[The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities].

The National Consensus was prepared with the participation of the National Medical Association for the Study of the Multimorbidity, Russian Scientific Liver Society, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians, National Society for Preventive Cardiology, Professional Foundation for the Promotion of Medicine Fund PROFMEDFORUM. The aim of the multidisciplinary consensus is a detailed analysis of the course of non-alcoholic fatty liver disease (NAFLD) and the main associated conditions. The definition of NAFLD is given, its prevalence is described, methods for diagnosing its components such as steatosis, inflammation and fibrosis are described. The association of NAFLD with a number of cardio-metabolic diseases (arterial hypertension, atherosclerosis, thrombotic complications, type 2 diabetes mellitus, obesity, dyslipidemia, etc.), chronic kidney disease and the risk of developing hepatocellular cancer were analyzed. The review of non-drug methods of treatment of NAFLD and modern opportunities of pharmacotherapy are presented. The possibilities of new molecules in the treatment of NAFLD are considered: agonists of nuclear receptors, antagonists of pro-inflammatory molecules, etc. The positive properties and disadvantages of currently used drugs (vitamin E, thiazolidinediones, etc.) are described. Special attention is paid to the multi-target ursodeoxycholic acid molecule in the complex treatment of NAFLD as a multifactorial disease. Its anti-inflammatory, anti-oxidant and cytoprotective properties, the ability to reduce steatosis an independent risk factor for the development of cardiovascular pathology, reduce inflammation and hepatic fibrosis through the modulation of autophagy are considered. The ability of ursodeoxycholic acid to influence glucose and lipid homeostasis and to have an anticarcinogenic effect has been demonstrated. The Consensus statement has advanced provisions for practitioners to optimize the diagnosis and treatment of NAFLD and related common pathogenetic links of cardio-metabolic diseases.

[Epithelial protective therapy in comorbid diseases. Practical Guidelines for Physicians].

This document was produced with the support of the National Medical Association for the Study of Comorbidities (NASС). In 2021 the first multidisciplinary National Consensus on the pathophysiological and clinical aspects of Increased Epithelial Permeability Syndrome was published. The proposed guidelines are developed on the basis of this Consensus, by the same team of experts. Twenty-eight Practical Guidelines for Physicians statements were adopted by the Expert Council using the "delphic" method. Such main groups of epithelial protective drugs as proton pump inhibitors, bismuth drugs and probiotics are discussed in these Guidelines from the positions of evidence-based medicine. The clinical and pharmacological characteristics of such a universal epithelial protector as rebamipide, acting at the preepithelial, epithelial and subepithelial levels, throughout gastrointestinal tract, are presented in detail.

Non-alcoholic fatty liver disease as a cause and consequence of cardio-metabolic complications. Role of the ursodeoxicholic acid in the pharmacotherapy.

The article presents an update of the role of non-alcoholic fatty liver disease (NAFLD) in cardiometabolic diseases and events: arterial hypertension and components of the metabolic syndrome. A review of NAFLD modern pharmacotherapy has been conducted. Particular attention is paid to the place of ursodeoxycholic acid in the complex treatment of NAFLD.

[Myocardial Contractile Function in Patients with Liver Cirrhosis and Syndrome of Bacterial Overgrowth Syndrome].

OBJECTIVE: to study myocardial contractile function in patients with liver cirrhosis and ascites in the presence of bacterial overgrowth syndrome (BOS) and pathological bacterial translocation. MATERIALS AND METHODS: We included in this study 59 patients with Child-Pugh class B and C liver cirrhosis (LC) of various etiology and ascites. Control group comprised 12 patients with ischemic heart disease complicated by chronic heart failure (CHF). Examination included history taking and laboratory and instrumental investigation. LC was diagnosed basing on clinical symptoms and instrumental studies. Child-Pugh and MELD scores were used for assessment of LC severity and prognosis. International ascites club grading system was used for evaluation of severity of ascites. Hydrogen breath test was applied for diagnosing BOS. Syndrome of pathological bacterial translocation was established based on blood levels of lipopolysaccharide-binding protein and detection of bacterial DNA in ascitic fluid. Structural-functional parameters of the myocardium and hemodynamics were assessed by echocardiography. Brain natriuretic peptide (BNP) concentration was measured in blood serum and ascitic fluid. RESULTS: In 13 of 59 patients with LC the hydrogen breath test was negative, in 33 positive and in 13 patients the positive hydrogen test was combined with the presence of BOS and pathological bacterial translocation. Blood serum and ascitic fluid BNP concentrations in LC patients were low and within normal limits (62.5±4.1 and 53.3±4.9 rg / ml, respectively), what contrasted with high BNP concentrations in patients with CHF (1820±95.5 and 497.1±39.6 rg / ml, respectively). Total protein level in ascitic fluid also was significantly lower in patients with LC than in patients with CHF (1.77±0.1 and 4.43±0.35 mg / dL, respectively). The serum-ascitic albumin gradient (SAAG) in both groups of patients exceeded 1.1 (1.58±0.13 in patients with CHF and 1.88±0.19 in patients with LC). Conclusions. In patients with liver cirrhosis the presence of BOS and bacterial translocation did not produce a distinct negative impact on contractile function.

