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Russian Journal of Gastroenterology, Hepatology, Coloproctology

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Vol 19, No 3 (2009)
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EDITORIAL

4-12 8
Abstract

The aim of review. To present mechanisms of regulation of liver immunological homeostasis and pathological reactions causing autoimmune diseases.

Original positions. Predisposition to autoimmune hepatitis is determined by carriage of HLA-DR B1*0301 or HLA-DR B1*0401 alleles. Patients with autoimmune hepatitis receiving no treatment and relapse phase of disease have deficiency or the functional failure of CD4+ CD25+ regulatory Т-cells. Th1-cells induce expression of HLA class I molecules on hepatocytes that increases sensibility of hepatocytes to attacks of cytotoxic CD8+ Т-cells. Th2-cells induce autoantibodies production by B-lymphocytes. Th17-cells are involved in development of inflammation and autoimmune reactivity. Congenital or acquired defects of expression of MDR3/ABCB4, CFTR, AE2/SLC4A2, genes that encode proteins of various transport systems of bile duct and tubule epithelium can take part in pathogenesis of primary biliary cirrhosis and primary sclerosing cholangitis. These genetic changes are accompanied by disorders of hydration, alkalinisation and colloidisation of bile, biliary thrombosis of tubules, inflammatory Т-cellular infiltration, development of cholangiogenic fibrosis and cirrhosis. Nuclear factor NF-kB represents the molecular bond bridging inflammatory, immune, protective and metabolic reactions in the liver. It is one of the key factors of pathogenic mechanisms, resulting in development of non-alcoholic steatohepatitis and hepatocellular carcinoma.

Conclusion. Understanding of mechanisms of autoimmune liver disease broadens diagnostic and clinical horizons of modern doctor and yields new medical methodology.

LECTURES AND REVIEWS

13-20 6
Abstract

The aim of review. To present up-to-date references, that allows to choose the optimal mode of antiviral therapy for patient with chronic hepatitis B (CHB).

Original positions. Chronic HBV-infection represents a major epidemiologic and economic problem all over the world. Liver cirrhosis (LC) and hepatocellular carcinoma (HCC) related to HBV infection are the causes for over 1 million deaths and 5–10% of transplantations of liver per year. The comprehension of the role of viral load in development of LC and HCC and introduction to the pharmaceutical market of new agents allow to improve guidelines on management of patients with chronic HBV-infection. The main criterion of efficacy of antiviral therapy (AVT) – the level of viral load. Monitoring of HBV DNA on the 12, 24, 48-th weeks of treatment enables to predict its efficacy and risk of development of resistance to nucleoside/nucleotides analogues. It is recommended to consider patients with CHB with viral load of over 2000 МЕ/ml (≈10000 copies/ml) and/ or elevation of alanineaminotransferase (ALT) activity, with signs of moderate to severe inflammatory-necrotic changes and/or liver fibrosis as candidates for AVT. Patients with LC are considered as candidates for AVT even at normal ALT levels irrespective of level of viral load. For decompensated LC patients nucleoside/ nucleotides analogues are the drugs of choice. New analogues nucleoside/nucleotides (telbivudine, entecavir, tenofovir) have direct antiviral action and good tolerability at long application.

Conclusion. Modern international references on management of patients with HBV-infection allows to increase efficacy of treatment by of rational application of antiviral agents, to improve survival rate, to reduce mortality and risk of LC and HCC development, to optimize treatment cost.

21-31 4
Abstract

The aim of review. To analyze a state of non-enzymatic physiological anti-oxidative system represented by water- and fat-soluble vitamins, at liver diseases of various etiology (toxic, drug-induced, alcoholic, metabolic, viral) and severity grades in clinical setting and experimental animals and to present original data on vitamin status in patients with chronic alcohol-induced hepatitis on a background of alcoholic liver cirrhosis (LC).

