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Concept on the pathogenesis and treatment of primary biliarycirrhosis

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World Journal of Gastroenterology 2006年第45期12卷 7250-7262页

作者： vasiliy ivanovich reshetnyak Scientific Research Institute of General Reaniamatology Russia Academy of Medical SciencesMoscowRussia

Primary biliary cirrhosis (PBC) is an organ-specific autoimmune disease that predominantly affects women and is characterized by chronic, progressive destruction of small intrahepatic bile ducts with portal inflammation and ultimately fibrosis, leading to liver failure in the absence of treatment. Little is known about the etiology of PBC. PBC is characterized by anti-mitochondrial antibodies and destruction of intrahepatic bile ducts. The serologic hallmark of PBC is the presence of auto-antibodies to mitochondria, especially to the E2 component of the pyruvate dehydrogenase complex (PDC). Current theories on the pathogenesis of PBC favor the hypothesis that the disease develops as a result of an inappropriate immune response following stimulation by an environmental or infectious agent. Some reports suggest that xenobiotics and viral infections may induce PBC. The pathogenetic mechanism is believed to be caused by a defect in immunologic tolerance, resulting in the activation and expansion of self-antigen specific T and B lymphocyte clones and the production of circulating autoantibodies in addition to a myriad of cytokines and other inflammatory mediators. This leads to ductulopenia and persistent cholestasis, by developing end-stage hepatic-cell failure. In this review are given our own and literary data about mechanisms of development of intrahepatic cholestasis and possible ways of its correction.

关键词： Primary biliary cirrhosis Pathogenesis Treatment

Significance of dormant forms of Helicobacter pylori in ulcerogenesis

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World Journal of Gastroenterology 2017年第27期23卷 4867-4878页

作者： vasiliy ivanovich reshetnyak Tatiana Magomedalievna reshetnyak VA Negovsky Research Institute of General Reanimatology of Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology Department of Systemic Connective Tissue Diseases VA Nasonova Research Institute of Rheumatology

Nearly half of the global population are carriers of Helicobacter pylori(H. pylori),a Gram-negative bacterium that persists in the healthy human stomach. H. pylori can be a pathogen and causes development of peptic ulcer disease in a certain state of the macroorganism. It is well established that H. pylori infection is the main cause of chronic gastritis and peptic ulcer disease(PUD). Decontamination of the gastric mucosa with various antibiotics leads to H. pylori elimination and longer remission in this disease. However,the reasons for repeated detection of H. pylori in recurrent PUD after its successful eradication remain unclear. The reason for the redetection of H. pylori in recurrent PUD can be either reinfection or ineffective anti-Helicobacter therapy. The administration of antibacterial drugs can lead not only to the emergence of resistant strains of microorganisms,but also contribute to the conversion of H. pylori into the resting(dormant) state. The dormant forms of H. pylori have been shown to play a potential role in the development of relapses of PUD. The paper discusses morphological H. pylori forms,such as S-shaped,C-shaped,U-shaped,and coccoid ones. The authors proposes the classification of H. pylori according to its morphological forms and viability.

关键词： Helicobacter pylori Forms of H. pylori Dormant forms of H. pylori Viable forms of H. pylori Non-viable forms of H. pylori Physiological states of H. pylori Culturable forms of H. pylori Unculturable forms of H. pylor Resuscitation of dormant H. pylori Ulcerogenesis

Concept of the pathogenesis and treatment of cholelithiasis

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World Journal of Hepatology 2012年第2期4卷 18-34页

作者： vasiliy ivanovich reshetnyak VA Negovsky Scientific Research Institute of General Reanimatology Russia Academy of Medical Sciences

