Milestones to optimize of transjugular intrahepatic portosystemic shunt technique as a method for the treatment of portal hypertension complications.

This editorial describes the milestones to optimize of transjugular intrahepatic portosystemic shunt (TIPS) technique, which have made it one of the main methods for the treatment of portal hypertension complications worldwide. Innovative ideas, subsequent experimental studies and preliminary experience of use in cirrhotic patients contributed to the introduction of TIPS into clinical practice. At the moment, the main achievement in optimize of TIPS technique is progress in the qualitative characteristics of stents. The transition from bare metal stents to extended polytetrafluoroethylene-covered stent grafts made it possible to significantly prevent shunt dysfunction. However, the question of its preferred diameter, which contributes to an optimal reduction of portal pressure without the risk of developing post-TIPS hepatic encephalopathy, remains relevant. Currently, hepatic encephalopathy is one of the most common complications of TIPS, significantly affecting its effectiveness and prognosis. Careful selection of patients based on cognitive indicators, nutritional status, assessment of liver function, etc., will reduce the incidence of post-TIPS hepatic encephalopathy and improve treatment results. Optimize of TIPS technique has significantly expanded the indications for its use and made it one of the main methods for the treatment of portal hypertension complications. At the same time, there are a number of limitations and unresolved issues that require further randomized controlled trials involving a large cohort of patients.

Contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis patients.

This editorial describes the contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis (LC) patients according to the current guidelines. Gastroesophageal variceal bleeding is the most dangerous complication of portal hypertension in LC patients. Risk stratification and determination of an individual approach to the choice of therapeutic measures aimed at their prevention and management has emerged as one of the top concerns in modern hepatology. According to the current guidelines, in the absence of clinically significant portal hypertension, etiological and non-etiological therapies of LC is advisable for the primary preventing gastroesophageal variceal bleeding, whereas its presence serves as an indication for the administration of non-selective ß-blockers, among which carvedilol is the drug of choice. Non-selective ß-blockers, as well as endoscopic variceal ligation and transjugular intrahepatic portosystemic shunt can be used to prevent recurrence of gastroesophageal variceal bleeding. Pharmacotherapy with vasoactive drugs (terlipressin, somatostatin, octreotide), endoscopic variceal ligation, endovascular techniques and transjugular intrahepatic portosystemic shunt are recommended for the treatment of acute gastroesophageal variceal bleeding. Objective and accurate risk stratification of gastroesophageal variceal bleeding will allow developing individual strategies for their prevention and management, avoiding the first and further decompensation in LC, which will improve the prognosis and survival of patients suffering from it.

Therapeutic possibilities of gut microbiota modulation in acute decompensation of liver cirrhosis.

The formation of liver cirrhosis (LC) is an unfavorable event in the natural history of chronic liver diseases and with the development of portal hypertension and/or impaired liver function can cause a fatal outcome. Decompensation of LC is considered the most important stratification variable for the risk of death. It is currently postulated that decompensation of LC occurs through an acute (including acute-on-chronic liver failure) and non-acute pathway. Acute decompensation of LC is accompanied by the development of life-threatening complications, characterized by an unfavorable prognosis and high mortality. Progress in understanding the underlying molecular mechanisms has led to the search for new interventions, drugs, and biological substances that can affect key links in the pathogenesis of acute decompensation in LC, for example the impaired gut-liver axis and associated systemic inflammation. Given that particular alterations in the composition and function of gut microbiota play a crucial role here, the study of the therapeutic possibilities of its modulation has emerged as one of the top concerns in modern hepatology. This review summarized the investigations that describe the theoretical foundations and therapeutic potential of gut microbiota modulation in acute decompensation of LC. Despite the encouraging preliminary data, the majority of the suggested strategies have only been tested in animal models or in preliminary clinical trials; additional multicenter randomized controlled trials must demonstrate their efficacy in larger patient populations.

