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Russian Journal of Gastroenterology, Hepatology, Coloproctology

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Vol 24, No 2 (2014)
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EDITORIAL

LECTURES AND REVIEWS

5-14 84
Abstract

The aim of review. To estimate possible interrelation between bacterial overgrowth syndromes in the small intestine (BOS) and irritable bowel syndrome (IBS).

Key points. BOS and IBS are extremely common syndromes, that contributes to their casual coexistence within same patient from epidemiological point of view. Clinical symptoms of BOS and IBS include meteorism, abdominal pain and disorders of defecation, that are difficult, at first sight, for differential diagnostics. From positions of pathophysiology it is possible to believe, that the IBS causes background for development of BOS, on the contrary, BOS increases risk of IBS development. Unfortunately, despite of huge quantity of studies, there is lack of convincing evidence to this for the present time. The evidential base is generated according to the studies showing high frequency of pathological breath tests in patients with IBS in comparison to healthy patients, however at IBS the rapid intestinal transit can promote false-positive results of breath tests. Other portion of evidential data is based on empirical application of nonabsorbable antibiotics that results in reduc tion of IBS symptoms. Failure to cure IBS by enteroantiseptic drugs requires necessity of search for new ways of treatment, including agents with enterosorptive action, capable to reduce BOS, velocity of intestinal transit and manifestations of IBS.

15-21 79
Abstract

The aim of review. To carry out analysis of reports and publications devoted to radiological methods of investigation in gastroenterology and to present up-todate options of these methods to doctors-gastroenterologists, experts in radiology and doctors of specialties.

Key points. Results of scientific studies and practical application of radiological methods in diagnostics of digestive diseases are presented. Application of radiological methods at detection and differential diagnostics of diseases of the liver, gallbladder, the pancreas, the spleen, gastro-intestinal tract, as well as for patients follow-up and at noninvasive interventions is reflected.

Conclusion. Expansion of the range of problems solved with application of radiological diagnostic methods of gastroenterological patients is marked.

ORIGINAL ARTICLES

22-30 104
Abstract

Aim of investigation. To reveal principles of development residual focal lesions various type and location in parenchymatous organs of patients after different noninvasive medical manipulations.

Material and methods. Overall 365 patients with focal lesions: metastases and cysts of the liver, residual foci in gallbladder area after endoscopic obliteration of organ cavity, malignant tumors and pseudo-cysts of the pancreas, chronic pancreatitis, abscesses of abdominal cavity of various localization, cysts and tumors of the spleen, cysts and tumors of kidneys, focal goiter, fibrous adenoma of breast gland were studied. Total of 1281 noninvasive medical manipulation at ultrasound guidance and X-ray navigation — installation of drainages/catheters and local treatment by antibiotics, intraportal injection of pharmaceuticals, sclerotherapy of 96% ethyl alcohol of liver and kidney cysts, metastases to the liver, interstitial laser photocoagulation of focal goiter, radio-frequency ablation of metastases in the liver, electrochemical destruction of liver metastases and fibrous adenomas of breast gland etc. was carried out. Ultrasound investigation was the basic diagnostic and control method; while helical x-ray computer tomography, X-ray fistulography, endoscopic retrograde cholangiopancreatography, scintigraphy, elastography, diagnostic punctures (aspiration biopsy, core needle biopsy, transcutaneous transhepatic cholangiography), laparoscopy, laparotomy, morphological investigation were used as methods of verification and control. Patients were followed up for 5 to 15 and more years.

Conclusion. It was revealed, that residual focal lesions of various type and location in parenchymatous organs after noninvasive procedures have similar consecutive stages of development, caused by common (clinical, pathomorphological) features.

31-35 93
Abstract

Aim of investigation. To estimate state of the pancreas in patients with combined trauma, to detect signs of traumatic pancreatitis.

