Vol 91, No 2 (2019)


Small intestinal diverticula

Parfenov A.I., Krums L.M., Pavlov M.V.


The prevalence of small intestinal diverticula (SID) in the population is 0.5-2.3%, and in most cases they are asymptomatic. In the presence of small intestinal bacterial overgrowth this results in chronic diarrhea and malabsorption. When it is complicated by diverticulitis it causes pain and other symptoms of inflammatory bowel disease. Inflammatory process progression may be accompanied by bleeding, invagination, intestinal obstruction, diverticulum abscess and perforation with peritonitis development. SID include separate nosological forms such as paraphateral diverticulum and Meckel's diverticulum. In diagnosis of SID ray and endoscopic methods are crucial. The basis of small intestine diverticular disease treatment is intestinal antiseptics, antibiotics as well as surgical intervention for severe complications. Two cases are discussed, the first one confirms a possibility of development of severe malabsorption syndrome with chronic diarrhea, and the second one is a complication in a form of severe diverticulitis, abscess with perforation and peritonitis.
Terapevticheskii arkhiv. 2019;91(2):4-8
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Important problems in the diagnosis and treatment of primary sclerosing cholangitis (based on the Russian consensus on diagnosis and treatment autoimmune hepatitis. Moscow, 2018)

Vinnitskaya E.V., Abdulkhakov S.R., Abdurakhmanov D.T., Alikhanov R.B., Bakulin I.G., Belousova E.A., Bueverov A.O., Burnevitch E.Z., Efanov M.G., Eremina E.Y., Ignatova T.M., Ilchenko L.Y., Karmazanovsky G.G., Knyazev O.V., Kulezneva Y.V., Lopatkina T.N., Nekrasova T.P., Nikitin I.G., Pavlenko V.V., Parfenov A.I., Podymova S.D., Raichelson K.L., Reisis A.R., Sayfutdinov R.G., Skazyvaeva E.V., Syutkin V.E., Khomeriki S.G., Haimenova T.Y., Sandler Y.G.


The article is published based on the results of the Russian Consensus on the diagnosis and treatment of primary sclerosing cholangitis (PSC), discussed at the 44th annual Scientific Session of the CNIIG "Personalized Medicine in the Era of Standards" (March 1, 2018). The aim of the review is to highlight the current issues of classification of diagnosis and treatment of patients with PSC, which causes the greatest interest of specialists. The urgency of the problem is determined by the multivariate nature of the clinical manifestations, by often asymptomatic flow, severe prognosis, complexity of diagnosis and insufficient study of PSC, the natural course of which in some cases can be considered as a function with many variables in terms of the nature and speed of progression with numerous possible clinical outcomes. In addition to progression to portal hypertension, cirrhosis and its complications, PSC can be accompanied by clinical manifestations of obstructive jaundice, bacterial cholangitis, cholangiocarcinoma and colorectal cancer. Magnetic resonance cholangiography is the main method of radial diagnostics of PSC, which allows to obtain an image of bile ducts in an un-invasive way. The use of liver biopsy is best justified when there is a suspicion of small-diameter PSC, autoimmune cross-syndrome PSC-AIG, IgG4-sclerosing cholangitis. Currently, a drug registered to treat primary sclerosing cholangitis which can significantly change the course and prognosis of the disease does not exist. There is no unified view on the effectiveness and usefulness of ursodeoxycholic acid and its dosage in PSC. Early diagnosis and determination of the phenotype of PSC is of clinical importance. It allows to determine the tactics of treatment, detection and prevention of complications
Terapevticheskii arkhiv. 2019;91(2):9-15
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European registry Helicobacter pylori (Hp-EuReg): how has clinical practice changed in Russia from 2013 to 2018 years

Bordin D.S., Embutnieks Y.V., Vologzhanina L.G., Ilchishina T.A., Voynovan I.N., Sarsenbaeva A.S., Zaitsev O.V., Alekseenko S.A., Abdulkhakov R.A., Dehnich N.N., Osipenko M.F., Livzan M.A., Tsukanov V.V., Burkov S.G., Bakulina N.V., Plotnikova E.Y., Tarasova L.V., Maev I.V., Kucheryavyi Y.A., Baryshnikova N.V., Butov M.A., Kolbasnikov S.V., Pakhomova A.L., Zhestkova T.V., Baranovsky A.Y., Abdulhakov S.R., Ageeva E.A., Lyalyukova E.A., Vasyutin A.V., Golubev N.N., Savilova I.V., Morkovkina L.V., Kononova A.G., Megraud F., O'Morain C., Ramas M., Nyssen O.P., McNicholl A.G., Gisbert J.P.


The multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group (EHMSG) is conducted in 27 countries in Europe. The data from the Russian part of the European registry for the management of Helicobacter pylori infection (European Registry on the management of Helicobacter pylori infection, protocol: “Hp-EuReg”) allows us to analyze the real clinical practice of diagnosis and treatment of H. pylori and compare it with international recommendations. Materials and methods. A comparative analysis of the data entered in the register by the Russian research centers “Hp-EuReg”, in the period from 2013 to 2018, was conducted. Results and discussion. Invasive diagnostic methods prevail for the primary diagnosis of H. pylori [histology - 20.3% (in 2013 year) - 43.9% (in 2018 year), rapid urease test - 31.7% and 47.8% respectively]. The most popular mode of eradication therapy is a 10-day triple therapy (62.8-76.2%), the effectiveness of which does not exceed 79% (per protocol). Invasive tests (histology) are the leading method for control the effectiveness of therapy, however, there is a tendency towards a wider use of non-invasive methods (H. pylori stool antigen - from 17% in 2013 to 29.3% in 2018 and urea breath test from 6.9 to 18.3%, respectively). Serological test to control the effectiveness of eradication is still used from 8.2% (2013) to 6.1% (2018). Eradication therapy was not performed in 28% of patients throughout the entire observation period. Conclusion. In Russia, despite approved domestic and international recommendations, deviations in clinical practice persist, both during eradication therapy and in monitoring the effectiveness of eradication therapy.
Terapevticheskii arkhiv. 2019;91(2):16-24
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Rebamipide increases the disaccharidases activity in patients with enteropathy with impaired membrane digestion. Pilot study

Parfenov A.I., Belostotsky N.I., Khomeriki S.G., Akhmadullina O.V., Bykova S.V., Sabelnikova E.A., Dbar S.R.


Aim. To evaluate the effectiveness of enteroprotector Rebamipide in the treatment of enteropathy with impaired membrane digestion (EIMD). Materials and methods. We examined 102 patients aged 18 to 50 years (41 men and 61 women) with clinical signs of irritable bowel syndrome (n=65), functional diarrhea (n=33), and functional constipation (n=4) according to Rome IV criteria (2016). The activities of glucoamylase (GA), maltase, sucrase and lactase were determined by Dahlquist-Trinder method in duodenal biopsies obtained during esophagogastroduodenoscopy. The control group consisted of 20 healthy people aged 23-47. They showed following average enzyme activity: lactase - 42±13 ng glucose on 1 mg of tissue per minute, GA - 509±176, maltase - 1735±446, sucrase - 136±35 ng glucose on 1 mg of tissue per minute. These numbers were taken as the norm. Results and discussion. The activity of the disaccharidases was reduced in 89.2% out of 102 patients, and they were diagnosed with EIMD. Thirteen patients with EIMD were recommended to maintain the FODMAP diet and take enteroprotector Rebamipide 100 mg 3 times a day for 12 weeks. After 3 months 11 patients reported decreased or no flatulence, abdominal pain, stool disorder; 2 patients reported no change. The activity of GA increased to an average of 149±82 (by 78%, p=0.016), maltase - to 864±472 (by 131%, p=0.0019), sucrase - 63±35 (by 95%, p=0.0041) and lactase - 10±8 ng glucose on 1 mg of tissue per minute. The activity of lactase did not change. Conclusion. We discovered a previously unknown phenomenon of the disaccharidases activity increase in duodenal mucosa and improved carbohydrates tolerance in the patients with EIMD taking Rebamipide in the dose 300 mg/day for 12 weeks.
Terapevticheskii arkhiv. 2019;91(2):25-31
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Prediction of features of the course of chronic hepatitis C using Bayesian networks

Samokhodskaya L.M., Starostina E.E., Sulimov A.V., Krasnova T.N., Rosina T.P., Avdeev V.G., Savkin I.A., Sulimov V.B., Mukhin N.A., Tkachuk V.A., Sadovnichii V.A.


