EDITORIAL
The aim of review. To present modern data on a role of adaptive immunodefence in development of chronic viral damage of liver and mechanisms of influence of hepatitis viruses B and C (HBV and HCV) on functional activity of cytotoxic lymphocytes (CTL).
Original positions. There are some mechanisms of HBV and HCV suppressing effect on immune response parts: exhaustion of virus-specific CTL functional activity as a result of persistence of high concentrations of viral antigens; elevation of activity of regulatory Т-cells; ability HBV to exist in the form of sustained endocellular template – covalently closed circular DNA (ccc DNA); mutations of genome HCV, allowing «to escape» from immune supervision; direct operation action of HCV proteins on Т-cells. The role of activated platelets in immunopathological reactions is also considered at chronic viral liver damage.
Conclusion. Application at chronic hepatitis B and C of up-to-date algorithms of antiviral therapy including agents like interferon, ribavirin and nucleotides/nucleosides analogues, does not allow to achieve at significant part of patients long-lasting suppression of viral replication that can result in persistence of replication HBV or HCV, activations of inflammatory and necrotic processes in the liver, clinically manifesting as relapse of hepatitis with subsequent development of liver cirrhosis and hepatocellular carcinoma. Evaluation of efficacy of antiviral therapy with the help of dynamic assessment of viral load and other viral markers yields only indirect representation of activity of pathological process. The recent scientific development offer idea of monitoring of parameters of innate (congenital) and adaptive (acquired) immunodefence at patients with chronic viral hepatites at antiviral treatment, and development of drugs, capable to sustain quantitative and functional stability of virus-specific Т-cells.
ORIGINAL ARTICLES
Aim of investigation. To study at chronic diseases of small and large intestine the concentration of immunoglobulins in intestinal contents, to estimate histological structure and severity of lymphoplasmacytic infiltration of lamina propria of proximal small intestine mucosa, to investigate a state of microbiocenosis of intestine.
Material and methods. Overall 287 patients with chronic bowel diseases have been included in original study: 73 with irritable bowel syndrome (IBS), 55 – with irritable bowel syndrome with diarrhea (IBAD), 48 – with malabsorbtion syndrome (MS), 60 – with celiac disease (CelD) and 51 – with ulcerative colitis (UC). Concentration sIgA, IgA, IgG and IgM in intestinal contents was assessed in all patients. Histological investigations of mucosa of small intestine (MSI) have been carried out at 155 patients. The group of control consisted of 27 generally healthy people. Microbiocenosis of intestine was investigated at 37 generally healthy and at 177 patients with chronic bowel diseases (IBS – 36, IBDD – 36, MS – 35, CelD – 38 and UC – 32). Tests for concentration of immunoglobulins in small intestine contents, evaluation of morphology of proximal region of jejunum, and microbiologic study of contents of the small intestine and stool were executed according to standard procedures.
Results. Atrophy of MSI, concentration of immunoglobulins in intestinal contents and disorders in microbiocenosis present in the different degree were the basic difference between groups of patients. At patients having UC, CelD and the MS, growing depression of secretion sIgA (from UC to CelD and MS) which severity coincided with depth of atrophy and density of infiltration of MSI by mononuclear cells was observed. Signs of bacterial overgrowth and change of microbial landscape of the intestine were present at all studied groups and intimately correlated with activity of function of immune elimination of the small intestine (sIgA) and grade of MSI atrophic changes. At IBS and IBSD changes of quantitative and qualitative parameters of intestinal microflora were mild or moderately severe. For these patients interrelation between activity of sIgA secretion at MSI both with degree of its bacterization by aerobic bacteria and with concentration in feces of lactobacilli (which was in inverse correlation to IgG) was characteristic. Diseases of the small intestine and UC were characterized by considerably more severe bacterization of proximal region of the small intestine in comparison to IBS. Significant decrease of function of immune elimination at the MS, CelD and UC was accompanied by overgrowth of opportunistic flora and depression of symbiotic microorganisms. Thus there were essentially new mutual relations between infectious and immune factors.
Conclusion. Comparing to results of original study and numerous literature data it is possible to postulate that disorders in unite three-dimensional interaction system between epithelial lining of the gut, its microflora and local immune system underlie development of chronic intestinal disease.
