LECTURES AND REVIEWS
The aim of review. To present recent literature data on features of course of hepatitis B during pregnancy and major risk factors of infection of children via vertical route.
Original positions. Course of chronic hepatitis B during pregnancy was studied in several cohort studies which demonstrated , that activity of serum transaminases in this period, as a rule, remains normal. At the same time, clinical cases of HBsAg-positive pregnant women indicating deterioration of liver function down to development of fulminant liver failure are described. Received results dictate necessity of careful monitoring of level of serum transaminases and functions of liver at women during pregnancy and puerperal period. The vast majority of cases of virus conduction occur immediately during delivery, this issue is not completely clear. Some researches showed that the risk of infection of the child has positive relation to level of mother’s viral load. As one of the concepts an option of infection of fetus at amniocentesis is considered. However HBV DNA is rarely present at umbilical blood and it is not found in amniotic fluid. It testifies for the benefit of that intra-uterine virus transfer takes place rarely, the risk of infection by hepatitis virus at amniocentesis looks to be low. Correctly immunized children can have breast feeding. Treatment of pregnant women with high viremia level at the last month of pregnancy can reduce number of newborns with ineffective vaccination. Among the nucleoside analogues registered in Russian Federation for treatment of chronic hepatitis B only telbivudine (Sebivo) has “B” category that means absence of risk for fetus on animal model. However, results of controlled studies in pregnant women up to now are inaccessible.
Conclusion. The best prophylaxis of vertical conduction of hepatitis B virus is combination of active and passive immunization of babies. Level of viremia at mother is associated with risk of conduction of hepatitis B virus to a child. Planning of pregnancy should be discussed with the genital age woman before onset of antiviral treatment.
The aim of review. To analyze state-of-the-art of surgical treatment of patients after neoadjuvant chemotherapy.
Original positions. Liver is the first organ on a way of hematogenous spread of tumor. Now the majority of oncologists accepted the point, that only treatment, that provide high survival rate, is surgical. In the last decade increasing numbers of patients are operated after a long-term chemotherapy. Taking into account systemic action of cytotoxic drugs, their severe immune-suppressive and hepatotoxic features, it was possible to expect dramatic deterioration of postoperative morbidity and mortality figures. However data of the majority of studies deny this assumption. Moreover, changes of hepatic parenchyma and as the consequence, course of perioperational period can depend on composition and mode of chemotherapy.
Conclusion. The knowledge of spectrum of hepatotoxic of cytotoxic drugs with comprehension of the processes, that determine functional and regenerative capacity of the liver, allows to choose optimal approach of the combined treatment of patients with colorectal cancer metastases.
The aim of review. To characterize potential of magnetic-resonance tomography (MRI) for differential diagnostics of cirrhosis and cancer of the liver.
Original positions. Initial MR-signs of liver cirrhosis include dilation of periportal space in portal area and atrophy of medial segment of the left lobe. Enlargement of gallbladder fossa may be a sign of progression of cirrhotic process. MR-signs of hepatocellular cancer include development of hyperintensive foci on a general background of low intensity parenchyma. Advantage of application of contrast agents on the basis of chelates of gadolinium, and nonspecific contrast agents such as cell-specific supermagnetic and paramagnetic contrast agents (iron oxides, manganese) during the study consist in capability of visualization of malignant focus of in regenerative node «node in the node» phenomenon. Feature that causes unequal accumulation of contrast agent in benign and malignant liver tissue is the absence of Kupffer’s cells phagocyting particles of the agent in neoplastic focus. Advantage of various modes of the study in diagnostics of focal lesions in liver is substantial increase of sensitivity of used methods.
Conclusion. At suspicion for volume lesions of the liver and cirrhosis MRI is justified and brings important diagnostic information, especially with application of contrast agents.
The aim of review. To present technological innovations in production of new drugs on the basis of essential phospholipids (EPL)
Original positions. The positive effect of EPL is known for over 100 years. For over 50 years commercial drugs on a basis EPL are applied, their efficacy is proven by numerous clinical and experimental studies. However, traditionally used technologies of treatment of EPL substance by active oxygen at production effecting drugs are not optimal, as they are accompanied by formation of hydroperoxides having potential toxicity. The alternative method used at production of new drug on EPL basis (RESALUT Pro), provides treatment of phospholipid substances by liquid nitrogen that allows to keep beneficial properties of natural (native) product.
Conclusion. The new technology utilised by treatment of agent on EPL basis (RESALUT Pro), is progressive, promoting improvement of safety profile and expected clinical effect.