Materials and methods. 253 patients with chronic hepatitis C (CHC) and liver cirrhosis were included in the study. Assessment of gene polymorphisms of genes involved in inflammatory reactions and antiviral immunity (IL-1β-511C/T, IL-10 -1082G/A, IL28B C/T, IL28B T/G, TNF-α -238G/A, TGF-β -915G/C, IL-6 -174G/C), activators of local hepatic fibrosis (AGT G-6A, AGT 235 M/T, ATR1 1166 A/C), hemochromatosis (HFE C282Y, HFE H63D), platelet receptors (ITGA2 807 C/T, ITGB3 1565 T/C), coagulation proteins and endothelial dysfunction (FII 20210 G/A, FV 1691G/A, FVII 10976 G/A, FXIII 103 G/T, eNOS 894 G/T, CYBA 242 C/T, FBG -455 G/A, PAI-675 5G/4G, MTHFR 677 C/T) was carried. Using Bayesian networks we studied the predictor value of clinical and laboratory factors for the following conditions - end points (EP): development of cirrhosis (EP1), fibrosis rate (EP2), presence of portal hypertension (EP3) and cryoglobulins (EP4). Results and discussion. In addition to traditional factors we have shown the contribution of the following mutations. Predicting EP1- liver cirrhosis - HFE H63D, C282Y, CYBA 242 C/T, AGT G-6G, ITGB31565 T/C gene mutations were significant. We also found a link between the rate of progression of liver fibrosis and gene polymorphisms of AGT G-6G, AGT M235T, FV 1691G/A, ITGB31565 T/C. Among the genetic factors associated with portal hypertension there are gene polymorphisms of PAI-I-675 5G/4G, FII 20210 G/A, CYBA 242 C/T, HFE H63D and Il-6 174GC. Cryoglobulins and cryoglobuliemic vasculitis (EP4) are associated with gene mutations MTHFR C677T, ATR A1166C and HFE H63D. Conclusion. The results obtained allow to detect the major pathophysiological and genetic factors which determine the status of the patient and the outcome of the disease, to clarify their contribution, and to reveal the significance of point mutations of genes that control the main routes of HCV course and progression.
Terapevticheskii arkhiv. 2019;91(2):32-39
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Efficacy and safety of long-term therapy with nucleos(t)ide analogues in chronic hepatitis B

Ibragimov E.K., Abdurakhmanov D.T., Rozina T.P., Nikulkina E.N., Tanaschuk E.L., Odintsov A.V., Panevkina S.V., Moiseev S.V.


Nucleos(t)ide analogues are first-line therapies for the treatment of chronic hepatitis B. However, the efficacy and safety of long-term treatment and the necessary duration of therapy remains the subject of discussion. Aim. To assess the efficacy and safety of long-term treatment with nucleos(t)ide analogues in patients with chronic hepatitis B. Materials and methods. We conducted an observational study in 101 chronic hepatitis B (HBeAg-negative and HBeAg-positive) patients treated (≥3 years) with entecavir, tenofovir or telbivudine. Results and discussion. Treatment with entecavir and tenofovir was associated with high rate of virologic and biochemical response (>95%) and HBeAg seroconversion (93% and 67%, respectively). Cumulative rate of virologic resistance was 0; 3.1% and 43.5% for tenofovir, entecavir and telbivudine, respectively. Long-term nucleos(t)ide analogues treatment resulted in a regress of liver fibrosis (from 8.92 to 7.18 kPa, р<0.0001) and reduction in the number of patients with advanced fibrosis (from 48.1% to 13.8%, р<0.0001). Entecavir and tenofovir were safe and well tolerated, while treatment with telbivudine was associated with development of myopathy in 13% of cases. Conclusion. Entecavir and tenofovir might be recommended for the treatment of chronic hepatitis B because of having potent antiviral effect, high genetic barriers against resistance and good safety.

Terapevticheskii arkhiv. 2019;91(2):40-47
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Comparative analysis of bile acid spectrum in non-alcoholic fatty liver disease and cholelithiasis

Vakhrushev Y.M., Lukashevich A.P., Penkina I.A., Suchkova E.V.