Aim of investigation. Studying of clinical pattern of functional dyspepsia (FD) and efficacy of ganaton (itopride hydrochloride) in its treatment.
Material and methods. Overall 509 patients with FD were investigated. Before and after 4-week course of ganaton (itopride hydrochloride) 50 mg tid, severity of clinical symptoms was estimated by 4-point system.
Results. High frequency of combination of FD to nausea, symptoms of gastroesophageal reflux disease (heartburn) and irritable bowel syndromes (meteorism, disorders of defecation) was marked. Application of ganaton promoted relief of complaints in 46,6% of patients, significant decrease of their severity – at 47,8%.
Conclusions. Ganaton is efficient agent in treatment of FD and concomitant functional disorders of gastro-intestinal tract.
Aim of investigation. To estimate frequency, factors of development of heartburn at pregnant women, to determine approach of pharmaceutical treatment by alginates.
Material and methods. At 110 pregnant women frequency and severity of heartburn were estimated by Likert scale, anthropometry and esophagogastroduodenoscopy at presence of heartburn were carried out.
Results. General frequency of symptom of heartburn in studied group was 56,4%. The weekly heartburn was revealed at every other pregnant woman (49,1%). The greatest effect on its development had: presence of heartburn prior pregnancy, excessive body weight or obesity before and during pregnancy, presence of the relatives having heartburn, presence of heartburn during previous pregnancy, smoking before pregnancy. Frequency and severity of heartburn without pharmacological correction grew along with gestation term. On a background of Gaviscon forte treatment 10 ml/day in on-demand mode by the 4-th week of the study significant decrease of total frequency and severity of heartburn, complete relief of weekly, daily and night heartburn was observed.
Conclusion. The heartburn is a frequent symptom at pregnancy, alginic acid drug can be successfully utilised for its treatment.
Aim of investigation. To determine clinical value of viral load level (VLL) of HBV in blood at patients with natural course of chronic HBV-monoinfection.
Material and methods. Overall 149 patients were investigated. Of them 68 (45,6%) were women and 81 man (54,4%) in the age of 16 to 71 years. Molecularbiological analysis for the presence of hepatitis B virus DNA in blood was carried out three times with 6 months intervals by polymerase chain reaction (PCR) method in a «real time» mode (test-sensitivity 103 copies/ml).
Results. At triple complex investigation 20% of HBsAg inactive carriers have been selected. At a single PCR – test at the majority (59,5%) of patients with chronic hepatitis B (CHB) no HBV DNA was determined in a blood, while at two-times and triple study the number of patients with not determined HBV DNA level reduced apparently (41 and 12,5% respectively). Analysis has indicated, that CHB patients have direct correlation between alanine transaminases (ALT) activity and HBV DNA VLL (r=0,385, р=0,008). Only in 9% of cases constantly high VLL was registered, mainly, on a background of elevated activity of ALT. The progressing form of CHB has been diagnosed in 21,7% of patients with natural course of chronic HBV-monoinfection for this they have been recognized as candidates for antiviral therapy.
Conclusions. In original study the direct correlation between parameters of HBV VLL and ALT activity at patients with natural course of chronic HBV-monoinfection was revealed. Only complex dynamic assessment of such patients helps to define absolute candidates for prescription of antiviral therapy and to determine proportion of inactive HBsAg carriers.
Aim of investigation. To reveal risk factors of a relapse of acute adhesive smallintestinal obstruction (AASIO) resolved conservatively, and to prove indications to planned adhesiolysis.
Material and methods. Analysis (by case records data) of conservative treatment of 82 patients with AASIO, discharged for 2001 to 2004 from city clinical hospital № 31 was carried out. Remote period was monitored in 50 cases. Observation time ranged from 3 to 7 years.
Results. AASIO relapse occurred in 54 % of patients. Risk factors of relapse included: presence of AASIO in past history, quantity of AASIO attacks in past history, leukocytosis, absence of pneumatosis of the large intestine, high volume of stomach aspirate, severe retardation of emptying of barium meal in the small intestine. The prognostic system for assessment of risk of AASIO relapse was generated.
