Vol 44, No 6 (2016)


The Russian consensus on diagnosis and treatment of chronic pancreatitis: points of debate

Khat'kov I.E., Maev I.V., Bordin D.S., Kucheryavyy Y.A., Grinevich V.B.


The most controversial provisions of the Russian Consensus on Diagnosis and Treatment of Chronic Pancreatitis (hereinafter, the Consensus) are presented. The debate has been initiated by the Russian Pancreatic Club and performed with the use of the Delphi system, based on interdisciplinary approach with participation of leading gastroenterologists, surgeons and pediatricians. This paper is the first in the series of the Consensus-related publications. Here we discuss the most controversial issues of Chapter 5 "Treatment of acute episodes" and Chapter 8 "Strategies of pain syndrome management". While discussing the conventional recommendation of a period of starvation for patients with clinical symptom of exacerbation of chronic pancreatitis, it was noted that for a long time it had been virtually the only way to provide functional rest for the pancreas. However, patients with chronic pancreatitis are frequently in malnutrition, therefore, starving may aggravate nutritional deficit that significantly affects the prognosis; therefore, early nutritional support is indicated. To alleviate functional strain of the pancreas, it is reasonable to use enteral nutrition elemental and semi-elemental formulas. The transition from formulas to conventional nutrition should be accompanied by administration of adequate pancreatin doses. The role of pancreatic enzymes, spasmolytics and proton pump inhibitors in the management of pain syndrome was also controversial.

Almanac of Clinical Medicine. 2016;44(6):654-660
pages 654-660 views

The Russian consensus on diagnosis and treatment of coeliac disease in children and adults


Accepted at 42nd Scientific Session of the Central Research Institute of Gastroenterology, Moscow, March 2-3, 2016.

The consensus has been developed by the leading experts in gastroenterology and pediatrics of Russia. It is based on the guidelines "Gluten enteropathy an interdisciplinary disease" (2006) and "Diagnosis and treatment of coeliac disease in children" (2010), the guidelines of the Society of Pediatric Gastroenterologists of Russia "Diagnosis and treatment of coeliac disease in children" (2010), the Federal clinical guidelines on medical care for children with coeliac disease developed by the Union of Russian Pediatricians (2015), Diagnostic criteria of coeliac disease by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (revised ESPGHAN criteria, 1990), American College of Gastroenterology Clinical Guideline: "Diagnosis and management of celiac disease" (2013), "Diagnosis and Management of Adult Coeliac Disease: Guidelines from the British Society of Gastroenterology" (2014), and approved by the 42nd Scientific session of the Central Research Institute of Gastroenterology (CRIG) "The principles of evidence-based medicine into clinical practice" (Moscow, March 2-3, 2016). The consensus is published in its short version: the document sections on diagnosis and treatment of adult coeliac disease are presented.

Almanac of Clinical Medicine. 2016;44(6):661-668
pages 661-668 views


Epidemiology of hepatitis C in the Moscow Region: data from the Moscow Regional Registry and screening for HCV antibodies

Bogomolov P.O., Bueverov A.O., Matsievich M.V., Petrachenkova M.Y., Voronkova N.V., Koblov S.V., Kokina K.Y., Beznosenko V.D., Fedosova E.V.