Aim. Сomparative studying of changes in the spectrum of bile acids in bile in patients with nonalcoholic fatty liver disease and cholelithiasis. Materials and methods. 140 patients were included in the survey: 50 - with nonalcoholic fatty liver disease and 90 - with cholelithiasis. The diagnosis of nonalcoholic fatty liver disease was established on the basis of ultrasound examination of the liver, the elasticity and fibrosis of liver by using the sonoelastography and liver biopsy. The prestone stage of cholelithiasis was established on the basis of ultrasound examination of the gallbladder and biochemical examination of bile. The level of total cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase and gamma glutamyl transpeptidase were studied using the analyzer "Labsystems" (Finland). The spectrum of bile acids in bile is studied by mass spectrometry on AmazonX apparatus (Bruker Daltonik GmbH, Bremen, Germany). Results and discussion. Biochemical blood test revealed increase of cholesterol, triglycerides, cytolysis markers, and cholestasis, the most pronounced in patients with nonalcoholic fatty liver disease. Biochemical study of bile showed increase of cholesterol, decrease the total amount of bile acids and cholatecholesterol coefficient in the vesicle and hepatic bile in patients with nonalcoholic fatty liver disease and cholelithiasis. Mass spectrometry showed decrease the total amount of free bile acids (choloidal, chenodeoxycholic, deoxycholic) and increase the content of conjugated bile acids (glycocholic, glycodesoxycholic, taurocholic, taurodeoxycholic, ursodeoxycholic), the most pronounced in patients with nonalcoholic fatty liver disease. Conclusion. Unidirectional changes in the spectrum of bile acids in nonalcoholic fatty liver disease and cholelithiasis give reason to believe that the trigger mechanism in the disturbance of bile acids metabolism is the liver. Reduction of primary bile acids, imbalance of phospholipids and cholesterol disrupt the stabilization of bile, resulting in unfavorable conditions in the bile ducts to form stones.

Terapevticheskii arkhiv. 2019;91(2):48-51
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Possibilities of therapeutic correction of hyperammonemia and minimal hepatic encephalopathy in patients with chronic hepatitis C at the pre-cirrhotic stage

Buyeverov A.O., Bogomolov P.O., Mayev I.V., Matsievich M.V., Uvarova O.V.


Aim. Study of the social consequences of cognitive disorders in minimal hepatic encephalopathy (MHE) in patients with chronic genotype 1 hepatitis C and the possibilities of their pharmacological correction with L-ornithine-L-aspartate (LOLA, Hepa-Merz). Materials and methods. The study group included 60 male patients diagnosed with chronic hepatitis C, genotype 1 with fibrosis stage F1 according to the METAVIR scale, and presented with MHE. The average age of the patients was 34.2±5.3 years. The control group included 20 healthy men aged 34.1±5.8 years without liver disease. Intermittent treatment with LOLA was given to the study group at 15 g once daily in the morning for 2 months with 2-month off-treatment intervals, with the total treatment duration of 12 months. In the course of treatment, MHE dynamics was assessed using the critical flicker fusion frequency (CFF) test and the number connecting test (NCT), as well as by serum concentrations of ammonium ion. The LOLA efficacy endpoint was the change in the frequency of violations of traffic rules (traffic code). Results and discussion. A significant decrease in the concentration of ammonium ion was observed after 5 months of treatment (135.53 and 82.9 μmol/L, p=0.002) and maintained throughout the study. The results of the CFF test significantly improved by the end of the 1st month of LOLA treatment (p=0.008), remaining at the achieved level for 9 months. The NCT parameters reached their minimum values after 5 months (p<0.001) and remained at this level throughout the study. During the study period, the frequency of traffic code violations by participants decreased from 60 to 40% (р=0.03). Conclusion. Fractional treatment with LOLA leads to a decrease in the blood concentration of ammonium ion and, consequently, to an improvement in psychometric test results and a decrease in the frequency of traffic code violations. The result achieved can have an impact on the accident rate reduction.
Terapevticheskii arkhiv. 2019;91(2):52-58
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Risk factors of unfavorable prognosis of chronic hepatitis C

Shchanitcyna S.E., Burnevich E.Z., Nikulkina E.N., Filatova A.L., Moiseev S.V., Mukhin N.A.


