Russian consensus on exo- and endocrine pancreatic insufficiency after surgical treatment.

The Russian consensus on exo- and endocrine pancreatic insufficiency after surgical treatment was prepared on the initiative of the Russian "Pancreatic Club" on the Delphi method. His goal was to clarify and consolidate the opinions of specialists on the most relevant issues of diagnosis and treatment of exo- and endocrine insufficiency after surgical interventions on the pancreas. An interdisciplinary approach is provided by the participation of leading gastroenterologists and surgeons.

[The Russian consensus on the diagnosis and treatment of chronic pancreatitis: Enzyme replacement therapy]. / Rossiiskii konsensus po diagnostike i lecheniiu khronicheskogo pankreatita: zamestitel'naia fermentnaia terapiia.

Pancreatology Club Professional Medical Community, 1A.S. Loginov Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow; 2A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow; 3Kazan State Medical University, Ministry of Health of Russia, Kazan; 4Kazan (Volga) Federal University, Kazan; 5Far Eastern State Medical University, Ministry of Health of Russia, Khabarovsk; 6Morozov City Children's Clinical Hospital, Moscow Healthcare Department, Moscow; 7I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia, Saint Petersburg; 8Siberian State Medical University, Ministry of Health of Russia, Tomsk; 9M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow; 10Maimonides State Classical Academy, Moscow; 11V.I. Razumovsky State Medical University, Ministry of Health of Russia, Saratov; 12I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow; 13S.M. Kirov Military Medical Academy, Ministry of Defense of Russia, Saint Petersburg; 14Surgut State Medical University, Ministry of Health of Russia, Surgut; 15City Clinical Hospital Five, Moscow Healthcare Department, Moscow; 16Nizhny Novgorod Medical Academy, Ministry of Health of Russia, Nizhny Novgorod; 17Territorial Clinical Hospital Two, Ministry of Health of the Krasnodar Territory, Krasnodar; 18Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia, Saint Petersburg; 19Rostov State Medical University, Ministry of Health of Russia, Rostov-on-Don; 20Omsk Medical University, Ministry of Health of Russia, Omsk; 21Russian Medical Academy of Postgraduate Education, Ministry of Health of Russia, Moscow; 22Novosibirsk State Medical University, Ministry of Health of Russia, Novosibirsk; 23Stavropol State Medical University, Ministry of Health of Russia, Stavropol; 24Kemerovo State Medical University, Ministry of Health of Russia, Kemerovo; 25N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow; 26A.M. Nikiforov All-Russian Center of Emergency and Radiation Medicine, Russian Ministry for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters, Saint Petersburg; 27Research Institute for Medical Problems of the North, Siberian Branch, Russian Academy of Sciences, Krasnoyarsk; 28S.P. Botkin City Clinical Hospital, Moscow Healthcare Department, Moscow; 29Tver State Medical University, Ministry of Health of Russia, Tver The Russian consensus on the diagnosis and treatment of chronic pancreatitis has been prepared on the initiative of the Russian Pancreatology Club to clarify and consolidate the opinions of Russian specialists (gastroenterologists, surgeons, and pediatricians) on the most significant problems of diagnosis and treatment of chronic pancreatitis. This article continues a series of publications explaining the most significant interdisciplinary consensus statements and deals with enzyme replacement therapy.

[Disorders of Vasoregulative Endothelial Function, Echocardiographic Assessment of Myocardial Dysfunction and Hemodynamics of Pulmonary Circulation in Cirrhosis of the Liver].

AIM: to study relationship between parameters of intracardiac hemodynamics assessed by Doppler echocardiography and functional activity of endothelium, hepatic blood flow and severity of portal hypertension in patients with cirrhosis of the liver (CL) of different etiology. RESULTS: We found that changes of structural and functional parameters of the heart in LC depended on the stage of compensation of portal hypertension and were accompanied by rearrangement of parameters of intracardiac hemodynamics. Pulmonary arterial hypertension (PAH) was found in 11.1% of patients with LC. PAH was moderate and was more frequent in patients with end-stage disease (Child-Pugh class C) compared with those with initial stage of LC (21.4% and 6.3%, p<0.05, respectively). CONCLUSION: Disorders of vasoregulating endothelial function in patients with CL were related to parameters of cardiopulmonary hemodynamics and functional state of the right ventricle and were more pronounced in patients with PAH.

