied their photocytotoxicity in L929 mouse fibroblast cell culture. It was found that liposomes containing furanocoumarins of Sosnovsky's hogweed juice are more toxic for L929 cells in comparison with liposomal forms of pure substances 8-methoxypsoralen and 5-methoxypsoralen. It was found that when exposed to UV radiation at 365 nm at a dose of 22.2 J/cm2, the liposomal form of furanocoumarins Sosnovsky's hogweed is 3 times more toxic to L929 cells than in the dark. It was found that the photocytotoxic effect of liposomal furanocoumarins Sosnovsky's hogweed is a strongly stimulation of apoptosis.The data obtained suggest that the raw material of Sosnovsky's hogweed claims to be a source of furanocoumarins, and the liposomal form, given the hydrophobic properties of furanocoumarins, is very suitable for creating a phototherapeutic drug.

Safety and Effectiveness of Essential Phospholipids Paste in Patients with Non-alcoholic Fatty Liver Disease or Viral Hepatitis.

BACKGROUND: Essential phospholipids (EPL) are used as adjuvant treatment in people with fatty liver disease and other chronic liver diseases. A new formulation of EPL paste was developed to improve patient compliance. The study was aimed to assess the safety, patient-reported outcomes, and impact on compliance of the new EPL paste formulation in patients with non-alcoholic fatty liver disease (NAFLD) or viral hepatitis. METHODS: The study enrolled 147 patients (48.3% male; mean ± standard deviation (SD) age 44.8 ± 10.5 years) in the intention-to-treat population; 72.8% had NAFLD and 27.9% had viral hepatitis B (HBV) or hepatitis C (HCV). Patients received EPL paste (one 600 mg sachet 3 times daily) for 12 weeks, with 4-, 8-, and 12-week scheduled visits and a 13-week follow-up visit. Patient-reported outcomes were evaluated at 4, 8, and 12 weeks compared with baseline using dedicated Likert scales. Compliance was assessed by comparing actual versus prescribed dosing of the EPL. RESULTS: After 12-week treatment with EPL paste, statistically significant improvements were observed in mean ± SD Global Overall Symptom scores (from 4.21 ± 1.09 to 1.87 ± 0.91; P < .01) and overall Gastrointestinal Symptom scores (from 19.91 ± 5.74 to 11.17 ± 3.57; P < .01), compared to baseline scores. Compliance with prescribed essential phospholipid treatment was 99% throughout the 12-week treatment period. CONCLUSION: Essential phospholipids paste had a favorable safety profile associated with improved gastrointestinal symptoms and with high levels of compliance in patients with NAFLD and viral hepatitis.

Current Helicobacter pylori Diagnostics.

The high prevalence of Helicobacter pylori and the variety of gastroduodenal diseases caused by this pathogen necessitate the use of only accurate methods both for the primary diagnosis and for monitoring the eradication effectiveness. There is a broad spectrum of diagnostic methods available for detecting H. pylori. All methods can be classified as invasive or non-invasive. The need for upper endoscopy, different clinical circumstances, sensitivity and specificity, and accessibility defines the method chosen. This article reviews the advantages and disadvantages of the current options and novel developments in diagnostic tests for H. pylori detection. The progress in endoscopic modalities has made it possible not only to diagnose precancerous lesions and early gastric cancer but also to predict H. pylori infection in real time. The contribution of novel endoscopic evaluation technologies in the diagnosis of H. pylori such as visual endoscopy using blue laser imaging (BLI), linked color imaging (LCI), and magnifying endoscopy is discussed. Recent studies have demonstrated the capability of artificial intelligence to predict H. pylori status based on endoscopic images. Non-invasive diagnostic tests such as the urea breathing test and stool antigen test are recommended for primary diagnosis of H. pylori infection. Serology can be used for initial screening and epidemiological studies. The histology showed its value in detecting H. pylori and provided more information about the degree of gastric mucosa inflammation and precancerous lesions. Molecular methods are mainly used in detecting antibiotic resistance of H. pylori. Cultures from gastric biopsies are the gold standard and recommended for antibiotic susceptibility tests.

