[The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities].

The National Consensus was prepared with the participation of the National Medical Association for the Study of the Multimorbidity, Russian Scientific Liver Society, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians, National Society for Preventive Cardiology, Professional Foundation for the Promotion of Medicine Fund PROFMEDFORUM. The aim of the multidisciplinary consensus is a detailed analysis of the course of non-alcoholic fatty liver disease (NAFLD) and the main associated conditions. The definition of NAFLD is given, its prevalence is described, methods for diagnosing its components such as steatosis, inflammation and fibrosis are described. The association of NAFLD with a number of cardio-metabolic diseases (arterial hypertension, atherosclerosis, thrombotic complications, type 2 diabetes mellitus, obesity, dyslipidemia, etc.), chronic kidney disease and the risk of developing hepatocellular cancer were analyzed. The review of non-drug methods of treatment of NAFLD and modern opportunities of pharmacotherapy are presented. The possibilities of new molecules in the treatment of NAFLD are considered: agonists of nuclear receptors, antagonists of pro-inflammatory molecules, etc. The positive properties and disadvantages of currently used drugs (vitamin E, thiazolidinediones, etc.) are described. Special attention is paid to the multi-target ursodeoxycholic acid molecule in the complex treatment of NAFLD as a multifactorial disease. Its anti-inflammatory, anti-oxidant and cytoprotective properties, the ability to reduce steatosis an independent risk factor for the development of cardiovascular pathology, reduce inflammation and hepatic fibrosis through the modulation of autophagy are considered. The ability of ursodeoxycholic acid to influence glucose and lipid homeostasis and to have an anticarcinogenic effect has been demonstrated. The Consensus statement has advanced provisions for practitioners to optimize the diagnosis and treatment of NAFLD and related common pathogenetic links of cardio-metabolic diseases.

[Rebamipide using in gastroesophageal reflux disease treatment].

Rebamipide is a mucoprotective drug which was developed in Japan in 1990. The therapeutic effect of rebamipide based on the induction of cyclooxygenase-2 and increasing level of prostaglandins, inhibition of oxygen free radicals production, epidermal growth factor stimulation, vascular endothelial growth factor, nitric oxide, and decreasing of lipid peroxidation and neutrophils migration. The combination of proton pump inhibitors and rebamipide is more effective in relieving of gastroesophageal reflux disease symptoms and reducing recurrence rate of disease. Using rebamipide in the treatment of gastroesophageal reflux disease is justified because this drug has a unique mechanism of action, which eliminating the main stages of pathogenesis of the disease.

Risk factors associated with portal vein thrombosis in liver cirrhosis: A case-control study.

AIM: 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 ß=1.853, р=0.001), ascites (ß=0.460, р=0.003), hepatocellular carcinoma without vascular invasion (ß=2.126, р=0.0001), endoscopic band ligation (ß=0.774, р=0.003), azygoportal disconnection (ß=2.734, р=0.001), portal hypertensive gastropathy (ß=0.793, р=0.017), portal vein diameter (ß=0.203, р=0.004), and local factors - ulcerative colitis flare, Clostridium difficile enterocolitis, spontaneous bacterial peritonitis, colorectal cancer, splenectomy, cholecystectomy (ß=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.

Modern achievements in the diagnosis and treatment of the refractory gastroesophageal reflux disease.

Purpose of the review to present up-to-date data on the causes, methods of diagnosis and treatment of the refractory form of gastroesophageal reflux disease (GERD). Refractory GERD is the preservation of typical symptoms of the disease and/or incomplete healing of the esophageal mucosa against the background of taking a standard dose of proton pump inhibitors (PPI) once a day for 8 weeks. The reasons for the lack of response to the treatment are divided into related to the patient, related to therapy, and not related to GERD. Diagnostic approaches include x-ray examination of the esophagus and stomach, endoscopy with biopsy, 24-hour Impedance-pH monitoring, esophageal manometry. Depending on the reasons for the lack of response to the therapy, treatment may include lifestyle changes, doubling the dose of PPI, replacing PPI with another, adding H2-receptor antagonists, prokinetics, antacids, alginates and adsorbents. If conservative treatment is ineffective, it is possible to consider alternative methods, such as surgical treatment. Refractory GERD is a serious clinical problem. The absence of an answer to 8-week therapy with PPI requires a thorough differential diagnosis using additional examination methods. The identification of the causes of refractory to the therapy allows to optimize the approaches to its overcoming and to choose the optimal treatment.

