The aim of review. To generalize accumulated data on C. difficile infection, diagnostics, treatment and prevention of C.difficile-associated disease.

Summary. C.difficile is unthrifty on breeding grounds, obligate anaerobic, gram-positive, sporeforming, cytotoxin-producing bacterium. C. difficile toxins A and B are protein molecules, classified as glycosyltransferases. Influence of toxins induces damage and inflammation of intestinal wall due to impairment of intestinal epithelial barrier, stimulation of proinflammatory cytokine production, apoptosis and necrosis of epithelial cells. Basic clinical symptom of C. difficileassociated disease is diarrhea or diarrhea with hematochezia (according to severity of the case). Feces of patients with diarrhea are sampled for C. difficile toxin detection. Nowadays there are several laboratory diagnostic tests for Clostridial infection: testing for C. difficile glutamate dehydrogenase, enzyme-linked immunoassay, polymerase chain reaction for toxigenic strain of C. difficile. However, which of these methods may be considered to be «the gold standard» is unclear yet. Metronidazole, vancomycin, dioctaedric smectite and probiotics are used for treatment of C. difficile infection. Rational use of antibiotics, shortening of hospital stay terms whenever possible, especially for patients of 65 years of age and older is recommended to reduce the risk of clostridial infection development. Preliminary, routine and general cleaning should be carried out in medical institutions as well as the cleaning of hands of medical personnel and medical stock according to sanitary-and-epidemiologic rules and specifications.

Conclusion. From the beginning of XXI century in many countries of the world prompt increase of C. difficile-associated disease cases is marked. This disease is the most frequent cause of intrahospital diarrhea resulting in significant mortality. This is why it is extremely important to be able to diagnose, treat in due terms this disease and to carry out prophylactic procedures.

Aim of investigation. To characterize radiological methods of diagnostics of surgical complications after simultateous pankreas-kidney transplantation (SPKT).

Material and methods. From January, 2008 to June, 2014 overall 40 patients with the type 1 diabetes mellitus complicated by terminal diabetic nephropathy, underwent SPKT, including 17 cases (42,5%) — of intraperitoneal transplantation and 23 (57,5%) — of retroperitoneal transplantation. Mean age of patients was 35,7±6,36 year. Of all recipients 19 were women (47,5%) and 21 — men (52,5%). Results. Of 15 patients after SPKT 21 surgical complications were diagnosed, overwhelming majority of them have been corrected successfully. Only in one case the pancreatic transplant was lost due to postoperative surgical complications.

Conclusions. Duly diagnostics and the proven choice of miniinvasive techniques for treatment of surgical complications became possible due to wide and urgent application of the whole spectrum of available radiological methods.

Aim of investigation. To carry out objective estimation of liver parenchyma state in children with the 1-st type hereditary tyrosinemia (НТ-1) by ultrasound method with quantitative estimation of hepatic parenchyma pattern.

Material and methods. Overall 14 children with the 1-st type tyrosinemia aged 3 months to 14 years (6 — with acute and subacute forms and 8 — with chronic form) were studied. Traditional ultrasound investigation and innovative non-invasive ultrasound technique of quantitative analysis of liver parenchyma acoustic pattern — Acoustic Structure Quantification (ASQ) were applied. Traditional US-investigation of hemodynamic parameters of portal system blood flow reveals early US-signs of portal hypertension. Color mapping (ASQ technique) allows visual estimation of fibrosis severity and amount of functioning parenchyma. Plotting of histograms and density probability functions of various zones of liver parenchyma allows to establish the stage of fibrosis. The density index provides quantitative characteristic of fibrosis stage.

Results. Neither absence of fibrosis or minimal and moderately severe fibrosis was observed in children with НТ-1. The density index range at severe fibrosis stage was 2,62 (2,62-2,72) (2,62-2,72), at stage of liver cirrhosis — 3,37 (3,21–3,80) (3,00–4,58). In the areas of normal liver parenchyma no significant differences from the control group were found and the range was equal to 1,10–1,35.