ORIGINAL ARTICLES
Aim of investigation. To determine the pathogenic significance of changes of general (adaptive) immunity in patients with chronic diseases of the stomach and intestine.
Material and methods. Original study included 68 patients with chronic active H. pylori-positive gastritis (CG Н.р.+), 41 – chronic active H. pylori-negative gastritis (CG Н.р.–), 34 – chronic multifocal atrophic gastritis (CMfAtrG), 36 – with peptic ulcer of the stomach (PUS), 31 patient with irritable bowel syndrome (IBS), 34 - with irritable bowel syndrome with diarrhea (IBSD), 34 - with malabsorbtion syndrome (MS), 41 – with celiac disease (CD) and 39 patients with ulcerative colitis (UC). The control group consisted of 65 generally healthy patients. Total number of T lymphocytes, along with absolute and relative contents of their subpopulations was determined by flow-cytometer EPICS C Cultronics USA and Facscan Becton Dicenson by standard procedure with application of monoclonal antibodies «ORTHO» USA, Becton Dicenson or Dako. Lymphocytes with receptors to CD3+, CD4+, CD8+ and B-lymphocytes carrying immunoglobulin receptors A, M, G were detected. Quantity of T-lymphocytes, B-lymphocytes and their subpopulations, as well as Т4/Т8 ratio and quantity of active Т-cells were analyzed in each of the specified groups of patients.
Results. The contents of Т3+-cells (general T-lymphocytes marker) in peripheral blood at chronic diseases of the stomach did not differ significantly from normal range except for the group of PUS, in which this parameter significantly exceeded control values, increase of Т4+-lymphocytes concentration was found in comparison to of CG Н.р.– and CMfAtrG groups. Comparative analysis of studied adaptive immunity parameters at chronic bowel diseases showed much higher diversification of immune system changes, than at stomach diseases. The most severe disorders in subpopulation content of Т- and B-lymphocytes were observed in groups of UC and CD. At IBSD and MS they became less apparent and virtually did not differ from control values at IBS.
Conclusion. Obtained data are in favor of two points. First, at UC severe elevation of activity of adaptive immunity is revealed. Second, investigation of parameters of adaptive immunity has diagnostic and differential-diagnostic value for clinical enterology and coloproctology.
Aim of investigation. Studying of motor function of the esophagus by out-patient 24-hours manometry at healthy people and patients with various forms of gastroesophageal reflux disease (GERD).
Material and methods. Overall 53 patients (24 men, 29 women) with established diagnosis of GERD were enrolled to original study. Esophagogastroduod enoscopy was used for diagnostics of erosive form of GERD with assessment of stage of esophagitis, nonerosive form of GERD (NERD) was diagnosed by concurrent 24-hour pH-metry with 24-hour manometry. The control group included 10 healthy subjects (5 men, 5 women). 24-hour out-patient monitoring of esophageal motility has been carried out by 7-Fr-catheter, with three diminutive electron pressure sensors. Out-patient 24- hour esophageal pH-metry was carried out with application of catheter, having antimony electrode. Data on motility and pH changes were registered by the chart recorder. After 24-hour period all data were downloaded to personal computer for statistical processing.
Results. During investigation various disorders of motor activity of the esophagus in patients with GERD which have occurred during 24-hour monitoring were revealed. Disorders of motility of the esophagus, including disorders of voltage, duration of contractions and changes of structure of peaks of contractions that causes development of peristaltic dysfunction have been found. Increase of time of acid exposure of mucosa of the esophagus as consequence of ineffective motor function which does not provide clearance of lumen of the esophagus from refluxate was is revealed.
Conclusions. Obtained data allow to consider disorders of motility of the esophagus in combination to other factors as one of mechanisms in pathogenesis of GERD. Ineffective peristalsis results in increase of time of exposure of aggressive contents of the stomach to esophageal mucosa, promoting damage and development of specific symptoms.
Aim of investigation. Evaluation of the functional state of cardial and pyloric sphincters, as well as the sphincter of Oddi in children with non-differentiated connective tissue dysplasia and with no dysplasia.
Material and methods. Eighty eight children with chronic gastroduodenitis were investigated: 50 – with non-differentiated connective tissue dysplasia (29 males and 21 females, aged 6–16 years) and 38 – without dysplasia (18 males and 20 females of the same age). All children underwent standard gastroenterological investigation. In patients of both groups functional state of cardiac and pyloric sphincters, along with the sphincter of Oddi was determined at gastroduodenoscopy. Besides that, the state of esophageal mucosa and frequency of reactive pancreatites (diagnosed according to changes of the pancreas at abdominal ultrasound and elevation of urine diastase level) were assessed.
