ESOPHAGEAL AND GASTRIC DISEASES
According to the Maastricht VI consensus, the triple therapy (PPI + clarithromycin + amoxicillin) and bismuth-based quadruple therapy (PPI + bismuth + tetracycline + metronidazole) are considered and may be proscribed empirically as first-line regimens in the regions with low clarithromycin resistance rates (<15%). In the regions with high clarithromycin resistance rates (> 15%), as well as in the regions with unknown resistance to this antibacterial agent, it is recommended to use classical quadruple therapy with bismuth drugs as the main choice and quadruple therapy without bismuth drugs (“simultaneous” or “concomitant”) as an alternative. The second-line regimens of empiric choice (when antimicrobial susceptibility testing is not available) include fluoroquinolone-based quadruple therapy (PPI + levofloxacin + amoxicillin + bismuth) or fluoroquinolone-based triple therapy (PPI + levofloxacin + amoxicillin) and bismuth-based quadruple therapy. The Maastricht VI consensus regulates the use of rifabutin-based triple therapy (PPI + amoxicillin + rifabutin) as a “rescue” therapy, if the above ET schemes are ineffective and there is no possibility to conduct an antimicrobial susceptibility test. In its latest clinical guidelines, the Russian Gastroenterological Association (RGA) recommends with a view to achieving maximum treatment efficiency during classic triple ET and levelling the risk of further progression of clarithromycin resistance in Russia to take additional measures to increase its effectiveness (detailed instruction of a patient and control over strict adherence to the prescribed regimen, prolonging the course up to 14 days; prescribing PPI at increased dose twice a day; the latest generation PPIs (rabeprazole and esomeprazole); adding bismuth tripotassium dicitrate (240 mg 2 times a day) to the standard triple therapy; adding cytoprotector rebamipide (100 mg 3 times a day) to the standard triple therapy; adding a probiotic with proven efficacy to the standard triple therapy within controlled studies).
Introduction. In recent decades, there has been a decrease in the prevalence of peptic ulcer (PU), but this trend does not correlate with the frequency of bleeding and mortality from PU: the disease remains the main cause of bleeding with a high mortality rate.
Aim. To study the predictors of urgent complications of PU, using endoscopic, laboratory and clinical signs of gastric bleeding.
Materials and methods. Observational cross-sectional (one-stage) study of 181 hospital patients diagnosed with ulcerative disease (84 men, 97 women), mean age 53 ± 27.6 (18–89) years. The stratification of endoscopic characteristics of ulcerative defects of the mucous membrane of the stomach and duodenum (DU) was carried out according to the Clinical guidelines “Diagnosis and treatment of PU in adults (2020)”, bleeding assessment – according to the Forrest classification (1974), selection of patients’ age by periods: 18–35 years (young age); 36–59 years (average age); 60–74 years old (old age); 75–89 years old (old age).
Results. The results of studies have shown that the potential for ulcer bleeding is increased in the presence of the following factors. An increase in the patient’s age (the proportion of middle age is 44.2%, the elderly – 35.4%) and male gender. Duration of ulcer history (46.9%), H. pylori-positivity (74.6%); comorbidities requiring anticoagulants, antiplatelet agents and non-steroidal anti-inflammatory drugs (NSAIDs) (70.1%), the presence of two or more risk factors (20.4%).
Conclusion. Not only predictors of urgent complications of PU have been established, but also a dissonance indicating a high frequency of occult bleeding in the disease. The frequency of laboratory symptoms of anemia – 55.8%; endoscopic signs – 19.3%, including stigmata of a high risk of rebleeding – 14.3%; clinical symptoms of gastric blood loss – 14.4%. The risk of complications and mortality is associated with both frequent latent course and escalation of NSAID consumption.
The prevalence of GERD in most European countries and the Russian Federation is at the level of 15–20%. Hydrochloric acid plays a significant and sometimes major role in damage to the mucosa of the upper gastrointestinal tract (GIT) in patients with various acid-related diseases. Despite the presence of various classes of drugs that reduce the damaging effect of hydro-chloric acid on the mucous membrane of the upper gastrointestinal tract, acid-related diseases continues to be an urgent medical problem. The review article discusses the issues of pharmacological treatment of acid-related diseases. Such classes of drugs as antacids, H2-histamine blockers, gastroprotectors, potassium-competitive blockers of hydrochloric acid secretion are described in detail. Particular attention is paid to the group of proton pump inhibitors (PPIs). The paper evaluates the merits of each class of drugs, their significance in the treatment of acid-related diseases. One of the most popular PPIs in the Russian Federation is omeprazole. The effectiveness of the drug is determined by pharmacokinetic parameters, in particular bioavailability. The bioavailability of omeprazole of various trade names varies widely. To increase the rate and completeness of dissolution, and hence the bioavailability of poorly soluble molecules in the modern pharmaceutical industry, various disintegrants are used as excipients. The addition of sodium superdisintegrant carboxymethyl starch to the new Omez® dosage form with MiniCaps technology promotes an accelerated and more complete intake of omeprazole into the systemic circulation, helping to increase bioavailability. In addition, the innovative dosage form has a volume that is 30% smaller than the classic capsule, which improves ease of use and adherence to treatment.