Aim. To investigate risk factors of unfavorable prognosis in patients with chronic hepatitis C (CHC), including liver cirrhosis (LC), decompensated cirrhosis, hepatocellular carcinoma (HCC), cryoglobulinemic vasculitis (CryoVas) and B-cell non-Hodgkin’s lymphoma. Materials and methods. This was a retrospective study using data of 824 patients with CHC hospitalized between 2010 and 2016 in clinic named after E.M. Tareev. We used multivariate analysis including logistic regression to calculate odds ratios (ORs) for potential risk factors/predictors associated with unfavorable outcomes in patients with CHC. Results and discussion. The rate of LC, decompensated LC, HCC, serious CryoVas and B-cell lymphoma in patients with CHC was 39.1% (322/824), 14.0% (115/824), 2.8% (23/824), 5.2% (43/824) and 1.2% (10/824), respectively. After adjustment for sex and age the rate of LC, decompensated LC, HCC was 22.8, 8.0 and 1.5%, respectively. Annual rate of LC in patients with CHC was 1.5%; in cirrhotic patients annual rate of decompensated LC and HCC was 2.9 and 1%, respectively. Risk factors independently associated with development of LC were elevated body mass index (OR 1.43), immunosuppressive therapy (OR 1.67), diabetes type 2 (OR 2.03), absence of antiviral therapy (OR 2.15), alcohol abuse (OR 2.34), duration of infection ≥20 years (ОR 2.74) and an absence of sustained virological responce (SVR) (OR 2.98). Independent risk factors for decompensation in cirrhotic patients included diabetes type 2 (OR 1.47), alcohol abuse (OR 1.53), an absence of antiviral therapy (OR 2.36) and an absence of SVR (OR 1.94). An episode of decompensation was the independent predictor of HCC in cirrhotic patients (OR 3.99). Genotype 1b (OR 1.66) and an absence of antiviral therapy (OR 3.31) were independently associated with serious CryoVas. Two prognostic scales were offered for risk evaluation of LC and its complications. Conclusions. Multivariate analysis showed several factors independently associated with higher risk for LC, decompensation of LC, HCC, serious CryoVas in patients with CHC. The rate of unfavorable outcomes of CHC is found, including rare extrahepatic manifestations.
Terapevticheskii arkhiv. 2019;91(2):59-66
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Prognosis factors of survival in patients with liver cirrhosis and portal hypertension

Olevskaya E.R., Dolgushina A.I., Tarasov A.N., Hihlova A.O.


Aim. To study prognostic factors for survival in patients of liver cirrhosis (LC) with portal hypertension (PG). Materials and methods. 155 patients (women - 49.4%, men - 50.6%, median age 56.4 years [51.3; 61.6]) were follow up for 36 months. Viral LC was diagnosed in 33.8%, alcohol LC - 22.1%, autoimmune LC - 15.6%, other causes and cryptogenic causes noted in - 28.5%. More than half of the patients had a class В of Child-Pugh (51.9%). Results and discussion. During the study period 42 patients (28.3%) died. The analysis of survival by various factors for Kaplan-Mayer was carried out. Significant predictors: Child-Pugh class, LC etiology, comorbidity in Charlson scores, adherence to endoscopic treatment of esophageal varices were included in the model of proportional Cox risks. In a single-factor analysis, the risk of death is higher in patients who violate the timing of endoscopic treatment, but this factor has lost significance in the multifactor model. Patient with Child-Pugh C, alcoholic LC, comorbidity more 5 points by Charlson score have a higher mortality risk. Conclusion. Identification of risk factors that affect the survival of LC patients will allow to use of an individual plan for the LC treatment and prevention of PG complications.
Terapevticheskii arkhiv. 2019;91(2):67-72
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Risk factors associated with portal vein thrombosis in liver cirrhosis: A case-control study

Nadinskaia M.Y., Kodzoeva K.B., Ulyanova K.A., Rogacheva S.I., Volkova A.S., Dekhanov A.S., Strelkova D.A., Ivashkin V.T.



Background. Portal vein thrombosis (PVT) in patients with liver cirrhosis is a common complication associated with adverse outcomes. The aim of the study was to build a predictive model for PVT in cirrhotic patients.

Materials and methods. A single centre case-control study was carried out. From the database of 1512 cirrhotic patients 94 with newly diagnosed PVT based on contrast-enhanced computed tomography were referred to the Case group. Malignant PVT was an exclusion criterion. Patients without PVT were stratified and matched according to sex, age and etiology of cirrhosis; case-control ratio was 1 : 3-4. The prevalence of PVT in the database, clinical, laboratory, instrumental parameters of the groups were evaluated. Logistic regression model was used to estimate association between variables and PVT.