Original positions. At diseases of liver of the various nature isolated deficiency as some vitamins in blood, tissues and organs, and disorders of vitamin status in general is observed. Subclinical manifestations of deficiency of bioanti-oxidative status as nonspecific signs and decrease of vitamin contents in the body are typical for the majority of chronic liver diseases. Clinical symptom-complex of vitamin insufficiency accompanies severe diseases: alcohol-induced liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, metabolic diseases. It is known, that in patients with chronic hepatitis on a background of LC of alcoholic etiology plasma level of hepatoflavins, В2, В6 and C is decreased in comparison to healthy middle-aged people by 40–90%, that of vitamin E and В1 – by 30–70%, malonic dialdehyde concentration is increased by 50– 180%. Application of traditional treatment for 25 days revealed significant increase of vitamins В1 (on 10,27%) and В6 (on 15,05%) content in plasma, and influenced level of vitamins C, Е, В2.

Conclusion. Oxydative stress is one of the important pathogenic parts of liver disease progression. Efficacy of treatment is determined by complex of the actions including including regeneration of the functional potential of physiological anti-oxidative system: activity of enzymes and bioantioxidative vitamin status. The review presents data on methods of application of vitamins at pharmacotherapy of hepatopathies.

32-37 4
Abstract

The aim of review. To describe prevalence, basic mechanisms, risk factors and variants of course of biliary sludge, and methods of its treatment.

Original positions. Biliary sludge consists of inhomogeneous structures, suspension and clots in bile. Its prevalence in general population ranges 1,7 to 4%, and is 7,5% of patients with gastroenterological complaints. Pathogenic mechanisms of biliary sludge include following: decrease of bile acids synthesis, disorders of neurohumoral synchronization of gallbladder contractility, resulting in its hypotony, qualitative changes of pronucleator composition of biliary sludge, in particular – glycosaminoglycans, accelerating process of vesicles coalescence in bile, that in general promotes increase of its lithogenicity. There are some classifications of this disease based on etiology, sonographic pattern and chemical composition of sludge. Cholelithiasis, diabetes mellitus, cholestasis of a various origin, pregnancy, intake of some medicines (ceftriaxone, octreotide, clofibrate, calcium-containing agents, etc.), sickle-cell anemia, etc. are known as major risk factors. Course of biliary sludge can be asymptomatic, with signs of biliary dyspepsia or with complications including pancreatitis, constrictive papillitis, acute cholangitis, etc. The most effective treatment agent is ursodeoxycholic acid, if of biliary sludge is combined to nonfunctioning gallbladder surgical intervention is indicated.

Conclusion. Gastroenterological patients, and patients with risk factors of biliary sludge should undergo investigation for revealing this disease, well-timed prescription treatment and early prophylaxis of complications.

ORIGINAL ARTICLES

38-41 7
Abstract

Aim of investigation. To study the prevalence Helicobacter pylori and gastroesophageal reflux disease (GERD) at various ethnic groups of Mongoloids and Caucasians of Eastern Siberia.

Materials and methods. Prevalence of H. pylori infection and GERD in Evenkia, Khakasia and Tuva had been studied by simultaneous (transverse) method. Frequency of heartburn was studied at 6678 Caucasians, 1445 Evenks, 2085 Khakases and 572 Tuvinians by continuous method. Esophagogastroduodenoscopy with biopsy sampling was carried out in these groups in 2125, 791, 630 and 250 patients respectively. H. pylori was determined by morphological, urease and immunoenzyme method in blood serum at 1492, 493, 533 and 414 subjects. Results. Prevalence of weekly heartburn was 6,4% in Evenks, 10,3% – in Khakases –, 12,9% – in Tuvinians, 12,3% – in Caucasians – (р1–3 < 0,001, р1–4< 0,001). Esophagitis is diagnosed in 5,4% of Caucasians, in 0,6% of Evenks, in 3,6% of Khakases, in 5,1% of Tuvinians (р 1–2< 0,001, р2–4< 0,001). Frequency of H. pylori infection in all populations was identical – about 90%.

