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.

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.

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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.

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.

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 β‐blockers if they have small esophageal varices and risk factors for variceal bleeding. Nonselective β‐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 β‐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.

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.

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.