Conclusion. Obtained data may be used for objective estimation of the process stage in children with the 1-st type tyrosinemia when liver biopsy is contraindicated.

Aim of investigation. Primary objective: to estimate the prevalence of NAFLD within the general practitioner’s and gastroenterologist’s patient flow.
Materials and methods. The prospective disease registry was carried out as epidemiologic, observational, cross-sectional, multicenter investigation to assess NAFLD prevalence at outpatient practice in the Russian Federation. A total of 50145 patients meeting the inclusion/exclusion criteria in 16 Russian cities were enrolled this study registry. Overall 1031 qualified doctors (GPs/therapists/gastroenterologists/pediatricians), providing outpatient care for the population, were study investigators. The epidemiological data were obtained and
recorded during two routine patient admissions to investigating centers. Acad. of the Russian Academy of science V.T. Ivashkin and Prof. O.M. Drapkina were national coordinators of the study.
Results. The rate NAFLD cases within primary or secondary patients, who admitted the healthcare institutions for any reason, including those with suspected NAFLD was 37,3%. The main trend for non-cirrhotic non-alcoholic fatty liver disease (NANCFLD) prevalence was the progressive increase along with age from 2,90% in 12–17 y.o. patients to 42,96% in 60–69 y.o. patients. The highest prevalence of non-alcoholic steatosis (NAS) was 34,26% in patients aged 70–80. Non-alcoholic steatohepatitis (NASH) was most frequent in patients aged 50–59 (10,95%).
Conclusion. Prevalence of NAFLD in outpatients in Russia increased from the year 2007 to 2015 and reached 37,3%. The high prevalence of NANCFLD was revealed in primary or secondary patients admitted healthcare institutions for any reason including those with suspected NAFLD (patients with obesity, type 2 diabetes mellitus, dyslipidemia, metabolic syndrome, hypertension, hypercholesterolemia).

The aim of review. To analyze antiviral activity of a new NS5A replication complex inhibitor daclatasvir in patients with chronic HCV-infection in relation to different genotypes, including patients with failure of previous antiviral therapy, with liver cirrhosis, within different modes of treatment.
Summary. Daclatasvir is NS5A inhibitor which has proven high antiviral activity in relation to all hepatitis C virus genotypes. Prescription of the drug in combination to pegilated interferon and ribavirin for treatment-naive patients made possible to reduce treatment duration from 48 to 24 weeks and to increase frequency of sustained virologic response (SVR) to 87% in 1b genotype
and to 100% — in 4-th genotype. Daclatasvir is no less effective within treatment modes that include other direct-acting antiviral agents as well. In combination to asunaprevir (second wave
protease inhibitor) it demonstrated high rate of SVR both in untreated patients (91%), and in «difficult to treat» groups patients — with liver cirrhosis and nonresponders to the previous therapy (up to 83%). Quadrotherapy including pegilated interferon, ribavirin and asunaprevir has allowed to increase treatment efficacy in nonresponders with 1b genotype even more (up to 98,9% of SVR). Combination of daclatasvir and sofosbuvir is considered to be effective as well, demonstrating 96% rate of SVR in patients with the 3-rd genotype without liver cirrhosis, irrespective of treatment experience. A safety profile and tolerability of daclatasvir is good, comparable to placebo group. The drug is not registered in Russia yet, its approval in combination to asunaprevir is expected soon.
Conclusion. Clinical trials have demonstrated that combination of daclatasvir with other medications possessing direct antiviral action, in particular with asunaprevir, and with pegilated interferon and ribavirin significantly increases treatment response rate at different categories of patients with chronic HCV-infection; that allows to reduce treatment duration of these patients
groups. The drug possesses favorable safety profile, including at treatment of liver cirrhosis.

The aim of the review. To analyze the main cellbased sources of hepatocyte for artificial liver generation, to describe the key features of each approach, to discuss benefits and shortcomings.