Material and methods. Analysis of ultrasound data in 680 patients with combined trauma was carried out. In 57 patients (42 men and 15 women, age 20 to 56 years) signs of traumatic pancreatitis of various severity were revealed at US examination. Patients were divided into two groups: the first group — 32 patients had combined trauma, including closed injury of the abdomen, the second group — 25 patients who in late terms after trauma revealed signs of acute pancreatitis on a background of developing multiorgan failure. Investigations was carried out at middle class ultrasound devices with 3,5 mHz convex probe.

Results. In patients with combined trauma and closed injury of the abdomen signs of acute pancreatitis emerged, as a rule, on the 1–7 day after the moment of trauma. All forms of acute pancreatitis, including suppurative complications requiring miniinvasive intervention with US guidance: punctures and drainages in these patients were followed up at dynamic US-study. In patients of the second group signs of acute pancreatitis were revealed at 2–3 week on a background of progressing multiorgan failure.

Conclusions. Traumatic pancreatitis in patients with combined trauma develops both due to direct damage of the pancreas, and as a result of developing multiorgan failure. Dynamic US-study allows to reveal in due time signs of acute pancreatitis as well as complications. Pancreatic changes may be considered as developing dysfunction of the organ at multiorgan failure.

36-42 94
Abstract

Aim of investigation. To determine potential of non-invasive ultrasound techniques of fibroelastometry (FEM) and Acoustic Structure Quantification (ASQ) at liver parenchyma assessment and fibrosis stage grading in children with cystic fibrosis (CF).

Material and methods. Overall 89 children in the age of 2 months to 18 years with pulmonary and intestinal form of cystic fibrosis were investigated. The course of CF in 64 patients was considered as moderate, in 25 — as severe. The diagnosis was established according to clinical and laboratoric investigation with analysis of past history data, DNA-diagnostics with assessment of genotype and positive sweat test.

Results. Evaluation of liver parenchyma with the help of traditional ultrasound investigation with assessment of blood flow in portal vessels and celiac trunk allows to determine degree of hepatic fibrosis severity and to reveal initial signs of portal hypertension. Application of ultrasound techniques of ASQ and FEM objectifies study results as alongside with the qualitative analysis of ultrasound echograms quantitative grading of liver parenchyma and fibrosis stage became possible.

Conclusions. ASQ in CF patients can be applied for early detection of fibrosis, follow-up of process development and rating of hepatoprotective treatment efficacy.

HEPATOLOGY

43-52 95
Abstract

The aim of review. To discuss options of telaprevir application and risk of adverse events at triple antiviral therapy (AVT) in patients with the 1-st genotype of chronic hepatitis C and compensated liver cirrhosis (LC), and options of pharmacological treatment of hematological complications by original clinical case example.

Key points. Introduction of NS3/4A protease inhibitor — telaprevir — to treatment mode for patients infected by the 1-st genotype of chronic hepatitis C, has allowed to increase treatment response rate considerably. Patients with LC who represent heterogenic group require the special approach. AVT with good efficacy and sufficient safety profile in patients with compensated cirrhosis, is as well as for patients in the Waiting list for liver transplantation currently possible. The most common complication of triple AVT are hematological adverse events — development of anemia, neutropenia and thrombocytopenia (or aggravation of severity of the latter in patients with severe fibrosis and LC). Nowadays thrombopoietin receptors agonist (eltrombopag) which allows to provide interferon-based AVT to patients with thrombocytopenia and to optimize it, is developed and approved for clinical application. Assessment of indications to thrombocytopoiesis stimulation, correction of dozes of drug and regular monitoring of peripheral blood parameters are important points.

Conclusion. Introduction of direct antiviral agents — viral proteases inhibitors (telaprevir) to practice has allowed to increase AVT efficacy in patients with CHC G1 and liver cirrhosis providing comprehensible safety profile of AVT. Pharmacological stimulation of thrombocytopoiesis by thrombopoietin receptors agonists (eltrombopag) prior or during AVT has allowed not only to take into account patients with initially severe thrombocytopenia as candidates for AVT, but also to carry out sufficient treatment without decrease or with lower frequency of interferon doze reduction, achieving higher rate of sustained virologic response.

