The aim of review. The Human microbiome project was designed for identification and characterization of set of human microorganisms as well as for studying the changes in the human health due to microbiome changes. The Human Genome Project assumes: development of the human genome variations database (HapMap; Human Variome Project), interpretation of human phenotype differences (Encyclopedia Of DNA Elements), modeling of human phenomenon (RECON), interpretation of epigenetic variants and hereditary changes in phenotypical manifestations. The Human Microbiome Project became the sequel of The Human Genome Project. Summary. The human microbiome represents a variety of microbial species with the differing metabolic activity. The main features of human microbiome include: great variety at the level of genus and at the level of species, varying modes of diversification within samples, variability of microbiome of separate individuals is much less in comparison to interindividual variability, metabolic pathways remain unchanged until the patient is healthy, the lack of pathogenic bacteria in healthy microbiomes serves as microbiota alteration evidence in the state of disease. Identification of «microbial core» in microbial taxon remains a fundamental problem. There is a need to study of possible effects of altered microbiome on drug interactions and the immune status. The model of bacterial involvement in colorectal cancer progression is under study. Besides, the increasing attention of doctors and scientists is attracted to the issue intestinal microflora changes at antibiotic treatment. Conclusion. «The Human microbiome project» is implemented within identification and characterization of the microorganisms associated to the different anatomical regions of the human body tasks of the project include the study of inand interindividual microbiome disorders and their possible effect on the human health. The theory and practice of microbiome causes high potential for justification of the pattern of healthy nutritional pattern, behavior and development of new therapeutic agents.

Aim of investigation. To estimate possible changes of peptic ulcer (PU) epidemiology: gender and age of patients, age at disease onset, ratio of the stomach ulcers (SU) to duodenal ulcers (DU), clinical features at relapse of PU, frequency of concomitant digestive diseases. Material and methods. Overall 79 case records of patients with PUD of the stomach (PUS) (16 men, 33 women), PUD of duodenum (PUD) (15 men, 9 women) and PUD of combined localization (1 man and 5 women) were included in the study by continuous sampling method. Symptom frequency at PUD relapse and accompanying changes was estimated independently for male and female groups. Results. At the present time there is a shift of PUS to PUD ratio towards more common stomach ulcer location, increase in female proportion of PU patients and mean patient age at the onset of disease. Epigastric pain that develop in fasting state or after food intake remains to be the leading symptom of PU relapse and is observed at 87.5% of male and 95.7% of female patients. Significant number of patients present with heartburn and belching, that is explained by high frequency of PU to gastroesophageal reflux disease (GERD) combination (in 93.8% of men and 83.0% of women). Positive test for Helicobacter pylori (H. pylori) infection were received in 94.9% of patients. Idiopathic H. pylori-negative ulcers were detected only in 5.1% of patients. Conclusions. The modern trend in the PU clinical course is characterized by shift of typical male to female ratio, as well as PUD to PUS ratio, the high frequency of PU to GERD combination. Most patients were admitted for relapse of PU were positive for H. pylori infection.

The aim of publication. To present clinical guidelines of the Russian Scientific Liver Society on diagnosis and treatment of alcoholic liver disease to general practitioners. Summary. Harmful alcohol intake is the burning issue for Russia. The alcoholic liver disease (ALD) is a clinical and morphological entity that encompasses several forms of the liver parenchyma lesions resulting from alcohol abuse, that range from steatosis to alcoholic hepatitis (steatohepatitis) followed by progression to fibrosis, liver cirrhosis and hepatocellular carcinoma. Alcoholic liver cirrhosis gives significant impact to digestive disease associated motility. Alcohol addiction screening may be carried out by estimation of the standard doses of alcohol, application of CAGE and AUDIT questionnaires. Gamma-glutamyltranspeptidase activity and the level of carbohydrate-deficient transferrin are recommended to verify regular alcohol abuse in clinical practice. Abstinence from alcohol is the first line and the basic therapeutic procedure for any form and stage of ALD. Short therapeutic interventions practice helps to cope with alcoholic issue at any stage, gives the chance to motivate the patient, including the treatment of addiction to alcohol, intake of drugs. Specific pharmaceutical therapy is carried out at alcoholic hepatitis in relation to severity and alcoholic liver cirrhosis. Conclusion. The amount of consumed alcohol and drinking pattern should be systematized in clinical practice of the doctor of any specialty, first of all - for patients with liver diseases. Life prognosis estimation, ALD treatment are selected according to the stage and severity and aimed to decline in ALD-related motility.

