Aim: to describe existing approaches to the treatment of gastroesophageal reflux disease (GERD) in accordance with the requirements of evidence-based medicine, as well as to discuss controversial issues in the management of GERD patients.

Key findings. Nonmedical GERD treatment should be based on the reduction of body weight by decreasing the calorie intake and its proper distribution throughout the day, as well as by increasing the level of physical activity. Proton-pump inhibitors (PPIs) are used as the main class of drugs for reflux esophagitis and non-erosive reflux disease (NERD), as well as in cases when the disease is characterized by certain specific features (e.g., the presence of night symptoms) and extraesophageal manifestations. The efficacy of PPI treatment may depend on the genetic polymorphism of the CYP2C19 cytochrome. Rabeprazole is characterized by a predominantly non-enzymatic pathway, providing a more stable pharmacokinetics profile, which is less dependent on the CYP2C19 polymorphism. The duration of the initial and maintenance PPI course is determined by the GERD form. Long-term PPI maintenance therapy is indicated for erosive esophagitis. In the presence of Barrett’s esophagus, this measure is considered from the standpoint of cancer prevention.

Conclusion. The use of PPIs is considered to be the key approach in the drug treatment of GERD. The choice of a PPI is based on factors that determine the efficacy and safety of such drugs, namely the rate of the onset of acid suppressive effects, the intensity of acid suppressive effects, the time of the onset of GERD clinical remission, the dependence on the CYP2C19 genetic polymorphism, the absence of significant interaction with other drugs, as well as the presence of pleiotropic effects.

Aim: to analyze the data that has so far been accumulated on the pathogenetic association of gallstone disease (GD) and non-alcoholic fatty liver disease (NAFLD), as well as to assess the effect of cholecystectomy on the NAFLD course.

Key findings. The relationship between GD and NAFLD is very complex and seems to be mutually aggravating. There is no doubt that there is an increased risk of GB in NAFLD patients, which is primarily associated with common pathogenetic mechanisms. These include central and peripheral insulin resistance, changes in the expression of transcription factors (liver X-receptor and farnesoid X-receptor) and the bile acid membrane receptors (TGR5). Conversely, the effect of GD on the NAFLD course is assumed, although the pathogenetic factors of this association are still unknown. In recent years, convincing data has emerged concerning the role of cholecystectomy in the NAFLD progression, which may be connected with the development of small intestinal bacterial overgrowth, as well as with the disruption of the endocrine balance and the signal function of bile acids.

Conclusion. The connection between NAFLD, GD and cholecystectomy is complex and multifaceted. The study of this connection will allow new methods of treatment to be developed.

Background. Non-alcoholic fatty liver disease (NAFLD) is the leading chronic hepatic condition worldwide and new approaches to management and treatment are limited.

Summary. L-ornithine L-aspartate (LOLA) has hepatoprotective properties in patients with fatty liver of diverse etiology and results of a multicenter randomized clinical trial reveal that 12 weeks treatment with oral LOLA (6–9 g/d) results in a dose-related reduction in activities of liver enzymes and triglycerides together with significant improvements of liver/spleen CT ratios. A preliminary report described improvements of hepatic microcirculation in patients with nonalcoholic steatohepatitis (NASH) following treatment with LOLA. Mechanisms responsible for the beneficial effects of LOLA in NAFLD/NASH involve, in addition to its established ammonia-lowering effect, metabolic transformations of the LOLA-constituent amino acids L-ornithine and L-aspartate into L-glutamine, L-arginine, and glutathione. These metabolites have well-established actions implicated in the prevention of lipid peroxidation, improvement of hepatic microcirculation in addition to anti-inflammatory, and anti-oxidant properties.

Key messages. (1) LOLA is effective for the treatment of key indices in NAFLD/NASH. (2) Mechanisms other than LOLA’s ammonia-lowering action have been postulated. (3) Further assessments in the clinical setting are now required.

Aim: to summarize the literature data on the treatment of rectal fistula using fibrin glue.