[ANALYSIS OF THE RESULTS OF ENDOSCOPIC AND MORPHOLOGICAL STUDIES OF THE STOMACH MUCOSA WITH REDUCED PEPSINOGEN-I IN PATIENTS WITH H. PYLORI (H.P.)--ASSOCIATED GASTRITIS IN TOMSK AND TOMSK REGION].

AIM OF INVESTIGATION: To explore and describe the endoscopic picture of HP--associated atrophic gastritis and to analyze the specificity of endoscopic markers indicating the presence of atrophic gastritis, intestinal metaplasia and dysplasia using high-tech methods of endoscopy in comparison with morphological characteristics of atrophic gastritis defining the degree of activity and stage of atrophic gastritis according to the system OLGA. MATERIALS AND METHODS: 40 people: males and females aged 40 to 70 years with a reduced level of pepsinogen I and a positive titre of antibodies to H. pylori in serum--were included into the study. THE RESULTS: Risk groups with atrophic gastritis based on indicators of pepsinogen 1 were formed. Endoscopic picture of H. Pylori--associated atrophic gastritis in patients with reduced level of pepsinogen I in serum is studied and described. Analysis of the specificity of endoscopic markers indicating the presence of AG, intestinal metaplasia and dysplasia using high-tech methods of endoscopy (endoscopy with high resolution, magnifying endoscopy, chromoendoscopy and narrow band imaging endoscopy (NBI) is made. Analysis of their sensitivity in comparison with the results of morphological studies of biopsy material is made. CONCLUSION: Thus, these studies show that high-resolution endoscopy in combination with magnification and chromoendoscopy allows accurately identify areas of atrophy, intestinal.Narrow band imaging endoscopy (NBI) provides a detailed picture of the vascular pattern of tissues, pattern changes typical for pathological areas of inflammatory genesis, as well as for precancers and early cancers. All these methods have high sensitivity and specificity in the diagnosis of HP-associated atrophic gastritis in comparison with the results of morphological studies of biopsy materials of stomach mucosa.

[IMMUNOGENETICS AND PROGRESSION OF CHRONIC VIRAL HEPATITES].

AIM OF INVESTIGATION: To estimate the role of polymorphic variants of genes IL4 (C-590T), IL4RA (I50V), TNF (G-308A) and SLC1IAI (D543N) in chronic viral hepatitis progression. MATERIAL AND METHODS: Overall 121 patients with chronic viral hepatitis C and B. RESULTS: Study results have demonstrated, that of all investigated polymorphic variants of genes IL4 (C-590T), IL4RA (150V), TNF (G-308A) and SLC11A1 (D543N) in patients with chronic liver diseases of various etiology the <> IL4RA gene variant (II50Val) is associated with HBV-infection chronization. The allele <> gene TNF-α (G-308A) is protective for chronic viral hepatitis and is associated with a low level of production by mononuclear cells of TNF-α and IL-12, high secretion of IL-4 and low degree of collagenopathy in the liver. Genotype <> of IL4 (C-590T) gene is an adverse marker for progression of chronic viral hepatitis B. There was significant correlation of polymorphic variants TNF (G-308A) and IL4 (C-590T) genes with production of the key interleukins, that determine type of immune response (Th-1, Th-2) and products of collagen metabolism that testifies genetic determination of system immune response and collagen formation processes in the liver at chronic viral hepatitis.

[A case of thoracic actinomycosis].

A case of thoracic actinomycosis manifest as round shadow in the lung is described. Diagnosis was based on the presence of actinomycetes in a transthoracic lung biopsy sample. Treatment for 3 months resulted in recovery. No relapse was documented during 1 year follow-up period.

[Somatopsychic manifestations in patients with chronic viral hepatitis].

