Seronegative autoimmune hepatitis (AIH) is a poorly understood problem in both adult patients and children. The key to the diagnosis of AIH is the presence of circulating autoantibodies, which are not detected in seronegative AIH. There is insufficient data on the contribution of autoantibodies to hepatocyte damage in seronegative AIH. The presence of plasma cells in liver biopsies of patients with seronegative AIH suggests that its pathogenesis involves physiopathological mechanisms similar to those of seropositive AIH. Unlike adults, in whom acute manifestations of the disease are rare, in children’s acute manifestations of seronegative AIH were observed in three quarters of patients. In addition to the absence of autoantibodies, the diagnosis is complicated by the low level of gammaglobulins in the blood in seronegative AIH. In seronegative AIH, hepatitis-associated aplastic anemia often develops. Morphological examination of liver biopsies may reveal infiltration with a predominance of CD8+ T cells. Treatment of seronegative AIH includes immunosuppressive therapy, as for seropositive AIH. The prognosis for seronegative AIH is usually favorable. Although seronegative autoimmune hepatitis is not uncommon, little is known about its diagnosis and treatment.

Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is a complex clinical disease with an estimated worldwide prevalence of 1-15%. The transmission routes for HCV and HBV are similar. During co-infection, four serological profiles are observed: codominant, HCV dominant, HBV dominant and non-replicative. Although both HBV and HCV replicate in hepatocytes, their life cycles are quite different. Viral replication in co-infected cells is characterized by the dominance of HCV replication over HBV replication. Three theories of interaction between HCV and HBV are discussed. There are no established recommendations for the treatment of HBV/HCV co-infection. Treatment of chronic hepatitis C without HBV suppression increases the risk of HBV reactivation. In the review, we evaluate studies of both direct-acting antivirals and interferon-based therapies. Screening and prevention of co-infection are important to prevent serious HBV reactivation.

The influence of the gut microbiota on the development of various diseases is of great interest to researchers. The conducted studies showed that in patients with chronic liver diseases, the dominant taxa of the gut microbiota were Bifidobacterium longum, Bifidobacterium adolescentis, Blautia massiliensis, and in healthy children — Neisseria flavescens. There is no comparative analysis of data on the taxonomic diversity of the intestinal microbiota in autoimmune and non-autoimmune liver diseases in children. Purpose. To investigate differences in the taxonomic diversity of fecal microbiota in patients with autoimmune and non-autoimmune liver diseases, as well as to evaluate potential biomarkers of 16S rRNA gene amplicons in these diseases by comparing the taxonomic composition. Material and methods. A metagenomic analysis of the intestinal microbiota of 24 children with chronic liver diseases (mean age 10,3 ± 4,7 years) was carried out with the isolation of the 16S rRNA gene region. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. Results. The conducted study revealed 684 types of microorganisms in the studied samples of patients’ feces. The analysis of the conducted studies showed that no dominant taxa were found in the fecal samples of children with autoimmune liver diseases, while Veillonella dispar, Veillonella parvula, Cloacibacillus porcorum, Prevotella histicola and Bacteroides eggerthii were the dominant taxa in patients with non-autoimmune liver diseases. Conclusion. Studies have shown differences in the composition of the gut microbiota in children with autoimmune and non-autoimmune liver diseases.

Etiology of autoimmune gastritis, particularly in children, is still unknown. However, the role of Helicobacter pylori and Epstein–Barr virus in the development of autoimmune gastritis is being considered. The formation of autoimmune gastritis is based on an autoimmune reaction mediated by CD4+ T-lymphocytes and the formation of antibodies to gastric parietal cells, the target of which is gastric Н+/К+-АТPase, with subsequent destruction of parietal cells and the development of mucosal atrophy. Autoimmune gastritis is considered a precancerous condition. The clinical picture of autoimmune gastritis in children is not associated with any specific symptoms of the digestive organs. Abdominal pain is uncommon. Specific manifestations of a dyspeptic nature are rare. Often there is a syndrome of chronic nonspecific intoxication. Red blood counts in most children with autoimmune gastritis are within the age norm. Iron deficiency anemia occurs in 13.8% of patients. Vitamin B12 deficiency anemia does not occur in children. Autoantibodies to the parietal cells of the stomach are considered to be a serum marker and diagnostic criterion for autoimmune gastritis in children. Treatment of autoimmune gastritis is aimed at preventing iron and/or vitamin B12 deficiency. No specific methods of treatment have been developed so far. Conclusion. The incidence of autoimmune gastritis in children is underestimated. The role of Helicobacter pylori in autoimmune gastritis has not been confirmed. There is a close correlation of antibodies to gastric parietal cells with Epstein–Barr viral DNA. Due to adverse outcomes and the risk of malignancy, early diagnosis of the disease is important. Atrophic gastritis and intestinal metaplasia are precancerous conditions, although extremely rare in childhood, they should not be neglected.