Introduction. The high frequency of complicated forms of the stomach and duodenum peptic ulcer (PU) in patients with atherosclerosis requires the study of additional factors of ulcerogenesis in addition to infection with Helicobacter pylori (H. pylori) and the use of non-steroidal anti-inflammatory drugs (NSAIDs). Currently, there is no clear understanding of the role of mesenteric artery (MA) atherosclerosis in the development of gastroduodenal ulcers.
The purpose of the study. To evaluate the contribution of MA atherosclerosis to the development of gastric and duodenal ulcer in patients with multifocal atherosclerosis.
Material and methods. The study included 91 patients with atherosclerosis of two or more vascular beds in the period from 2019 to 2021. The examination included the determination of the gastrin-17, pepsinogen I, pepsinogen II and antibodies to H. pylori IgG concentration in blood serum, as well as multispiral computed tomoangiography of the abdominal aortic branches and esophagogastroduodenoscopy with histological examination.
Results. The patients were divided into two groups: group I – 36 (39.6%) patients with PU, group II – 55 (60.4%) patients without PU. A more frequent occurrence of hemodynamically significant stenosis of the MA and a higher percentage of the superior mesenteric artery (SMA) stenosis in group I were noted. A positive correlation was found between the severity of erosive and ulcerative lesions and the percentage of SMA stenosis, levels of pepsinogen I and pepsinogen II. The combination of PU and MA atherosclerosis is characterized by a lesser severity of abdominal pain syndrome (p = 0.049). Risk factors for PU were identified: MA atherosclerosis (OR 4.953; CI 1.571–15.608); more than 8 points on the HADS depression scale (OR 2.970; CI 1.062–8.320) and on the Audit questionnaire (OR 5.787; CI 1.348–24.837).
Conclusions. Risk factors for PU in patients with multifocal atherosclerosis were identified: MA atherosclerosis, subclinical depression, and health-threatening alcohol consumption. PU in patients with multifocal atherosclerosis is characterized by asymptomatic course.
Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disease characterized by occurrence of typical symptoms associated with an increase in esophageal acid exposure. The transient lower esophageal sphincter relaxations (TLESRs) and hypotension is the key pathophysiological mechanisms of the development of reflux disease. For a long time, it was assumed that certain nutritional and lifestyle factors affect the mechanisms of the onset and progress of GERD. However, the accumulated scientific findings show contradicting results regarding contribution of these factors to the development of reflux disease. The treatment of GERD requires lifestyle modifications, diet therapy, pharmacotherapy, and, if necessary, surgery. Proton pump inhibitors (PPIs) form the basis of pharmacotherapy. Lifestyle modifications, including dietary therapy, is also part of the treatment plan for patients with reflux symptoms, however no clear guidelines in this regard are determined due to the lack of good evidence base. Yet, while the problems associated with the long-term use of PPIs are explored, patients and physicians are increasingly interested in the role of diet in the treatment of GERD. The article provides an overview of the dietary aspects in GERD with a focus on nutritional components and their impact on the pathophysiology and treatment of this disease. Although sequential food-group elimination in GERD is common in clinical practice, literature data demonstrate a broader approach, including reduction of sugar intake, increase of dietary fibres in the diet, and changes in patterns of eating habits as a general principle.