Summary. Artificial liver transplantation could be an alternative for traditional transplantation. For the artificial liver generation specialized cells are required. So far several sources of hepatocyte-like cells generation are known. This review presents alternative approaches for liver failure treatment: inhibition of epithelial-mesenchymal transformation, e.g. by induction of proliferation (gene therapy with HGF), and by influence on immune imbalance (T-regulatory lymphocytes application).

Conclusion. Evaluation of the main sources of autologous hepatocytes would provide insights into priority directions of future studies, and lead to progress in liver failure treatment.

Aim of investigation. To define computer-tomography (CT) densitometry features of hepatocellular carcinoma (HCC) at different stages of histological differentiation and to correlate CT vascularisation degree to morphological features.

Material and methods. The study was based on the clinical and morphological data of 19 patients (12 men and 7 women, aged 18–72 years), with hepatocellular carcinoma (HCC) without coexistent liver cirrhosis. At a preoperative stage all patients underwent helical CT with bolus contrast enhancement (four phases study), with estimation of arterial and venous density gain of
the lesion and CT-vascularization index. The morphometric analysis of HCC blood vessels was carried out in immunehistochemical specimens stained for CD34 and CD105.

Results. According to CT and immunohistochemistry data highly differentiated carcinomas were the most vascularized (hypervascular), while poorly differentiated HCC were the least vascularized. Hemodynamic functionality in moderately-differentiated tumor nodes was significantly higher as compared to well differentiated tumor. The poorly differentiated tumor was characterized by decrease in both total number of blood vessels, and the quantity of neovasculatures that underlies transition of cells to anaerobic way of metabolism.

Conclusion. Decrease in histological differentiation grade and concomitant gain of malignant potential of neoplasm is associated to reduction of the total area ofbarterial blood vessels. Computer tomography scores should be applied as additional criteria of the tumor malignant potential and for estimation of treatment efficacy as well.

The aim of review. To analyze and present data of the foreign pharmacogenetic studies devoted to improvement of pharmacological therapy of colorectal cancer (CRC), in particular those, focused on the drugs with general cytostatic action: 5-fluorouracil derivatives, irinotecan and platinum agents.
Summary. In the oncological diseases frequency spectrum CRC traditionally occupies the leading positions all over the world. The success of CRC chemotherapy depends significantly on the individual genetic features of the patient influencing both efficacy of pharmacological effects, and degree of side effects severity. If efficacy and necessity of pharmacogenetic investigation for such drugs of targeted therapy, as cetuximab, is already proven for the present time, it is still underestimated for the widely applied drugs of general cytostatic action. This review presents systematic and generalized data on the most informative genetic markers which analysis can be used for optimization of treatment of CRC patients at multicomponent modes of chemotherapy, such as FOLFIRI and FOLFOX.

The aim of review. To present literature data on clinical presentation, pharmacodynamic and economic efficiency of standard dozes of proton pump inhibitors (PPI) for gastroesophageal reflux disease (GERD).

Summary. PPI are the most effective pharmaceuticals for treatment of acid-related diseases (ARD). Control of intragastric рН level is the key moment of healing of erosions and ulcers of the upper gastro-intestinal tract, as well as for Н. рylori eradication efficacy. Functional state of stomach mucosa and efficacy of antisecretory therapy was estimated by 24-hour pH or рН-impedance measurement. The standard dozes of PPI provided acid-suppressive effect for up to 18 hs. Already after the first dose intake at 24-hour рН monitoring the stomach рН>3 was recorded for 56,1% (±20,94) of total monitoring time, and рН>4 — for 44,0% (±18,72), that promoted rapid symptom relief. Terms of activation and efficacy of Н+/К+-ATPase inhibitors is determined by pH of the media and pKa values for each pharmaceutical. Intensity of acid-suppressive action of PPI depends on drug metabolic pathways and genetically determined features of cytochrome P450 system. Mutations of CYP2C19 alleles allow to divide the studied patients population into groups of rapid, mediun and slow «metabolizers» that it is necessary to take into account at prescription of the certain drug. At a choice of PPI dose or shift from one PPI to another it is necessary to be guided by the concept of equivalent dosages according to the instruction leaflet on the drug application. Long-term maintenance therapy by PPI for GERD enables reduction of expenses for treatment of disease preserving clinical efficacy.