Differential diagnosis of ascites in internal medicine: clinical case.

Ascites and hydrothorax may be the symptoms of congestive heart failure and do not always reflects presense of the decompensated liver cirrhosis. Clinical examination of patient with chronic hepatitis C which cyanosis of the lips, cervival veins pulsation, a triple heart rhythm indicated on pathology of the heart (constrictive pericarditis), which was confirmed by instrumental methods. Congestive heart failure has lead to the congestive liver in a young female patient. Regression of all the symptoms of heart failure occurred after surgical treatment (pericardectomy).

[Possibilities of using cepeginterferon alpha-2b in double (cepeginterferon alfa-2b and ribavirin) and triple (simeprevir, cepeginterferon alpha-2b, and ribavirin) antiviral therapy regimens for chronic hepatitis C. A review of clinical trials and experience of everyday clinical practice]. / Vozmozhnosti primeneniia tsepeginterferona al'fa-2b v sostave dvukh- (tsepeginterferon al'fa-2b i ribavirin) i trekhkomponentnoi (simeprevir, tsepeginterferon al'fa-2b i ribavirin) skhem protivovirusnoi terapii khronicheskogo gepatita S. Obzor klinicheskikh issledovanii i opyta povsednevnoi klinicheskoi praktiki.

Since the incidence of chronic hepatitis C (CHC) increases steadily, the priority of national health care is to provide antiviral therapy (AVT) for the maximum number of patients infected with hepatitis C virus (HCV). The regimens including pegylated interferons (PEG-IFN) are still in demand in the Russian Federation. A number of clinical trials have been conducted to evaluate the efficacy and safety of cepeginterferon alpha-2b (cePEG-IFN alpha-2b), an original PEG-IFN-α developed in the Russian Federation. Their results have shown that cePEG-IFN alpha-2b in the two-component AVT regimen has at least no less clinical efficacy than PEG-IFN alpha-2b and PEG-INF alpha-2a in HCV monoinfected and HCV/HIV co-infected patients. The pooled analysis of data has indicated that the use of cePEG-IFN alpha-b in combination with ribavirin allows an average of 80% of the patients with HCV genotypes 2 and 3 and 62% of those with HCV genotype 1 to achieve a sustained virological response (SVR). In clinical practice when the two-component AVT regimen (cePEG-IFN alpha-b and ribavirin) was used in patients with early-stage CHC and mild fibrosis, SVR was recorded in 90.7% of the patients with HCV genotype 2/3 and in 75% of those with HCV genotype 1. The experience in using cePEG-IFN alpha-2b as a component of the three-component AVT regimen (simeprevir, cePEG IFN alfa-2b, and ribavirin) has been published. The observational program manly covered young patients with mild or moderate fibrosis. SVR was observed in 94% of the patients. Another paper describes the experience with the triple AVT therapy (simeprevir, cePEG-IFN alfa-2b, and ribavirin) in 22 patients, the majority of whom had advanced fibrosis. SVR was recorded in 71.4% of those who had completed treatment. Thus, an individual approach and assessment of predictive response factors to two- or three-component AVT regimens including cePEG-IFN alpha 2b can achieve successful treatment outcomes in most patients with CHC, which is, in some cases, more economically sound than interferon-free regimens used as first-line therapy.

A multicentre, randomized study to evaluate the safety and efficacy of histamine dihydrochloride and interferon-alpha-2b for the treatment of chronic hepatitis C.

Interferon- (IFN-)alpha is currently the standard of care treatment for patients with chronic hepatitis C virus (HCV) infection. A significant part of the benefit of IFN-alpha in chronic hepatitis C is believed to be related to the activation of lymphocytes such as T cells and natural killer (NK) cells, which participate in the elimination of infected cells. Histamine dihydrochloride (HDC) has been shown to potentiate the IFN-alpha-induced activation of T cells and NK cells by a mechanism that involves the protection of these lymphocytes against oxygen radical-induced functional inhibition and apoptosis. This study was designed to examine the efficacy and safety of HDC in combination with IFN-alpha-2b in treatment-naïve patients with chronic HCV infection. All patients received IFN-alpha-2b, 3 MIU, three times weekly via subcutaneous injection, and were randomized to one of four HDC regimens (1 mg of either: once a day, three times a week; once a day, five times a week; twice a day, three times a week or; twice a day, five times a week). The doses of HDC in combination with IFN-alpha-2b resulted in sustained viral response rates ranging from 31% to 38%. Sustained biochemical response rates ranged from 28% to 41% across the four treatment groups. Patients infected with HCV genotype 1, and those with high baseline viral levels, which are characteristics associated with poor prognosis, had sustained virologic response rates ranging from 18% to 42% and 15% to 39%, respectively. Combination treatment was generally well tolerated. We propose that the potential benefit of HDC + IFN therapy for chronic HCV infection should be the focus of further investigation.