Rationale: Extraintestinal manifestations (EIM) of an inflammatory bowel disease (IBD) are a sign of its more severe course. Joint lesions are most common among IBD EIM.Aim: To evaluate the prevalence and types of joint lesions in the population of IBD patients of the Moscow region.Materials and methods: We performed a retrospective analysis of medical files of the patients who were admitted to the Moscow Region Inflammatory Bowel Disease Center (MONIKI) for examination and treatment from August 1, 2019, to March 1, 2020. The study included 70 patients with confirmed diagnoses of IBD and confirmed or suspected involvement of the joints.Results: Thirty six of 70 patients with IBD and EIM (51.43%) had been diagnosed with Crohn's disease (CD), and 34 (48.57%) with ulcerative colitis (UC). The CD group included more men (n=21, 58.33%), whereas their proportion in the UC group was 47.02% (n=16). The mean age at CD diagnosis in the UC and CD groups was comparable: 38.3±13.7 years in men with CD and 40.5±12.8 years in men with UC, 37.7±11.1 years in women with CD and 35.7±14.0 in women with UC. The most prevalent among all IBD patients were X-ray negative peripheral arthralgias. Among joint lesions confirmed by radiological diagnostics, sacroileitis was most prevalent both in all IBD patients (24.3%), as well as in the UC group (17.6%), whereas in the CD patients its frequency was the same as that of ankylosing spondyloarthritis (AS) (30.6% of the cases). AS ranked second in the prevalence of joint lesions in the UC group (8.8%) and all IBD (20%). Psoriatic arthritis was diagnosed only in the CD patients (2 / 36). We describe a clinical case of CD with AS, complicated with psoriatic rash, treated with a monoclonal antibody to tumor necrosis factor alfa (anti-TNF-α).Conclusion: Peripheral arthropathias were most prevalent among all joint lesions in the group studied. EIM mirror a more aggressive phenotype of the disease and higher glucocorticosteroids requirements. Administration of anti-TNF-α agents allows for the control of both intestinal IBD manifestations and of the joint syndrome. However, drug-associated skin adverse event can occur during treatment with this drug class. In such a case, it is possible to switch the biological therapy to another class of drugs that we have demonstrated with the given clinical example.

Crohn's disease and multiple myeloma are pathological entities, the development of which, at least in part, is associated with an immune disregulation. Crohn's disease is often combined with extra-intestinal manifestations from different organs and systems (joints, skin, eyes, etc.). Hematological extra-intestinal manifestations, such as myelodysplastic syndrome, aplastic autoimmune anemia, autoimmune thrombocytopenia, B12-deficiency anemia are less common. The list of extra-intestinal manifestations of Crohn's disease is constantly expanding, including more and more descriptions of the combination of Crohn's disease with diseases of the blood system. The paper presents a rare clinical case of a combination of Crohn's disease and multiple myeloma. The female patient is 53 years old. In 1993 ulcerative colitis was diagnosed and she received Sulfasalazine 4gr per day. In 2015, with the recurrent attack, the diagnosis was transformed towards Crohn's disease basing on colonoscopy. She received steroid therapy. In 2018 the control examination revealed an increase in the level of total protein to 117gr/l. Patient underwent a sternal biopsy. Multiple myeloma was diagnosed on the basis of a myelogram.