Aim of investigation. To estimate efficacy and safety of narlaprevir (NVR) with ritonavir (RTV), pegilated interferon (peg-IFN) and ribavirin (RBV) at treatmentnaïve and earlier treated noncirrhotic patients with chronic hepatitis C caused by the 1st virus genotype in double blind placebo-controlled 3rd phase study (PIONEER). Material and methods. The main group received NVR (200 mg od orally) in combination to RTV (100 mg) and pegIFN/RBV for 12 weeks that was followed by peg-IFN/ RBV for 12 weeks. Comparison group received pegIFN/ RBV for 48 weeks, for the first 12 weeks in combination to placebo. Results. The sustained virologic response in 24 weeks after treatment termination (SVR24) in the main group (NVR/RTV, PEG IFN/RBV)) was achieved in 89.1% (163/183) of treatment-naïve and 69.7% (69/99) of earlier treated patients. SVR24 was achieved in 86.5% (32/37) of patients with relapse after previous peg-IFN/ RBV treatment course. The viral load decreased for the mean of 5.3 log10 in 2 weeks and 5.9 log10 in 4 weeks of treatment in the main group vs 1.5 log10 in 2 weeks and 2.5 log10 in 4 weeks in comparison group. In treatment-naïve patients from the main group SVR24 was achieved in 90.8% at initial METAVIR F0-F2 liver fibrosis stage and in 75% at F3 liver fibrosis stage. In those who were previously treated by peg-IFN/RBV, in the main group SVR-24 was attained in 72.6% at liver fibrosis stage F0-F2 and in 53.3% with F3 liver fibrosis stage. NVR/RTV addition to peg-IFN/RBV treatment did not alter safety profile as compared to peg-IFN/RBV therapy. Conclusions. In PIONEER study the narlaprevir combination therapy was characterized by high efficacy, convenience of administration and favorable safety profile.

Introduction. The options of antiviral therapy (AVT) in the stages of severe liver fibrosis and cirrhosis (LC) as well as in the patients with comorbidities for the long time were limited to the standard therapy by pegilated interferon (peg-IFN) in combination to ribavirin (RBV). Before official registration of interferon-free treatment modes in 2015 experience of the application was limited to clinical trials or treatment within early approach programs. Aim of investigation. To analyze the efficacy of PTV for chronic hepatitis C within the named patient program of expanded access to daclatasvir. Material and methods. Approval of Ministry of Healthcare of the Russian Federation to import of drugs was received for the treatment of 101 HCV-infected patients with compensated LC, who, been untreated had an urgent need for effective therapy, with estimated life expectancy less than 12 months, in 12 centers of the Russian Federation. The patients with 1b HCV genotype received treatment by combination of daclatasvir and asunaprevir 100 mg, patients with 2 and 3 HCV genotypes, and those with 1b HCV genotype after the liver transplantation received daclatasvir to sofosbuvir combination. Results. Sustained virologic response for 24 wks (SVR24) in early approach program was 89% (83 of 93) of patients with severe liver disease who urgently needed effective treatment with estimated life expectancy of less than 12 months if been untreated. In group of the patients receiving treatment mode of daclatasvir + asunaprevir the frequency of SVR24 achievement was 90%. Of 93 patients who underwent complete treatment course no severe adverse effects were registered. During treatment infrequent nonspecific adverse events, such as a headache and fatigue were observed. No significant elevation of alanine transaminase and aspartate aminotransferase activity, or bilirubin level were detected. Conclusions. Daclatasvir combination to asunaprevir or sofosbuvir demonstrated high efficacy, including that at treatment of patients with poor prognostic signs.

Aim of review. To present comparative assessment of diagnostic and treatment approaches at non-alcoholic fatty liver disease (NAFLD) in the Russian Federation and People’s Republic of China. Summary. NAFLD is the leading disease entity among the other chronic liver diseases in the countries of various regions of the world, at the present time it is considered to be one of the main causes for cryptogenic liver cirrhosis development. The pathogenesis of NAFLD closely correlates to both hepatic and cardiovascular involvement that significantly influences both treatment choice and life prognosis. According to the international clinical guidelines, NAFLD screening methods should include elastometry and serological tests to rule out severe liver fibrosis (F> 2). Liver biopsy is carried out at contradictory data of liver elastometry and serological fibrosis markers. Treatment of NAFLD should integrate the range of measures including correction of patients dietic habits and physical activity up to pharmacological treatment. Pharmacotherapy is recommended in the case of nonalcoholic steatohepatitis (NASH) progression (bridging fibrosis ³ F2 and cirrhosis), as well as the earlier stages of NASH with two and more fibrosis progression risk factors (age over 50 years, diabetes mellitus, metabolic syndrome, alanine transaminase elevation). Bicyclol is a drug developed in Materia Medica institute of Academy of medical sciences of China. The study is carried on by Chinese physicians have demonstrated efficacy of the drug for treatment of chronic liver diseases of various etiology, along with its antiinflammatory and antifibrotic properties. The drug registration studies conducted in the Russian Federation revealed high clinical performance of Bicyclol. Conclusion. Etiological and pathogenetic features of NAFLD require diverse therapeutic actions from dietic recommendations and physical activity correction of the prescription of various pharmacological agents. Results of clinical efficacy estimation of the new drug Bicyclol in the Russian market, that it was developed in the People’s Republic of China demonstrate reduction of severity of inflammation, steatosis, fibrosis and decrease of NAFLD activity scores.