Currently, proton pump inhibitors (PPIs), H2-histamine receptor blockers (H2-blockers), antacids, and anticholinergics are used to treat acid-dependent diseases of the gastrointestinal tract. PPIs are considered the most effective drugs for the treatment of acid-dependent diseases of the gastrointestinal tract. However, in real clinical practice, interest remains in the use of antacids in acid-dependent diseases. This is due to the fact that antacids not only adsorb hydrochloric acid in the gastric lumen (by buffering the HCl present in the stomach, without a significant effect on its production) and reduce the proteolytic activity of gastric juice (reducing/ neutralizing the activity of pepsin), but also have a number of other pharmacotherapeutic properties demanded by the gastroenterological patient. Antacids in addition to antisecretory action have: 1) cytoprotective, primarily gastroprotective, action, which is mediated by: a) stimulation of the synthesis of bicarbonates and prostaglandins; b) mucoprotection – an increase in the production of protective mucus by epithelial cells; c) switching of the epithelial growth factor and its concentration in the area of erosive and ulcerative defects, which in turn activates angiogenesis, cell proliferation and local reparative and regenerative processes; 2) enveloping and adsorbing action, through chelation of lysolecithin and bile acids, which have an aggressive damaging effect on the upper gastrointestinal tract; 3) regulate gastroduodenal motility due to: a) antispasmodic action and streamlining gastroduodenal evacuation; b) decrease in intracavitary pressure in the stomach and duodenum; b) obstacles to the formation of duodenogastric reflux. To date, combined preparations, the basic composition of which includes magnesium hydroxide and aluminum hydroxide, meet the basic requirements for non-absorbable antacids. In conclusion, the authors present a number of clinical situations, indicating that today rationally prescribed antacid drugs successfully and significantly solve the main tasks of symptomatic therapy of acid-dependent and other diseases of the gastrointestinal tract, significantly improving the quality of life of patients.
Helicobacter pylori infection can serve as one of indications to clarithromycin prescription. H. pylori eradication is performed commonly as a treatment for diseases caused by this pathogen and conditions with an increased risk of complications (precancerous changes of the gastric mucosa, unspecified iron deficiency anemia, idiopathic thrombocytopenic purpura, long-term NSAIDs use, anti-platelet drugs use etc). A number of H. pylori functional characteristics determines specific requirements for eradication schemes: high sensitivity of the pathogen, the ability of antibacterial drugs to penetrate and accumulate in gastric tissue and mucous,a stimulation of microorganism’s reproduction and protection of acid-resistant drugs by reducing gastric acid production as well. If the latter is provided by the use of proton pump inhibitors, then clarithromycin fully provides the other issues above. In Russia, standard triple therapy is used as the first-line treatment of H. pylori infection due to current clarithromycin resistance less than 15%. The article gives detailed reasoning and factual evidence of commitment to the first-line therapy under the increasing prevalence of the most recent antibiotic resistance (local resistance to levofloxacin has reached 20%), the high potential for multi-drug resistant H. pylori strains appearing, low ensuring medical facilities with relevant resistance test-systems, a role of generic drugs (clarithromycin and proton pump inhibitors) with compromised pharmaceutical characteristics in creation and erroneous interpretation of a pseudoresistance to clarithromycin.
Chronic gastritis is a complex, polyetiological pathology with no clear clinical presentation. The most significant etiological factor of gastritis to date is H. pylori infection. A common clinical manifestation is the dyspepsia syndrome, which is caused by impaired motility. Symptoms can significantly affect a patient’s quality of life, necessitating rapid and effective pharmacotherapy. This paper discusses the algorithm of the physician actions in the case of a patient with uninvestigated dyspepsia. PPI has significant negative impact on the accuracy of H. pylori diagnostic test results. In this regard, it is proposed to use empirical therapy with prokinetics before diagnostic test would be performed. Among the prokinetics available on the Russian market, itopride hydrochloride stands out due to its high safety profile and proven efficacy. Current evidence supports the use of the prokinetic Ganaton® (itopride hydrochloride) as empirical therapy for dyspepsia of undetermined etiology, including patients with a preliminary diagnosis of gastritis. Due to its dual mechanism of action, itopride hydrochloride alleviates dyspeptic symptoms by improving gastric evacuation and can be used for an extended period. Several studies have shown the superiority of itopride in treating functional dyspepsia compared to other prokinetics, including metoclopramide and domperidone. Thus, prescribing the prokinetic Ganaton® (itopride hydrochloride) as empirical therapy for dyspepsia of undetermined etiology, including patients with a preliminary diagnosis of gastritis, is a pathogenetically justified approach aimed at improving the patient’s condition in the short term before establishing a final clinical diagnosis.
DISEASES OF THE PANCREAS
Introduction. Dietary nutrition is a physiological therapeutic and prophylactic approach for chronic pancreatitis during an exacerbation. Given the acute reaction of patients to various foods, specialized dietary products designed specifically for this pathology are of great importance.
Aim. Evaluation of the clinical efficacy, safety and tolerability of the use of specialized therapeutic nutrition – jelly “Pancreatic” in chronic pancreatitis in the acute stage.
Materials and methods. 20 patients of the main group with pancreatitis, along with standard therapy, received a dietary food product twice a day. The dynamics of pain, dyspeptic syndromes and intestinal dysfunction syndrome was studied; dynamics of the ultrasound picture of the pancreas; intestinal motility according to carbolene test; safety and tolerability of therapy by registering side effects and assessing the quality of life according to the SF-36 questionnaire, assessing well-being according to the visual analogue scale, and the organoleptic properties of the medicinal product. The comparison group consisted of 20 patients who received only standard pharmacotherapy.