Results. The overall prevalence of PVT was 6.2% with the highest rates among the patients with HBV infection – 16.7%, nonalcoholic steatohepatitis – 15.6%, alcohol abuse in combination with HCV infection – 11.7%. The best predictive model included variables: Child-Pugh classes B-C (coefficient of regression b=1.853, р=0.001), ascites (b=0.460, р=0.003), hepatocellular carcinoma without vascular invasion (b=2.126, р=0.0001), endoscopic band ligation (b=0.774, р=0.003), transabdominal esophagogastric devascularization procedure (b=2.734, р=0.001), portal hypertensive gastropathy (b=0.793, р=0.017), portal vein diameter (b=0.203, р=0.004), and local factors – ulcerative colitis flare, Clostridium difficile enterocolitis, spontaneous bacterial peritonitis, colorectal cancer, splenectomy, cholecystectomy (b=2.075, р=0.017). The model had accuracy 85.8% (95% CI 81.7-89.4%), sensitivity – 55.1% (95% CI 43.4-66.4%), specificity – 95% (95% CI 91.6-97.3%), and AUC – 0.871 (95% CI 0.826-0.916).

Conclusion. Child-Pugh classes B-C, severe portal hypertension, hepatocellular carcinoma without vascular invasion, and local factors were estimated as risk factors of PVT in cirrhotic patients.

Terapevticheskii arkhiv. 2019;91(2):73-81
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The state of the immune system in abdominal sepsis

Koshelev R.V., Vatazin A.V., Zulkarnayev A.B., Faenko A.P.


Sepsis is a serious condition characterized by a complex dysfunction of internal organs and systems. In the basis of the pathogenesis of sepsis, the leading role is played by the dysregulation of the immune response to the infectious agent, in particular endotoxin of gramnegative bacteria, which is an obligate lipopolysaccharide of the bacterial wall. Aim. To evaluate the prognostic value of cytokine profile, phagocytosis activity indices, endotoxin concentration and activity in blood in gram-negative sepsis. Materials and methods. 78 patients with abdominal sepsis were included in a one-center prospective cohort study, of them 45 died. All the patients were evaluated for the concentration of circulating cytokines (TNF-α, IFN-γ, IL-6, IL-8, IL-10), cellular molecules (CD3, CD45RO, CD95 and HLA-DR), bactericidal and phagocytic activity of neutrophils and endotoxin (lipopolysaccharide) level in peripheral blood. Results and discussion. The concentrations of all cytokines were slightly lower in the survivors. Significant differences were noted for TNF-α (p=0.001), IL-6 (p=0.001), and IL-8 (p=0.007). The expression of HLA-DR molecules was slightly higher (p=0.055), and CD95 was lower (p=0.146) in survivors than in the dead. However, the differences have not reached the required level of statistical significance. The phagocytic (p<0.001) and bactericidal activity (р=0.002 for stimulated activity and p=0.001 for spontaneous activity) of neutrophils is significantly different. In survived patients, we noted large values of stimulated bactericidal activity and phagocytic index than the dead. Level of spontaneous activity in survivors was lower. In subsequently deceased patients, the level of endotoxin load was higher than in the surviving patients: level of lipopolysaccharide concentration (p=0.002), endotoxin activity (p=0.032) and neutrophils activity (p=0.028). Conclusion. Evaluation of cytokine levels is informative, but due to the high spread of indicators in different patients, should be carried out in the dynamics. The most informative prognostic parameters in sepsis are the concentration and activity of lipopolysaccharides (endotoxin), phagocytic and bactericidal activity of neutrophils. The EAA (endotoxin activity assay) assessment should be conducted in conjunction with the neutrophil "response" assessment.
Terapevticheskii arkhiv. 2019;91(2):82-86
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Celiac disease associated with ulcerative colitis

Krums L.M., Babaian A.F., Bykova S.V., Lishchinskaia A.A., Khomeriki S.G., Gudkova R.B., Sabel'nikova E.A., Kniazev O.V., Parfenov A.I.


The article provides clinical observation of a patient who was diagnosed with celiac disease when he was 52 years (Marsh stage IIIB). Following gluten-free diet (GFD) clinical remission and restoration of small intestinal mucosa (SIM) structure occurred, however in 6 years ulcerative colitis developed and an impairment of SIM morphological structure was identified (Marsh stage IIIA). Ulcerative colitis and celiac disease remission is supported by GFD, anti-cytokine therapy (adalimumab) in combination with mesalazine.
Terapevticheskii arkhiv. 2019;91(2):87-90
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Capsule endoscopy for diagnosis of celiac disease

Alimetov A.Y., Poliakov P.P., Onopriev A.V., Avakimyan A.V., Zanin S.A., Kade A.K.