Correlation of Objective Endpoints and Subjective Patient-Reported Outcomes in NAFLD Treatment with Essential Phospholipids: Real-World Data Based on Pooled Analysis of Observational Studies.

BACKGROUND: While no "gold-standard" pharmacotherapy for nonalcoholic fatty liver disease (NAFLD) is yet established, essential phospholipids (EPLs) are reported to decrease steatosis and improve laboratory parameters. OBJECTIVE: This analysis evaluated adherence and satisfaction with EPL treatment as patient-reported outcomes and their relationship with changes in laboratory and ultrasound parameters among Russian patients with NAFLD. METHODS: Data were pooled from three observational Russian studies-MANPOWER (2015-2016), LIDER 1 (2012-2013), and LIDER 2 (2013)-in which EPLs were used for at least 12 weeks in the treatment of liver diseases and which measured both subjective and objective endpoints. Only patients who had NAFLD were included in this analysis. The main endpoints were to determine treatment adherence and satisfaction with 12 weeks of EPL therapy, relationship between adherence/satisfaction and changes in the laboratory and ultrasound parameters. A secondary subgroup analysis was performed to identify patients with NAFLD who responded better (or worse) to 24 weeks of adjunctive EPL treatment. RESULTS: Overall, 3384 patients were included. A total of 82.2% of patients were adherent to 12 weeks of EPL treatment; high/very high satisfaction was reported by 15.3%/65.9% of clinicians and 15.9%/64.4% of patients. There was positive correlation between patients' adherence and satisfaction and significant improvement in laboratory (transaminases, lipid profile; p < 0.001) and ultrasound (steatosis, p < 0.001) parameters, and improvement in symptoms (p < 0.001) after 24 weeks of EPL. Male patients, patients with unhealthy lifestyles, and those with more comorbidities showed a better response in laboratory and ultrasound parameters. CONCLUSIONS: Patients with NAFLD treated with adjunctive EPL therapy in real-world clinical practice in Russia showed good treatment adherence and treatment satisfaction. Improvements in laboratory and ultrasound parameters, as well as dynamics of patient symptoms, were positively correlated with adherence and satisfaction.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease, and patients have a risk of liver cancer and needing transplantation. Patients with advanced NAFLD are usually recommended to use medication. Clinical trials in patients with NAFLD showed that essential phospholipids (EPLs) comprising phosphatidylcholine improved liver fat accumulation (known as steatosis), so treatment guidelines in several countries recommend they be added to the usual therapy. EPLs have been associated with both objective and subjective improvements. This real-world study evaluated three observational studies to assess how patient adherence and satisfaction with EPL treatment were related to changes in clinical parameters in 3384 Russian patients with NAFLD. Overall, 82.2% of patients were adherent with 12 weeks of EPL therapy, and almost two-thirds of patients (64.4%) and clinicians (65.9%) reported very high satisfaction with treatment. Patients' adherence and satisfaction increased alongside significant improvements in liver enzymes, lipid levels, liver fat content (steatosis), and fewer symptoms after 24 weeks of EPL therapy. Male patients, those with an unhealthy lifestyle, and those with other comorbid conditions had the best response to EPL therapy. This study shows that Russian patients with NAFLD have good adherence and satisfaction with EPL therapy in routine clinical practice and highlights the importance of adherence to EPL therapy in these patients.

Differences in In Vitro Properties of Pancreatin Preparations for Pancreatic Exocrine Insufficiency as Marketed in Russia and CIS.