Results. The use of a dietary therapeutic food product is accompanied by a significant decrease in the frequency of nausea, belching, heaviness and flatulence in patients of the main group. The terms of relief or reduction in the intensity of symptoms of bitterness, nausea, heaviness in the abdomen, feelings of rapid satiety, flatulence were significantly lower in the main group (5–8 days compared to the control group (10–14 days). A significant normalization of GGT and CRP levels was established in the main group, while in the comparison group there was only a decrease in CRP. The ongoing complex therapy was accompanied by an improvement in the ultrasound picture of the pancreas, potentiation of the effects of pharmacotherapy and a significant improvement in the quality of life of patients.
Conclusions. The conducted studies have shown high efficiency, good tolerability and safety of the therapeutic product “Pancreatic jelly” in the treatment of patients with chronic pancreatitis. Kissel “Pancreas” is recommended by the authors for active use in patients with pancreatitis as a therapeutic diet.
DISEASES OF THE BILIARY SYSTEM AND LIVER
Ursodeoxycholic acid (UDCA) is a natural hydrophilic bile acid, which is present in humans as a small fraction of the total amount of bile acids (5%). Its unique properties underlie its use in a number of liver diseases as a first-line therapy. The ability of UDCA to reduce the secretion of cholesterol into bile, form mixed micelles (liquid crystals) with cholesterol molecules and interact with multifunctional nuclear receptors, are actively used in the treatment and prevention of cholelithiasis. UDCA has the ability to stimulate hepatobiliary secretion, promotes the secretion of bicarbonate by cholangiocytes, which is relevant for patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). UDCA activates transporter proteins such as bile acid export pump (BSEP), multiresistance protein 2 (MRP2) – conjugates transporter, type 2 anion exchanger (AE2), and promotes their movement to the canalicular membrane of cells. UDCA acts as a pleiotropic agent that plays a unique role in modulating the classical mitochondrial pathway of apoptosis in various cell types. Double molecular bonds of UDCA serve as a trap for free radicals, which suppresses the processes of lipid peroxidation. The ability of UDCA to penetrate into mitochondrial membranes leads to suppression of the activity of mitochondrial oxidase enzymes responsible for the production of superoxide anion. UDCA activates autophagy and promotes the elimination of toxic fatty acids from hepatocytes, reducing liver steatosis, UDCA has anti-inflammatory, antifibrotic, immunomodulatory and anticarcinogenic effects. UDCA is included in international and Russian clinical guidelines for the treatment of patients with various liver diseases (PBC, PSC, intrahepatic cholestasis of pregnancy, drug-induced cholestasis, alcoholic liver disease with cholestatic component), cholelithiasis, cystic fibrosis. In the pharmacotherapy of non-alcoholic fatty liver disease, UDCA is the only drug that has a bi-directional effect on the liver and cardiovascular system.
Introduction. According to the analysis of indicators of the hemostasis system in liver pathology, there are multidirectional data in the literature, which may be associated with the examination of patients with varying degrees of severity and etiology of the process.
Aim. The aim of the study was to study the indicators of hemostasis and markers of endothelial damage in patients with non-alcoholic steatosis and liver fibrosis of viral etiology.
Materials and methods. A total of 64 people were examined. The first group included 32 patients with non-alcoholic liver steatosis on the background of obesity of 1–2 degrees, with an average age of 46.3 ± 4.3 years (12 men and 20 women). The second group consisted of 22 patients with liver fibrosis on the background of chronic hepatitis C (HCV) with an average age of 36.8 ± 4.7 years (12 men and 10 women). The control group included 10 practically healthy individuals with an average age of 38.9 ± 5.3 years without liver pathology. The number of platelets, platelet aggregation with ADP inducers, collagen and ristocetin, functional activity of Willebrand factor (vWF), coagulation hemostasis and fibrinolysis system, and serum concentration of vascular endothelial growth factor (VEGF) were determined. Statistical processing of the obtained data was carried out using the program “Stat2015”.
Results. Induced platelet aggregation in steatosis and liver fibrosis significantly decreased with ADP agonists and collagen against the background of a normal platelet count. In both study groups, signs of endothelial damage with a tendency to increase the functional activity of vWF and VEGF hyperproduction were found. An elongation of thrombin time was also recorded, more significantly in patients with steatosis.
Conclusion. Patients with non-alcoholic liver steatosis and liver fibrosis on the background of HCV are characterized by disorders in the vascular-platelet (endothelial damage and thrombocytopathy in the form of platelet hypocoagulation) and coagulation (hypocoagulation) links of hemostasis.
