REVIEWS
Aim. To suggest a new perspective on chronic alcohol intoxication by means of investigating the associated severe multiple organ pathology, which frequently becomes the cause of lethal outcome in patients suffering from drunkenness and alcoholism.
Key points. The empirical basis of the study consisted in the analysis of autopsy results obtained from 1,115 corpses of persons having abused alcohol during their lifetime. In addition, 800 experiments on rats were carried out. As a result, a concept of alcoholic disease (AD) is proposed. AD is defined as a condition, in which chronic ethanol intoxication leads to the development of morphological changes in organs and systems: from minimal injuries of the microcirculatory pathway to a multiple organ pathology showing signs of alcoholism. AD pathogenesis is demonstrated to undergo 3 major stages, from (1) episodic alcohol intoxication, through (2) drunkenness and to (3) alcoholism. It is noted that, while the morphological changes are considered to be reversible during the first two stages, they become irreversible at the stage of alcoholism.
Conclusion. It is concluded that the forms of the disease that involve the described morphological changes in organs and systems should be primarily treated by physicians, not by psychiatrists and narcology practitioners who are only capable of dealing with the psychological aspect of the problem.
Aim. To generalize the results of existing research studies carried out to investigate autoimmune hepatitis (AIH) in children, and the contemporary approaches to the diagnosis and therapy of the disease.
Key points. According to the results of serological studies, two types of AIH can be distinguished in children. AIH of type 1 is diagnosed, when anti-smooth muscle autoantibodies (ASMA) and/or antinuclear autoantibodies (ANA) have been detected. AIH of type 2 AIH is diagnosed, when liver kidney microsomal autoantibodies (anti-LKM-1) and/ or anti-liver cytosolic autoantibodies (anti-LC-1) have been detected. Liver parenchymal inflammation responds well to a standard immunosuppressive therapy with prednisolone and azathioprine. Disease relapses are observed in about 40% of patients during treatment. It is expedient to treat children at least for 2–3 years before attempting to cancel the treatment, which decision should be considered only when the levels of transaminases have remained normal and IgG has been negative, or autoantibody titers have been low (1:20 using immunofluorescence method) for at least a year. Before attempting to cancel the therapy, liver biopsy and histological study should be repeated in order to exclude the possibility of residual inflammatory changes. For a small number of patients, who do not respond to standard treatment and those who suffer from frequent disease relapses, it is advisable to offer an alternative immunosuppressive treatment, the effectiveness of which is still ambiguous and poorly understood (including, in order of priority, mycophenolate mofetil, calcineurin inhibitors, rituximab, Inhibitor of tumor necrosis factor-alpha). In cases of refractoriness to therapy and the disease progression to liver cirrhosis and its decompensation, liver transplantation is justified. It is shown that AIH might relapse after liver transplantation. De novo AIH develops after liver transplantation as a result of non-autoimmune diseases; it is characterized by the presence of autoantibodies (ANA, ASMA and typical or atypical anti-LKM-1), and histologically characterized by a pattern similar to that of AIH. De novo AIH after liver transplantation responds well to a classical immunosuppressive therapy, but not to a standard antiretroviral therapy. In the review, we discuss issues associated with the clinical manifestations and diagnosis of AIH in children. Approaches to the treatment and long-term observation of such children are reviewed, including, i.e., those formulated by the main group of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) members.
Conclusion. Autoimmune hepatitis (AIH) in children has a progressive course with the outcome to liver cirrhosis. The presented review has summarized approaches to the diagnosis and selection of AIH therapy in children.
Aim. This paper is aimed at reviewing existing literature that investigates the role of angiogenesis in portal hypertension pathogenesis in liver cirrhosis and the possibilities of its antiangiogenic therapy, along with the description of angiogenesis inhibiting drugs and their action mechanisms.
Key points. A relevant literature and reference list search was performed using PubMed and RSCI and Google Scholar, and covered the 2000–2017 period. The following keywords were used: liver cirrhosis, portal hypertension, pathogenesis, angiogenesis, antiangiogenic therapy. The inclusion criteria were limited to the antiangiogenic therapy of portal hypertension. Angiogenesis is shown to play an important role in the pathogenesis of liver cirrhosis. Angiogenesis is the basis for the development of associated portal hypertension that causes its characteristic complications. The experimental studies reviewed in this paper investigate the action mechanism of angiogenesis inhibiting drugs and their effect on portal hypertension. It is shown that, so far, only tyrosine kinase inhibitors have been tested in patients with liver cirrhosis as an antiangiogenic therapy for portal hypertension.