Conclusions. Planned operative treatment of patients with AASIO conservatively resolved, is indicated to patients with high risk of relapse of disease. The differentiated approach at planning surgical adhesiolysis allows to avoid unreasonable surgical interventions and to improve quality of treatment of patients.
NATIONAL COLLEGE OF GASTROENTEROLOGISTS, HEPATOLOGISTS
The aim of review. To analyze similarity and differences of clinical manifestations and data of additional investigations methods at irritable bowel syndrome (IBS) and celiac disease.
Original positions. Data on pattern of clinical manifestations and basic laboratory and histological markers of celiac disease is cited. Possible similarity of basic signs of IBS and celiac sprue is pointed out, especially at low-symptom, subtle course of the latter. Taking into account essentially different prognosis of these diseases, well-timed recognition and treatment of celiac disease is important. Groups of risk, sensitivity and specificity of various serological tests and information value of histological study of mucosa of small intestine at celiac sprue are presented. Necessity of combined investigation of basic serological markers of celiac sprue – antibodies to tissue transglutaminase and antibodies to endomysium at patients with prospective diagnosis of IBS with diarrhea-predominant and mixed variant is rationalized.
Conclusion. It is necessary to recognize, that according to Rome-III criteria it is not obviously possible to exclude convincingly the presence of celiac disease at patients with symptoms of IBS with diarrhea and mixed type. It is expedient to recommend a test for antibodies to tissue transglutaminase and antibodies to endomysium to these patients.
NEWS OF COLOPROCTOLOGY
Aim of investigation. Assessment of capability of virtual colonoscopy (VCS) in revealing of neoplasms of the large intestine and representation of it as a probable method for screening diagnostics colorectal cancer (CRC).
Material and methods. Original study have included 148 patients in the age of 2 to 82 years. Indications for VCS were: complaints of change of a normal bowel habit, positive test for tumor markers, positive fecal occult blood test.
Results. Overall 85 mass lesions have been revealed at VCS, of which 12 appeared to be colorectal cancer, the other 73 – polyps. The smallest polyp was 4 mm in size. Sensitivity of VCS in comparison to endoscopic colonoscopy in revealing of mass lesions was 93%, specificity – 78%.
Conclusions. This procedure is indicated at incomplete or contraindicated endoscopic colonoscopy, studying of prestenotic regions of intestine, at children for revealing anomalies of development. VCS can be recommended for screening programs of diagnostics of diseases of the large intestine.
The aim of review. To present modern methods of diagnostics, treatment and monitoring of patients with Wilson disease (WD).
Original positions. Diagnosis of Wilson disease should be excluded at each patient with liver disease of non-specified etiology at the age of 3 to 55 years. Dramatic decrease of ceruloplasmin level (CP) in blood serum (less than 50 mg /l or less 5 mg/dl) should be regarded as the convincing proof for the benefit of WD diagnosis. At moderate or subnormal values of this parameter it is necessary to carry out further tests . Normal CP level cannot exclude WD diagnosis. To specify the diagnosis investigation of copper metabolism is required. Evaluation of neurologic status and radiological study of the brain (preferably – magnetic-resonance) should be done prior to onset of treatment in all patients with neurologic form of WD, radiological methods serve for differential diagnostics purpose. Genetic analysis is expedient at diagnostic difficulties. At each patient with acute liver failure and negative Coombs test for intravascular hemolysis, moderate elevation of serum aminotransferases activity or decreased level of alkaline phosphatase WD should be excluded. Primary treatment of patients with clinical symptomatology should include chelating agent (DPenicillaminum or trientine). It is necessary to avoid the use of food products and water with high contents of copper, especially in the first year of treatment. Treatment of presymptomatic patients or patients at maintenance therapy can be carried out with the help of chelator or Zinc. The acute liver failure caused by WD, serves as the indication for immediate liver transplantation. Patients with decompensated cirrhosis, tolerant to chelator therapy, should be regarded as candidates for transplantation. During pregnancy WD treatment proceeds, but by the lower doses of copper chelators.
Conclusion. Wilson disease – is one of the first diseases of liver for which effective method of treatment has been found. WD was a fatal disease before methods of its treatment have been developed 50 years ago. Discovering and introduction of D-Penicillamine in clinical practice revolutionized WD treatment. The most effective method, allowing to keep life to the patient, is orthotopic transplantation of the liver.