Introduction. The gradual progression of liver cirrhosis with the development of complications has a negative impact on the life quality of patients with this disease. Modern therapeutic strategies are aimed not only at disease compensating, but much attention is paid to improving the quality of life. No data exists on the effect of serum albumin levels, their structural and functional activity, on the quality of life of patients with cirrhosis.
Aim. To evaluate the relationship between serum albumin concentration, its structural configuration (DR), functional properties (BE, RTQ, DTE) and life quality in patients with decompensated liver cirrhosis.
Materials and methods. The severity of the structural and functional properties of albumin was evaluated in decompensated patients (n = 50) using electron paramagnetic resonance spectroscopy (EPR spectroscopy). Patients’ quality of life was examined using a standardised SF-36 questionnaire.
Results. Pathological changes in DR were observed in 100% of patients, a decrease in BE – in 90%, a violation of RTQ – in 82% of cases, a decrease in DTE was recorded in 76% of patients. The correlation between the level of serum albumin and indicators of physical functioning (PF), role functioning due to emotional state (RE) was ρ = 0,294. Structural and functional albumin properties were related to low indicators of the physical component of health (p < 0,05).
Conclusions. А decline in serum albumin levels, a violation of its conformation and functional properties has a negative impact on the quality of life of patients with decompensated liver cirrhosis.
Currently, non-alcoholic fatty liver disease is one of the most common chronic liver diseases. In recent years, this condition has been considered as a hepatic manifestation of the metabolic syndrome, which is associated with overweight and impaired glucose and fat metabolism. Despite the obvious role of lifestyle in the development of this disease, it is increasingly being suggested that disorders in the metabolism of fats and carbohydrates have a genetic basis, which determines the tendency to develop NAFLD. Mutant polymorphisms of the HSD17B13, GCKR, HFE, and CP genes have been shown to affect the course of NAFLD, but these effects require further study. Therefore, the aim of this work was to analyze and systematize the available data from foreign articles over the past 10 years. In this study, 573 articles were analyzed, the most important 64 original research works were used here. Mutations in the HSD17B13 gene are associated with a milder course of NAFLD, while GCKR gene polymorphisms, on the contrary, are associated with more severe histological manifestations of this disease, such as steatosis and fibrosis. The HFE and CP genes, although not directly related to macronutrient metabolism, nevertheless contribute to the development of more severe forms of NAFLD, which may be associated with the development of inflammation and oxidative stress caused by excessive accumulation of iron in hepatocytes.
Liver cirrhosis (LC) is an advanced stage of liver disease in which healthy liver tissue is replaced with scar tissue and the liver is irreversibly damaged. The clinical course of LC is mostly determined by the progressive increase of portal hypertension, hyperdynamic circulation, bacterial translocation, and activation of systemic inflammation. Different degrees of disease severity in patients, including compensated and decompensated cirrhosis, are related to the progression of these mechanisms and may be recognized by hemodynamic or clinical characteristics. A multi-state approach has been considered to describe the clinical course of the disease. An acute exacerbation of a chronic liver failure may occur either in decompensated or in compensated cirrhosis and is always associated with a high short-term mortality. The increasing severity of disease states prompted the assessment of the LC states using different diagnostic and prognostic scales accounting for competing risks for prognosis and LC treatment efficacy. When choosing the disease management in patients with LC, it is required to assess the severity of their condition, taking into account the results of various liver function tests. The Child-Turcotte-Pugh score is most often used for this purpose. The diagnosis of LC includes evaluation of patients for alcohol disorder and signs of advanced liver disease. The degree of liver fibrosis is determined using ultrasound imaging, transient elastography, MRI, measurements of serum biomarkers, and liver biopsy histology. Alcohol abstinence achieved through psychosomatic intervention is the best non-drug treatment for all stages of the disease. The concept of pharmacotherapy of alcoholic LC and their complications is based on the influence on the pathogenetic components of this pathology. If the disease progresses to decompensated cirrhosis or hepatocellular carcinoma, liver transplantation may be required. The clinical case discusses the management of a patient with LC of alcoholic origin using modern methods of differential diagnosis and treatment of this pathology
Introduction. The feasibility and risks of glucocorticosteroids (GCS) in severe alcoholic hepatitis (SAH) are actively discussed, and there is a real need to develop new biomarkers both to determine indications for the GCS use and to evaluate their effectiveness.
Аim. Тo evaluate the effectiveness of GCS in SAH using a marker of hepatocyte apoptosis and inflammatory cytokines along with traditional laboratory parameters.