Conclusion. Antiangiogenic therapy, selectively directed at unusually growing newly-formed vessels, can be a pathogenetically justified method for treating portal hypertension in liver cirrhosis on its subclinical stage.
ORIGINAL ARTICLES
Aim. In this work, we aim to analyze the efficacy of treatment for heartburn and pathological gastroesophageal refluxes (GERs) using alginate-antacid medication. We assess the dynamics of inflammatory process in patients with gastroesophageal reflux disease (GERD) treated with alginate-antacid medication used at conventional dosage, both as a monotherapy and as part of a GERD combination therapy. To this end, we set out to confirm the formation of the layer of unbuffered acidic gastric juice over the gastric chyme after eating, as well as to determine the acidneutralizing effect of alginate-antacid medication upon its interaction with the acidic contents of the stomach.
Materials and methods. 36 case records of GERD patients were analyzed (20 women and 16 men, mean age 47.03 years old). All patients were asked to report the heartburn intensity (according to a Likert scale) prior and during the treatment. They were subjected to esophagogastroduodenoscopy (EGD) and 24-hour pH impedance monitoring prior and on the 14th day of treatment. Before treatment, high-resolution esophageal manometry was performed to exclude the esophageal hiatal hernia (EHH) and to determine the upper and lower boundaries of the lower esophageal sphincter (LES). Group 1 included patients with non-erosive reflux disease (NERD), who were receiving monotherapy with alginate-antacid. Patients with the I-II degree of erosive esophagitis (EE) comprised groups 2 and 3, respectively, and were receiving proton pump inhibitor (PPI) monotherapy and PPI and alginate-antacid medication combination therapy, respectively. In group 1, 10 patients were examined using a probe pull-through technique with the purpose of determining pH levels in the cardiac stomach, in the area of the gastro-esophageal junction and in the esophagus at a level of 5 cm above the LES, both in the fasting state and after eating, as well as prior and after using alginate-antacid preparations.
Results. On the third day of treatment, a complete heartburn relief was observed in 5 (41.6 %) patients of the NERD patient group (group 1), who were receiving a monotherapy with alginate-antacid medication. Heartburn relief was achieved in 3 EE (25 %) and 6 EE patients (50 %) following a PPI treatment course and a PPI and alginate-antacid medication treatment course, respectively. On the 5th day of treatment, heartburn was neutralized in 8 (66.7 %), 7 (58.3 %) and 9 (75 %) patients, with these numbers having risen to 10 (83.3 %), 9 (75 %) and 10 (83.3 %) patients (in the respective groups) on the 14th day. Before treatment, no significant differences in the heartburn intensity were identified between the groups. On the 3rd day of treatment, a significant difference was observed in the dynamics of heartburn intensity between groups 1 – 2 and 2 – 3 (p < 0.05), with this difference having disappeared by the 5th day. According to EGD in the NERD group, inflammation were eliminated in 10 (83.3 %) patients. In EE patients of the 2nd and 3rd groups, the healing of erosions was confirmed in 8 (66.7 %) and 10 (83.3 %) patients, respectively. In general, during the 24-hour pH impedance monitoring, pathological acid, weakly acid and non acid GERs were diagnosed in 28 (77.8 %), 15 (41.7 %) and 9 (25 %) patients, respectively. Under a course of alginate-antacid medication monotherapy, acid reflux was eliminated in 100 % of NERD patients. Among ERD patients undergoing PPI monotherapy, acidic GERs were eliminated in 9 (75 %) patients; however, the addition of alginate-antacid medication to a PPI treatment regimen allowed this result to be increased to 91.7 %. Weakly acid GERs were eliminated in 70 % and 33.3 % of patients in groups 1 and 2, respectively. In group 3, where patients were receiving a PPI and alginate-antacid medication combination treatment, weakly acid GERs were eliminated in 75 % of cases. Non acid refluxes were eliminated in groups 1 and 3 in 50 %, and in 2 – in 33.3 % of cases. When pulling the probe in the fasting state, a sharp change in pH values from acid (0.9–2 units) to weakly acid, and then non acid (5.5–7.6 units), was observed in 100 % of cases. After a meal and before the administration of alginate-antacid medication, the layer of unbuffered acidic gastric juice (pH < 2) was detected in the proximal stomach of 9 patients (90 %). After administration of alginate-antacid medication, the pH ranged from 6.1 to 7.7 units in 7 (70 %) patients, and increased to 4.2 units in 3 people (30 %).