Pathophysiological mechanisms of cardiovascular disorders in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease is one of the main liver diseases worldwide. The most common cause of death in patients with non-alcoholic fatty liver disease is cardiovascular disease. The relationship between these two conditions has been well established. Indeed, identical reasons may contribute to the development of cardiovascular disease and non-alcoholic fatty liver disease with lifestyle factors such as smoking, sedentariness, poor nutritional habits, and physical inactivity being major aspects. This review focuses on potential pathophysiological mechanisms of cardiovascular disorders in non-alcoholic fatty liver. PubMed, EMBASE, Orphanet, MIDLINE, Google Scholar, and Cochrane Library were searched for articles published between 2006 and 2022. Relevant articles were selected using the following terms: "Non-alcoholic fatty liver disease," "Сardiovascular diseases," "Pathophysiological mechanisms." The reference lists of all identified articles were searched for other relevant publications as well. The pathophysiological mechanisms of cardiovascular disorders in non-alcoholic fatty liver remain largely speculative and may include systemic low-grade inflammation, atherogenic dyslipidemia, abnormal glucose metabolism and hepatic insulin resistance, endothelial dysfunction, gut dysbiosis, as well as the associated cardiac remodeling, which are influenced by interindividual genetic and epigenetic variations. It is clear that the identification of pathophysiological mechanisms underlying cardiovascular disorders in non-alcoholic fatty liver disease will make the selection of therapeutic measures more optimal and effective.

Pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis.

Liver fibrosis is a complex pathological process controlled by a variety of cells, mediators and signaling pathways. Hepatic stellate cells play a central role in the development of liver fibrosis. In chronic liver disease, hepatic stellate cells undergo dramatic phenotypic activation and acquire fibrogenic properties. This review focuses on the pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis. They enter the cell cycle under the influence of various triggers. The "Initiation" phase of hepatic stellate cells activation overlaps and continues with the "Perpetuation" phase, which is characterized by a pronounced inflammatory and fibrogenic reaction. This is followed by a resolution phase if the injury subsides. Knowledge of these pathophysiological mechanisms paved the way for drugs aimed at preventing the development and progression of liver fibrosis. In this respect, impairments in intracellular signaling, epigenetic changes and cellular stress response can be the targets of therapy where the goal is to deactivate hepatic stellate cells. Potential antifibrotic therapy may focus on inducing hepatic stellate cells to return to an inactive state through cellular aging, apoptosis, and/or clearance by immune cells, and serve as potential antifibrotic therapy. It is especially important to prevent the formation of liver cirrhosis since the only radical approach to its treatment is liver transplantation which can be performed in only a limited number of countries.

Risk score for predicting abdominal complications after coronary artery bypass grafting.

BACKGROUND: Although early abdominal complications after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) are rare, the associated mortality remains high. AIM: To develop a risk score for the prediction of early abdominal complications after CABG with CPB. METHODS: This retrospective study was performed in the Federal State Budgetary Establishment "Federal Center of Cardiovascular Surgery" of the Ministry of Health of Russia (the city of Chelyabinsk) and included data of 6586 patients who underwent CABG with CPB during 2011-2017. The risk factors taken for evaluation were compared between patients with early abdominal complications (n = 73) and without them (n = 6513). We identified the most important risk factors and their influence on the development of early abdominal complications after CABG with CPB. RESULTS: Gender and the presence of postinfarction cardiosclerosis, chronic kidney disease, or diabetes in the anamnesis did not affect the occurrence of abdominal complications. The leading risk factors of the early abdominal complications after CABG with CPB were multifocal atherosclerosis, extracorporeal membrane oxygenation, intra-aortic balloon pump, atrial fibrillation, perioperative myocardial infarction, and the need for resternotomy in the postoperative period. The average value of the predicted probability was 0.087 ± 0.015 in patients with early abdominal complications after CABG with CPB and 0.0094 ± 0.0003 in patients without these complications. The percentage of correct classification turned out to be 98.9%. After calculating a score for each of the leading risk factors, we counted a total score for each particular patient. The highest risk was noted in patients with a total score of 7 or more. CONCLUSION: The developed score predicts the risk of early abdominal complications after CABG with CPB and makes it possible to stratify patients by risk groups.

Primary prevention of bleeding from esophageal varices in patients with liver cirrhosis: An update and review of the literature.