In this review we analyzed the guidelines for diagnosis and management of celiac disease, as well as the recent studies published on this issue. Capsule endoscopy could be used in patients unwilling or unable to undergo conventional endoscopy, in patients who have discordant results between serological and histopathological investigation, in patients with nonresponsive or refractory celiac disease.
Terapevticheskii arkhiv. 2019;91(2):91-96
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MutYH-associated polyposis

Toboeva M.K., Shelygin Y.A., Frolov S.A., Kuzminov M.A., Tsukanov A.S.


MutYH-associated polyposis is the only polyposis syndrome with an autosomal recessive type of inheritance, often phenotypically similar to a weakened form of familial adenomatous polyposis. For the development of the disease mutations in both alleles of the gene are required, but an increased risk of developing colorectal cancer in carriers of monoallelic mutations is noted. The diagnosis of MutYH-associated polyposis should be suspected in a patient with colorectal cancer over 45 years old on the background of polyps in the colon. The review presents modern algorithms for diagnostic and treatment of the disease.
Terapevticheskii arkhiv. 2019;91(2):97-100
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The use of Tofacitinib in the treatment of inflammatory bowel disease

Nasonov E.L., Abdulganieva D.I., Fairushina I.F.


Major advances in pharmacology of the 21st century include the development of a new class of drugs, which are low-molecular, chemically synthesized molecules (the so-called "small molecules"), the point of application of which is Janus kinase (Janus kinase, JAK) involved in intracellular cytokine signaling. The review examines the molecular aspects of the JAK-STAT signaling pathway, justifying the use of the JAK-kinase inhibitor (tofacitinib) in the treatment of inflammatory bowel disease.
Terapevticheskii arkhiv. 2019;91(2):101-108
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Non-alcoholic fatty liver disease as a cause and consequence of cardio-metabolic complications. Role of the ursodeoxicholic acid in the pharmacotherapy

Maevskaya M.V., Ivashkin V.T., Ivashkin K.V., Lunkov V.D., Liusina E.O., Zozula V.N., Leshchenko V.I.


The article presents an update of the role of non-alcoholic fatty liver disease (NAFLD) in cardiometabolic diseases and events: arterial hypertension and components of the metabolic syndrome. A review of NAFLD modern pharmacotherapy has been conducted. Particular attention is paid to the place of ursodeoxycholic acid in the complex treatment of NAFLD.
Terapevticheskii arkhiv. 2019;91(2):109-117
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Vitamins in diet of patients with metabolic syndrome

Kodentsova V.M., Risnik D.V., Sharafetdinov K.K., Nikityuk D.B.


Aim - analysis of data on the role of vitamin and carotenoid deficiency in the development of metabolic syndrome (MS), the consumption of individual vitamins and vitamin supplements, as well as estimation of the effectiveness of the use of vitamins in patients with MS. A review of the existing literature has been carried out in the databases of RINC, CyberLeninka, Google Scholar, Pubmed. The lack of vitamins is a risk factor for MS and its components. The diet of people with MS is characterized by excessive caloric content and at the same time contains an inadequate amount of most vitamins. The most frequent in patients with MS is the deficiency (blood level) of vitamin D, E, B vitamins, carotenoids. Among patients with MS, individuals with a reduced concentration of vitamins in the blood plasma are often found. In turn, among those with a deficiency of vitamins, MS is more often found. Low concentrations of 25(OH)D in the serum are associated with an increased risk of MS. An inverse association between the concentration of the hormonal form of vitamin 1.25(OH)2D3 in the serum and the development of MC has been found. In patients with MS, the α-tocopherol concentration associated with lipids is lower than in healthy individuals, and γ-tocopherol, on the contrary, is higher. Taking high doses of one of the vitamin E homologues shifts the balance between tocopherols in the blood plasma. Sufficient supply of the body with all vitamins involved in the formation of metabolically active forms of vitamins (D, B6, PP) is a necessary condition for the exercise of these biological functions by these vitamins. The lack of vitamins is a risk factor for MS and its components. Enrichment of the diet of patients with MS should be considered as a necessary favorable background for its treatment. Since the body has functional connections between vitamins, it is advisable to use not individual vitamins, but their complexes.
Terapevticheskii arkhiv. 2019;91(2):118-125
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Phenotype of obesity and gastroesophageal reflux disease in the context of comorbidity in patients with cardiovascular diseases

Maev I.V., Yurenev G.L., Mironova E.M., Yureneva-Thorzhevskaya T.V.