Background: Epidemiological characteristics of chronic hepatitis C virus (HCV) infection presented in the literature are not representative for the real situation with its incidence and prevalence in the Russian Federation. In the Moscow Region, which is the second largest population in the Russian Federation (7.2 million people), the Moscow Regional Registry of patients with hepatic disorders has been continuously maintained since 2010, as well as screening programs for anti-HCV positive individuals. Analysis of this data allows for generalization of the results obtain to the general population and for description of the prevalence of the infection among adult population of the Russian Federation. Aim: To analyze the epidemiological situation with chronic hepatitis C in the Moscow Region. Materials and methods: We analyzed data from the Moscow Regional Registry of patients with hepatic disorders as per April 2016, as well as the results of large scale screening of the population of the Moscow Region with oral express test for anti-HCV antibodies (OraQuick HСV Rapid Antibody Test). Based on the registry, we assessed the following parameters of the patient cohort with chronic HCV infection (n = 17 182): age, gender, HCV genotype, grade of liver fibrosis, allele variants of interleukin 28В. Within the large scale screening program among the population of the Moscow Region, 1447 individuals from 6 districts of the region were screened for anti-HCV antibodies. Results: As per April 2016, the proportion of patients with chronic viral hepatitis in the Registry was 75.3% (n = 12 938 of 17 182). The vast majority of them (80.3%, or n = 10 393) had chronic hepatitis C, with 84% (n = 8726) of referrals were patients of productive age (from 20 to 50 years). 8.4% (n = 873) of all HCV infected patients had liver cirrhosis. Although the proportion of patients with cirrhosis was negligibly low (< 1.5%) in patients below 30 years of age, it was progressively increasing with age, with a maximum of 23.8% in those above their 50-es. As far as the HCV genotype distribution is concerned, it was as follows: genotype 1, 54.1% (n = 5622) of patients, genotype 2, 7.2% (n = 747), genotype 3, 38.4% (n = 3990). According to the results of assessment of IL28B genetic polymorphisms (n = 3212), СС rs12979860, which is associated with the most favorable sensitivity to interferon α, was found in 27.5% (n = 883), СТ allele, in 58.4% (n = 1876), and ТТ in 14,1% (n = 453). Prevalence of HCV infection in the Moscow Region, assessed by the screening program, is 1.38% of adults, or 77 200 anti-HCV positive persons, whereas estimated number of patients with chronic hepatitis C may amount to 54 000 to 61 700. Conclusion: HCV infection is the most prevalent among other viral hepatites in the Moscow Region (80.3%), and the largest numbers of infected individuals are of productive age. Almost three quarters of these patients are referred for medical care at the stage of minimal liver injury, and antiviral therapy can be used on an elective basis. Knowing the proportion of patients with liver cirrhosis (8.4%) allows for planning of the need in emergency treatments. The true prevalence of HCV infection estimated from the results of the screening program is at least 5-fold higher than that in the Registry. This indicates the necessity to upgrade the system of primary assessments. In particular, it seems reasonable to include detection of anti-HCV antibodies into the list of obligatory screening laboratory tests.

Almanac of Clinical Medicine. 2016;44(6):689-696
pages 689-696 views

Association of gene polymorphisms of the reninangiotensin system and endothelial dysfunction with development and severity of portal hypertension in patients with chronic hepatitis C

Taratina O.V., Samokhodskaya L.M., Krasnova T.N., Mukhin N.A.


Background: At present, much attention is paid to genetic factors explaining the clinical course of chronic hepatitis C. Aim: To evaluate an association of the gene polymorphisms involved in the formation of endothelial dysfunction (NOS3 894G/T, CYBA 242C/T, MTHFR 677C/T) and encoding components of the renin-angiotensin system (ATR1 1166A/C, AGT (-6)G/T and 235M/T) with development and severity of portal hypertension syndrome in patients with chronic hepatitis C. Materials and methods: 162 patients with chronic hepatitis C and HCV-related cirrhosis (114 women and 48 men) were divided into the following groups: no portal hypertension (n = 98), "compensated" (n = 19) and "decompensated" (n = 45) portal hypertension. The gene polymorphisms were assessed by molecular genetic methods. Results: TT genotype of CYBA was more common in patients with portal hypertension than in those without (odds ratio (OR) for TT = 3.59, p = 0.031). This difference becomes larger when comparing the decompensated portal hypertension group with the no portal hypertension group (OR TT = 5.46, p = 0.009). Other gene polymorphisms were not associated with development or decompensation of portal hypertension. Multivariate analysis of the impact of genetic, clinical and demographic factors showed that portal hypertension was associated primarily with patients age at the time of the study (Wald's х2 = 14.99) and with their body mass index (Wald's х2 = 4.35). After exclusion of these population-wide risk factors from the model, the development of portal hypertension correlated with the carriage of 235TT genotype of CYBA (Wald's х2 = 6.07, OR = 4.29) and (-6)AA genotype AGT (Wald's х2 = 4.73, OR = 4.13), as well as with the lack of protective 235TT genotype AGT (Wald's х2 = 4.06, OR = 0.33). The combined effects of the studied gene polymorphisms on decompensation of the portal hypertension in patients with chronic HCV infection were similar. Conclusion: The development and increase in severity of portal hypertension syndrome in patients with chronic hepatitis C is directly correlated with the carriage of AA genotype of AGT (-6)G/A and TT genotype CYBA 242C/T and the absence of TT genotype AGT 235M/T.

Almanac of Clinical Medicine. 2016;44(6):698-712
pages 698-712 views

ABX203, a novel therapeutic vaccine for chronic hepatitis B patients

Lobaina Mato Y., Aguilar Rubido J., Guillén Nieto G.