Background: For a long time there has been a discussion about how chronic pancreatitis (CP) and diabetes mellitus (DM) are related to each other. If a patient has both conditions, should they be viewed as two separate disorders, or one of them is a plausible consequence of the other? If the latter is true, what are pathophysiological mechanisms of DM in CP? Current consensus documents by specialists in pancreatic diseases pay little attention to this issue, and their main statements have low level of evidence. The Russian consensus on the diagnosis and treatment of CP (2016) contains no statements on DM. In the Russian guidelines and consensus documents to be developed, it is necessary to include provisions on the pancreatogenic DM as an independent “other type DM’, with consideration of its pathophysiological mechanisms and clinical particulars.Aim: To characterize the state-of-the-art in pancreatogenic DM, to demonstrate its differences from DM types 1 and 2 from pathogenetic and clinical perspectives.Methods: The review is based on the results of meta-analyses, systematic reviews and main provisions of the existing clinical guidelines and consensus documents available from PubMed and E-library.Results: According to various sources, Type 3c DM, or latent impaired glucose tolerance in CP, can eventually develop in 25 to 80% patients with CP. Impaired glucose tolerance is found in 40 to 60% of patients with acute pancreatitis, with persistent hyperglycemia after acute episode seen in 15 to 18% of the patients. Exocrine pancreatic insufficiency is commonly seen in Type 1 and Type 2 diabetic patients, although the data on its prevalence are highly contradictory indicating a lack of knowledge in the field. Type 3c DM is characterized by its manifestation at later stages of CP, concomitant excretory deficiency of the pancreas, brittle course with proneness to hypoglycemia and no ketoacidosis. The highest risk group includes patients with longstanding CP, previous partial pancreatic resection and patients with early calcifying pancreatitis, mainly of the alcoholic origin. Optimal and rational medical treatment of pancreatogenic DM still remains disputable, while the evidence base of the efficacy and safety of various anti-diabetic agents in this disease is lacking, and no consensus on the issue has been yet reached. General treatment guidelines given in a number of international consensus documents are limited to cautious insulin administration.Conclusion: Pancreatogenic DM differs from Type 1 and Type 2 DM in a number of aspects, namely, mechanisms of hyperglycemia, hormonal profiles, clinical particulars and treatment approaches. Endocrine pancreatic insufficiency in CP is caused by secondary inflammatory injury of the pancreatic islets. The key to specifics of Type 3c DM lies in anatomical and physiological interplay of the exocrine and endocrine compartments of the pancreas. At presents, most provisions on pancreatogenic DM are empirical and seem to be rather declarative, because intrinsic mechanisms of this type of diabetes and moreover its pathogenetically based treatment have been poorly studied. Nevertheless, all patients with CP or other pancreatic diseases should be assessed for pancreatogenic DM.

Crohn's disease and multiple myeloma are pathological entities, the development of which, at least in part, is associated with an immune disregulation. Crohn's disease is often combined with extra-intestinal manifestations from different organs and systems (joints, skin, eyes, etc.). Hematological extra-intestinal manifestations, such as myelodysplastic syndrome, aplastic autoimmune anemia, autoimmune thrombocytopenia, B12-deficiency anemia are less common. The list of extra-intestinal manifestations of Crohn's disease is constantly expanding, including more and more descriptions of the combination of Crohn's disease with diseases of the blood system. The paper presents a rare clinical case of a combination of Crohn's disease and multiple myeloma. The female patient is 53 years old. In 1993 ulcerative colitis was diagnosed and she received Sulfasalazine 4gr per day. In 2015, with the recurrent attack, the diagnosis was transformed towards Crohn's disease basing on colonoscopy. She received steroid therapy. In 2018 the control examination revealed an increase in the level of total protein to 117gr/l. Patient underwent a sternal biopsy. Multiple myeloma was diagnosed on the basis of a myelogram.

Inflammatory bowel diseases (IBD) are commonly associated with extraintestinal manifestations, hematological disorders being the most special among them. In some cases, they dominate the clinical picture masking the intestinal manifestations of the underlying disease. Aplastic anemia is an extremely rare extraintestinal IBD manifestation. There are only two clinical cases of aplastic anemia associated with ulcerative colitis and non with Crohn's disease reported in the literature. Combination of Crohn's disease and В₁₂-deficient anemia is more prevalent, but is seen usually only after more than 20 cm of the ileus has been resected. The first clinical case presented in this paper is a combination of severe fistula-forming Crohn's disease with a constriction in the terminal part of the ileus and profound pancytopenia as an outcome of aplastic anemia. This profound pancytopenia is associated with an extremely high risk of life-threatening complications both of surgical treatment, as well as of several chemotherapeutic agents, which made the management of this patient difficult. The second clinical case demonstrates the manifestation of Crohn's disease as ileocolitis starting from the symptoms of cobalamin deficiency: severe В₁₂-deficient anemia, funicular myelosis and sensory ataxia, with blunted intestinal symptoms. This made the initial diagnosis and timely treatment difficult. Replacement therapy with cobalamin injections and treatment with glucocorticoids and antibacterials led to endoscopically confirmed remission of Crohn's disease and normalization of hematological parameters, with persistent polyneuropathy. Thus, management of patients with Crohn's disease should be multidisciplinary. In the case of anemia, leucopenia and/or thrombocytopenia in IBD patients it is necessary to exclude potential myelodysplasia and bone marrow aplasia. In the event of megaloblastic anemia and/or progressive polyneuropathy one should bear in mind potential cobalamin deficiency. However, in severe anemia it is important to perform diagnostic assessment for IBD, first of all, for Crohn's disease, especially, if any intestinal symptoms are present.