BACKGROUND: Pancreatic enzyme-replacement therapy (PERT), provided as pancreatin to patients with pancreatic exocrine insufficiency (PEI), is considered an essential substitute for the pivotal physiological function the pancreas fulfills in digestion. PEI involves a reduction in the synthesis and secretion of pancreatic enzymes (lipase, protease, amylase), which leads to an inadequate enzymatic response to a meal and consequently to maldigestion and malabsorption of nutrients. The efficacy of PERT is strongly dependent on enzyme activity, dissolution, and pancreatin particle size. OBJECTIVE: The physiological properties of eight pancreatin preparations (nine batches; five different brands) available in Russia and CIS (Commonwealth of Independent States: Armenia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Uzbekistan) were investigated. METHODS: The lipase activity, dissolution, and particle size distribution of samples from multiple batches of pancreatin of different strengths were measured. RESULTS: Regarding lipase activities, all pancreatin preparations except Micrazim® matched the labeled content. Considerable differences were observed in particle size and dissolution. CONCLUSION: Pancreatin preparations available in Russia and CIS demonstrate product-to-product and batch-to-batch variability regarding the measured properties of lipase activity, dissolution, and particle size. This may impact the efficacy of PERT and therefore clinical outcomes.

A New, Non-Invasive Scale for Steatosis Developed Using Real-World Data From Russian Outpatients to Aid in the Diagnosis of Non-Alcoholic Fatty Liver Disease.

INTRODUCTION: The current non-invasive tools for the diagnosis of non-alcoholic fatty liver disease (NAFLD) have methodological limitations. We aimed to develop a non-invasive scale to assist in the diagnosis of NAFLD. To achieve our aim, we conducted a secondary analysis of data from a large observational study conducted in Russia. METHODS: This retrospective analysis assessed the frequency of NAFLD in the population of patients in the DIREG_L_06725 study, an epidemiological, observational, cross-sectional, multicenter study performed in 50,145 outpatients from 16 Russian cities. Among the cohort of patients diagnosed with NAFLD, we identified factors associated with the risk of NAFLD. To develop a non-invasive tool for diagnosing NAFLD, we also determined the frequency of steatohepatitis. RESULTS: Our analysis included 48,297 patients; NAFLD was present in 20,281 patients (42.0%). The majority (64.1%) were women (80.3% post-menopause), and 87% had a body mass index (BMI) > 27.0 kg/m2. We developed a fully non-invasive scale (St-index) that showed a specificity of 91.4% for ruling in steatosis, and a sensitivity of 93.8% for ruling out steatosis. Multivariate regression analyses conducted in the subgroups of patients aged ≥ 12 and < 18 years and those with BMI < 25.0 kg/m2 produced area under the receiver operating characteristic (AUROC) curve values of 0.8243 and 0.7054, respectively. The factors most strongly associated with the development of NAFLD were age > 35 years, presence of type 2 diabetes mellitus, and a waist circumference/height ratio > 0.54. CONCLUSION: Our non-invasive steatosis scale, St-index, can help physicians diagnose NAFLD in high-risk patients in the absence of ultrasound data.

Torque teno virus in liver diseases: On the way towards unity of view.

The review presents the data accumulated for more than 20 years of research of torque teno virus (TTV). Its molecular genetic structure, immunobiology, epidemiology, diagnostic methods, possible replication sites, and pathogenicity factors are described. TTV is a virus that is frequently detectable in patients with different viral hepatitides, in cases of hepatitis without an obvious viral agent, as well as in a healthy population. There is evidence suggesting that biochemical and histological changes occur in liver tissue and bile duct epithelium in TTV monoinfection. There are sufficient histological signs of liver damage, which confirm that the virus can undergo a replicative cycle in hepatocytes. Along with this, cytological hybridization in TTV-infected cells has shown no substantial cytopathic (cell-damaging) effects that are characteristic of pathogenic hepatotropic viruses. Studying TTV has led to the evolution of views on its role in the development of human pathology. The first ideas about the hepatotropism of the virus were gradually reformed as new data became available on the prevalence of the virus and its co-infection with other viruses, including the viruses of the known types of hepatitides. The high prevalence of TTV in the human population indicates its persistence in the body as a virome and a non-pathogenic virus. It has recently been proposed that the level of TTV DNA in the blood of patients undergoing organ transplantation should be used as an endogenous marker of the body's immune status. The available data show the polytropism of the virus and deny the fact that TTV can be assigned exclusively to hepatitis viruses. Fortunately, the rare detection of the damaging effect of TTV on hepatic and bile duct epithelial cells may be indirect evidence of its conditionally pathogenic properties. The ubiquity of the virus and the variability of its existence in humans cannot put an end to its study.