According to modern concepts, chronic gastritis is a group of phenotypically similar diseases, the basis of which is the lesion of the gastric mucosa of different genesis and different regeneration potential. Of particular interest is the group of patients (children in the presented article) in whom gastric mucosa lesions are associated with the current infectious process caused by a combination of two causative factors - Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV). The data obtained as a result of the study of cellular and humoral immunity, autoimmunity and interferon system show significant disorders of immunological reactivity in children with chronic gastritis associated with H. pylori and VEB. The imbalance of T-lymphocyte subpopulations, impaired function of B-lymphocytes, dysimmunoglobulinemia and pronounced imbalance of interferon system with a significant decrease in induced synthesis of IFN-α and IFN-γ by blood leukocytes were revealed. The suppressive effect of VEB on various links of immunity was proved, which necessitates immunocorrective treatment. The results of the study may indicate the trigger role of VEB in the development of autoimmune gastritis.

Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is a complex clinical disease with an estimated worldwide prevalence of 1-15%. The transmission routes for HCV and HBV are similar. During co-infection, four serological profiles are observed: codominant, HCV dominant, HBV dominant and non-replicative. Although both HBV and HCV replicate in hepatocytes, their life cycles are quite different. Viral replication in co-infected cells is characterized by the dominance of HCV replication over HBV replication. Three theories of interaction between HCV and HBV are discussed. There are no established recommendations for the treatment of HBV/HCV co-infection. Treatment of chronic hepatitis C without HBV suppression increases the risk of HBV reactivation. In the review, we evaluate studies of both direct-acting antivirals and interferon-based therapies. Screening and prevention of co-infection are important to prevent serious HBV reactivation.

Ursodeoxycholic acid is a secondary bile acid (BA), present in humans at low concentrations, with well-known therapeutic properties, and was originally used to treat cholestatic liver disease. However, there are very few studies on the effect of ursodeoxycholic acid on the composition of the gut microbiota, especially in children with chronic liver diseases. Purpose . To determine differences in the taxonomic diversity of the fecal microbiota in children with chronic liver disease who receive or do not receive ursodeoxycholic acid. Material and methods . A metagenomic analysis of the intestinal microbiota of 24 children with chronic liver diseases (mean age 10.3 ± 4.7 years) was carried out with the identification of the V3–V4 region of the 16S rRNA gene. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. 17 children received ursodeoxycholic acid. The comparison group consisted of 7 children who did not receive ursodeoxycholic acid. Results . This study found that fecal samples from patients treated with ursodeoxycholic acid do not differ in the taxonomic diversity of the gut microbiota from samples from patients not treated with ursodeoxycholic acid. A more detailed study to determine the existing taxonomic diversity in samples of patients treated with ursodeoxycholic acid and not treated with ursodeoxycholic acid, using the sPLS-DA method, showed that taxa such as Streptococcus anginosus, Coprococcus eutactus, Desulfovibrio desulfuricans, Angelakisella massiliensis and Gemella haemolysans dominated in patients not treated with ursodeoxycholic acid. And for patients receiving drugs with ursodeoxycholic acid, the dominance of the taxon Anaerostipes hadrus is typical. An analysis of differences in the percentage of intestinal microbiota bacterial species showed that patients receiving ursodeoxycholic acid had a higher count of Anaerostipes hadrus, while in patients not receiving ursodeoxycholic acid preparations, the count of Bacteroides dorei, Akkermansia muciniphila was significantly increased, and the counts of other bacteria were also increased. Conclusion . Studies have shown that ursodeoxycholic acid has a positive effect on the intestinal microbiota in children with chronic liver disease by increasing the number of microorganisms that produce short-chain fatty acids.

The impact of gut microbiota on the development of various diseases is of great interest to researchers. However, data on the taxonomic diversity of the intestinal microbiota in chronic liver diseases in children are lacking. Purpose . To study the taxonomic diversity of the fecal microbiota in children with chronic liver diseases in comparison with healthy patients. Material and methods . A metagenomic analysis of the intestinal microbiota of 24 children with chronic liver diseases (mean age 10.3 ± 4.7 years) was carried out with the isolation of the target fragment of the 16S rRNA gene. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. The comparison group consisted of fecal samples of 34 apparently healthy children. Results . The conducted study revealed 684 types of microorganisms in the studied samples of patients’ feces. An analysis of the conducted studies showed that fecal samples of healthy children and patients with chronic liver diseases differ in bacterial diversity. The dominant taxa in healthy children were Neisseria flavescens, in patients with chronic liver diseases, the dominant taxa were Bifidobacterium longum, Bifidobacterium adolescentis, Blautia massiliensis. At the same time, Bifidobacterium longum, Bifidobacterium adolescentis, Blautia massiliensis in fecal samples of patients with chronic liver diseases was 8 times as high. Conclusion . Studies have shown differences in the composition of the intestinal microbiota in healthy children and children with chronic liver diseases.