The relevance of studying such problems as gastroesophageal reflux disease (GERD) and obesity is caused by their high prevalence in the developed countries of the world. Epidemiological data indicate that obesity is a significant risk factor for developing GERD due to increased intra-abdominal pressure and gastroesophageal gradient, slowing of gastric evacuation and formation of hiatal hernia. Abdominal obesity increases the likelihood of complications of GERD: erosive esophagitis, Barrett's esophagus and adenocarcinoma. This fact is connected with humoral influences: increased production of pro-inflammatory cytokines and leptin, and decreased secretion of adiponectin. Treatment of comorbid patients requires higher dosages and longer courses of antisecretory medicines, and an additional prescription of ursodeoxycholic acid.
Terapevticheskii arkhiv. 2019;91(2):126-133
pages 126-133 views

Ademethionine in the treatment of fatigue in liver diseases: a systematic review

Raikhelson K.L., Kondrashina E.A.


Fatigue has a significant effect on the condition of patients with liver disease. Ademethionine is considered one of the most promising drugs for its treatment. Aim. To systematize the published data on the treatment of hepatogenic fatigue with аdemethionine. Materials and methods. Search was performed using databases PubMed, EMBASE, Embase®, Medline®, eLIBRARY.ru, published in 1952-2018. Results and discussion. 16 articles were found on the use of ademethionine in liver diseases and the assessment of the dynamics of the symptom of fatigue, including 1 double-blind, randomized, placebo-controlled study, 3 open randomized studies; most of the works were multicenter open observation programs. The studies included 3238 patients (of which 2820 were included in the final data analysis) and a wide range of liver diseases: alcoholic liver disease, nonalcoholic fatty liver disease, primary biliary cholangitis, primary sclerosing cholangitis, cirrhosis of different causes, viral hepatitis, drug-induced liver injury. Different doses, routes of administration of аdemethionine and the duration of the course were used. Conclusions. Ademethionine, regardless of the route of administration, is effective in the treatment of fatigue due to different liver disease in the short and long term. The dose-dependent effect of the drug and the possibility of maintaining post-effect after end of the treatment course should be assumed, but this requires further study in randomized clinical trials.
Terapevticheskii arkhiv. 2019;91(2):134-142
pages 134-142 views

Role of intestinal microbiota in the formation of non-alcoholic fatty liver disease

Akhmedov V.A., Gaus O.V.


The article provides an overview of modern views on the role of intestinal microbiota in the formation of non-alcoholic fatty liver disease. The general questions of the pathogenesis of the syndrome of excessive bacterial growth in the intestine, the participation of opportunistic microflora, the deficit of representatives of normal microflora, changes in the species composition of bile acids in the pathogenesis of nonalcoholic fatty liver disease are considered.
Terapevticheskii arkhiv. 2019;91(2):143-148
pages 143-148 views

Gene therapy of type 2 diabetes mellitus: state of art

Stafeev Y.S., Menshikov M.Y., Parfyonova Y.V.


Type 2 diabetes mellitus (T2DM) and other metabolic diseases are essential links in the structure of morbidity and mortality in the modern world. The accepted strategy for the correction of T2DM and insulin resistance is drug therapy aimed at delivering insulin from the outside, stimulating the secretion of own insulin and reducing the concentration of blood glucose. However, modern studies demonstrate a great potential for the use of gene therapy approaches for the correction of T2DM and insulin resistance. In the present review, the main variants of plasmid gene therapy of T2DM using the genes of adiponectin and type 1 glucagon-like peptide, as well as the main variants of viral gene therapy of T2DM using the genes of type 1 and leptin are considered. T2DM gene therapy is currently not ready to enter into routine clinical practice, but, subject to improvements in delivery systems, it can be a powerful link in combination therapy for diabetes.
Terapevticheskii arkhiv. 2019;91(2):149-152
pages 149-152 views

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