Effectiveness of phosphatidylcholine as adjunctive therapy in improving liver function tests in patients with non-alcoholic fatty liver disease and metabolic comorbidities: real-life observational study from Russia.

Objective: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal results of liver function tests. Earlier research showed that polyenylphosphatidylcholine (PPC) has hepatoprotective effects and thus can be used for the treatment of NAFLD and the prevention of its progression. Accordingly, the aim of this observational study was to evaluate if PPC administered as adjunctive therapy in routine clinical practice can effectively improve liver function tests of NAFLD in Russian patients with associated metabolic comorbidities. Design: A total of 2843 adult patients with newly diagnosed NAFLD, who had a least one of four comorbidities, namely, overweight/obesity, hypertension, type 2 diabetes mellitus, and hypercholesterolaemia, and who were prescribed 1.8 g/day of PPC as an adjunctive treatment to standard care, were enrolled during 2015-2016. Laboratory data were collected at baseline and 12 and 24 weeks of the study, and included liver function tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT)), fasting plasma glucose, and lipid profile. Results: Overall, 2263 patients (79.6%) had at least two metabolic comorbidities associated with NAFLD, and overweight/obesity was the most common comorbidity reported in 2298 (80.8%) patients. At 24 weeks, there was a significant decrease in liver enzyme levels (all p<0.001 compared with baseline). Across the four comorbidity subgroups, there was a mean drop of ALT levels ranging from 19.7 to 22.0 U/L, AST from 16.9 to 18.4 U/L, and GGT from 17.2 to 18.7 U/L. Similar findings were reported in subgroups with either one, two, three, or four comorbidities, with a significant decrease in liver enzyme levels ranging from 18.4 to 22.4 U/L for ALT, 14.8 to 18.7 U/L for AST, and 15.5 to 19.5 U/L for GGT. Conclusions: Adjuvant treatment with PPC resulted in consistent improvements in liver enzymes in patients with newly diagnosed NAFLD and associated metabolic comorbidities. Trial registration number: NCT00063622.

Effectiveness of phosphatidylcholine in alleviating steatosis in patients with non-alcoholic fatty liver disease and cardiometabolic comorbidities (MANPOWER study).

Objective: The concept of using naturally occurring compounds such as polyenylphosphatidylcholine (PPC) as an adjunctive therapy to treat non-alcoholic fatty liver disease (NAFLD) and alleviate or reverse hepatic steatosis appears a very attractive option for liver protection. We aim to evaluate if PPC adjunctive therapy can effectively improve the ultrasonographic features of NAFLD in routine clinical practice in Russian patients with cardiometabolic comorbidities. Design: This 24-week, observational, prospective study was carried out in 174 medical sites across 6 federal districts of Russia. A total of 2843 adult patients with newly diagnosed NAFLD, who had a least one of four comorbidities, namely overweight/obesity, hypertension, type 2 diabetes mellitus and hypercholesterolaemia, and who received PPC as an adjunctive treatment to standard care, were enrolled. The assessment of liver ultrasonography was qualitative. Results: Overall, 2263 (79.6%) patients had at least two metabolic comorbidities associated with NAFLD, and overweight/obesity was the most common comorbidity reported in 2298 (80.8%) patients. Almost all study participants (2837/2843; 99.8%) were prescribed 1.8 g of PPC administered three times daily. At baseline, the most frequently identified abnormalities on ultrasound were liver hyperechogenicity (84.0% of patients) and heterogeneous liver structure (62.9%). At 24 weeks, a significant (p<0.05) improvement in liver echogenicity and in liver structure was observed in 1932/2827 (68.3%) patients (95% CI 66.6% to 70.1%) and in 1207/2827 (42.7%) patients (95% CI 40.9% to 44.5%), respectively. The analysis of ultrasonographic signs by number of comorbidities revealed similar findings-liver echogenicity improved in 67.2%-69.3% and liver structure in 35.6%-45.3% of patients depending on the number of comorbidities. Conclusion: This study showed that PPC adjunctive therapy may be useful in improving the ultrasonographic features of NAFLD in patients with associated cardiometabolic comorbidities. It also supports evidence regarding the role of PPC in the complex management of NAFLD.