53-64 89
Abstract

Aim of investigation. Comparative study of efficacy and safety of Algeron in dozes of 1,5 and 2,0 mkg/kg and PegIntron in combination to ribavirin within combined mode of treatment of patients with chronic hepatitis C (CHC) with subsequent assessment of therapeutic doze of Algeron.

Material and methods. In open randomized «noninferiority» clinical study of II–III phase 150 previously untreated by interferon adult CHC patients (genotypes 1, 2, 3) were randomized in three medical groups: Algeron 1,5 mkg/kg, Algeron 2,0 mkg/kg and active control group — PegIntron 1,5 mkg/kg. All patients received ribavirin 800-1400 mg/day for 24-48 wks in relation to genotype. Early virologic response (EVR) rate was used as a primary endpoint of efficacy. Intentto-treat the analysis was applied at rating of obtained results.

Results. The comparative analysis has demonstrated, that EVR at the 12-th week in group of Algeron 1,5 mkg/kg was observed in 100 % of patients with genotypes 2/3 and in 88,5% of patients with genotype 1. In Algeron 2,0 mkg/kg group it was registered at 95,7 and 92,6 % of patients respectively, in control group – in 95,5 and 82,1% (р> 0,05 in comparison of all scores between groups). As no distinctions in Algeron efficacy were revealed, at more favorable safety profile of low doze, the therapeutic doze of 1,5 mkg /kg/wk has been chosen. After the first 12 wks of treatment all patients of the 1-st and 2-nd groups received Algeron in the chosen doze of 1,5 mkg/kg up to termination of the treatment course. Therefore the response at the end of treatment (direct virologic response, DVR) and sustained virologic response (SVR) were estimated for patients of the 1-st and 2-nd groups in common (n=100). Among patients with HCV 2/3 genotypes, receiving Algeron, DVR was observed in 93,6%, in control group – in 81,8%, in patients with the 1-st virus genotype — in 83 and 71,4 % of cases respectively (р>0,05 at comparison of all scores between groups). In patients with 2/3 genotypes HCV, at Algeron therapy, SVR was reached in 83 % of cases, in PegIntron group — in 81,8 %. In patients with the 1-st virus genotype it was observed in 67,9 and 57,1 % respectively (p> 0,05). The adverse events were registered during treatment by Algeron, in dose-dependent manner, however their frequency had did not exceed that in patients receiving standard PegIntron dozes.

Conclusions. Study results prove high efficacy and safety of Algeron in suppression of hepatitis C virus replication and allow to recommend its application at previously untreated patients with CHC in a doze of 1,5 mkg/kg/wk for 24-48 wks in relation to genotype HCV.

65-68 79
Abstract

Aim of investigation. To study efficacy and safety of domestic recombinant interferon α-2b Altevir® in combination to ribavirin in previously untreated patients with chronic hepatitis C (CHC).

Material and methods. Retrospective treatment results rating of 85 patients (49 men (57%) and 36 women (43%)) was carried out. All patients received 3 million IU per day of Altevir® subcutaneously and ribavirin (Ribapeg). Treatment duration was 48 wks for patients with 1-st genotype of hepatitis C virus (HCV) and 24 wks — for patients with 2nd and 3а HCV genotypes. Results. Aviremia in 24 wks after the end of therapy (sustained virologic response — SVR) has been achieved in 100% of patients with 2-st HCV genotype, in 95,8% patients with 3а HCV genotype and in 65,6% patients with 1b HCV genotype. The registered adverse effects, well-known for interferon α-2b therapy, as a rule, were mild or moderate, AVT cancellation was not required in any patient.

Conclusions. For patients with CHC with 2-st, 3а HCV genotypes and favorable prognosis of virologic response at combined AVT, including Altevir® and ribavirin, SVR frequency can reach 100 and 96% respectively. At AVT, including Altevir® and ribavirin to CHC patients with 1b genotype of HCV and favorable prognosis of virologic response, 66% SVR rate can be achieved.