All patients with liver cirrhosis and portal hypertension should be stratified by risk groups to individualize different therapeutic strategies to increase the effectiveness of treatment. In this regard, the development of primary prophylaxis of variceal bleeding and its management according to the severity of portal hypertension may be promising. This paper is to describe the modern principles of primary prophylaxis of esophageal variceal bleeding in patients with liver cirrhosis. The PubMed and EMbase databases, Web of Science, Google Scholar, and the Cochrane Database of Systematic Reviews were used to search for relevant publications from 1999 to 2019. The results suggested that depending on the severity of portal hypertension, patients with cirrhosis should be divided into those who need preprimary prophylaxis, which aims to prevent the formation of esophageal varices, and those who require measures that aim to prevent esophageal variceal bleeding. In subclinical portal hypertension, therapy should be etiological and pathogenetic. Cirrhosis with clinically significant portal hypertension should receive nonselective ß-blockers if they have small esophageal varices and risk factors for variceal bleeding. Nonselective ß-blockers are the first-line drugs for the primary prevention of bleeding from medium to large-sized esophageal varices. Endoscopic band ligation is indicated for the patients who are intolerant to nonselective ß-blockers or in the case of contraindications to pharmacological therapy. In summary, the stratification of cirrhotic patients by the severity of portal hypertension and an individual approach to the choice of treatment may increase the effectiveness of therapy as well as improve survival rate of these patients.

Left atrial appendage aneurysm: A case report.

BACKGROUND: An aneurysm of the left atrial appendage is one of the rare but potentially hazardous heart defects. The risk of lethal complications grows with its size. To date, about 150 cases of this defect have been described in the literature. We present a case of left atrial appendage aneurysm with the deformation of the mitral valve and the left main coronary and circumflex artery, which required mitral valve annuloplasty and bifurcation stenting. CASE SUMMARY: A 58-year-old man presented to our hospital complaining of shortness of breath, general weakness, dizziness during physical exertion, and fatigue. Based on the results of echocardiography, an aneurysm of the left atrium was suspected. A free-breathing real-time cine magnetic resonance imaging with electrocardiograph synchronization confirmed the diagnosis of left atrial appendage aneurysm. The patient underwent an aneurysmectomy via a median sternotomy with cardiopulmonary bypass. Intraoperative transesophageal echocardiography revealed relative mitral insufficiency that was corrected with an annuloplasty ring. Intraoperative coronary angiogram showed impaired blood flow in the left main coronary and circumflex artery and 60% stenosis. For this reason, bifurcation stenting was performed. The patient had an uneventful postoperative clinical course and was discharged from the hospital on the 10th day in a satisfactory condition. CONCLUSION: Left atrial appendage aneurysm is a rare and dangerous heart pathology that requires surgery to prevent related complications.

Current approaches to the management of patients with cirrhotic ascites.

This review describes current approaches to the management of patients with cirrhotic ascites in relation to the severity of its clinical manifestations. The PubMed database, the Google Scholar retrieval system, the Cochrane Database of Systematic Reviews, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 1991-2018 using the keywords: "liver cirrhosis," "portal hypertension," "ascites," "pathogenesis," "diagnostics," and "treatment." Uncomplicated and refractory ascites in patients with cirrhosis were the inclusion criteria. The literature analysis has shown that despite the achievements of modern hepatology, the presence of ascites is associated with poor prognosis and high mortality. The key to successful management of patients with ascites may be the stratification of the risk of an adverse outcome and personalized therapy. Pathogenetically based approach to the choice of pharmacotherapy and optimization of minimally invasive methods of treatment may improve the quality of life and increase the survival rate of this category of patients.

Antiangiogenic therapy for portal hypertension in liver cirrhosis: Current progress and perspectives.