Real-world comorbidities and treatment patterns among patients with non-alcoholic fatty liver disease receiving phosphatidylcholine as adjunctive therapy in Russia.

OBJECTIVE: Previous research conducted in Russia showed that the number of patients with non-alcoholic fatty liver disease (NAFLD) and associated metabolic comorbidities is large. We conducted an observational study to describe the management of NAFLD in patients with metabolic syndrome in Russia. DESIGN: A total of 2843 adult patients from 174 medical sites across 6 federal districts of Russia with newly diagnosed NAFLD, who had at least one of four comorbidities, namely overweight/obesity, hypertension, type 2 diabetes mellitus, and hypercholesterolaemia, and who received phosphatidylcholine (PPC) as an adjunctive treatment to standard care, were enrolled during 2015-2016. RESULTS: Overall, 2263 patients (79.6%) had at least two metabolic comorbidities associated with NAFLD; overweight/obesity was the most common comorbidity reported in 2298 patients (80.8%). Simple steatosis was the most frequently identified clinical form of NAFLD, diagnosed in 2128 patients (74.9%). Among hypertensive patients, ACE inhibitors, statins, and sartans were most commonly prescribed. Biguanides were administered in more than half of diabetic patients. In patients with overweight/obesity and hypercholesterolaemia, statins were the most frequently prescribed medications. Almost all patients (2837/2843; 99.8%) were treated with 1.8 g of PPC three times per day. PPC therapy was associated with a 90.5% 6-month compliance rate, high treatment satisfaction, and a favourable safety profile. However, almost 15% of diabetic patients and 40% of overweight/obese patients received no further treatment. CONCLUSIONS: In Russia, patients with newly diagnosed NAFLD represent a population heavily burdened by comorbidities, mainly overweight/obesity and hypercholesterolaemia. A significant part of these patients did not receive a comprehensive pharmacotherapy, highlighting the existing unmet need in the current management of NAFLD patients with metabolic syndrome in Russia.

Efficiency of the Inclusion of Rebamipide in the Eradication Therapy for Helicobacter pylori Infection: Meta-Analysis of Randomized Controlled Studies.

BACKGROUND: There has been a negative trend in the effectiveness of classic eradication therapy regimens for Helicobacter pylori (H. pylori), which has largely been determined from the emergence and spread of antibiotic resistance. Several studies have shown that adding rebamipide to eradication regimens leads to an increase in the effectiveness of treatment. AIM: To evaluate the efficacy and safety of including rebamipide in the eradication regimens for H. pylori infection. METHODS: The literature search was conducted in the MEDLINE/PubMed, EMBASE, Cochrane Central Register, Korean Medical Citation Index, and Russian Science Citation Index databases. All identified randomized controlled trials comparing rebamipide supplementation with non-rebamipide-containing eradication regimens for the treatment of H. pylori infection were included in the final analysis. RESULTS: We identified 11 randomized controlled trials (RCTs) involving 1227 patients (631 in groups with rebamipide and 596 in groups without rebamipide). The meta-analysis showed that the addition of rebamipide to eradication regimens significantly increased the effectiveness of treatment (odds ratio (OR) 1.753, 95% confidence interval (CI) 1.312-2.333, p < 0.001). The subgroup analysis demonstrated that rebamipide significantly increased the effectiveness of eradication when added to a dual therapy regimen (OR 1.766, 95% CI: 1.167-2.495, p = 0.006); however, no significant improvement in effectiveness was observed when it was added to the triple therapy regimen (OR 1.638, 95% CI 0.833-3.219, p = 0.152). CONCLUSION: This meta-analysis demonstrated that the addition of rebamipide to H. pylori eradication regimens significantly increases the effectiveness of treatment.