Materials and methods. Prednisolone at a dose of 40 mg per day was received by 68 patients with SAH. The effectiveness of therapy was assessed after 7 days by the Lille index, the level of cytokeratin-18 fragments (FCK-18) and cytokines – IL-1β, TNF-α, IL-6 and IL-8.
Results. A positive effect of GCS was noted in 50 (73.5%) patients, after 7 days the Lille index was 0.23 ± 0.09, the levels of FCK18, IL-6, IL-8, TNF-α were significantly reduced, with subsequent decrease and improvement in hepatic functional parameters. These patients had a 100% short-term (within 28 days) survival rate. Eighteen (26.5%) patients had a negative result, the Lille index was 0.61 ± 0.11, there was no significant decrease in FCK-18 and cytokines. After GCS was discontinued, they developed liver failure, 1/3 developed bacterial infections, all patients died of multiple organ failure within 28 days.
Conclusion. The short-term effect of GCS therapy in SAH patients was 73.5%. Along with the traditional Lille index, the following indicators demonstrated diagnostic significance: fragments of cytokeratin-18, cytokines IL-6, IL-8, and, to a lesser extent, TNF-α and IL-1β.
Introduction. Despite great attention to the pathogenesis of chronic viral hepatitis C (CVHC), many aspects of the immune response in this pathology remain unclear.
Aim. To study the subpopulation composition of blood cytotoxic T cells by flow cytometry, depending on the severity of clinical and morphological manifestations of CVHC with genotype 1 or 3.
Materials and methods. Clinical, laboratory examinations, determination of liver fibrosis by elastometry using the METAVIR scale and study of the subpopulation composition of cytotoxic T cells in the blood were carried out in 144 patients with CVHC, including 74 patients with genotype 1 and 70 individuals with genotype 3, and in 20 people of the control group. The study of the subpopulation composition of cytotoxic T cells in the blood was carried out on a flow cytometer Navios (Beckman Coulter, USA) with the determination of CD3, CD8, CD45R0 and CD62L markers.
Results. Changes in the subpopulation composition of blood cytotoxic T cells were more associated with the severity of liver fibrosis in patients with 1 and 3 genotypes of CVHC, than with inflammatory activity and viral load. In patients with CVHC genotype 3, a marked decrease in the content of TEMRA T-cytotoxic cells (CD3+ CD8+ CD45R0–CD62L–) and effector memory T-cytotoxic cells (CD3+ CD8+ CD45R0+ CD62L–) was registered in patients with METAVIR liver fibrosis stage F3-F4 in comparison with persons with METAVIR liver fibrosis stage F0-F1 (Kruskal-Wallis test, respectively, p = 0.02 and p = 0.04 In persons with CVHC genotype 1, similar associations were expressed to a lesser extent.
Conclusion. We obtained an association of deterioration in the indices of the blood cytotoxic T cells subpopulation in patients with CVHC with an increase in the severity of liver fibrosis, which had some differences in patients with genotypes 1 and 3.
Ferritin is one of the key proteins, which has involved in the regulation of iron homeostasis in the body. Ferritin reduced values are often associated with changes in the total iron supply in the body. In addition, ferritin is involved in immune processes and can have both pro-inflammatory and anti-inflammatory effects. Ferritin changes in laboratory values is a rather nonspecific sign that occurs with immunoinflammatory and infectious diseases, as well as the development of iron overload. It can, among other things, accompany the course of new coronavirus infection (COVID-19) and chronic viral hepatitis C (CHC) in patients. Hyperferritinemia in these two diseases may be a marker of a more severe course and adverse patient outcome, making the study of ferritin levels an extremely important task for the practitioner. Therefore, the purpose of this review of the scientific literature was to investigate the possible relationship between Hyperferritinemia, COVID-19 and CHC. It has been reported that hyperferritinemia is quite often associated with a more severe form of both COVID-19 and CHC. Several studies have suggested that the risk of mortality may be increased if they are combined. In this regard, an important conclusion was made about measuring baseline ferritin levels with subsequent dynamic monitoring in this group of patients.
Introduction. In the last decade, approaches to the treatment of chronic viral hepatitis C (HCV) have undergone significant changes. The new WHO strategy aims to eliminate HCV by 2030 by reducing the number of new infections and deaths by simplifying hepatitis C therapy. The development of drugs for the treatment of patients with chronic HCV has a number of features, which requires compliance with special recommendations for conducting clinical bioequivalence studies.
Aim. The study was to analyze the guidelines and protocols of bioequivalence studies of drugs for HCV therapy.
Materials and methods. An information and analytical method was used to evaluate recommendations for conducting bioequivalence studies of HCV drugs according to the US Food and Drug Administration, the European Medicines Agency, and WHO. Separately, an analysis of permitted clinical trials was carried out according to the data of the GRLS of the Ministry of Health of the Russian Federation.