Despite the existence of effective prophylactic vaccines, chronic hepatitis B remains a major public health problem, with more than 350 million people infected   worldwide.  Chronic  infection   increases the  risk of serious  liver diseases  such  as cirrhosis and  hepatocellular carcinoma.  Available therapies for chronic  hepatitis  B  have  limited  efficacy and require  long-term   continuous  treatments;  that  is why the  development of therapeutic vaccines has been  investigated as  promising  approach.  In this sense, a novel  vaccine  formulation  called ABX203 (HeberNasvac), based  on  the  combination of the hepatitis B virus nucleocapsid and surface antigens, was developed. ABX203 has been studied in phase I, phase II and phase III clinical trial in treatment-naïve chronically infected  patients  in Bangladesh  and  in healthy  volunteers  in Cuba with promising  results. In the present work we reviewed the main preclinical and   clinical  results  of  ABX203 development. Altogether, the data demonstrates safety and immunogenicity of ABX203 vaccine and support  its use as a novel and competitive treatment alternative for chronic hepatitis B. The vaccine has been granted marketing authorization in Cuba.

Almanac of Clinical Medicine. 2016;44(6):713-718
pages 713-718 views

Inflammatory bowel disease with a very early onset

Kornienko E.A., Krupina A.N., Gabrusskaya T.V., Kalinina N.M.


Inflammatory bowel disease (Crohn's disease and ulcerative colitis) has a tendency to manifest at earlier age. In childhood (< 6 years of age) it has an especially severe course and is characterized by high grade inflammation, predominantly in the colon, by complication and extra-intestinal autoimmune injury. At younger age, Crohn's disease and ulcerative colitis require more aggressive treatment with frequently poor results. From genetic point of view, monogenic mutations controlling the immune response are characteristic for these diseases with an early onset; therefore, they are frequently associated with primary immunodeficiency. This implies various immunologic deficits, such as breakdown of the epithelial barrier, phagocytic dysfunction and dysfunction of Т and В lymphocytes and regulatory Т cells. Depending on this, a number of primary immunodeficiencies are identified associated with monogenic mutations of more than 50 genes. There some age-related specific features at manifestation. Thus, defects in interleukin 10 and FOXP3 manifest in the first months of life, whereas severe combined immunodeficiencies and phagocytosis defects become evident somewhat later. Virtually all 24 children with very early onset of inflammatory bowel disease, whom we examined, had immunologic defects and one child had a XIAP gene mutation. After identification of a specific immunologic defect, one can understand the mechanism of the disease and suspect one or another genetic defect with subsequent reasonable assessment of mutations in candidate genes. Detection of immunologic and genetic defects in children with a very early onset of inflammatory bowel disease allows for choosing an adequate strategy of non-conventional treatment that may differ depending on the mechanism of the disease.

Almanac of Clinical Medicine. 2016;44(6):719-733
pages 719-733 views

Steroid resistance in inflammatory bowel disease

Kharitonov A.G., Shchukina O.B., Kondrashina E.A.


Systemic glucocorticosteroids are widely used in the treatment of inflammatory bowel disease, and despite the introduction of new anti-inflammatory drugs, remain the first-line therapy for induction of remission in moderate and severe ulcerative colitis and Crohn's disease. However, in some patients steroid resistance is observed when glucocorticosteroids are not effective enough. The paper gives a detailed discussion of the criteria of steroid resistance, possible mechanisms of it's development, including secondary resistance resulting from complications of ulcerative colitis and Crohn's disease and associated opportunistic infections. Special attention is paid to the modern treatment of steroid-refractory inflammatory bowel disease.

Almanac of Clinical Medicine. 2016;44(6):734-743
pages 734-743 views

Confocal laser endomicroscopy in the diagnosis of colorectal diseases: image interpretation criteria

Shcherbakov P.L., Kirova M.V.


Confocal laser endomicroscopy is a rapidly emerging area of gastroenterology that bridges endoscopy and histological examination. This newest technique has enabled endoscopists to assess the microstructure of gastrointestinal mucosa in vivo during the endoscopic procedure ("virtual biopsy"), and has stimulated growing interest to its application in clinical practice. During colonoscopy, the use of confocal laser endomicroscopy is justified for assessment of post-resection margins after excision of epithelial neoplasms, for differential diagnosis of polyps and assessment of the colon in patients with inflammatory bowel disorders. This article presents the interpretation criteria of confocal images in various colon diseases and the published data on the diagnostic value of the method.

Almanac of Clinical Medicine. 2016;44(6):744-750
pages 744-750 views

Upper and lower gastrointestinal tract disorders in patients with newly diagnosed acromegaly

Titaeva A.A., Belousova E.A., Tereshchenko S.G., Velikanov E.V.