Conclusions. The inclusion of alginate-antacid medication into treatment schemes for managing ERD patients significantly increases its effectiveness, reliably increasing the rate of the onset of the clinical effect. alginate-antacid medication is shown to be an effective monotherapy for NERD. An important advantage of alginate-antacid medication in the treatment of GERD postprandial symptoms consists in its ability to neutralize and displace distally the layer of unbuffered acidic gastric juice, which forms above the chyme surface.
Aim. The aim of this study was to develop an algorithm for identifying various types of jejunum and ileum tumour lesions based on video capsule endoscopy (VCE), which can be used by physicians in the process of decision making.
Materials and methods. In the study, we analysed data on the examination and treatment of 65 patients (35 men and 30 women aged 18–80 years (mean age 46 ± 28 years)), who underwent VCE in the City Clinical Hospital No. 31 and in the Clinica K+31 during the period October 2008 — April 2017. The indications for VCE were a search for a reason of gastrointestinal bleeding, the anaemia of unknown etiology and suspected tumour of the small intestine. According to the VCE results, 181 cases of various changes in the jejunum and ileum were revealed. Each tumour object had been histologically verified before our study. Capsule endoscopy was performed using equipment produced by Olympus (Japan), MicroCam Intromedic (Korea), PillCam Given Imaging (Israel), OMOM Chongqing Jinshan Science & Technology (China).
Results. Following expert interviews, 30 signs and their gradations were identified for assessing the type of lesion in the jejunum and ileum using video capsule endoscopy images. Among them, 8 were found to be statistically significant (affecting the division of objects into groups): patient gender, gut wall/lumen deformation, path of intestinal folds, polypoid changes, vascular pattern, mucosal regularity, mucosal lobulation and colour. Using a Bayesian heterogeneous diagnostic procedure and the calculation of diagnostic factors, a three-level algorithm has been developed for the differential diagnosis of jejunum and ileum lesions.
Conclusions. The application of the proposed algorithm in clinical practice will not only allow the presence or absence of the jejunum or ileum tumour lesion to be verified, but also the type of this lesion to be determined with an accuracy of more than 86%. The developed diagnostic algorithm can support decision making by the clinician within the task of differentiating jejunum or ileum tumour lesions into three main types: benign epithelial tumours, benign non-epithelial tumours and malignant tumours. Differential diagnosis of the type of jejunum or ileum tumour lesion using the proposed diagnostic algorithm facilitates not only the development of a treatment tactic for managing such patients (dynamic observation, conservative therapy, operative treatment), but also the determination of terms (emergency, urgent, planned) and methods (endometrial luminal, laparoscopic, laparotomic) of surgical treatment.
Aim. This research is aimed at investigating the experience of applying trimebutine maleate in the daily practice of physicians managing patients with functional dyspepsia syndrome (FDS).
Materials and methods. The study included 100 patients diagnosed with FDS. The patients were asked to complete a 7 × 7 and SF36 questionnaires before and on the 7th, 14th, 28th days of treatment. The treatment was performed using trimebutine (Trimedat®) in a standard dosage of 200 mg × 3 times a day for 28 days.
Results. In the group under study, 45 (45 %), 3 (3 %) and 52 (52 %) patients suffered from epigastric pain syndrome (EPS), postprandial distress syndrome (PPDS) and a combination of both syndromes, respectively. The combination of FDS with gastroesophageal reflux disease (GERD) was noted in 15 patients (15 %). Irritable bowel syndrome (IBS) was present in 21 cases (21 %). Trimebutine maleate (Trimedat®) has been proven effective in all FDS forms, such as EPS, PPDS and their combination. In the course of treatment, the average score of the patients’ physical and mental health increased from 48.02 ± 5.62 to 52.97 ± 4.17 points (p < 0.0001), and from 48.48 ± 10.83 up to 51.79 ± 8.51 points (p < 0.0001), respectively.
Conclusion. The main clinical forms of functional dyspepsia syndrome (EPS and PPDS) are frequently manifested in combination either with each other (52 %), or with IBS (21 %) and GERD (15 %). The use of trimebutine in the treatment of patients with FDS is shown to result in a decrease in the severity of its main symptoms and a reliable increase in the quality of patients’ life.
In the Russian Federation, liver diseases are most frequently represented by two their nosological forms, i.e., nonalcoholic and alcoholic fatty liver disease (NAFLD and ALD). A successful management of such patients, along with improving the functional state of the liver, requires a careful analysis of patients’ nonspecific complaints. In particular, it is important to investigate asthenic syndrome, which can indirectly result in the exacerbation of liver diseases, thus incurring additional economic costs to national healthcare systems. Therefore, the elucidation of the nature of asthenic syndrome and a search for methods for its resolution seem to be highly relevant research tasks.