Key findings: The prevalence of rectal fistula is about 9 cases per 100,000 population. Patients with rectal fistulas are frequently represented by the able-bodied middle-aged population group. The disease is extremely rarely observed in children and elderly people. Thus, this problem has a socially significant character. Fistula elimination is possible only by surgery, which is accompanied by the risk of fistula recurrence and the development of postoperative incontinence. In this regard, low-invasive techniques for the treatment of rectal fistulas, such as the use of fibrin glue, are being actively investigated.

Conclusion: The use of fibrin glue as a sphincter-preserving technique eliminates the development of postoperative anal failure, while new technologies and materials aim to reduce the risk of the disease recurrence.

Aim: to analyze the dynamics of morbidity and mortality from digestive diseases, as well as their causes, in the RF Northwestern Federal District (NWFD).

Materials and methods. A statistical analysis was carried out on the basis of the 2007–2017 annual reports of the Medical Information and Analytical Center (MIAC) in St. Petersburg and the reports of the chief gastroenterologists of the Northwestern Federal District subjects.

Results. In the RF Northwestern Federal District, an increase in both morbidity and mortality from digestive diseases is observed. The main non-oncological reasons for the development of these disorders include alcoholic liver disease, chronic alcoholic pancreatitis, peptic ulcer complications and NSAID-associated gastropathies. Along with a decrease in the incidence of gastric cancer, an increase in the incidence of colorectal cancer, as well as pancreatic cancer, is observed. A decrease in mortality from all the aforementioned cancer localizations is revealed.

Conclusions. The main reasons for the increase in morbidity and mortality due to gastroenterological diseases in the RF Northwestern Federal District include alcohol abuse among the population, inadequate prevention of gastric helicobacteriosis, insufficient expertise of physicians in terms of Helicobacter pylorieradication and cancer prevention.

The natural history of liver cirrhosis (LC) is characterized by two stages: compensated and decompensated. Current clinical and laboratory prognostic models, such as Child-Pugh and MELD scales, do not take into account immune dysregulation, as well as it potential impact on the LC decompensation and the survival. Neutrophil to lymphocyte ratio (NLR) is simple and affordable parameter, representing the imbalance of two distinct immune pathways.

Aim: to evaluate relationship between NLR level, mortality and SIRS development in patients with DC.

Materials and methods. In this retrospective study 36 patients with DC which were hospitalized in Hepatology Department of V.H. Vasilenko clinic of propaedeutics and internal diseases, gastroenterology and hepatology, Sechenov University from January 2009 to December 2017 were enrolled. Correlation analysis, univariate and multivariable analysis were provided to find factors statistically significantly associated with lethal outcome and SIRS. The optimal cut-off levels for the NLR associated with adverse outcome were determined.

Results. AIn multivariable analysis, NLR > 4 (p < 0,001) was statistically significantly associated with lethal outcome in patients with DC during hospitalization (OR: 1.57, [95 % CI 1.125–2.209], p = 0.008). Sensitivity and specificity of this cut-off is 100 % and 79.17 %, respectively. NLR > 4.8 was associated with SIRS development during hospitalization (OR: 1.484, [95 % CI 1.103–1.997], p = 0.009) with 100 % sensitivity and 90 % specificity.

Conclusions. NLR is an independent risk factor of lethal outcome and SIRS development in patients with decompensated liver cirrhosis.

Aim: to improve the results of treating patients with anastomotic biliary strictures of the bile ducts after orthotopic liver transplantation.

Materials and methods. This study is based on the results of the endoscopic treatment of 36 patients with biliary complications after orthotopic liver transplantation, who were admitted to the N.V. Sklifosovsky Research Institute for Emergency Medicine from December 2001 to December 2017. The endoscopic treatment program included diagnostic ERCP, endoscopic papillosphincterotomy (EPST), bilioduodenal stenting, nasobiliary drainage, balloon dilatation.