Gallstone disease(GD) is a chronic recurrent hepatobiliary disease,the basis for which is the impaired metabolism of cholesterol,bilirubin and bile acids,which is characterized by the formation of gallstones in the hepatic bile duct,common bile duct,or *** is one of the most prevalent gastrointestinal diseases with a substantial burden to health care *** can result in serious outcomes,such as acute gallstone pancreatitis and gallbladder *** epidemiology,pathogenesis and treatment of GD are discussed in this *** prevalence of GD varies widely by *** prevalence of gallstone disease has increased in recent *** is connected with a change in lifestyle:reduction of motor activity,reduction of the physical load and changes to *** of the important benefits of early screening for gallstone disease is that ultrasonography can detect asymptomatic cases,which results in early treatment and the prevention of serious *** pathogenesis of GD is suggested to be multifactorial and probably develops from complex interactions between many genetic and environmental *** suggests that corticosteroids and oral contraceptives,which contain hormones related to steroid hormones,may be regarded as a model system of cholelithiasis development in *** achievement in the study of the physiology of bile formation and the pathogenesis of GD has allowed expanding indications for therapeutic treatment of GD.

关键词： Gallstone disease:Epidemiology Pathogenesis of cholesterol stones Treatment

New insights into the pathogenesis of primary biliary cholangitis asymptomatic stage

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世界胃肠病学杂志:英文版 2023年第37期29卷 5292-5304页

作者： vasiliy ivanovich reshetnyak Igor Veniaminovich Maev Department of Propaedeutics of Internal Diseases and Gastroenterology A.I.Yevdokimov Moscow State University of Medicine and DentistryMoscow 127473Russia

Primary biliary cholangitis(PBC)is a chronic cholestatic progressive liver disease and one of the most important progressive cholangiopathies in *** to cholangiocytes triggers the development of intrahepatic cholestasis,which progresses to cirrhosis in the terminal stage of the *** data indicate that damage to biliary epithelial cells[(BECs),cholangiocytes]is most likely associated with the intracellular accumulation of bile acids,which have potent detergent properties and damaging effects on cell *** mechanisms underlying uncontrolled bile acid intake into BECs in PBC are associated with pH change in the bile duct lumen,which is controlled by the bicarbonate(HCO3-)buffer system“biliary HCO3-umbrella”.The impaired production and entry of HCO3-from BECs into the bile duct lumen is due to epigenetic changes in expression of the X-linked microRNA *** on the growing body of knowledge on the molecular mechanisms of cholangiocyte damage in patients with PBC,we propose a hypothesis explaining the pathogenesis of the first morphologic(ductulopenia),immunologic(antimitochondrial autoantibodies)and clinical(weakness,malaise,rapid fatigue)signs of the disease in the asymptomatic *** review focuses on the consideration of these mechanisms.

关键词： Primary biliary cholangitis Antimitochondrial autoantibodies MicroRNA 506 Inositol-1,4,5-trisphosphate receptor type 3 Chloride/bicarbonate anion exchanger 2 Biliary bicarbonate umbrella Dihydrolipoyl transacetylase(E2 subunit) Pyruvate dehydrogenase complex

Helicobacter pylori:Commensal,symbiont or pathogen?

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World Journal of Gastroenterology 2021年第7期27卷 545-560页

作者： vasiliy ivanovich reshetnyak Alexandr Igorevich Burmistrov Igor Veniaminovich Maev Department of Propaedeutic of Internal Diseases and Gastroenterology A.I.Yevdokimov Moscow State University of Medicine and DentistryMoscow 127473Russia

This review considers the data on Helicobacter pylori(***),which have been accumulated over 40 years since its description as an etiological factor in gastrointestinal *** majority of modern publications are devoted to the study of the pathogenic properties of the microorganism in the development of chronic gastritis,peptic ulcer disease,and gastric cancer,as well as methods for its ***,in recent years,there have been more and more studies which have suggested that *** has a beneficial,or potentially positive,effect on the human *** authors have attempted to objectively analyze the information accumulated in the literature on *** studies consider it as one of the recently identified human bacterial pathogens,and special attention is paid to the evidence suggesting that it is probably part of the composition of the human microbiome as a commensal(commensal from French to English is a table companion)or even a *** presented data discussing the presence or absence of the effect of *** on human health suggest that there is an apparent ambiguity of the *** re-assessment of the data available on *** infection is important in order to answer the question of whether it is necessary to create a program of mass *** eradication or to apply a more personalized approach to treating patients with ***-associated gastrointestinal diseases and to perform eradication therapy.