Results. Dysfunction of sphincters was revealed in 82% of children with dysplasia and in 84,2% – with no dysplasia. In children with connective tissue dysplasia no increase in frequency of motor disorders of cardiac and pyloric sphincters in comparison to children without dysplasia was revealed. At patients of both groups function of pyloric sphincter was usually normal. Dysfunction of cardiac sphincter was revealed at 52% of children with dysplasia and at 65,8% – without dysplasia, mostly – as incompetence and frequently was complicated by development of refluxes-esophagitis. Dysfunction of sphincter of Oddi in both groups occurred in 64 and 60,5% of cases respectively and mostly of the spastic type, promoting pancreatic lesion.
Conclusions. Obtained data indicate necessity of complex investigation of children with diseases of gastro-intestinal tract and differentiated approach to treatment.
Aim of investigation. To define the leading part of viruses B and C in pathogenesis of chronic hepatitis of mixed viral etiology.
Material and methods. Overall 249 patients (m 185, f 64) were investigated: 91 – with HBV and HCV markers (HBsAg+antiHCV) and 158 – with HBV and HDV (HBsAg+antiHDV). Mean age of patients was 38±0,4 years. At all patients level of virus B DNA, RNA and genotype of virus C, RNA of virus D by polymerase chain reaction (PCR) method were determined. Along with general clinical tests biochemical investigation of functional liver potential (bilirubin and its fractions, aminotransferase, 5-НТ, alkaline phosphatase) was done, at 48 patients biopsy specimens of liver were taken.
Results. At chronic hepatites of mixed viral etiology (HBsAg+antiHCV, HBsAg+antiHDV or their combinations) series of virologic situations which determine features of pathological process course can be observed. In the case of mixed viral etiology of chronic hepatites the hepatitis virus C with moderate viremia (59%), genotype 1b and mild clinical and morphological course of disease has leading role. At predominance of virus B replication (with and without virus D apposition) the chronic hepatitis develops with severe activity and sclerosis of porto-portal type.
Conclusion. According to clinical and virologic, biochemical and morphological analysis of results of investigation of 249 patients by chronic hepatites of the mixed viral etiology it was found out, that in relation to replicative activity of specific virus clinical course of process varies.
Aim of investigation. Investigation of microbial flora of pigment gallstones by analysis of ribosomal 16S RNA gene.
Material and methods. Seven samples of pigment gallstones were obtained at cholecystectomy from children infected by H. pylori. DNA amplification method (PCR) was used for identification of microorganisms. Ligation, E. coli transformation and creation of clonal libraries were carried out. Nucleotide sequence was determined. Computer analysis of the obtained information was done; belonging of the read nucleotide sequences to certain microorganism by NCBI database was accomplished.
Results. In 4 samples of black pigment stones no bacterial DNA was revealed. In 3 samples of brown pigment stones libraries of 16S rRNA gene fragments were created, their sequences were determined and microorganisms to which they belong were identified.
Conclusion. At children infected by H. pylori, this microbe is not the cause of gallstones development.
NATIONAL COLLEGE OF GASTROENTEROLOGISTS, HEPATOLOGISTS
The aim of review. Basing on analysis of clinical studies carried out in Russia and abroad, devoted to evaluation of efficacy and safety of alginate-containing of drugs, to demonstrate mechanisms of their effect and potential of application in pediatric practice.
Original positions. Prevalence of gastroesophageal reflux disease (GERD) among different age groups necessitates development of new approaches to its treatment. Comparative characteristic and specificity of antacid, antisecretory and alginate-containing drugs action at treatment of GERD at adult patients, pregnant women and children of various age as mono- and combined therapy is presented. Mechanisms and features of effect of drugs Gaviscon and Gaviscon-forte are discussed. Significant safety and confirmed efficacy of alginatecontaining drugs was demonstrated at various clinical symptoms of GERD at children from the 2-weeks age, pregnant women at the second and third trimesters of pregnancy and at adult patients. Data of instrumental investigations, including esophagogastroduodenoscopy and 24-hour intraesophageal pH-metry, showing statistically significant positive effect of these drugs are presented.
Conclusion. Antireflux, cytoprotective, prokinetic and sorption properties of Gaviscon and Gavisconforte along with absence of any significant undesirable effects, proves feasibility of their application at treatment of GERD, including pediatric practice both as monotherapy and within combined treatment modes, in relation to severity of clinical manifestations.