Background: Increased growth hormone production in acromegaly results in enlargement of inner organs, their dysfunction and morphological abnormalities. Of special interest are patients with newly diagnosed acromegaly, because their gastrointestinal mucosa can be assessed without consideration of the influence of medications used for the treatment of the underlying disorder. Aim: To describe characteristic features of upper and lower gastrointestinal tract disorders in patient with treatment-naive acromegaly. Materials and methods: We examined 37 patients with newly diagnosed acromegaly, aged from 22 to 73 years (mean age, 49.9 ± 2.1 years). All patients underwent esophagogastroduodenoscopy with biopsy for identification of Helicobacter pylori, colonoscopy, morphological examination of biopsy samples taken from neoplasms of the upper gastrointestinal tract, as well as of the colon. The control group included 35 individuals without acromegaly who were ageand gender compatible with the patients of the main group. Results: Cardiac insufficiency was diagnosed in 23 patients with acromegaly and in 13 in the control group (p < 0.05), simultaneous lesions of the stomach and duodenal bulb (erosions), in 7 and 2 patients, respectively (p > 0.05), gastric polypoids, in 6 patients of the main group and in no patient from the control group (p < 0.05). There were no significant differences between groups on esophagitis Savary Miller Grade 1 and 2 (grading, Grade 1 in 7 and 5 patients and Grade 2 in 3 and 2, respectively), as well as on contamination with Helicobacter pylori (19 patients in each of the groups). Colon abnormalities were found in patients with acromegaly more frequently than in the control group: dolichosigma, in 12 and 4 (p < 0.05), colonic polyps, in 13 and 2, respectively (p < 0.01). Diverticles were found in 9 with acromegaly and in 3 in the control group (p > 0.05). At histological examination, hyperplastic gastric polyps were found only in patients with acromegaly (6 patients, p < 0.05), colonic polyps in 8 patients from the main group and in 2 from the control one (p > 0.05). Tubular adenomas were diagnosed only in patients with acromegaly, in 2 of them they were located in the stomach (p > 0.05) and in 5, in the colon (p < 0.05). Conclusion: Right from the diagnosis, patients with acromegaly should undergo an examination of upper and lower gastrointestinal tract, because of the high probability of various disorders under high production of the growth hormone.
Almanac of Clinical Medicine. 2016;44(6):751-756
pages 751-756 views


The potential of radiologic procedures in the diagnosis of inflammatory bowel disease

Dubrova S.E., Stashuk G.A.


At present, there is no "golden standard" of diagnosis of inflammatory bowel disease. Each and every individual case requires a thorough analysis of clinical symptoms in their association with endoscopic, histological, radiological and laboratory data. This review paper analyzes both conventional and novel methods of radiological investigations. Some of them have changed their significance from the "golden standard" to rare and limited application and from promising, then frequent and currently sporadic use of small bowel enema. Traditional ileocolonoscopy maintains its diagnostic potential, especially as a tool for follow up of patients with colonic and ileac disorders. The state-of-the-art non-invasive (ultrasound examination) and limitedly non-invasive (computerized tomography and magnetic resonance imaging) procedures are considered to be the most accurate methods for assessment of inflammatory bowel disorders in patient with already confirmed diagnosis and those with suspected cases of Crohn's disease and ulcerative colitis. The paper describes preparation of patient for each method, assessment technique, advantages and limitations for use, diagnostic criteria for intestinal wall thickness, accuracy of methods and discusses the perspectives of their use. The main sign of inflammatory bowel disease is thickening of intestinal wall. Usually its mean thickness in Crohn's disease (11 to 13 mm) is higher than that in ulcerative colitis (7 to 8 mm). This may provide a diagnostic key during differential diagnosis of an isolated colon disease. The amount of the contrast cumulated by the intestinal wall directly correlates with inflammation activity. Intensive contract cumulation in the intestinal wall after intravenous contrast enhancement is a symptom of active inflammatory process. However, despite progression in the technologies, initial signs of inflammatory bowel diseases are quite superficial and remain hardly visible, being below the resolution ability of any diagnostic investigation.

Almanac of Clinical Medicine. 2016;44(6):757-769
pages 757-769 views

The microbiota of upper parts of gastrointestinal tract and its role in the development of obesity in children

Bokova T.A., Koshurnikova A.S.


Evaluation of qualitative and quantitative composition of microflora of different habitats of the human body and definition of their role in the development of metabolic disorders are of great interest for investigators worldwide. The gut microbiota is an obligatory contributor to the synthesis, recirculation and metabolism of steroid hormones, lipids, and bile acids. Infectious agents and their biologically active compounds initiate the atherogenesis. Disorders of lipid metabolism are associated with a change in bacterial enterotypes. Microbiotal colonization of gastrointestinal tract starts at birth. Its composition in a newborn depends on a variety of environmental and nutritional factors, maternal health, the course of pregnancy and delivery. Infants born by cesarean section have a higher incidence of obesity, which is thought to be associated with a delay of bifidobacterial colonization of gastrointestinal tract.