The aim of the work was to study somatopsychic manifestations in patients with chronic viral hepatitis (CVH). MMPI profiles, state and trait anxiety were assessed in 110 patients. Boundary psychic problems were evaluated using the Beck scale. It was shown that mean MMPI T-score in patients with CVH was above 50; half of them developed "neurotic triad"; hypochondria occurred in 37.3%, depression in 42.7%, and hysteria in 37.1%. The highest level of state anxiety was documented in patients with HCV infection and isolated HBCor At. The CVH-1b genotype was associated with enhanced occurrence of depression in patients having virus-positive blood for 1-5 years. The level of state and trait anxiety in them was lower than in patients with duration of viremia over 5 years.

[Myocardial structural and functional changes in patients with chronic viral hepatitis concurrent with chronic opisthorchiasis].

The aim of the investigation was to study the myocardium in patients with chronic viral hepatitis concurrent with chronic opisthorchiasis. Ninety patients with chronic viral hepatitis, including 52 patients with this disease concurrent with chronic opisthorchiasis, were examined. Doppler echocardiography indicated a statistically significant increase in left ventricular mass regardless of the presence of Opisthorchis infestation. Analysis of left ventricular diastolic dysfunction showed its great degree in chronic hepatitis C. Single-photon emission computed tomography with 99mTc-pyrophosphate revealed focal tracer incorporation in the myocardium of most patients with Opisthorchis infestation. A third of patients with chronic viral hepatitis showed moderate diffuse trace accumulation that was significantly more frequently found in chronic hepatitis C. Single photon-emission tomography with labeled leukocytes demonstrated abnormal accumulation in none of the patients; troponin T levels were in the normal allowable range. Myocardial lesion was detected in the chronic course of viral hepatitis C concurrent with chronic opisthorchiasis that was unattended by cardiomyocyte necrosis and that was dystrophic.

[Liver cirrhosis patogenetics: polymorphism of glutation S-transferase genes].

Association of deletion polymorphism in GSTT1 and GSTM1 genes and polymorphic variant A313G of GSTP1 gene with cirrhosis diseases and 4-year survival rate for the Tomsk region (West Siberia) patients were tested. Homozygous deletion of GSTM1 gene (null genotype) was a protective factor for alcoholic and mixed (HCV, HBV and alcohol) liver cirrhosis development. The patients from the joint group (all etiology forms) as well as having alcoholic and mixed cirrhosis had lower frequency of GSTM1 null genotype (39.2, 39.0, and 34.2%, respectively) in comparison with the control group (64.6%). The GSTM1 null genotype and GSTP1 gene A313G polymorphic variant correlated with the patients' survival rate. The patients survived in comparison with the dead had higher frequency of a GSTM1 null genotype (46.6 vs. 30.2%) and GSTP1 AA genotype (63.1 vs. 40.5%), and lower frequency of GSTP1 AG (A313G) genotype (31.1 vs. 51.2%). A survival rate was 2.5 times higher for patients having GSTP1 AA genotype in comparison with the GG and AG genotype carriers and 2 times higher for patients having GSTM1 null genotype than the gene carriers. A 4-year fatal case probability was 2.3 times higher among the patients having heterozygous AG GSTP1 genotype in comparison with homozygous AA and GG genotype carriers.

[The parameters of collagen proteolytic and metabolic systems in chronic liver diseases of viral and toxic etiologies].