Inflammatory bowel diseases (IBD) are commonly associated with extraintestinal manifestations, hematological disorders being the most special among them. In some cases, they dominate the clinical picture masking the intestinal manifestations of the underlying disease. Aplastic anemia is an extremely rare extraintestinal IBD manifestation. There are only two clinical cases of aplastic anemia associated with ulcerative colitis and non with Crohnu0027s disease reported in the literature. Combination of Crohnu0027s disease and В₁₂-deficient anemia is more prevalent, but is seen usually only after more than 20 cm of the ileus has been resected. The first clinical case presented in this paper is a  combination of severe fistula-forming Crohnu0027s disease with a constriction in the terminal part of the ileus and profound pancytopenia as an outcome of aplastic anemia. This profound pancytopenia is associated with an extremely high risk of life-threatening complications both of surgical treatment, as well as of several chemotherapeutic agents, which made the management of this patient difficult. The second clinical case demonstrates the manifestation of Crohnu0027s disease as ileocolitis starting from the symptoms of cobalamin deficiency: severe В₁₂-deficient anemia, funicular myelosis and sensory ataxia, with blunted intestinal symptoms. This made the initial diagnosis and timely treatment difficult. Replacement therapy with cobalamin injections and treatment with glucocorticoids and antibacterials led to endoscopically confirmed remission of Crohnu0027s disease and normalization of hematological parameters, with persistent polyneuropathy. Thus, management of patients with Crohnu0027s disease should be multidisciplinary. In the case of anemia, leucopenia and/or thrombocytopenia in IBD patients it is necessary to exclude potential myelodysplasia and bone marrow aplasia. In the event of megaloblastic anemia and/or progressive polyneuropathy one should bear in mind potential cobalamin deficiency. However, in severe anemia it is important to perform diagnostic assessment for IBD, first of all, for Crohnu0027s disease, especially, if any intestinal symptoms are present.

Rationale: Search for predictors of aggressive course of chronic hepatitis C virus (HCV) infection in individual patients, including genetic studies, is considered to be a major urgent goal. High rates of fibrosis progression in chronic HCV infection is associated with several gene polymorphisms coding for the components of renin-angiotensin system and involved in the formation of endothelial dysfunction and oxidative stress.Aim: To develop a predictive model to assess the probability of rapid fibrosis progression in patients with chronic HCV infection based on the combination of the known genetic markers, clinical and demographic parameters.Materials and methods: One hundred and nine patients with chronic HCV infection (79 women and 30 men) of known duration and liver fibrosis were categorized into the groups with “rapid fibrosis” (n = 54, the rate of fibrosis progression ≥ 0.13 fibrosis units / year) and with “slow fibrosis” (n = 55, the rate of progression < 0.13 fibrosis units / year). Polymorphisms of the studied genes were assessed by molecular genetic assays. Multivariate analysis of the influence of combination of genetic variants, as well as of the interaction of genetic, clinical and demographic factors on the rate of fibrosis progression in the patients with chronic HCV infection was performed by logistic regression method. Results: The rapid rate of fibrosis progression was significantly associated with patient's age at the time of infection (Wald statistics 14.955; p = 0.00011), male gender (Wald statistics 6.787; p = 0.00918), (-6)АА genotype of the AGT gene carriage (Wald statistics 6.512; p = 0.01072), 242ТТ-genotype of the CYBA gene (Wald statistics 4.347; p = 0.03708), and 235МТ genotype of the AGT gene (Wald statistics 4.306; p = 0.03799). The model to predict the probability of rapid fibrosis progression in individuals with chronic HCV infection included the above mentioned factors; its use was demonstrated with two clinical cases.Conclusion: The analysis of the AGT gene (M235T and G-6A loci) and the СYBA gene (C242T locus) polymorphisms are relevant to identify patients at risk of rapid liver fibrosis progression. In this case, 242ТТ genotype of the CYBA gene and (-6)AA and 235MT genotypes of the AGT gene are considered unfavorable. To refine the prognosis, it is necessary to take into account demographic parameters (gender and age at the moment of infection contraction), because male gender and older age of getting the infection would increase the probability of rapidly progressive of hepatitis C.