EXCHANG OF EXPERIENCE
The aim of review. To present the definition of probiotics, to indicate principle of their action and international requirements to probiotic products, to review clinical studies of probiotic application in gastroenterology.
Original positions. Original studies assume a set of positive properties of probiotics. Most frequently strains of lactobacilli and bifidobacteria are used as probiotics, brewing yeast and some Escherichia coli strains also serve for this role can. Specific influence on health of the person can be attributed only to particular researched strain or strains, but not to species and not to the whole group of lactic acid bacteria or other probiotics as a whole. Probiotics are designed to aid a human body which has intestinal flora by virtue of evolutionary development. Some of them are used for prophylaxis of diarrhea caused by application of antibiotics, or as a part of complex treatment of antibiotic-associated colitis. Various effects of probiotics are known at numerous diseases, including inflammatory bowel disease, irritable bowel syndrome, vaginal infections and disorders of immunodefence. Properties of some probiotics have also been studied in atopic eczema, rheumatoid arthritis and liver cirrhosis. There is clinical evidence of a role of probiotics in decrease of level of cholesterol, but results of various studies are equivocal. Recent investigations showed efficacy of Lactobacillus casei DN-114 001 Actimel, DanActive (Danone/ Dannon) in prophylaxis of antibiotic-associated diarrhea and diarrhea caused by C. difficile. There is an opinion, that some strains of probiotics and prebiotic oligofructose are effective for stimulation of immune response. Indirect proof of this is obtained in studies directed on prophylaxis of acute infections (e.g., winter epidemy of flu). Study of H. Duez et al. serves as evidence, that probiotics remain alive during small-intestinal transit, which proved presence of Bifidobacterium animalis DN-173 010 strain in human excrements samples by immunoblotting method.
Conclusion. The further study of probiotics efficacy in treatment of patients with inflammatory bowel diseases, cardio-vascular diseases and many other morbid conditions is required. High-quality clinical investigations with good design are essential for this. Results of these studies should provide demonstrative base and yield clear references concerning a dose, mode and duration of intake of probiotics, prebiotics and synbiotics.
The aim of review. To analyze the literature data on application of prebiotics in treatment of metabolic disorders at diseases of the liver.
Original positions. As it is known, diverse functions of gastro-intestinal tract are related to vital activity of intestinal microflora. The normal microflora sustains colonization resistance of the body, prevents development of pathogenic and opportunistic flora. In the case of disorders of this major function the number of potentially pathogenic microorganism is increased and the spectrum extends, their translocation through intestinal wall may occur that can be accompanied by development of endogenous infection or superinfection. Recently the role of bacterial overgrowth in pathogenesis of non-alcoholic steatohepatitis is widely discussed. At obesity entry of free fatty acids in the liver is increased and steatosis of the liver develops that is considered to be «the first blow». The oxydative stress («the second blow») which takes place at bacterial overgrowth syndrome as well due to increased endogenous secretion of ethanol and lipopolysaccharides, stimulating excessive production of proinflammatory cytokines by Kupffer’s cells, educes consequtively or simultaneously. Bacterial overgrowth syndrome along with immunodepression, change of permeability of intestinal wall also participates in pathogenesis of bacterial translocation, and then — in development of infections at liver cirrhosis (LC).
Conclusion. Scientific studies showed efficacy of prebiotics (alimentary fibers) as the drugs providing normal activity of intestinal microflora that promotes prophylaxis and treatment of liver diseases, including at patients with the LC, bacterial overgrowth, minimal hepatic encephalopathy, non-alcoholic steatohepatitis.
INFORMATION
L.A. Semenyuk – Erosive-ulcerative form of gastroesophageal reflux disease in children: risk factors, clinical presentation, diagnostics and treatment.
O.S. Shifrin – Features of medical approach in patients with chronic pancreatitis of moderate severity of various etiology.
Ye.Yu. Shkatova – Mechanisms of intractable gastroduodenal ulcer development. Advancement of multifactor prediction system and pathogenic treatment.
ISSN 2658-6673 (Online)