AIM: To study a relationship of the plasma activity of elastase-like and collagenase-like proteinases and their inhibitors to hepatic collagen metabolism and to detect the serum markers of fibrosis severity. SUBJECTS AND METHODS: Three hundred and fifty-nine patients with chronic liver diseases (CLD), including 118 patients with chronic viral hepatitis (CVH), 113 with CVH concurrent with alcoholic liver disease (ALD), 109 with ALD, and 19 with CLD in the presence of opiomania were examined. The activities of alpha1-proteinase inhibitor and alpha2-macroglobulin (alpha2-MG) were determined by the unified spectrophometric assay from the inhibition of N-benzoyl-arginine ethyl ester hydrolysis. The activity of elastase-like proteinases was determined by enzymatic assay from the hydrolysis of the synthetic substrate N-butyloxycarbonyl-L-alanine-para-nitrophenyl ester. That of collagenase-like proteinases was determined, by using a collagen type 1 substrate and expressed in terms of micromoles of the resultant hydroxyproline. The content of hydroxyproline was determined by a color reaction with demethylbenzaldehyde, a free, peptide- and protein-bound hydroxyproline; their fraction was obtained under various conditions of plasma protein isolation and hydrolysis. Plasma fibronectin levels were measured by solid-phase immunoassay. Liver biopsy specimens were morphologically studied in the majority of patients to determine the histological hepatitis activity index and the stage of fibrosis. RESULTS: Fibrois formation in the liver in its chronic diseases was attended by a significant reduction in the activity of collagenase-like proteinases hydrolyzing collagen and by the lower activity of alpha2-MG, an inhibitor limiting collagen formation. CONCLUSION: The identified changes make themselves evident just in early fibrosis, which suggests the rapid onset of imbalance in the mechanisms responsible for regulation of connective tissue synthesis and promotes intensified fibrosis formation.

[Quality of life indices in patients with chronic viral hepatitis].

AIM: to estimate quality of life (QL) indices in patients with chronic viral hepatitis (CVH) and their relationships to the clinical characteristics of the disease. SUBJECTS AND METHODS: One hundred and ten patients with chronic viral hepatitis (CVH), including 58 patients with chronic hepatitis C (CHC), 27 with chronic hepatitis B, and 25 with CHC + HBCor, were examined. The personality psychological profile, reaction and personality anxiety were evaluated; the Beck inventory was used to identify borderline mental disorders. The test developed by the Karelian Research Center, Russian Academy of Medical Sciences, modified by Ya. M. Rutgaizer, and the Nottingham Health Profile were applied to estimate QL indices. RESULTS: Parameters characterizing the social and personality indices of life, such as qualitative performance of paid work, participation in social life, impossibility of adequate rest, and sexual life are most frequently influenced. The main indicators of worse QL were diminished vitality (vital energy), sleep disorders, and emergence of emotional reactions. This was largely seen in patients with active CVH infection and in those who had isolated HBcor antibodies. CONCLUSION: QL is directly related to the duration of viral infection.

[Association of immune system gene polymorphisms with quantitative features which are pathogenetically important in chronic viral hepatitis].

Association study was performed for genetic polymorphisms IL4 C(-590)T, IL4RA Ile50Val, TNF G(-308)A, to estimate their effect on quantitative features which are pathogenetically important for chronic viral hepatitis course, i.e. levels of IL4, IL10, IL12, tumor necrosis factor alpha, fibronectin, collagenase, protease inhibitors, macroglobulines, elastases, free and protein-bound hydroxyproline. It has been shown that A allele of TNF G(-308)A polymorphism is associated with decreased TNF-alpha, increased IL4 and IL12, as well as with low level of protein-bound hydroxyproline. In addition, association of CT genotype of IL4 C(-590)T polymorphism and high level of protein-bound hydroxyproline has been identified.

[Genetics factors determining predisposition to chronic course of virus hepatitis and fibrosis in liver].

Polymorphic variants of several genes IL4 C(-590)T, IL4RA Ile50Val, TNF G(-308)A were studied for their association with extent of the disease chronization which is marked by hepatic fibrosis stage. Gradual decrease in A allele frequency of polymorphic marker G(-308)A in TNF gene, from patients with weak fibrosis to patients with cirrhosis. Group of patients with weak fibrosis was characterized by higher frequency of A allele (24.5%) comparing with patients with moderate and pronounced fibrosis (13.4%) and cirrhosis (8.7%). Differences in heterozygous genotype frequencies of IL4 C(-590)T were found between patients with cirrhosis (68.2%) and groups of patients with moderate and marked fibrosis (39.1%).

[The diagnostic value of the detection of hepatic fibrosis serum markers in chronic viral hepatitis].