Aim of review. To present the systematic overview of the stomach cancer risk factors to determine prophylactic measures and to define high-risk groups of population that can be included to the screening programs. Summary. Stomach cancer (SC) represents one of the leading causes for morbidity and mortality among malignant neoplasms worldwide. SC is asymptomatic at early stages that causes higher rate of locally advanced and disseminated forms of the tumor at primary diagnosis. SC early detection screening programs demonstrated high efficacy only in the Asian region. The main role in early detection of this disease is played by oncological alertness of doctors at outpatient clinics and gastroenterologists, as well as the patient education. The understanding of basic etiologic and predisposing factors and mechanisms of SC development, knowledge of key risk factors allow to distinguish high-risk groups from the general population and to carry out active revealing of premalignant lesions and early forms of SC. Conclusion. Stomach cancer is a multifactorial disease which develops under effect and interaction of external and internal factors. Intestinal type SC and diffuse type SC have various pathogenesis and risk factors. Risk factor estimation provides effective prophylaxis of the disease, and also to reveal high risk groups for preventive and screening programs.

Aim of investigation. To compare results of radical surgery in IBD-associated colorectal cancer (IBD-CRC) and sporadic colorectal cancer (spCRC) patients. Material and methods. The main group included retrospective cases of IBD-CRC with total colectomy and D3 lymph node (LN) dissection. The control group included matched cases of spCRC in 1:3 ratio according to localization and stage. Results. Overall 6 IBD-CRC and 18 spCRC patients were matched. IBD-CRC patients had longer operation time (313±37 vs 240±16 min, p=0.05), while there was no significant difference in mean volume of blood loss and postoperative stay duration (383±145 and 186±29 ml, p=0.24; 15.7±3.2 and 14.1±0.9 days, p=0.5 respectively). IBD-CRC patients spent longer time in ICU than spCRC (2.3±0.6 and 1.17±0.2 days, p=0.02) and had later bowel peristalsis restoration (2.0±0.4 and 1.3±0.1 days, p=0.02), however, time to first gas and stool discharge via stoma didn’t differ (2.5±1.4 and 2.1±0.6 days, p=0.5; 4.2±3.4 and 2.4±0.7 days, p=0.3). Tumor grade, histological type and adenoma rate didn’t differ between groups. Average number of involved LN in IBDCRC and spCRC was 39±16 and 30±5 (p=0.6). The rate of metastatic LN was 33.3% in both groups. The mean follow-up time was 27.3±5.3 months. Distant metastases were detected in 33.3% and 16.7% of IBD-CRC and spCRC cases respectively (p=0.4), without local recurrence in both groups. Conclusion. Tumor and LN characteristics in spCRC and IBD-CRC were similar, therefore radical surgery with extended LN dissection is recommended for IBDCRC patients.

Aim of publication. To present proceedings of Advisory council on postcholecystectomy syndrome (August 25, 2017; Prague, Czech Republic) with support of the Adamed Group company. Summary. The Advisory council proposed algorithm for investigation and management of patients with postcholecystectomy syndrome (PCS). Gallstone disease (GSD) is diagnosed in 10-25% of the population of various age, with obvious trend to involvement of the younger patient categories in the last decades. The total number of GSD patients increases every decade no less than twice. Cholecystectomy remains the basic method of surgical treatment of symptomatic GSD. Nowadays laparoscopic cholecystectomy became universally popular and earned the status of the «gold standard» of surgical treatment. At the same time at asymptomatic GSD the watchful waiting approach avoiding active treatment is considered to be the most expedient. Biliary sludge and microlithiasis including cases undiagnosed at routine investigation can be one of important factors for development of the PCS. Pharmacological treatment of sphincter of Oddi dysfunction that develop at GSD/PCS include following of dietary recommendations, intake of selective spasmolytics, digestive enzymes and ursodeoxycholic acid. Conclusions. Follow-up program for the patient of the cholecystectomy should include regular assessment of clinical symptoms for duly diagnostics of acute and/or severe complications and associated diseases, that may require surgical treatment. Treatment has to include regular courses of selective antispasmodics, the presence of indications - prescription of bile acid supplements, when required - methods of endoscopic surgery.