[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.

[[Current approaches to diagnosing and treating nonalcoholic fatty liver disease].

Nonalcoholic fatty liver disease (NAFLD) is associated with major cardiovascular risk factors, such as type 2 diabetes mellitus, obesity, dyslipidemia, hypertension, and insulin resistance, and has been recently considered to be a new component of metabolic syndrome and it serves as a criterion for the hepatic manifestation of the latter. The review considers the present-day views and approaches to diagnosing and treating NAFLD and its dangerous manifestation - fibrosis (sclerosis), which may lead to cirrhosis and hepatocellular carcinoma. Fibrogenesis is a widespread and universal process that is a final path of chronic inflammation of and damage to different tissues (including those of the liver and cardiovascular system). Although the mechanisms for developing NAFLD remain unclear, insulin resistance, an obesity-related slowly progressive inflammatory response, and elevated levels of free fatty acids with their lipotoxicity along with possible genetic, dietary, and environmental (lifestyle) factors play a key role in the pathogenesis of this disease. So it is important for patients at high risk for NAFLD or with existing liver disease to pay attention to their life style, proper balanced diet, and slow and gradual weight loss. At present there are drugs that can improve liver function. Success in NAFLD therapy will be determined by the identification of the most significant pathogenetic factors in a specific patient and by the purposeful action on them.

[Pharmacotherapy of portal hypertension and its complications: analysis of efficacy of preparations for clinical practice and discussion of promising methods of treatment].

Bleeding from oesophageal varicose veins is the terminal stage of a sequence of complications of liver cirrhosis caused by progressive fibrosis, circulation blockade, and development of portal hypertension syndrome followed by collateral shunt. It leads to progressive vein dilation and their rupture. The main issue of today is to prevent the development of successive stages of portal hypertension, to search for therapeutic and surgical methods for marked reduction of pressure in the portal system, and to prevent the risk of hemorrhage from varicose veins. Another approach is to use local endoscopic treatment of varicose veins for prevention of their rupture. The authors analyse the efficacy of pharmacotherapy in patients with liver cirrhosis and portal hypertension and discuss the existing recommendations on the prevention of hemorrhage with special reference to the yet unsolved problems and prospects for the improvement of therapy.

[The prevalence of liver and gallbladder pathologies in overweight and obese patients].

This paper reports data on the prevalence of liver and gallbladder pathologies in ovenrweight and obese patients based on the examination of 1506 subjects (684 men, 820 women) aged 25-65 years. Changes in the liver and gall bladder constituted principal pathology of the gastrointestinal tract associated with excessive body mass and obesity. Body mass index (BMI) positively correlated with triglyceride, VLDLP and HDLP cholesterol levels (p = 0.001). 39.5% of the obese patients had elevated plasma triglyceride levels. Insulin resistance was diagnosed in 76% of the patients with morbid obesity (56.2% in grade II obesity and 51.4 in grade I obesity vs. 15.2% in controls). The occumrrence of insulin iresistance increased with BMI (p = 0.0001). Nonalcoholic fatty liver disease was diagnosed using hepatic elastography and senrum markers (FibroMax and SteatoScreen tests). Non-alcoholic steatohepatitis was foumnd in 6.74% of the overweight patients and in 13.1% of those with obesity The occurrence of this condition in obese patients increased with BMI (10.1, 14.3. 14.9% in grade I, II and III obesity respectively). 6.7% of the patients with excessive body mass and 11.6% with obesity had signs of cholelithiasis in their medical histories.