Aim. This study aims to investigate the effect of the antioxidant drug (the extract of the Amur maackia wood) on the organic and functional components of asthenic syndrome in patients with NAFLD and ALD, who do not show signs of the disease decompensation.
Materials and methods. An observational program was carried out under the conditions of daily clinical practice in three Russian cities: Moscow, Chelyabinsk and Vladivostok. 80 patients (40 with NAFLD, 40 with ALD) were comprehensively examined according to a developed program. A number of laboratory indicators that reveal inflammatory processes in the liver were studied, including leukocytes, ESR, ALT, AST, GGTP and CRP. The patients’ psycho-emotional status was assessed using a Daily Fatigue Impact Scale (D-FIS) and a four-dimensional scale for assessing distress, depression, anxiety and somatisation (4DSQ).
Results. According to the D-FIS questionnaire, all the patients showed fatigue. According to the 4DSQ questionnaire, a correlation of distress with the level of laboratory indicators was revealed among all the patients. No such a correlation was noted for depression and anxiety in the patients with NAFLD. On the contrary, in the case of ALD, all psycho-emotional disorders (except for somatisation) were positively correlated with the markers of inflammation. It is shown that asthenic syndrome in patients with both NAFLD and ALD has a complex origin, being associated both with inflammatory processes in the liver and psycho-emotional disorders. In all cases under study, the prescription of the preparation led to a decrease in the studied laboratory indicators (inflammation markers) and an increase in the patients’ psycho-emotional status. The latter improvement was manifested in the reduction of distress, depression, anxiety and somatisation, according to the 4DSQ questionnaire, as well as in the reduction of fatigue, according to the D-FIS questionnaire.
Conclusion. The results of the observational program have shown that patients with NAFLD and ALD frequently experience such components of asthenic syndrome as distress, depression, anxiety, somatisation and fatigue. The prescription of the preparation is found to result in a decrease in laboratory inflammatory indicators. In addition, the preparation is determined to positively affect the components of asthenic syndrome in patients with NAFLD and ALD. In the course of the treatment, no clinically significant side effects were documented.
Aim. In this work, we set out to assess the specific features of vascular endothelium in patients suffering from severe (pan-ulcerative) and complicated forms of ulcerative colitis (UC) and Crohn’s disease (CD).
Materials and methods. The research sample consisted in 65 patients with UC (n = 45) and CD (n = 20), who were either in the acute phase or had been diagnosed with such conditions for the first time. For assessing endothelial dysfunction (ED), we used such markers as levels of vascular endothelial growth factor (VEGF) in the blood serum and the number of plasma desquamated endotheliocytes (DEC).
Results. The indicators of vascular endothelial dysfunction are shown to be significantly higher in patients with severe, pan-ulcerative forms of inflammatory bowel diseases (IBD). A statistically significant relationship has been established between ED indicators and the severity and localisation of the pathological process, the extra-intestinal manifestations and complications of the disease. A dependence of the endothelial dysfunction indicators on the UC endoscopic activity has been determined. A positive correlation between the levels of VEGF and DEC and the markers of systemic inflammation (ESR, CRP and fibrinogen) has been revealed.
Conclusion. It is determined that, in IBD patients, endothelium dysfunction is manifested in an increase in the VEGF and DEC levels. The indicators of endothelial dysfunction are shown to be directly correlated with the serum markers of systemic inflammation. Therefore, VEGF and DEC values can be used not only as criteria for assessing the intensity of IBD, but also as predictors of a complicated disease course.
NATIONAL COLLEGE OF GASTROENTEROLOGISTS, HEPATOLOGISTS
Aim. This review study is aimed at characterizing the nutrition of patients with non-alcoholic fatty liver disease (NAFLD).