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.

Aim of investigation. To estimate relation of polymorphism of genes encoding reninangiotensin system components (AGT G-6A, AGT M235T and ATR1 A1166C) with rate of liver fibrosis progression in patients with chronic hepatitis C (CHC).Material and methods. Overall 109 patients with CHC and liver cirrhosis C with established stage of fibrosis and duration of disease have been divided into group of «rapidly progressing fibrosis» (55 patients, ≥0,130 fibrosis points/year) and «slowly progressing fibrosis» (54 persons, <0,130 fibrosis units/year). Assessment of polymorphism of studied genes was carried out by molecular genetic methods.Results. In CHC patients of «rapidly progressing fibrosis» group in comparison to «slowly progressing fibrosis» group minor A-allele (50,0 and 33,3% respectively, p=0,0126) and «mutant» АА-genotype (27,3 and 11,1%, р=0,0324; OR АА=3,00; 95% CI 1,07-8,45), AGT gene on locus G-6A, as well as minor T-allele (р=0,0407) of AGT gene in M235T locus were significantly more common while MM genotype of M235T polymorphism of AGT gene (20,8 and 44,4%, respectively, p=0,0090; OR MM=0,33; 95%-CI 0,15–0,73) were significant less frequent. No significant differences between groups in distribution of alternative alleles and genotypes of ATR1 gene on A1166C locus have been revealed.Conclusion. Carriage of mutant alleles of angiotensinogen gene on any of loci (G-6A or M235T) is the factor predicting more rapid progression of disease. As chronic hepatitis C is multifactorial disease, it is rational to use testing of allelic variants of angiotensinogen gene in patient-specific approach at CHC management.

AIM:To assess the association of the CYBA, NOS3, and MTHFR gene polymorphisms and a rate of fibrosis progression in chronic hepatitis C (CHC).SUBJECTS AND METHODS:One hundred and nine CHC patients with the verified stage of liver fibrosis and cirrhosis at its onset were examined. The disease duration was determined in all the patients and additional risk factors of liver lesion were absent. A group of rapidly progressive fibrosis comprised 55 patients with a calculated fibrosis progression rate of 0.130 fibrosis units/year or higher and 54 patients with a progression rate of less than 0.130 fibrosis units/year were assigned to a slow fibrosis group. A compression group consisted of 299 healthy blood donors. The polymorphism of the genes under study was determined by polymerase chain reaction-restriction fragment length polymorphism analysis.RESULTS:The mutant TT genotype of the CYBA gene was significantly more common in the CHC patients with rapidly progressive fibrosis than in those with slowly progressive fibrosis (odds ratio for TT 9.09 at 95% confidence interval, 1.09 to 74.83; p = 0.0161). No significant differences were found in the distribution of the alleles and genotypes of the NOS3 and MTHFR genes between the groups of patients with slowly and rapidly progressive fibrosis.CONCLUSION:The findings make it possible to regard the TT genotype of the CYBA gene from the C242T locus as profibrogenic and as one of the markers of the poor course of CHC.