[Syndrome of extrahepatic portal hypertension and chronic abdominal ischemia in patient with subleukemic myelosis and congenital immunodeficiency].

The article demonstrates objective difficulties and subjective mistakes in assessment of a clinical picture in a patient with subleukemic myelosis and thrombosis of the portal system. A careful examination of such patients is necessary to reveal latent disorders (in this case--a complete selective IgA deficiency) influencing treatment policy.

[The scope of clinical applications of noninvasive methods for the assessment of liver fibrosis results of orginial studies in a multi-field hospital].

Potential and limitations of non-invasive methods for the evaluation of hepatic fibrosis are discussed (hepatic elastography, fibrotest, ultrasound dopplerography of portal vessels). Each non-invasive method was assessed in terms of threshold values it provides for the characteristic of successive stages ofhepatic fibrosis. The data obtained were used to develop the optimal algorithm for the diagnosis of hepatic fibrosis in patients with chronic viral liver infection.

[The peculiarities of the clinical picture and the effectiveness of antiviral therapy of chronic hepatitis related to alcohol consumption plus hepatitis C virus effect].

The purpose of this study was to describe the features of chronic hepatitis when the damaging action of alcohol was combined with that of hepatitis C virus, and to investigate the effectiveness of combined antiviral therapy in this category of patients. The study showed that patients with chronic hepatitis of combined ethiology (alcohol plus HCV) had higher biochemical and histological activity of the disease, as well as certain histological features. The effectiveness of combined antiviral therapy was comparable in both alcohol consumers and non-consumers with hepatitis C, which makes it possible to consider the former category as candidates for antiviral treatment under the condition that they follow doctor's recommendations and abstain from alcohol consumption.

[The peculiarties of nitric oxide synthesis in patients after coronary bypass surgery].

Nitric oxide (NO) participates in many physiological processes including those taking place in the cardiovascular system. The peculiarities of NO synthesis in patients after coronary bypass surgery were studied. The systems of NO generation responded in different ways. Changes in the levels of end-products of NO metabolism may be used as an additional prognostic criterion of the course of the postoperative period. The study found a direct correlation between the levels of end-products of NO metabolism and left ventricular ejection fraction as well as a reverse correlation between the level of end-products of NO metabolism and atherogenic lipids.

[Methods of early diagnostics of hepatic fibrosis and cirrhosis].

The article covers the functional and clinical importance of hepatic fibrosis. Contemporary principles of invasive and non-invasive diagnostics of fibrotic changes are described. The article deals with the main types of fibrosis, chronic hepatic diseases in which they develop, and the most wide-spread systems of semiquantitative evaluation of fibrotic process' morphologic signs.

[Apoptosis of peripheral blood mononuclears and evaluation of the effectiveness of antiviral therapy of chronic C hepatitis].

The effects of combined antiviral therapy on the apoptosis of peripheral blood mononuclears (PBM) were investigated in 54 patients with chronic hepatitis C (CHC), including patients with chronic viral-and-alcohol hepatitis (CVAH). Simultaneously, serum concentrations of cytokines (tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukins 10 and 12) using flow cytofluorimetry were taken. The results demonstrate an increase in the intensity of PBM apoptosis in patients with CHC and CVAH vs. controls; there was a tendency of lesser apoptosis intensity in the CVAH subgroup. In both groups IFN-gamma and TNF-alpha concentrations were increased, and there was a direct correlation between the level of apoptosis and TNF-alpha concentration. The study found an increase in the intensity of apoptosis in CHC patients with primary virological response to antiviral therapy with IFN-alpha and riboflavin, which can be considered an additional prognostic factor of the effectiveness of treatment.

[Connective tissue dysplasia syndrome in cardiological practice]. / Sindrom displazii soedinitel'noi tkani v praktike vracha-kardiologa.

Ehlers-Danlos syndrome was diagnosed in an elderly patient who had been long observed as a patient with ischemic heart disease, then dilated cardiomyopathy. Ehlers-Danlos is a rare type of connective tissue dysplasia syndrome.

