Аim: to present data of Russian and foreign studies about association between physical activity (PA) and gallstone disease (GSD).

Key point. A low PA level is one of the four major risk factors for chronic non-infectiuos diseases. The frequency of low PA in men and women of the Russian Federation (according to the medical examination in 2016) is 19 %. The global prevalence of GSD is up to 20 % among adults. Many systematic reviews and meta-analyses have confirmed an inverse association between GSD and PA in the world, regardless of potential risk factors for GSD, with a clear dose-dependent effect — the relative risk (RR) of GSD was 0.87 (95 % CI 0.83–0.92) per 20 metabolic equivalents (MET) of PA per week. According to our results of an epidemiological survey in the framework of the WHO MONICA program in Novosibirsk (n = 870) among women aged 25–64 with low total PA (less than 800 MET/min/week), as well as with the first class of PA in leisure-time, GSD occurred much more often (class 1 — 33 %, classes 2–4 — 8.7–11.0 %, p < 0.01). PA favorably affects almost all mechanisms of gallstone formation: improves cholesterol metabolism in bile, increases serum HDL cholesterol, bile acid synthesis, stimulates the release of cholecystokinin, reduces mucin hypersecretion, increases the diversity and richness of the intestinal microbiota. Daily PA serves as a preventive measure for GSD: the risk of GSD is reduced by 66 % (95 % CI 0.18–0.86).

Conclusion. EASL has recognized PA as a protective agent against gallstone formation.

Аim: Evaluation of methods for pain prevention and pain reduction after anorectal surgery at all stages of treatment based on publications found in available databases.

Key points. Most anorectal diseases are benign and do not affect life expectancy, meanwhile about 40 % of the population suffer from it. Mainly anorectal disorders affect middle-aged people reducing their life quality. At the same time many articles aimed at studying only postoperative anesthesia. 2 researchers independently searched for articles published in Medline, Scopus, Cochrane, Web of Science, E-library databases using keywords. A total of 54 publications were included. A multimodal approach should include the pain prevention during pre-, intra- and postoperative periods. Acetaminophen is recommended for pain reduction according to the dosing protocols. Acetaminophen combined with other systemic analgesics is advisable for patients with severe pain. The opioids use is justified only for moderate-severe postoperative pain. Metronidazole and lidocaine with nitroglycerin ointment/ nifedipine/сorticosteroids effectiveness has been proven for local postoperative anesthesia. Prophylactic use of antibiotics and bowel preparation do not reduce postoperative pain. Stool softeners are recommended for reducing postoperative pain severity. Additional local anesthesia such as nerve blockade or infiltration anesthesia is recommended for all patients. Modern minimally invasive treatment methods of hemorrhoid are associated with less severe postoperative pain.

Conclusion. The recommended scheme of multimodal anesthesia for patients after anorectal surgery is shown on Fig.1. Further studies are needed to evaluate preoperative anesthesia effectiveness, the feasibility of the perioperative flavonoids use, as well as comparisons of various minimally invasive treatment methods of anorectal diseases.

Аim: to identify predictors of insufficient effectiveness of proton pump inhibitors based on the evaluation of the results of 24-hour pH-impedance and high-resolution esophageal manometry in patients with Barrett's esophagus.

Materials and methods. 52 patients with histologically confirmed Barrett's esophagus who are on therapy with proton pump inhibitors were examined. All patients underwent daily pH-impedance and high-resolution esophageal manometry.

Results. According to daily pH-impedance, group 1 consisted of 37 patients who responded satisfactorily to antisecretory therapy, group 2 of 15 patients who demonstrated insufficient response to acid-suppressive therapy, 11 of whom had no clinical manifestations. The total number of reflux averaged 55 in group 1 and 106 in group 2. The average number of acid reflux in group 1 was 5.68, in group 2 — 48.5. The average number of non-acid reflux prevailed in patients of group 2 and averaged 58, in group 1 the indicator averaged 47. Evaluation of the results of high-resolution esophageal manometry showed that violations of the structure and function of the esophago-gastric junction were detected in 21 patients out of 52. Disorders of the motility of the thoracic esophagus were detected in 31 patients out of 52. When comparing the frequency of motor disorders from the thoracic esophagus in groups 1 and 2, no significant differences were obtained. However, significantly more frequent registration of violations of the structure and/or function of the esophago-gastric junction was found in the group with unsatisfactory effectiveness of proton pump inhibitors.