The value of the liver–gut axis is increasingly recognized as a major modulator of autoimmunity. There is no comparative analysis of data on the taxonomic diversity of the intestinal microbiota in chronic liver diseases in children. Purpose. To investigate the taxonomic diversity of the intestinal microbiota in children with chronic liver diseases compared with healthy patients, to identify differences in bacterial diversity in autoimmune and non-autoimmune liver diseases, as well as the impact of immunosuppressive therapy on the intestinal microbiota. Material and methods. A metagenomic analysis of the gut microbiota of 24 children with chronic liver diseases (mean age 10,3 ± 4,7 years) was carried out with the identification of the V3–V4 region of the 16S rRNA gene. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. The control group consisted of fecal samples of 34 apparently healthy children. Results. When comparing fecal samples of children with autoimmune liver diseases with samples of healthy children, the taxa of Bacteroides dorei, Collinsella aerofaciens, Ruminococcus caffidurs prevailed, and for children of the control group — Neisseria flavescens. When comparing samples of patients with non-autoimmune liver diseases and the control group, it was found that the taxa Bacteroides fragilis, Klebsiella pneumoniae, Bifidobacterium longum prevailed in healthy children. When comparing fecal samples from children with autoimmune and non-autoimmune liver diseases, it was found that Veillonella dispar, Cloacibacillus porcorum, Veillonella parvula, Prevotella histicola and Bacteroides eggerthii taxa dominate in patients with non-autoimmune diseases. No dominant taxa of the gut microbiota were found in children with autoimmune liver diseases. It has been established that the taxa Veillonella dispar, Faecalibacterium prausnitzii, Roseburia inulinivorans, Bacteroides xylanisolvens and Alistipes obesi prevail in patients receiving immunosuppressive therapy, and the taxa Phascolarctobacterium succinatutens, Bacteroides ovatus, Solobacterium mooreis and Holdemanella massilien prevail in patients not receiving immunosuppressive therapy. Conclusion. A recent study of the gut microbiota in children with chronic liver disease shows differences in the imbalance of the gut microbiota compared to the results obtained in adults. The gut microbiota model is capable of distinguishing autoimmune liver diseases from non-autoimmune diseases. Immunosuppressive therapy is accompanied by the dominance of taxa that reduce the production of short-chain fatty acids.

Исследования кишечного микробиома в настоящее время вызывают большой интерес у клиницистов. Это связано с тем, что результаты проведенных исследований показывают тесную взаимосвязь кишечного микробиома с развитием различных заболеваний. В статье представлены современные методы отбора проб для исследований, охарактеризованы мультиомические методы исследования (метагеномика, метапротеомика, метатранскриптомика, метаболомика) и возможности их применения в клинической практике с указанием их преимуществ и недостатков. Описаны наиболее распространенные методы исследования (при этом особое внимание уделено изучению кишечного микробиома), в которых можно получить оптимально объективные результаты и точность вычислительного анализа данных. Эти исследования будут способствовать развитию персонализированной медицины, которая будет применяться в самых различных областях — от точной идентификации патогенных штаммов для целенаправленного лечения до тщательного мониторинга дисбаланса микробных сообществ при заболеваниях и до персонализированного и рационального плана манипуляций с микробиомом.

The article presents the results of a review of publications devoted to the study of the problems of drug-induced liver damage in inflammatory bowel diseases (IBD). The hepatotoxic effect of thiopurines (azathioprine and 6-mercaptopurine) — hepatotoxicity from 0% to 17%; sulfasalazine and mesalamine (hepatotoxicity from 0% to 4%); methotrexate (hepatotoxicity from 15% to 50%); tumor necrosis factor inhibitors (hepatotoxicity up to 75% of cases.), anti-integrins (hepatotoxicity from 2% to 5%); an interleukin 12/23 inhibitor (hepatotoxicity from 0,5% to 2%); Janus-kinase inhibitors is considered (hepatotoxicity from 1% to 2%).Conclusion. The drugs currently used to treat IBD require periodic liver function tests to rule out drug-induced lesions that require therapy correction. As the range of new drugs is rapidly expanding, this requires special observation and discussion in terms of their adverse effects on the liver.