The diagnostic significance of serum markers of fibrosis was investigated in 92 patients with chronic viral hepatitis (CVH) by studying the collagenolythic activity of blood, proteasic inhibitor activity, collagen metabolism products (oxyproline fraction), and fibronectin. At the same time, the patients underwent puncture biopsy of the liver, which made it possible to determine the degree of process activity and the stage of its chronization. As the degree of fibrosis grew, the collagenase serum activity increased significantly, while the alpha1-proteinase inhibitor activity fell, the content of oxyproline (its fractions) increased, and the fibronectin level decreased. Hence, the measurement of the noted parameters allows for noninvasive diagnostics of CVH stages.

[Alleles distribution of polymorphic promoter region C-590T in interleukin-4 genes and Q-576r and Ile-50Val regions in IL-4 receptor gene IL-4RA in patients with HCV-infection].

81 patients with confirmed HCV-infection and 48 healthy volunteers were examined. In healthy Caucasian participants living in Siberian region significant predominance of C/T genotype in promoter region C-590T of interleukin-4 (IL-4) gene and Q/Q and Ile/Val genotypes in points -50 and -576 of IL-4RA gene that codes alpha-chains of IL-4 receptor were revealed. In patients with HCV-infection predominance of C/T genotype in C-590T region in IL-4 gene (OR = 1.86), R/R genotype in Q-576R region of IL-4RA gene (OR=7.86), and Val/Val genotype in point Ile-50Val (OR = 2.6) of the same gene. Summary predictive coefficient of hepatitis C development in carriers of these genotypes approached to 95%. During analysis of role of allelic polymorphism of IL-4 genes in predisposition to hepatitis C development it is necessary to consider not only presence of allelic variants of promoter regions of the IL-4 genes, but also the polymorphism of genes coding molecules binding with this cytokine on target cells membranes and in its soluble form.

Role of genetically determined production of immunoregulatory cytokines in immunopathogenesis of chronic viral hepatitides.

Immunopathogenesis of chronic viral hepatitides was studied by modern immunological, molecular, genetic methods. We revealed an imbalance in the production of immunoregulatory cytokines by mononuclear leukocytes (primarily of the Th2 type). The risk of progression and chronic course of viral hepatitides in Caucasian population was associated with alleles of promoter regions -330G and -592A in the IL-2 and IL-10 genes, respectively, as well as with the T/T genotype of the polymorphic region C590T in the IL-4 gene. The C/C genotype of the IL-10 gene promoter region C592A was shown to be a factor determining resistance to long-term persistence of hepatitis B and C viruses.

[Psychovegetative disturbances in patients with chronic non-calculous cholecystitis combined with chronic opisthorchosis].

A complex clinico-instrumental, laboratory and psychological examination of 122 patients with chronic non-calculous cholecystitis (CNCC), 63 of who had chronic opisthorchosis (CO), was conducted. The controls were 33 healthy individuals. Patients with CNCC and CO had hypomotoric dyskinesia, Oddi's sphincter dysfunction, higher levels of personal anxiety and depression more often than others.

[Immunoregulatory cytokines and chronization of type C hepatitis: matching of clinical and immunological manifestations].

The study demonstrates significant changes of cytokine-producing ability of mononuclear blood leucocytes in type 'hepatitis, correlating with the degree of hepatic lesion. The results showed that various morphologic types of chronic virus type C hepatitis were associated with disbalance in production of pro- and antiinflammatory cytokines, i.e. decrease of tumor necrosis factor (TNF)-alpha concentration and a significant rise of interleukin (IL)-4 and IL-10 concentations, which were the most prominent in cases of severe hepatic fibrosis and high histologic activity of hepatitis. The study established a direct correlation between increase of the ability of mononuclear blood leucocytes to synthesize IL-4, and the progress of the pathologic process.

Molecular mechanisms of changes in TNF-alpha production by blood mononuclears in chronic viral hepatitis C.

Chronic viral hepatitis C is associated with decreased production of TNF-alpha by the peripheral blood mononuclear leukocytes irrespective of virus genotype and degree of the morphological activity of the process in the liver. This process positively correlates with the increase in the content of TNF-alpha soluble receptor (molecular weight 55 kDa), which can play a role in the mechanisms of immunopathogenesis of long persistence of hepatitis C virus in the body.