Results. Against the background of the staged endoscopic treatment, the stable remission of anastomotic biliary strictures (ABS) was achieved in 17 (53.1 %) patients, with 4 of them (12.5 %) showing a successfully resolved insufficiency of biliobiliary anastomosis (BBA). The average duration of endoscopic treatment was 12 ± 1.9 months. The number of ERCPs performed for each patient varied from 1 to 12 and averaged 3. In the majority of patients (75 %) who received one or more courses of endoscopic treatment, a successful correction of anastomotic strictures with no recurrence within 2–5 years was achieved.

Conclusion. Staged endoscopic treatment is established to be highly effective in patients with anastomotic biliary strictures and the insufficiency of bilobiliary anastomoses occurred after orthotopic liver transplantation. Such a treatment allows good long-term results to be achieved by a minimally invasive method.

Oral sulphate solution (OSS: sodium sulphate, potassium sulphate and magnesium sulphate) is a low-volume osmotic agent for cleansing the intestines.

Aim: in a multicentre, prospective, randomized, 3rd phase study with two parallel groups, the effectiveness, safety and tolerability of OSS was evaluated in comparison with Macrogol 4000 with electrolytes (a reference preparation for bowel cleansing in Russia) in adult patients who were scheduled for routine diagnostic colonoscopy.

Methods. This study was conducted in three Russian research centres during the March–December, 2015 period. Men and women over the age of 18 scheduled to undergo routine diagnostic colonoscopy were randomly assigned either to the OSS group or to the Macrogol group with a fractional use mode before the colonoscopy. The colonoscopy researchers were not aware of which preparation had been taken by the patients. Anonymized video records were centrally analysed by three experts. The primary end point was the proportion of patients with a successful bowel preparation for colonoscopy ≥6 points, as determined by the Boston Bowel Preparation Scale of quality assessment (BBPS scale).

Results. 296 patients were randomized in the study (147 patients were treated with OSS, 149 patients received Macrogol); 294 participants were included in the Intention to Treat population (ITT-population), and 274 participants were included in the population of patients who completed the study according to the protocol (Per-Protocol; PP-population) (139 patients received OSS, 135 patients received Macrogol). The proportion of patients with a successful bowel preparation (BBPS ≥6 scores) was high in both groups (OSS [PP-population]: 97.2 % (95 % confidence interval [CI] 89.5–99.3), Macrogol [PP-population]: 97.7 % (95 % CI: 90.7–99.4)). The corrected difference between the groups was -0.5 % (95 % CI: -4.2–3.3), thereby demonstrating “no less effective” of OSS as compared to Macrogol. Compliance with the drug use regime was higher in the OSS group than in the Macrogol group (95.7 % versus 82.3 %, respectively, p-value = 0.0011, ITT-population).

The most common symptom reported in patients was nausea (27.9 % in the OSS group and 12.9 % in the Macrogol group). The proportion of patients who developed nausea was significantly higher in the OSS group than in the Macrogol group (25.2 % compared with 10.2 % when taking the first dose of the preparation (p = 0.0008) and 19.7 % compared with 6.8 % when taking the second dose of the preparation (p = 0.0016)). Differences in other symptoms (bloating, abdominal pain or abdominal discomfort) between the groups were not significant, with the severity of symptoms being generally mild. The safety profile of the investigated preparations in patients with inflammatory bowel disease (IBD) in remission did not differ from that in the general patient population.

The differences in terms of secondary endpoints were not identified, including BBPS assessment for different sections of the colon, the level of polyp detection, the duration and completeness of colonoscopy, and the investigator’s satisfaction with the procedure. The analysis by subgroups also did not reveal any significant differences.

Conclusion. In this study, the “not less effectiveness” of the sulphate solution was demonstrated as compared to Macrogol in a fractional use mode. Both preparations were well tolerated. Despite the higher incidence of nausea in the OSS group, the patients showed significantly higher compliance with the OSS mode as compared to that of Macrogol.