[The role of Fas/FasL system in induction of hepatocyte apoptosis in chronic viral hepatitides]. / Rol' sistemy Fas/FasL v induktsii apoptoza gepatotsitov pri khronicheskikh virusnykh gepatitakh.

The aim of the study was assessment of hepatocyte apoptosis depending on expression of Fas and FasL proteins by various liver cells in patients with chronic viral hepatitis B (CVHB) or chronic viral hepatitis C (CVHC). The symptoms of hepatocyte apoptosis were observed in 3 of 12 patients with CVHB and in 9 of 14 patients with CVHC, the proportion of apoptotic cells being 12-65%. Hepatocytes of healthy people and patients with hepatitis B or C express Fas protein in the cytoplasm diffusely, as granules or on cell membrane. In health, hepatocytes do not express FasL, but in CVH they do. The highest apoptosis was observed in Fas protein location as granules in cytoplasm or in their preferable location on the cell membrane. The severity of hepatocyte apoptosis in CVH directly correlated with FasL expression by the cells of the lymphoid-histiocytic infiltrate in the liver and inversely correlated with FasL expression by hepatocytes. Thus, a great part of hepatocytes in CVH are killed by the virus; Fas/FasL interaction is leading in damage to hepatocytes in CVH.

[The role of apoptosis and proliferation of epitheliocytes in morphogenesis of Helicobacter pylori-associated gastritis]. / Rol' protsessov apoptoza i proliferatsii épiteliotsitov v morfogeneze Helicobacter pylori-assotsiirovannogo gastrita.

77 patients with chronic Helicobacter gastritis verified endoscopically and exacerbation of duodenal ulcer were examined. H. pylori infection was identified by the rapid ureasa test (CLO-test) and Giemza staining. The patients received 7-day three-component therapy for eradication of H. pylori. Apoptosis and proliferation were studied in 16 patients in serial sections with the use of monoclonal antibodies. Eradication of H. pylori resulted in relief of inflammation and transformation of active gastritis in inactive one. H. pylori-associated gastritis is associated with activation of apoptosis of gastric mucosa epithelial cells and epitheliocytes proliferation. H. pylori eradication alters correlation between apoptosis of epitheliocytes and their proliferation: successful eradication of the infection decreases apoptosis, high proliferative activity of epitheliocytes persists reflecting enhancement of regeneration in gastric mucosa.

[Cytokine system in patients with chronic hepatitis C during treatment with interferon-alfa]. / Sistema tsitokinov u bol'nykh khronicheskim gepatitom C pri lechenii interferonom-al'fa.

AIM: To study changes in serum levels of interleukine-1 beta (IL-1b), IL-6, TNF-alpha (TNFa), HM-HMF and TFR-1 beta (TFR-1b), expression of surface antigens CD14 and CD95 on blood monocytes from patients with chronic hepatitis C (CHC) treated with interferon-alpha (INFa). MATERIAL AND METHODS: Examinations covered 25 CHC patients and 25 healthy controls. Concentrations of proinflammatory cytokines and growth factors in blood serum were measured with ELISA (kits by "R&D systems", USA). CD14 and CD95 antigen expression on monocytes of venous blood were studied using flow cytoflowmeter (Partes, USA) before and after a 12-week course of INFa. RESULTS: Before INFa treatment CHC patients had significantly elevated serum concentrations of TNFa, HM-KSF and TFR-1b. Coexpression of antigens CD14+ and CD95+ was found on 61% of blood monocytes. Three-month INFa treatment lowered levels of TNFa, GM-KSF and CD95+ expression on monocytes as well as TFR-1b concentration in the serum which correlated with a positive trend in the standard clinicolaboratory and virusological indices in the examinees. CONCLUSION: Changes in serum indices of proinflammatory cytokines and growth factors, in expression of CD95 on blood monocytes from CHC patients treated with INFa show an important role of cytokines system activation and mechanisms of programmed cell death in pathogenesis of chronic HCV infection.