The clinical guidelines for the diagnosis and treatment of the3 functional disorders of the digestive system in children were prepared by a Group of Experts, domestic leading specialists in the field of the pediatric gastroenterology, who generalized the foreign guidelines and domestic experience, suggesting the tactics for the pediatrician actions in the everyday practice. Part 3 of the Guidelines discusses the billiard tract dysfunctions and functional constipations. There are no biliary tract dysfunctions in the Pediatric Sections of Rome Consensus IV; however, the Russian pediatric school of thought has always considered them as important in terms of one of the causes for abdominal pain in children. This attitude was supported by the experts, and it is maintained in these Guidelines. The functional constipations are common in the children of different ages, and they present not only a medical problem, but also a serious social one for both children and their parents. That is why the considerable attention has been paid to this pathology considering the psychosocial aspects of the correction.

The tolerance, efficacy and safety of use in the nutrition of children from 12 to 36 months, diagnosed with acute respiratory infection, who received antibacterial therapy, were assessed, food/juice drinks enriched with prebiotic, minerals and vitamins for the nutrition of young children. The study included 60 children aged 12 to 36 months diagnosed with acute respiratory infection, who received a course of antibiotic therapy. The children of the main group (30 patients) received, after discharge from the hospital, a juicecontaining drink enriched with inulin, calcium, iron, vitamins C, E, A and D3, 130 ml once a day for 90 ± 1 day (3 months). The comparison group (control) included 30 patients who did not receive this product after discharge. Analysis of the data obtained showed that the daily use of non-adapted fermented milk products for children contributed to the prevention of dyspeptic disorders associated with the intake of antibacterial drugs, comfortable digestion, and an increase in the levels of secretory immunoglobulin A and lysozyme in the feces. Juice drinks enriched with inulin, calcium, iron, vitamins C, E, A and D3 are recommended to be included in the daily diet of healthy children over 12 months old and the diet of children over 12 months old with functional disorders of the gastrointestinal tract (constipation), used in diet therapy for prevention intestinal dysbiosis, in the daily diet of children who are often and for a long time ill, acute period of acute respiratory infections and acute respiratory viral infections, as well as at the stage of convalescence.

Sclerosing cholangitis is one of the most common hepatologic extraintestinal manifestations of inflammatory bowel disease. The article discusses the phenotype of the combination of sclerosing cholangitis and inflammatory bowel disease. The authors present their theories of the etiopathogenesis of sclerosing cholangitis in patients with inflammatory bowel disease, as well as some features of the phenotype of both mixed and monogenic forms of diseases.Sclerosing cholangitis in combination with inflammatory bowel disease is commonly associated with pancolitis, but the endoscopically visualized activity of inflammatory bowel diseases is significantly lower and clinical symptoms are less pronounced. The authors have established that the patients with the combination of sclerosing cholangitis and inflammatory bowel disease are at the increased risk of developing malignant neoplasms. The formation mechanisms of a combination of inflammatory bowel disease and sclerosing cholangitis remain poorly understood, although this pathology is influenced by lymphocytic cross-reactivity, aberrant recognition of microbiotic epitopes and intestinal microbiota imbalance. New biological agents aimed at correcting the interaction between the immune system and target organs may provide new ways of treatment for sclerosing cholangitis associated with inflammatory bowel disease.

The tolerance, efficacy and safety of use in the nutrition of children from 12 to 36 months, diagnosed with acute respiratory infection, who received antibacterial therapy, were assessed, food/juice drinks enriched with prebiotic, minerals and vitamins for the nutrition of young children. The study included 60 children aged 12 to 36 months diagnosed with acute respiratory infection, who received a course of antibiotic therapy. The children of the main group (30 patients) received, after discharge from the hospital, a juicecontaining drink enriched with inulin, calcium, iron, vitamins C, E, A and D3, 130 ml once a day for 90 ± 1 day (3 months). The comparison group (control) included 30 patients who did not receive this product after discharge. Analysis of the data obtained showed that the daily use of non-adapted fermented milk products for children contributed to the prevention of dyspeptic disorders associated with the intake of antibacterial drugs, comfortable digestion, and an increase in the levels of secretory immunoglobulin A and lysozyme in the feces. Juice drinks enriched with inulin, calcium, iron, vitamins C, E, A and D3 are recommended to be included in the daily diet of healthy children over 12 months old and the diet of children over 12 months old with functional disorders of the gastrointestinal tract (constipation), used in diet therapy for prevention intestinal dysbiosis, in the daily diet of children who are often and for a long time ill, acute period of acute respiratory infections and acute respiratory viral infections, as well as at the stage of convalescence.

The article presents a clinical case of omentum lymphangioma in a child, which was successfully resected by open laparoscopy. This clinical case indicates the need for caution in relation to tumors of the abdominal cavity, which for a long time can occur against the background of nonspecifi c complaints or asymptomatically, and also shows positive dynamics against the background of the therapy.