Conclusions. Differences in prevalence of GERD were registered both between Caucasians and local population, and between various ethnic groups of Mongoloids. Between Caucasians and Mongoloids of Eastern Siberia there is no association between H. pylori infection and GERD.

42-46 7
Abstract

Aim of investigation. To study the functional state of endothelium at patients with chronic hepatitis C (CHC).

Materials and methods. Forty patients with CHC in relapse phase were investigated. In all cases activity of inflammatory process was assessed, indication of НСV RNA was carried out and assessment of HCV genotype in blood serum, quantity of desquamated endotheliocytes (DEC), level of nitric oxide (NO), endothelin-1 (Et-1) and functional activity of von Willebrand factor (vWF) in blood plasma was investigated.

Results. At patients of CHC elevation of DEC quantity has been registered in comparison to group of generally healthy persons (5,9±1,18·104/l and 3,02±1,2·104/l respectively, р=0,001), decrease of NO level (18,6±3,02 and 29,43±3,34 mcmol/l, р=0,001), increase of Et-1 concentration (0,7±0,21 and 0,3±0,13 fmol/l, р=0,0001) and vWF functional activity (102,1±4,75 and 80,11±2,77%, р=0,003) in blood plasma. At evaluation of dynmics of endothelial disorders during combined antiviral the rapy (AVT) studied parameters in the basic group of patients (n=10) underwent significant changes: DEC amount decreased by 35,5% from initial value, NO level increased by 35%, concentration Et-1 decreased by 63%, vWF functional activity decreased by 16% from an initial level that testifies decrease of damage activity and dysfunction of endothelium.

Conclusions. At CHC there are signs of damage and dysfunction of endothelium. Combined AVT by Reaferon in combination to ribavirin at such patients is accompanied by significant improvement of endothelium functional parameters.

46-50 6
Abstract

Aim of investigation. Improvement of results of surgical treatment of patients with the diffuse peritonitis by repeated programmed interventions method on the basis of finalization criteria.

Materials and methods. Results of 87 cases with diffuse peritonitis underwent statistical analysis. On the basis of obtained data prognostic system of evaluation of the programmed debridement was designed. The system included the most indicative intraabdominal features observed at the next debridement, and severity of general state and multiorgan failure.

Results. Original system was utilized at treatment of 23 patients. This resulted in decrease of number of «ondemand» operations from 18,4 to 8,7%. Diagnostic sensitivity of system was 91,3%, diagnostic efficacy – 90%, diagnostic specificity – 90,7%.

Conclusions. Premature finalization of program of repeated debridements occurs quite frequently in surgical practice at treatment of diffuse peritonitis. Performance of «on-demand» operations has negative effect on prognosis and increases mortality in this group. Original integrated prognostic system of evaluation of the programmed debridement allows reliable planning of abdominal debridement cycle duration and to prove its termination with high probability level.

NATIONAL COLLEGE OF GASTROENTEROLOGISTS, HEPATOLOGISTS

51-56 3
Abstract

The aim of the lecture. To discuss physiological mechanisms of absorbtion in gastro-intestinal tract (GIT).

Original positions. In the literature data issues are covered from three sides: 1) topography of absorbtion of substances in various GIT segments: the stomach, duodenum, jejunum, ileum and the large intestine; 2) the basic functions of enterocytes; 3) the basic mechanisms of absorbtion in intestine. Seven basic mechanisms of absorbtion of substances in intestine are discussed.

Conclusion. Of all GIT parts jejunum and ileum are characterized by the widest spectrum of absorbtion of various compounds. Comprehension of physiological mechanisms of absorbtion in small intestine is of great importance in practical gastroenterology.

57-62 3
Abstract

Issues of diagnostics, classification, variants of clinical manifestations of Hirschsprung disease (HD) at children of various age are presented. Treatment approaches, variants of surgical intervention (advantages, disadvantages, complications), prognosis at this disease are
considered. Clinical demonstration of 10 years old child
with HD is presented.

NEWS OF COLOPROCTOLOGY

63-69 3
Abstract

Aim of investigation. To develop medical approach at acute anaerobic paraproctitis (AAP).