Results and discussions. According to the results of the study, it was noted that for the WHO guidelines on the bioequivalence of drugs for HCV therapy, it is common to develop common principles for planning and conducting research. Special attention is paid to the preferred design of the study. It is also necessary to analyze data on the variability of the pharmacokinetic parameters of the substance under study, which are used to calculate the required number of volunteers to be included in the study.
Conclusions. Direct antiviral drugs under development for HCV therapy, for which clinical bioequivalence studies are currently being conducted in the Russian Federation, cover a large list of INN. The entry of new reproduced drugs into the pharmaceutical market will improve patients’ access to effective treatment of hepatitis C. In order to conduct a high-quality bioequivalence study, it is necessary to thoroughly familiarize yourself with nosology manuals, critical assessment and analysis of information, which will allow you to choose the appropriate design of the study and correctly plan its conduct.
BOWEL DISEASES
The main symptom of irritable bowel syndrome (IBS), a recurrent functional GI disorder, is abdominal pain associated with defecation, a change in the frequency of bowel movements and a change in the consistency of stool. Until recently, it was the only specific disease that was included in the international classification of the 10th revision. Another 53 functional disorders will be included in the classification of the 11th revision and receive the status of ICD diseases. There are four main variants of IBS: IBS with constipation, IBS with diarrhea, IBS with mixed bowel habit and IBS unclassified. The very concept of IBS was fast-changing. The latest Rome IV (2016) guidelines suggested a mechanism of intraepithelial contact disruption as one of the pathogenetic mechanisms, which activates a minor intramucosal inflammation. It could be relevant to the chronicity of the process and require the use of anti-inflammatory drugs and agents in the treatment that restore intraepithelial contacts, which increases the percentage of patients with a positive treatment effect. The report provides data on the pharmacotherapy of drugs that have a combination (concomitant) effect of action, for example, Meteospasmyl®, which is superior to drugs with antispastic action or action that restores impaired motility in terms of the final effect of the action. The author of this report invites to participate in the discussion about the feasibility of introducing a new IBS variant, which may have a chronic course, and the inclusion of anti-inflammatory drugs in the combination treatment (if drugs that affect motor disorders have insufficient effect).
The treatment of Crohn’s disease is a complex process in which it is necessary to take into account not only the current condition of the patient and the risks of disease progression, but also the sequence of therapy. To date, only biological drugs can change the course of the disease, but their number is limited and they should be prescribed taking into account the choice of the optimal sequence for each patient, since the effectiveness of any biological drug is affected by previous treatment. Unfortunately, there are no common recommendations on the sequence of choosing biological drugs, and the issue of choosing a first-line drug is relevant. Ustekinumab is a biologic agent targeting interleukin-12 and 23 that has been shown to be effective and safe in the treatment of both patients after TNF-alpha inhibitors and bionaive patients. It has also been shown to be effective in the treatment of strictures and perianal manifestations of Crohn’s disease. Ustekinumab is also effective against articular extraintestinal manifestations such as arthralgia and psoriatic arthritis. A high response rate to ustekinumab was also found in patients with dermatological manifestations – psoriasis, pyoderma gangrenosum, and erythema nodosum. In addition, a good safety profile allows its use in elderly patients. Of particular interest is the direct comparison of biologics. To date, there is only one randomized head-to-head trial of ustekinumab and adalimumab showing comparable efficacy results. And there is also data from a post hoc analysis of randomized trials, where its effectiveness is comparable to infliximab. Thus, ustekinumab can be prescribed for the treatment of Crohn’s disease, including in the first line of therapy.
This paper highlights the problem of functional constipation, its epidemiology, etiology, features of the clinical picture during prolonged immobilization in injured patients, and approaches to therapy. Stool retention in patients undergoing prolonged immobilization is an urgent medical problem, since it occurs in most of these patients. The paper presents a clinical example of managing a patient with an injury to the musculoskeletal system and functional constipation. Functional constipation is associated with a number of pathophysiological processes: genetic characteristics, lifestyle (lack of physical activity) and eating style characteristic of Western cultures (low intake of dietary fiber and water), intestinal movement disorders that can be caused by numerous causes (neurogenic factors , diseases of the endocrine glands, circulatory disorders in the intestinal vessels, taking certain medications), anatomical features (dolichosigma), as well as social factors (late awakening, morning rush, work in different shifts, changes in the usual living and working conditions) and psychological patient features. The possibilities of lifestyle modification in patients with injuries of the musculoskeletal system are very limited, and special attention should be paid to correcting nutrition and observing the drinking regimen. The key point in the treatment of functional constipation in such patients will be the appointment of stimulant laxatives, one of which is sodium picosulfate. At the stages of treatment and rehabilitation, the patient should be recommended measures for modifying lifestyle and nutrition, exercise therapy in accordance with his physical capabilities and clinical recommendations for the treatment of constipation.