General findings. A high-calorie diet, followed even for a short period of time, can lead to an increase in the lipid content in hepatocytes and an increase in ALT values. These changes occur much earlier than weight gain, glucose metabolism disorders and other clinically obvious changes. So far, only the Mediterranean diet (or the Mediterranean type of food) has been scientifically confirmed as beneficial for human health. It is recommended for patients with NAFLD both by Russian and international clinical guidelines. The molecular mechanisms of beneficial effects on human health have been confirmed for such Mediterranean diet components as polyphenols, carotenoids, oleic acid, polyunsaturated fatty acids and dietary fiber. The enrichment of the Mediterranean diet with olive oil (+10 g) reduces the risk of diabetes mellitus by 40 %. The addition of Omega-3 fatty acids to food reduces the risk of hepatocellular cancer. A balanced ratio of omega 3 and omega 6 in the diet is more important than the absolute amount of individual fatty acids. Vegetables and fruit contain two main classes of antioxidants: polyphenols and carotenoids. In patients with NAFLD, they exhibit an anti-inflammatory and antifibrotic effect both in vivo and in vitro. Food produced from whole grain has a lower energy potential as compared to that produced from refined grain. Meat contains various nutrients, such as proteins, iron, zinc, B12 vitamin, as well as sodium, saturated fatty acids and cholesterol, which serve as risk factors for the development of NAFLD and other cardio-metabolic disorders. In this paper, we present a clinical observation of a 51-year-old patient with NAFLD and cardio-metabolic disorders. Practical recommendations are given on changes in his lifestyle and the choice of optimal therapy with the application of multifunctional drugs affecting all disease aspects.
Conclusion. The concepts of ‘correct or healthy’ nutrition and ‘lifestyle modification’ are increasingly attracting much attention both in terms of the prevention and treatment of liver diseases. Proper nutrition is important for a good life prognosis in patients with non-alcoholic fatty liver disease (NAFLD).
Aim. The aim of this work was to investigate the problem of constipation associated with a deficiency in dietary fibre and to develop principles for the nutritional management of this condition.
Main findings. In countries characterized by the Western-style diet, only about 10% of people consume an optimal amount of fibre daily. As a result, primary normal-transit constipation is a common problem. A special role in maintaining the function of the colon belongs to carbohydrates. Keeping a food diary helps to choose an optimal type of nutrition for a patient and reduce the likelihood of flatulence. Food fibres (oligosaccharides and polysaccharides) play an especially important role. Viscous fibres are most capable of swelling, thus exhibiting metabolic effects at the level of the small intestine. Non-viscous and insoluble fibres increase the volume of feces, stimulate peristalsis and exert a prebiotic effect. A low content of fibre in the diet is a factor provoking intestinal dysbiosis followed by a decrease in Bacteroides and Ruminococcus populations. Flavonoids also play an important role in the regulation of intestinal peristalsis and secretion. Under constipation of functional origin, the microbiota contains a significantly reduced amount of Bifidobacterium and Bacteroides. Changes in the composition of microflora correlate with psychopathological symptoms. Strains capable of exhibiting a therapeutic effect in constipation include Escherichia coli Nissle 1917, a probiotic mixture of VSL#3, Florasan-D combined bacterium, DN-173 010 Bifidobacterium lactis (B. lactis), HN019 Bifidobacterium lactis and Lactobacillus rhamnosus GG. For the prevention and management of constipation, functional food products enriched with oligo-, polysaccharides and probiotics are developed. Thus, various products of the Activia brand contain DN-173 010 Bifidobacterium lactis (ActiRegularis) at a concentration of at least 108 CFU / g. The consumption of fermented milk products with DN-173-010 Bifidobacterium lactis contributes to the elimination of subclinical discomfort in the abdomen in practically healthy people, reduces the time of colon transit and helps to normalise the frequency of defecation.
Conclusion. In most cases, the first stage in managing constipation is the normalisation of the diet by means of adding dietary fibre and probiotics into the composition of functional foods or medical preparations.
CLINICAL CASES
Aim. This clinical observation was aimed at analysing the course of the disease in a patient with a protracted persistence of HBsAg and HBV DNA in the blood in the outcome of acute hepatitis B and the possible formation of a latent HBV infection in the phase of clinical recovery.
General findings. We carried out a 31-month observation study of a patient suffering from acute hepatitis B. Subsequently, we performed a dynamic assessment of the viral kinetics and qualitative and quantitative assessment of HBsAg in the blood using highly sensitive analytical methods. These methods allowed a protracted persistence of HBV DNA in the blood and a late seroconversion of HBsAg/anti-HBs to be revealed.
Conclusion. The described clinical case demonstrates the possibility of an atypically protracted persistence of HBsAg in the outcome of acute hepatitis B, which is followed by a clinical and laboratory picture of recovery and the formation of latent chronic HBV infection, as an example of the 5th phase of chronic HBV infection (HBsAg-negative), according to a new classification, reflected in the clinical guidelines for the treatment of hepatitis B (EASL 2017).
ISSN 2658-6673 (Online)