Conclusion. In a number of patients with Barrett's esophagus, there is an insufficient effect of acid-suppressive therapy and at the same time an asymptomatic course of the disease, which may increase the risk of its progression. Predictors of insufficiently successful treatment of patients with Barrett's esophagus may be both insufficient pharmacological effect of proton pump inhibitors themselves, and motility disorders that cause the presence of non-acid reflux, decreased esophageal clearance, which in turn may cause the patient's symptoms to persist and adversely affect the condition of the esophageal mucosa.

Аim: to conduct a comparative analysis of serum albumin's structural and functional properties in decompensated cirrhotic patients by means of spin prob EPR spectroscopy.

Materials and methods. The main study group included 70 patients with decompensated liver cirrhosis and ascites. The control group consisted of 12 healthy volunteers, comparable in gender and age, without liver diseases. To assess the structural and functional ability, serum albumin was analyzed by EPR spectroscopy.

Results. Albumin levels within reference intervals were found in 37 patients (59.8 %). The native albumin index decrease in cirrhotic patients as the disease progressed with the lowest values in the Child – Pugh C group (p < 0.001). The binding efficiency of albumin decreased in accordance with the severity of cirrhosis with minimal albumin binding capacity in the Child – Pugh C (Me = 25.43 %; n = 30; p < 0.001). The transport activity of RTQ albumin decreased in patients with decompensated cirrhosis, the lowest transport ability was observed in the Child – Pugh C group (Me = 26.09 %). In patients with decompensated disease the detoxification potential was significantly reduced: Child – Pugh B — Me = 44.03 %; Child – Pugh C — Me =17.16 %. Despite the normal values of serum albumin in 72.5% of patients with cirrhosis B and in 26.7% in the cirrhosis C group, only 12.3% in the cirrhosis B group had normal albumin function and in cirrhosis C nо patients had normal albumin function.

Conclusion. There were not only serum concentration depletion in cirrhotic patients, but also albumin physiological non-oncotic properties were violated. The severity of these changes increased with the progression of cirrhosis. Our data allow us to raise the question of the need to use the EPR test to determine indications for albumin replacement therapy in patients with cirrhosis and the presence of ascites, even at normal values of its serum concentration.

Аim: to evaluate the state of small intestine permeability by the “double sugar test” in patients with overlap syndrome (autoimmune hepatitis / primary biliary cholangitis (AIH / PBC)).

Materials and methods. Prospectively, 56 people were included in the study. Of these, 26 were diagnosed with AIH/PBC, 30 were in the control group. The diagnosis was made in accordance with the current recommendations. The average age of patients was 49.7 ± 13.8 years, healthy volunteers — 48.6 ± 9.2 years. The determination of the permeability of the small intestine was carried out by a “double sugar test” (the ratio of lactulose/mannitol in urine), using the method of high-performance liquid chromatography — mass spectrometry.

Results. In patients with AIH/PBC, an increase in intestinal permeability was found — 0.20 [0.09; 0.30] (p < 0.001) compared with the control group 0.01 [0.01; 0.02]. We divided patients at the stage of liver damage. An increased small intestinal permeability was revealed: hepatitis stage — 0.19 [0.13; 0.30] (p < 0.001), liver cirrhosis stage — 0.18 [0.09; 0.30] (p < 0.05) compared with the control group. In the early stages of disease (1 month from the onset of the disease) had an increased lactulose/mannitol ratio — 0.13 [0.05; 0.26] (p < 0.001) compared to the control group. In the presence of portal hypertension (PH), small intestinal permeability was increased — 0.18 [0.09; 0.30] (p < 0.001) compared with the control group.

Conclusions. An increase in small bowel permeability was found in patients with overlapping syndrome. All patients had increased intestinal permeability (regardless of the presence of extrahepatic manifestations).

Аim: to reveal the rate of large rearrangements in the genes responsible for familial adenomatous polyposis, MUTYH-associated polyposis and Peutz–Jeghers syndrome.

Materials and methods. The MLPA method was used for identification of large rearrangements. A total number of 135 patients was included in the study: 83 patients with a clinical diagnosis of “familial adenomatous polyposis”, 18 — with suspected MUTYH-associated polyposis, and 34 — with a clinical diagnosis of “Peutz–Jeghers syndrome”.

Results. Seven large deletions and one large duplication in the APC gene were identified in 83 patients with classic familial adenomatous polyposis, with rate of large rearrangements 9.6 % (8/83). In 18 patients with suspected MUTYH-associated polyposis, no large rearrangements were found in the MUTYH gene. Four large deletions in the STK11 gene (12 %, 4/34) were detected in 34 patients with Peutz–Jeghers syndrome.