Irritable bowel syndrome (IBS) is a common functional disease of the gastrointestinal tract, affecting a large number of adults worldwide, and leads to a significant decrease in the quality of life. IBS places a heavy burden on patients, most of whom are able-bodied population, as well as doctors and the healthcare system. The pathogenesis of this disease is multifactorial and includes the brain-intestine axis, disorders of the immune function of the mucous membrane, visceral hypersensitivity, changes in the motility of the gastrointestinal tract, changes in the microbial composition of the intestine. Based on the fact that changes in intestinal motility and visceral hypersensitivity are among the key factors in the pathogenesis of the disease, he use of antispasmodic drugs as part of complex therapy is justified. Mebeverin is a myotropic antispasmodic drug recommended for use in patients with IBS according to Rome IV Criteria, as well as clinical recommendations of the Russian Gastroenterological Association and the Association of Coloproctologists of Russia. According to available data, mebeverin has proven to be an effective and safe antispasmodic used to treat patients with IBS. The article presents a clinical case demonstrating the experience of effective use of the drug Mebespalin®. A patient with a diagnosis of IBS with a predominance of constipation is recommended to take an antispasmodic, as well as lifestyle modification – the addition of fiber-rich foods, sufficient drinking regime and increased physical activity. A week after the start of treatment, the patient noted an improvement in her condition – abdominal pain did not bother, the stool normalized.
In recent decades, there has been a steady increase in the incidence of ulcerative colitis worldwide. The purpose of the work was to analyze the literature data on modern features of the treatment of ulcerative colitis, as well as to present our own results and cases from practice. Mesalazine remains the mainstay of remission and often its induction in patients with ulcerative colitis. Currently, the nature of the treatment of ulcerative colitis is determined by the target level of remission. The fact of the onset of endoscopic remission is known to occur much later than subjective clinical improvement. In recent years, this provision has been supplemented by evidence of a delay in histological, laboratory (fecal calprotectin) and transmural remission from endoscopic. There is increasing evidence that the duration and quality of remission depends on the depth of remission. When using ultrasound, it is not difficult to urgently assess the activity and prevalence of inflammation by the parameters of the intestinal wall. Together with the level of fecal calprotectin, this information may be key to the choice of induction, escalation, maintenance or de-escalation treatment options. Of course, endoscopic examination with colon biopsy remains a necessary planned component of the management of a patient with ulcerative colitis. There are 3 cases from practice in which the achievement of transmural remission was carried out during the treatment with mesalazine. The possibility of monitoring the activity of the inflammatory process and its prevalence in the colon with the help of ultrasound examination of the intestinal wall has been clearly demonstrated. According to the results of our study, it was found that with a high activity of the disease according to the scale of Doppler mapping of the colon wall (Limberg 4), an erosive-ulcerative process was recorded in all patients according to the results of endoscopic examination (Mayo 3). Detection of the normal intestinal wall on the echogram in all cases was accompanied by the absence of endoscopic activity (Mayo 0) or its minimal manifestations (Mayo 1).
Introduction. Metabolic correction of the consequences of extensive (especially combined) intestinal resections requires enormous efforts due to weight loss, a decrease in plasma albumin concentration of less than 30 g/l, electrolyte disorders, organ failure, etc. There are consequences in the form of short small intestine syndrome, postcolectomy syndrome and the combined consequences of resections of the small and large intestine. The most severe changes are after combined thin-thick-intestinal resections, the prevalence of which continues to increase. Nevertheless, the data on the occurrence of combined resections (thin-colon) are very contradictory.
Aim. To analyze the effectiveness of nutritional correction programs in SBS syndrome due to extensive combined small-colonic resections and to characterize possible ways of correcting metabolic complications with the help of nutritional correction, taking into account the optimization of absorption in the intestine.
Materials and methods. We examined 208 patients with combined extensive resection of the small intestine with right-sided hemicolectomy (65% of men and 35% of women). Metabolic changes, nutritional characteristics and reparation under the influence of nutritional correction in this category of patients are described.
Results. Data on the restoration of lost functions are presented, which is based on the analysis of the mechanisms of adaptation and cellular regeneration. Regenerative aspects of hormonal (enteroglucagon) regulation of intestinal functions after its extensive resection and artificial alimentation are closely related.
Conclusion. It is advisable to introduce teduglutide into the treatment structure to stimulate rehabilitation absorption processes after extensive combined intestinal resections.
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