Reduction of bifidobacteria counts in the gut in infants below 12 months of age predisposes to obesity in later life. Children born to mothers with obesity have significant differences in the composition of the gut microflora, compared to children born to normal weight mothers. This review presents the data on the association between metabolic disorders, such as obesity and type 2 diabetes, and persistence of Helicobacter pylori infection. Further in-depth research in this area would increase the knowledge on the mechanisms of hormonal and metabolic disorders in childhood and may help to develop algorithms for effective treatment and preventive measures.

Almanac of Clinical Medicine. 2016;44(6):770-774
pages 770-774 views

Cirrhotic cardiomyopathy and liver transplantation

Malinovskaya Y.O., Moiseev S.V., Moysyuk Y.G.


Cirrhotic cardiomyopathy is a syndrome, which includes systolic and diastolic dysfunction and electrophysiological abnormalities in patients with liver cirrhosis in the absence of any cardiac disease. Several mechanisms seem to be involved in the pathogenesis of cirrhotic cardiomyopathy, such as impaired signaling of beta-receptors, altered trans-membrane ion currents and excess production of vasodilators. Clinical manifestation of cirrhotic cardiomyopathy is non-specific and is usually masked by the symptoms of cirrhosis. Despite frequent regression of cirrhotic cardiomyopathy after liver transplantation, myocardial dysfunction may lead to cardiac complications during transplantation surgery and post-operatively. Severe myocardial dysfunction may affect liver transplantation outcomes with an increase in cardiovascular mortality. Therefore, timely identification of cirrhotic cardiomyopathy is crucial for assessment of candidate patients for liver transplantation. At present, there is no specific therapy for cirrhotic cardiomyopathy. Recommended treatment should be aimed at support of myocardial function and prevention of decompensation.

Almanac of Clinical Medicine. 2016;44(6):775-784
pages 775-784 views


Comprehensive diagnostic and medical endoscopy of gastric diseases prior to planning a surgical intervention for cardiovascular disorders: a case study of a bezoar

Mecheva L.V., Tereshchenko S.G., Grigor'ev N.S., Kaluzhskiy A.A.


Big bezoars are rare foreign bodies of the stomach. In the literature, the problem of bezoars has been described mainly as isolated clinical cases. In this publication we present a case of endoscopic removal of a big bezoar, along with the diagnostics and treatment of concomitant erosive and ulcerative lesions, as well as detection of a gastric malignancy (tubular adenoma with severely dysplastic foci). The active endoscopic approach allowed for a timely preparation of the patient for a reconstructive surgery on the low extremity vasculature. The paper may be of interest for   internists,   gastroenterologists,   surgeons, providing them with a motivation to perform a regular follow up of upper gastrointestinal tract in patients after surgical interventions on the stomach and duodenum. This clinical observation is a good example for endoscopists of a successful diagnostics and treatment of a rare comorbid disorder.

Almanac of Clinical Medicine. 2016;44(6):785-789
pages 785-789 views

A case of selective immunoglobulin A deficiency associated with autoimmune gastritis

Moskalets O.V., Yazdovskiy V.V., Nikitina N.Y.


Selective immunoglobulin A (IgA) deficiency is considered to be the most common primary immune deficiency. Up to now, no specific genetic mutation causing this disorder has been found. True prevalence of selective IgA deficiency in the population is unknown, because in most cases it is asymptomatic and occurs as an incidental laboratory finding. In some patients, it can manifest by respiratory and gastrointestinal infections, as well as allergic and autoimmune disorders. According to the literature, autoimmune disorders in patients with selective IgA deficiency have a more aggressive course and a worse prognosis. This clinical case of a combination of selective IgA deficiency and autoimmune gastritis demonstrates that patients with primary immunodeficiency, especially adults, may not know about their disease for a long time. The paper may be of interest for practicing doctors of various specialties, first of all, for gastroenterologists, internists, general practitioners, and is intended to increase awareness about diagnosis of selective IgA deficiency. There is no specific treatment for this immunodeficiency, but one should bear in mind that blood transfusions and intravenous immunoglobulin preparations with high IgA content are contra-indicated in these patients due to a high risk of anaphylactic reactions.

Almanac of Clinical Medicine. 2016;44(6):790-795
pages 790-795 views

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