Conclusion. For the first time, the expediency of including the method of detecting large rearrangements in routine DNA test list for Russian patients with various hereditary polyposis syndromes is demonstrated. Routine use of MLPA method makes it possible to increase the total frequency of detection of pathogenic variants in the APC and STK11 genes above 90 %. At the same time, the need for searching of large rearrangements in the MUTYH gene were not justified.

Аim: to analyze the main pharmacokinetic properties of proton pump inhibitors (PPIs) and their significance in the treatment of gastroesophageal reflux disease (GERD).

Key points. Pantoprazole has a high bioavailability, the absolute bioavailability of pantoprazole at a dose of 40 mg is 77 % from the first dose and does not change with repeated use. Pantoprazole shows a faster onset of action than omeprazole. Simultaneous food intake does not change the bioavailability of pantoprazole. Suppression of hydrochloric acid production while taking pantoprazole accompanies by the achievement of endoscopic remission of GERD by day 28 in 91 % of patients with reflux esophagitis and by day 56 in all patients in the PANSTAR studies. Pantoprazole has little effect on CYP2C19 compared to other PPIs, minimizing the risk of drug-drug interactions. Pantoprazole is the most pH-selective PPI, which determines the specificity of action only in the parietal cells of the stomach and the greatest safety of long-term use in patients with comorbid pathology.

Conclusion. PPIs form the basis of the therapy of acid-dependent diseases, and, in particular, gastroesophageal reflux disease. Pantoprazole is distinguished from other PPIs by its persistent high bioavailability, long-term antisecretory effect, and very low affinity for cytochrome P450.

Аim: to describe clinical cases of Wilson – Konovalov disease in pediatric patients.

Key points. The first clinical case demonstrates the manifestation of Wilson – Konovalov disease with unexplained mild elevation of aminotransferases at the age of 6 years. Despite the persistent hyperenzymemia, no additional laboratory tests were prescribed. At the age of 10, the patient showed signs of liver failure and neurological symptoms. Laboratory and instrumental examination enabled to diagnose Wilson – Konovalov disease at the stage of liver cirrhosis. The diagnosis was confirmed at the Federal medical center. The diagnosis was delayed and made 4 years after the hyperenzymemia was first revealed. The relief of clinical signs was observed after the orthotopic transplantation of the right lobe of the liver from a living related donor. The patient was under surveillance for 10 years after the transplantation.

The second clinical case shows another variant of the course of the Wilson – Konovalov disease manifested as an acute hepatitis. To clarify the etiology of the disease, the patient was hospitalized. In 2 weeks, the patient developed symptoms of acute liver failure, progressive hemorrhagic syndrome, acute hepatic encephalopathy. Death from fulminant hepatitis occurred in 3 weeks after the disease onset after the disease onset.

Conclusion. Healthcare workers should be aware of clinical signs of Wilson – Konovalov disease. Screening for the disease is recommended for children with an unexplained increase of liver transaminases, acute liver failure, chronic hepatitis and liver cirrhosis.

Аim: diagnosis and treatment algorithms in the clinical recommendations intended for general practitioners, gastroenterologists, infectious disease specialists, hepatologists on the of chronic hepatitis C are presented.

Summary. Chronic viral hepatitis C is a socially significant infection, the incidence of which in the Russian Federation remains significantly high. Over the past 10 years, great progress has been made in the treatment of hepatitis C — direct acting antiviral drugs have appeared. The spectrum of their effectiveness allows to achieve a sustained virological response in more than 90 % of cases, even in groups that were not previously considered even as candidates for therapy or were difficult to treat — patients receiving renal replacement therapy, after liver transplantation (or other organs), at the stage of decompensated liver cirrhosis, HIV co-infected, etc. Interferons are excluded from the recommendations due to their low effectiveness and a wide range of adverse events. The indications for the treatment have been expanded, namely, the fact of confirmation of viral replication. The terms of dispensary observation of patients without cirrhosis of the liver have been reduced (up to 12 weeks after the end of therapy). Also, these recommendations present approaches to active screening of hepatitis in risk groups, preventive and rehabilitation measures after the end of treatment.

Conclusion. Great success has been achieved in the treatment of chronic hepatitis C. In most cases, eradication of viral HCV infection is a real task even in patients at the stage of cirrhosis of the liver, with impaired renal function, HIV co-infection, after solid organs transplantation.