This study is registered with the ClinicalTrials.gov Registry of Clinical Trials, No. NCT02321462.

Aim: to review available data confirming the pathogenetic role of the intestinal microbiota in the formation of irritable bowel syndrome (IBS).

Key findings. Changes in the intestinal biotope cause the development of visceral hypersensitivity and impaired intestinal motor activity, as well as neuroimmune transmission. This article discusses the main aspects of the biological properties of probiotic bacteria in terms of their action within the “brain — intestine — microbiota” chain. The results of experimental and clinical studies elucidating the mechanisms of action of probiotic cultures have been generalized. The understanding of these mechanisms allows practitioners to make informed decisions in prescribing probiotics to IBS patients. Key concepts concerning fecal microbiota transplantation, as well as the prospects and difficulties of implementing this approach are considered.

Conclusions. The term “microbiota — intestine — brain” clearly demonstrates the correlation between the main functional components of IBS. Meta-analyses and systematic reviews confirm the efficacy of probiotics in IBS. However, further research into probiotic therapy options is needed to identify specific bacterial strains with proven clinical efficacy. The fecal microbiota transplantation method also requires further research, since many issues associated with this approach remain unclear.

Aim: to demonstrate the clinical picture and the tactics of differential diagnosis between ulcerative colitis and Clostridium difficile-associated disease in a patient with APS-1, as well as to describe the tactics of managing such patients.

Key findings. A 25-year-old patient with autoimmune polyglandular syndrome type 1 (APS-1) complained of loose stools up to 10 times a day with blood admixture, rapidly growing weakness and a weight loss of 5 kg per week. When examined on the day of admission, surgical pathology was excluded. Further differential diagnostics between Clostridium difficile-associated disease and ulcerative colitis was carried out, with the possibility of combining these diseases being not excluded. The examination confirmed Clostridium difficile-associated disease, while the diagnosis of ulcerative colitis needed further verification. APS-1 is often combined with other diseases and is likely to be pathogenetically related with them; however, the mechanisms of such interrelations still remain unknown. Previous research has reported the relationship between APS-1 and clostridial infection. The combination of ulcerative colitis with APS-1 has not thus far been described.

Conclusion. A specific feature of the described clinical case consists in the development of severe Clostridium difficile-associated disease against the background of autoimmune polyglandular syndrome type 1. The management of patients with APS-1 should take into account the possibility of developing a clostridial infection, since these diseases can co-occur. When treating a patient with APS-1 in non-endocrine hospital units, consultation with an endocrinologist is necessary.

Aim. Clinical guidelines for the management of adult patients suffering from drug-induced liver injuries (DILI) are intended for all medical specialists, who treat such patients in their clinical practice.

Key findings. The presented recommendations contain information about the epidemiological data, terminology, diagnostic principles, classification, prognosis and management of patients with DILI. The recommendations list pharmacological agents that most commonly cause DILI, including its fatal cases. Dose-dependent and predictable (hepatotoxic), as well as dose-independent and unpredictable (idiosyncratic) DILI forms are described in detail, which information has a particular practical significance. The criteria and types of DILI are described in detail, with the most reliable diagnostic and prognostic scales and indices being provided. The pathogenesis and risk factors for the development of DILI are considered. The clinical and morphological forms (phenotypes) of DILI are described. The diseases that are included into the differential diagnosis of DILI, as well as the principles of its implementation, are given. The role and significance of various diagnostic methods for examining a patient with suspected DILI is described, with the liver biopsy role being discussed. Clinical situations, in which DILI can acquire a chronic course, are described. A section on the assessment of causal relationships in the diagnosis of DILI is presented; the practical value of using the CIOMS-RUCAM scale is shown. All possible therapeutic measures and pharmacological approaches to the treatment of patients with various DILI phenotypes are investigated in detail. A particular attention is paid to the use of glucocorticosteroids in the treatment of DILI.

Conclusion. The presented clinical recommendations are important for improving the quality of medical care in the field of hepatology.