Conclusion. PPI are of the drugs of choice in ARD therapy. PPI should be applied in the least effective doze, including on demand treatment and intermittent treatment. The individual approach to PPI prescription, based on the careful analysis of clinical presentation, as well as on data of esophagogastroduodenoscopy, 24-hour pH or pH plus impedance measurement is required. Reasonable cost to efficacy ratio is no less important.

The aim of review. To present current approach for NSAIDs-gastropathy prevention.

Summary. Upper gastrointestinal lesions, related to intake of nonsteroid anti-inflammatory drugs (NSAIDs) represent a serious social and medical problem. This is related to increase in NSAIDs and low dozes of aspirin users number, who are mostly elderly people, often having combination of several diseases with serious risk of drug-induced complications. Even after safer class of NSAIDs, i.e. selective cyclooxygenase-2 (COX-2) inhibitors were introduced to clinical practice and obvious successes in treatment of H. pylori-associated peptic ulcers, frequency of NSAIDs gastropathy still remains high. Besides that, NSAIDs gastropathy complications, such as bleeding and perforations, are accompanied by high mortality and serious treatment expenditures. This requires adequate prophylaxis of this pathology. Proton pump inhibitors (PPIs) play a special role as the main class of drugs used for NSAIDs gastropathy prevention at the present time. This review presents advantages of pantoprazole — a PPI, that possesses the minimal risk of unfavorable pharmacological interaction with drugs of other pharmacological classes.

Conclusion. Application of less aggressive NSAIDs — selective COX-2 inhibitors and H. pylori eradication reduce risk of serious complications, but does not eliminate it completely. Therefore long-term PPI application is required for prevention of NSAID-related ulcers and gastro-intestinal bleeding in patients who receive NSAIDs on regular basis, in the case if they have risk factors for NSAIDs-gastropathy.

The aim of review. To present the diagnostic and treatment algorithm for abdominal pain at out-patient/ polyclinic healthcare institutions and to demonstrate potential of hyoscine butylbromide application during diagnostic process and for relief of abdominal pain at irritable bowel syndrome.

Summary. From 20% to 50% of all admissions to medical institutions are related to abdominal spasms and pain caused by irritable bowel syndrome (IBS). According to the Clinical guidelines of the Russian gastroenterological association and abdominal pain management algorithm at outpatient reception, the doctor on the basis of interviewing, inspection and physical data first of all should exclude acute abdominal diseases (acute pain, parietal pain) requiring urgent examination by the surgeon or gynecologist and subsequent hospitalization. In the case of visceral pain the minimal range of laboratory and instrumental tests is indicated. If the history of visceral pain is more than 6 months and there are no alarm symptoms, doctor should define specific features of clinical presentation already during outpatient visit, taking into account pain location, that provides formulation of preliminary diagnosis. Epigastric pain (dyspepsia), biliary pain, abdominal pain which can be accompanied by impaired frequency and consistency of stool determine the further investigation plan. Implementation of diagnostic algorithm allows to distinguish the organic disease or to establish
the diagnosis of functional disease. Hyoscine butylbromide at short-term treatment will relieve abdominal spasm as a symptomatic agent. Course treatment effectively reduces intensity and frequency of abdominal pain at IBS. The rate of adverse events and tolerability of hyoscine butylbromide are comparable to that of placebo.

Conclusion. Symptomatic treatment by antispasmodic drugs is justified from the moment of referral for medical aid to outpatient department. Hyoscine butylbromide can be prescribed for relief of acute and chronic pain at any stage of diagnostic process. Course intake of antispasmodics has proved its efficacy for pain relief at IBS.