The aim of review. To give the characteristic of exocrine pancreatic insufficiency in diabetes mellitus (DM).
Original positions. Exocrine function of the pancreas is reduced in 40–80% of patients with insulindependent and in 15–73% of patients with 2nd type diabetes mellitus. Exocrine pancreatic insufficiency is more frequently of mild or moderate degree, severe insufficiency with development of steatorrhea occurs rarely. Mechanism of decrease of exocrine pancreatic secretion at DM is related to disbalance of hormones inhibiting and stimulating pancreatic secretion, fibrosis of the gland as a result of diabetic angiopathy as well as immune disorders, autonomous neuropathy, disorders of production of gastrointestinal regulatory mediators (motilin, pancreatic polypeptide, etc.), inhibiting effect of diabetic acidosis on exocrine secretion of pancreas. At DM of the 2nd type mechanisms, secondary to metabolic syndrome are involved in pathogenesis of exocrine pancreatic failure. Clinical manifestations related to digestive organs in diabetes mellitus are caused by diabetic gastro-, entero-, colopathy, as well as by exocrine pancreatic insufficiency. In the treatment adequate enzyme supplementation therapy and treatment of hyperglycemia play major role.
Conclusion. Exocrine pancreatic insufficiency plays major role in development of pain syndrome, dyspepsia, disorders of stool at patients of DM.
NEWS OF COLOPROCTOLOGY
Aim of investigation. Studying of results of optimization of diagnostic procedures and choice of medical tactics at complicated forms of diverticular disease of large intestine from position of up-to-date non-invasive and mini-invasive technologies.
Material and methods. In retrospective study we compared results of treatment of 1251 patients with complicated forms of diverticular disease which were treated in proctologic departments, and 168 patients treated in departments of general surgery.
Results. Mortality at complicated forms of diverticular disease was 11,9% of cases in general surgery hospitals, while at the presence of coloproctological service – 2,2%.
Conclusion. Absence of therapeutic and diagnostic algorithm of management this category of patients results in tactical errors and increase of mortality.
Aim of investigation. Assessment of frequency and level of perinuclear antineutrophilic cytoplasmatic antibodies (pANCA) in patients with ulcerative colitis (UC) and Crohn’s disease (CD) in relation to location and spread of lesion of the large intestine, clinical activity, course of disease and applied treatment methods.
Material and methods. Overall 160 patients were investigated: 104 – with UC, 36 – with CD and 20 – with irritable bowel syndrome (IBS). pANCA were determined in blood serum of patients by indirect immunofluorescence method on ethanol-fixed neutrophiles («Bio-Rad» test-system, USA).
Results. pANCA have been found in 47,3, 25,0 and 5,0% of patients with UC, CD and IBS respectively (р<0,001 – UC in comparison to IBS, р<0,02 – CD in comparison to IBS, р<0,05 – UC in comparison to CD). At total, left-sided and distal forms of UC they were present in 47,7, 58,8 and 27,3% of patients respectively, at acute, chronic relapsing and chronic persistent course – in 14,3, 45,1 and 67,5% (р<0,001). In patients with severe, moderate course and in phase of remission pANCA have been revealed in 42,8, 56,0 (р<0,05) and 20,0% of cases respectively. They were found in 72,7% of patients with active total UC with chronic persistent course. pANCA titer of >1:80 was observed in 10 of 27 patients with chronic persistent course of disease and in 1 of 14 (р<0,05) with chronic recurrent course. Frequency of pANCA has tendency to increase in steroid-resistant patients and to decrease after subtotal colectomy. pANCA were found in 9 of 26 (34,6 %) patients with CD with large intestinal lesion (ileocolitis, CD of the large intestine) and were absent in 10 (p<0,01) patients with terminal ileitis. No difference between subgroups of patients with CD with high activity of process and in phase of remission was revealed.
Conclusions. It was demonstrated, that at UC pANCA in greater degree are associated to diffuse lesion of the large intestine, phase of clinical activity and chronic persistent course with tendency to increase in frequency at steroid-resistant patients and to decrease after resection of affected 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.
INFORMATION
N.A. Vlasova – Features of clinical course, pathogenesis, prophylaxis and treatment of cholelithiasis on a background of hypercholesterinemia.
V.Ye. Kulikov – Systemic changes of hemodynamics in patients with chronic liver diseases with portal hypertension signs.
ISSN 2658-6673 (Online)