Developing medicines for hemodynamic disorders that are characteristic of cirrhosis of the liver is a relevant problem in modern hepatology. The increase in hepatic vascular resistance to portal blood flow and subsequent hyperdynamic circulation underlie portal hypertension (PH) and promote its progression, despite the formation of portosystemic collaterals. Angiogenesis and vascular bed restructurization play an important role in PH pathogenesis as well. In this regard, strategic directions in the therapy for PH in cirrhosis include selectively decreasing hepatic vascular resistance while preserving or increasing portal blood flow, and correcting hyperdynamic circulation and pathological angiogenesis. The aim of this review is to describe the mechanisms of angiogenesis in PH and the methods of antiangiogenic therapy. The PubMed database, the Google Scholar retrieval system, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 2000-2017 using the keywords: "liver cirrhosis", "portal hypertension", "pathogenesis", "angiogenesis", and "antiangiogenic therapy". Antiangiogenic therapy for PH was the inclusion criterion. In this review, we have described angiogenesis inhibitors and their mechanism of action in relation to PH. Although most of them were studied only in animal experiments, this selective therapy for abnormally growing newly formed vessels is pathogenetically reasonable to treat PH and associated complications.

Hepatic hydrothorax: An update and review of the literature.

This review considers the modern concepts of pathogenesis, diagnostic methods, and treatment principles of hepatic hydrothorax (HH). HH is the excessive (> 500 mL) accumulation of transudate in the pleural cavity in patients with decompensated liver cirrhosis but without cardiopulmonary and pleural diseases. It causes respiratory failure which aggravates the clinical course of liver cirrhosis, and the emergence of spontaneous bacterial pleural empyema may be the cause of death. The information was collected from the PubMed database, the Google Scholar retrieval system, the Cochrane reviews, and the reference lists from relevant publications for 1994-2016 using the keywords: "liver cirrhosis", "portal hypertension", "hepatic hydrothorax", "pathogenesis", "diagnostics", and "treatment". To limit the scope of this review, only articles dealing with uncomplicated hydrothorax in patients with liver cirrhosis were included. The analysis of the data showed that despite the progress of modern hepatology, the presence of HH is associated with poor prognosis and high mortality. Most patients suffering from it are candidates for orthotopic liver transplantation. In routine clinical practice, stratification of the risk for an adverse outcome and the subsequent determination of individual therapeutic strategies may be the keys to the successful management of the patient's condition. The development of pathogenetic pharmacotherapy and optimization of minimally invasive treatment will improve the quality of life and increase the survival rate among patients with HH.

Mechanisms of adaptation of the hepatic vasculature to the deteriorating conditions of blood circulation in liver cirrhosis.

PubMed, EMBASE, Orphanet, MIDLINE, Google Scholar and Cochrane Library were searched for articles published between 1983 and 2015. Relevant articles were selected by using the following terms: "Liver cirrhosis", "Endothelial dysfunction", "Sinusoidal remodeling", "Intrahepatic angiogenesis" and "Pathogenesis of portal hypertension". Then the reference lists of identified articles were searched for other relevant publications as well. Besides gross hepatic structural disorders related to diffuse fibrosis and formation of regenerative nodules, the complex morphofunctional rearrangement of the hepatic microvascular bed and intrahepatic angiogenesis also play important roles in hemodynamic disturbances in liver cirrhosis. It is characterized by endothelial dysfunction and impaired paracrine interaction between activated stellate hepatocytes and sinusoidal endotheliocytes, sinusoidal remodeling and capillarization, as well as development of the collateral microcirculation. In spite of the fact that complex morphofunctional rearrangement of the hepatic microvascular bed and intrahepatic angiogenesis in liver cirrhosis are the compensatory-adaptive reaction to the deteriorating conditions of blood circulation, they contribute to progression of disease and development of serious complications, in particular, related to portal hypertension.

Current approaches to the management of patients with liver cirrhosis who have acute esophageal variceal bleeding.