69-77 73
Abstract

Aim of investigation. To estimate relation of polymorphism of genes encoding reninangiotensin system components (AGT G-6A, AGT M235T and ATR1 A1166C) with rate of liver fibrosis progression in patients with chronic hepatitis C (CHC).

Material and methods. Overall 109 patients with CHC and liver cirrhosis C with established stage of fibrosis and duration of disease have been divided into group of «rapidly progressing fibrosis» (55 patients, ≥0,130 fibrosis points/year) and «slowly progressing fibrosis» (54 persons, <0,130 fibrosis units/year). Assessment of polymorphism of studied genes was carried out by molecular genetic methods.

Results. In CHC patients of «rapidly progressing fibrosis» group in comparison to «slowly progressing fibrosis» group minor A-allele (50,0 and 33,3% respectively, p=0,0126) and «mutant» АА-genotype (27,3 and 11,1%, р=0,0324; OR АА=3,00; 95% CI 1,07-8,45), AGT gene on locus G-6A, as well as minor T-allele (р=0,0407) of AGT gene in M235T locus were significantly more common while MM genotype of M235T polymorphism of AGT gene (20,8 and 44,4%, respectively, p=0,0090; OR MM=0,33; 95%-CI 0,15–0,73) were significant less frequent. No significant differences between groups in distribution of alternative alleles and genotypes of ATR1 gene on A1166C locus have been revealed.

Conclusion. Carriage of mutant alleles of angiotensinogen gene on any of loci (G-6A or M235T) is the factor predicting more rapid progression of disease. As chronic hepatitis C is multifactorial disease, it is rational to use testing of allelic variants of angiotensinogen gene in patient-specific approach at CHC management.

NEWS OF COLOPROCTOLOGY

78-84 90
Abstract

Aim of investigation. Lynch's syndrome is hereditary syndrome caused by germline mutation in one of reparation genes not coupled bases and causing high risk of colorectal cancer development. At present there are no criteria, allowing to reveal all mutation carriers, and development of new guidelines is still going on, that became a task for original study. Material and methods. Search of microsatellite instability (MSI), characteristic for Lynch's syndrome, was carried out in tumor samples of 73 patients by fragment analysis method. At its detection search of germline mutations by polymerase chain reaction methods, electrophoresis and direct sequencing was carried out.

Results. Microsatellite instability was found out in 17 neoplastic samples (23%, 17 of 73). At 9 person germline mutations that has allowed to attribute this group to patients to Lynch's syndrome were revealed. Three of 9 mutations were described for the first time in the world.

Conclusions. According to neoplastic MSI, age and family history two new criteria for Lynch's syndrome search in the Russian patients have been offered. Efficacy of the first criterion was 60%, that of the second — 85,7%.

NATIONAL COLLEGE OF GASTROENTEROLOGISTS, HEPATOLOGISTS

85-91 191
Abstract

The aim of review. To discuss modern concepts on the structure and functions of intestinal microflora and its possible effect on development of certain diseases, as well as the basic methods of diagnostics of disorders of its qualitative and quantitative structure.

Key points. Intestinal microflora plays important role in maintenance of normal ability to live of a human body. Its qualitative and quantitative pattern can vary under effect of environmental factors, in relation to age, gender and climatic geographical conditions. New data on relation of disorders of microflora with diseases of cardio-vascular system, disorders of metabolism, autoimmune and allergic diseases have appeared. From the middle of XX century bacteriological method of investigation based on obtaining of pure culture was widely applied in rating of microflora pattern. However, during the last decade modern methods of diagnostics which allow to investigate structure and functions of microorganisms at a genetic level, even at the presence of single bacterial cell in a sample.

Conclusion. Application of modern methods of diagnostics allows to receive the unwrapped representation of microbic landscape of small and large intestine, and also to estimate character of metabolism of the defined microorganisms.

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ISSN 1382-4376 (Print)
ISSN 2658-6673 (Online)