关键词： Helicobacter pylori Pathogen Commensal Microbiome Peptic ulcer Gastric cancer Asthma Inflammatory bowel diseases

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Hepatitis G virus

World Journal of Gastroenterology 2008年第30期14卷 4725-4734页

作者： vasiliy ivanovich reshetnyak Tatiana Igorevna Karlovich Ljudmila Urievna Ilchenko Scientific Research Institute of General Reanimatology Russia Academy of Medical Sciences M.P. Chumakov Institute of Poliomyelitis and Viral Encephalitides Russia Academy of Medical Sciences

A number of new hepatitis viruses (G, TT, SEN) were discovered late in the past century. We review the data available in the literature and our own findings suggesting that the new hepatitis G virus (HGV), disclosed in the late 1990s, has been rather well studied. Analysis of many studies dealing with HGV mainly suggests the lymphotropicity of this virus. HGV or GBV-C has been ascertained to influence course and prognosis in the HIV-infected patient. Until now, the frequent presence of GBV-C in coinfections, hematological diseases, and biliary pathology gives no grounds to determine it as an "accidental tourist" that is of no significance. The similarity in properties of GBV-C and hepatitis C virus (HCV) offers the possibility of using HGV, and its induced experimental infection, as a model to study hepatitis C and to develop a hepatitis C vaccine.

关键词： Hepatitis G virus Markers of GBV-C Epidemiology Clinical manifestations

Primary biliary cirrhosis: Clinical and laboratory criteria for its diagnosis

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World Journal of Gastroenterology 2015年第25期21卷 7683-7708页

作者： vasiliy ivanovich reshetnyak V.A. Negovsky Research Institute of General Reanimatology

Primary biliary cirrhosis(PBC) is a chronic progressive cholestatic granulomatous, and destructive inflammatory lesion of small intralobular and septal bile ducts, which is likely to be caused by an autoimmune mechanism with a the presence of serum antimitochondrial antibodies and a potential tendency to progress to cirrhosis. Despite the fact that the etiology of this disease has beenunknown so far, there has been a considerable body of scientific evidence that can reveal the clinical and laboratory signs of PBC and the individual components of its pathogenesis and elaborate diagnostic criteria for the disease and its symptomatic therapy. Deficiencies in autoimmune tolerance are critical factors for the initiation and perpetuation of the disease. The purpose of this review is to summarize the data available in the literature and the author's findings on clinical and laboratory criteria for the diagnosis of PBC. This review describes the major clinical manifestations of the disease and the mechanisms of its development. It presents the immunological, biochemical, and morphological signs of PBC and their significance for its diagnosis. A great deal of novel scientific evidence for the problem of PBC has been accumulated. However, the inadequate efficiency of therapy for the disease lends impetus to the quest for its etiological factors and to further investigations of its pathogenetic mechanisms and, on this basis, to searches for new methods for its early diagnosis.

关键词： Primary biliary cirrhosis Clinical criteria Laboratory criteria Immunological signs Biochemicalsigns Morphological signs

Mechanism for development of malnutrition in primary biliary cholangitis

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World Journal of Meta-Analysis 2022年第3期10卷 81-98页

作者： vasiliy ivanovich reshetnyak Igor Veniaminovich Maev Department of Propaedeutic of Internal Diseases and Gastroenterology A.I.Yevdokimov Moscow State University of Medicine and DentistryMoscow 127473Russia

Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease that is associated with impaired biliary excretion *** with the development of cholestasis,there is a deficient flow of bile acids into the intestinal lumen causing malnutrition(MN)that is manifested in deficiencies of both macro-and *** mechanism for development of trophological insufficiency is ***,the trigger of MN in PBC is impaired enterohepatic circulation of bile *** ingress of bile acids with a detergent effect into the general bloodstream,followed by elimination via the kidneys and skin,triggers a cascade of metabolic disturbances,which leads to the gradual development and progression of calorie *** latter gradually transforms into protein-calorie MN(PСM)(as marasmus)due to the insufficient entry of bile acids into the duodenum,which is accompanied by a decrease in the emulsification,hydrolysis,and absorption of fats and fat-soluble vitamins,as well as disturbance of intestinal motility and bacterial ***-soluble vitamin deficiencies complement PСM with vitamin and mineral *** development of hepatocellular failure enhances the progression of PСM due to the impaired protein synthetic function of hepatocytes in the advanced stage of PBC,which results in deficiency of not only the somatic but also the visceral pool of proteins.A mixed PСM form of marasmus and kwashiorkor *** recognition of energy,protein,micronutrient,and macronutrient deficiencies is of great importance because timely nutritional support can improve liver function and quality of life in patients with *** this case,it is important to know what type(energy,proteincalorie,vitamin,and vitamin-mineral)and form(marasmus,marasmuskwashiorkor)of MN is present in the patient and how it is associated with the stage of the ***,it is recommended to screen all patients with PBC for MN,from the early asymptomatic stage of the disease in order

关键词： Primary biliary cholangitis Malnutrition Calorie Protein-calorie Vitamin-mineral malnutrition Marasmus and marasmus-kwashiorkor malnutrition

Reperfusion injury after critical intestinal ischemia and its correction with perfluorochemical emulsion "perftoran"

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World Journal of Gastroenterology 2005年第45期11卷 7084-7090页

作者： Vyacheslav Leontjevich Kozhura Dmitriy Alexeevich Basarab Marina Innokentievna Timkina Arkadiy Mikhailivich Golubev vasiliy ivanovich reshetnyak Viktor Vasiljevich Moroz Research Institute of General Reanimatology

AIM： To investigate the anti-ischemic properties of perfluorochemical emulsion ＂perftoran＂ in mesenteric region. METHODS： Experiments were conducted on 146 nonlinear white male rats weighing 200-350 g. Partial critical intestinal ischemia was induced by thorough atraumatic strangulation of 5-6 cm jejunal loop with its mesentery for 90 rain. Global critical intestinal ischemia was made by atraumatic occlusion of the cranial mesenteric artery （CMA） for 90 rain also. Perftoran （PF, 0.8-1.0 mL per 100 g） in experimental groups or 0.9% sodium chloride in control groups was injected at 75 rain of ischemic period. Mean systemic arterial blood pressure （BPM） registration, intravital microscopy and morphological examination of ischemic intestine and its mesentery were performed in both groups. RESULTS： During 90 min of reperfusion, BPM progressively decreased to 27.3±7.4% after PF administration vs 38.6±8.0% in the control group of rats with partial intestinal ischemia （NS） and to 50.3±6.9% vs 53.1±5.8% in rats after global ischemia （NS）. During the reperfusion period, full restoration of microcirculation was never registered; parts with restored blood flow had leukocyte and erythrocyte stasis and intra-vascular clotting, a typical ＂non-reflow＂phenomenon. The reduction of mesenteric 50-400 μm feeding artery diameter was significantly less in the PF group than in the control group （24±5.5% vs 45.2±3.6%, P〈0.05） 5 min after partial intestinal ischemia. This decrease progressed but differences between groups minimized at the 90th min of reperfusion （41.5±4.2% and 50.3±2.8%, respectively）. In reperfusion of rat＇s intestine, a significant mucosal alteration was registered. Villous height decreased 2.5-3 times and the quantity of crypts decreased more than twice. In the group of rats administered PF, intestinal mucosal layer was protected from irreversible post-ischemic derangement during reperfusion. Saved cryptal epithelial cells were the source of regeneration of the epithelium

关键词： Rats Ischemia-reperfusion injury Gut Intestine Perfluorocarbon emulsions