Materials and methods. In 1997–2006 in urgent proctology department The SSC of coloproctology 4046 patients with various types of acute paraproctitis were operated. Original study included 140 patients, 20 to 86 years old (mean age made 57,1±3,9 years) with anaerobic paraproctitis. Investigation included general physical examination, digital examination of the rectum and rectoromanoscopy, transabdominal and transrectal ultrasound, bacteriological study of wound exudate and morphological study of affected pararectal fat. Ultrasound investigation was supplemented by computer tomography for differential diagnostics. Surgical interventions in all cases was carried out under urgent indications. Severity of patients state and efficacy of treatment was evaluated by SAPS and SOFА scoring systems.

Results. Three clinical forms of AAP were defined: fulminant, acute and subacute. In relation to etiological agent type following forms of anaerobic paraproctitis were determined: clostridial, non-clostridial and purulent. Forty-five percent of patients admitted in severe and extremely severe state, 25,7% addressed for medical care 7 days and later after onset of disease. Mortality was 15,7% – all of the were patients, that admitted in extremely severe state. Extrasphincter fistulas were formed in 11 (10,8%) patients.

Conclusion. The success of treatment of patients with AАП in many respects depends on early diagnostics of inflammatory process, early urgent surgery with essential and extensive enough necretomy and adequate intensive care.

EXCHANG OF EXPERIENCE

70-75 6
Abstract

The aim of review. To present results of randomized studies of efficacy of agents, containing medical herbs, in the treatment of hepatitis C and expediency of their application in these patients.

Original positions. Efficacy of treatment of patients with viral hepatitis C by traditional Chinese herbs was evaluated by 7 randomized studies. Assessment of efficacy and safety of this treatment method is inconvenient due to key differences in composition of herb gathers, poor quality of original studies and small number of enrolled patients. Investigations of thistle agents application for 1 week to four years demonstrated no significant efficacy in this respect. Four randomized studies of efficacy and safety of licorice (Glycyrrhiza glabra) drugs in treatment of a hepatitis C were published. Most of the studies prove the ability of drugs, containing glycyrrhizin to decrease necroinflammatory activity in chronic hepatitis C, justifies its application in patients with restrictions for use of combined antiviral therapy by standard or pegilated interferon in combination to ribavirin. Data on efficacy of long-term treatment by glycyrrhizin for prophylaxis of hepatocellular carcinoma require further studying.

Conclusion. Up to now in the world over ten clinical randomized studies of efficacy and safety of the drugs based on herbs were carried out. Ability of agents containing glycyrrhizin to decrease biochemical activity at chronic hepatitis C is quite important, as the domestic agent with high content of this substance is presented in the Russian market.

76-81 8
Abstract

The aim of review. To characterize advantage of application of a leukocytic interferon a (IFN-a) for prophylaxis of cytopenia at antiviral therapy of chronic hepatitis C (CHC).

Original positions. Hematological undesirable effects of antiviral agents represent the most serious complication of etiological treatment of CHC. Thus development of neutropenia and thrombocytopenia is related first of all to application of IFN-a. The basic approach to cope with hematological complications includes prescription of hemopoietic factors at already developed cytopenia. Possible delay of correcting preparation action and increase of the total treatment cost is disadvantage of this approach. Choice of the most safe medicine that is justified, first of all, at patients with initially present cytopenias or having those at previous courses of antiviral therapy may be an alternative. It is possible to offer leukocytic IFN-a «Alfaferone» As such a drug, which efficacy, at least in CHC patients with non-1-st genotype, is not lower, and even is higher, than that of recombinant analogues. At prescription of leukocytic IFN-a necessity in hemopoietic factors maintenance therapy develops rather rarely, in which case significantly lower doses and duration of treatment is required.

Conclusion. Application of leukocytic IFN-a within antiviral therapy of CHC is characterized by high efficacy and safety that allows to recommend it as a drug of choice at «difficult» categories of patients.

CLINICAL GUIDELINES



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