OBJECTIVE: Esophageal variceal bleeding is the most dangerous complication in patients with liver cirrhosis, and it is accompanied by high mortality. Their treatment can be complex, and requires a multidisciplinary approach. This review examines current approaches to the management of patients with liver cirrhosis who have acute esophageal variceal bleeding. METHODS: PubMed, Google Scholar, and Cochrane Systematic Reviews were searched for articles published between 1987 and 2015. Relevant articles were identified using the following terms: 'esophageal variceal bleeding', 'portal hypertension' and 'complications of liver cirrhosis'. The reference lists of articles identified were also searched for other relevant publications. Inclusion criteria were restricted to the management of patients with liver cirrhosis who have acute esophageal variceal bleeding. RESULTS: It is currently recommended to combine vasoactive drugs (preferable somatostatin or terlipressin) and endoscopic therapies (endoscopic band ligation as first choice, sclerotherapy if endoscopic band ligation not feasible) for the initial treatment of acute variceal bleeding. Antibiotic prophylaxis must be regarded as an integral part of the treatment. The use of a Sengstaken-Blakemore tube is appropriate only in cases of refractory bleeding if the above methods cannot be used. An alternative to balloon tamponade may be the installation of self-expandable metal stents. The transjugular intrahepatic portosystemic shunt is an extremely useful technique for the treatment of acute bleeding from esophageal varices. Although most current clinical guidelines classify it as second-line therapy, the Baveno VI workshop recommends early transjugular intrahepatic portosystemic shunt with expanded polytetrafluoroethylene-covered stents within 72 h (ideally <24 h) in patients with esophageal variceal bleeding at high risk of treatment failure (e.g. Child-Turcotte-Pugh class C < 14 points or Child-Turcotte-Pugh class B with active bleeding) after initial pharmacological and endoscopic therapy. Urgent surgical intervention is rarely performed and can be considered only in case of failure of conservative and/or endoscopic therapy and being unable to use a transjugular intrahepatic portosystemic shunt. Among surgical operations described in the literature are a variety of portocaval anastomosis and azygoportal disconnection procedures. CONCLUSIONS: To improve the results of treatment for patients with liver cirrhosis who develop acute esophageal variceal bleeding, it is important to stratify patients into risk groups, which will allow one to tailor therapeutic approaches to the expected results.

Restructuring of the vascular bed in response to hemodynamic disturbances in portal hypertension.

In recent years, defined progress has been made in understanding the mechanisms of hemodynamic disturbances occurring in liver cirrhosis, which are based on portal hypertension. In addition to pathophysiological disorders related to endothelial dysfunction, it was revealed: There is the restructuring of the vasculature, which includes vascular remodeling and angiogenesis. In spite of the fact that these changes are the compensatory-adaptive response to the deteriorating conditions of blood circulation, taken together, they contribute to the development and progression of portal hypertension causing severe complications such as bleeding from esophageal varices. Disruption of systemic and organ hemodynamics and the formation of portosystemic collaterals in portal hypertension commence with neovascularization and splanchnic vasodilation due to the hypoxia of the small intestine mucosa. In this regard, the goal of comprehensive treatment may be to influence on the chemokines, proinflammatory cytokines, and angiogenic factors (vascular endothelial growth factor, placental growth factor, platelet-derived growth factor and others) that lead to the development of these disorders. This review is to describe the mechanisms of restructuring of the vascular bed in response to hemodynamic disturbances in portal hypertension. Development of pathogenetic methods, which allow correcting portal hypertension, will improve the efficiency of conservative therapy aimed at prevention and treatment of its inherent complications.

Contemporary concepts of the medical therapy of portal hypertension under liver cirrhosis.

Severe complications of liver cirrhosis are mostly related to portal hypertension. At the base of the pathogenesis of portal hypertension is the increase in hepatic vascular resistance to portal blood flow with subsequent development of hyperdynamic circulation, which, despite of the formation of collateral circulation, promotes progression of portal hypertension. An important role in its pathogenesis is played by the rearrangement of vascular bed and angiogenesis. As a result, strategic directions of the therapy of portal hypertension under liver cirrhosis include selectively decreasing hepatic vascular resistance with preserving or increasing portal blood flow, and correcting hyperdynamic circulation and pathological angiogenesis, while striving to reduce the hepatic venous pressure gradient to less than 12 mmHg or 20% of the baseline. Over the last years, substantial progress in understanding the pathophysiological mechanisms of hemodynamic disorders under liver cirrhosis has resulted in the development of new drugs for their correction. Although the majority of them have so far been investigated only in animal experiments, as well as at the molecular and cellular level, it might be expected that the introduction of the new methods in clinical practice will increase the efficacy of the conservative approach to the prophylaxis and treatment of portal hypertension complications. The purpose of the review is to describe the known methods of portal hypertension pharmacotherapy and discuss the drugs that may affect the basic pathogenetic mechanisms of its development.