Drug correction of the portal hypertension syndrome in chronic active hepatitis and liver cirrhosis

The dissertation is devoted to the study of hemodynamic disturbances in portal hypertension syndrome in patients with chronic active hepatitis and liver cirrhosis at the pre-ascitic stage. The work examines the features of portal-hepatic blood flow, central hemodynamics, and systemic microcirculation, as well as their correlation with clinical manifestations and biochemical changes in liver diseases of viral etiology (HBV and combined).

The author carried out a comparative analysis of the effectiveness of pharmacological correction of the identified disturbances using the angiotensin-converting enzyme inhibitor enalapril, the β-adrenoblocker propranolol, and the venous vasodilator nitrosorbide. On the basis of the comprehensive study, differentiated pathogenetic therapy schemes were developed, making it possible to improve the prognosis, stabilize the condition of patients, and optimize the duration and cost of treatment.

Relevance of the topic. Scientific interest in the problem of portal hypertension, which is a complication of diffuse liver lesions of various etiologies, continues unabated. This is associated, above all, with its considerable prevalence. The deterioration of the environmental situation, the widespread introduction of synthetic medications into healthcare, and the increase in the number of blood transfusions and surgical interventions lead to a substantial rise in the incidence of liver diseases. According to WHO experts, there are more than 200 million carriers of HBsAg worldwide. Each year, more than 1 million people across the globe fall ill with acute viral hepatitis. It is characteristic that among patients with acute and chronic viral hepatitis, persons of young working age predominate, which significantly worsens the indicators of employment, disability, and invalidity in society [22, 46].

A number of experimental and clinical studies indicate disturbances of portal-hepatic blood flow that arise already in the early stages of the development of an acute or chronic pathological process in the liver and frequently precede changes in the functional state of the organ, occupying one of the leading places in the pathogenesis of the disease [3, 32]. However, the study of inter-organ connections and interactions in a number of diseases and the development, on this basis, of rational diagnostic methods and optimal approaches to the treatment of patients acquire great importance [16]. Among such interactions are changes in the state of the cardiovascular system in acute and chronic viral hepatitis, which exert a significant influence on the severity of the condition, the course, the prognosis, and the treatment strategy of such patients [46, 50].

There are studies confirming changes in the cardiovascular system in liver diseases [46, 50, 62, 81, 91]. For the most part, such studies are devoted to changes in central hemodynamics in the form of the formation of a hyperkinetic type of circulation in patients with liver cirrhosis.

At the same time, the available literature lacks sufficient information on the mechanisms of formation of one or another type of hemodynamics in patients with chronic hepatitis and liver cirrhosis. Changes in portal-hepatic blood flow and microcirculation in patients with chronic hepatitis and cirrhosis caused by HBV, HDV viruses and their combination remain insufficiently studied. Differentiated approaches to the treatment of changes in central hemodynamics and portal-hepatic blood flow in patients with chronic hepatitis and liver cirrhosis, taking into account modern diagnostic and treatment methods, have not been developed.

The study of the correlation between indicators of central hemodynamics and portal-hepatic blood flow in patients with chronic hepatitis and liver cirrhosis may contribute to the development of a strategy for the differentiated treatment of these patients, the selection of optimal doses and effective combinations of drugs, as well as the prevention of severe complications and, accordingly, the improvement of the prognosis in liver diseases.

Aim of the study

To clarify the features of the clinical manifestations of portal hypertension syndrome and hemodynamic disturbances (portal-hepatic blood flow, central hemodynamics, systemic microcirculation) in patients with chronic active hepatitis and liver cirrhosis, and to develop methods for their pharmacological correction.

Tasks of the study

1. To clarify the features of the clinical manifestations of portal hypertension syndrome and hemodynamic disturbances (within this syndrome) in patients with chronic active hepatitis and liver cirrhosis at the pre-ascitic stage.

2. To study the features of portal hypertension syndrome and its severity in correlation with biochemical disturbances.

3. To study the degree of reversibility of PH syndrome against the background of traditional therapy for CAH and LC and therapy aimed at the correction of portal hypertension syndrome.

4. To study the effectiveness of the influence of angiotensin-converting enzyme inhibitors—enalapril—on the main clinical manifestations and functional indicators of the liver in patients with chronic active hepatitis and liver cirrhosis with portal hypertension syndrome in comparison with the β-adrenoblocker propranolol and nitrosorbide.

5. To study the effectiveness of the angiotensin-converting enzyme inhibitor enalapril on hemodynamic disturbances (portal-hepatic blood flow, central hemodynamics, systemic microcirculation) in comparison with the β-adrenoblocker propranolol and nitrosorbide.

6. To develop the most optimal schemes of therapeutic correction of hemodynamic disturbances in portal hypertension syndrome in patients with chronic active hepatitis and liver cirrhosis.

Scientific novelty of the work

For the first time in patients with chronic active hepatitis and liver cirrhosis with PH syndrome at the pre-ascitic stage, depending on the clinical and functional manifestations of the disease, a comprehensive study of portal-hepatic blood flow, central hemodynamics, and systemic microcirculation has been carried out. For the first time, pathological correlational relationships between indicators of portal hemodynamics, central hemodynamics, and systemic microcirculation have been revealed, which made it possible to develop optimal differentiated pathogenetic therapy for portal hypertension syndrome in patients with CAH and LC. For the first time, comparative studies of the effectiveness of angiotensin-converting enzyme inhibitors on portal-hepatic blood flow, central hemodynamics, and microcirculation have been carried out in comparison with venous vasodilators and β-adrenoblockers. For the first time, an attempt has been made to assess the degree of reversibility of hemodynamic disturbances in the portal vein system, central hemodynamics, and systemic microcirculation against the background of the use of therapeutic agents for the correction of portal hypertension.

Practical significance of the work

The studies conducted have made it possible to develop rational schemes for the examination and treatment of patients with chronic active hepatitis and liver cirrhosis. Timely correction of changes in portal blood flow, alongside traditional treatment, has made it possible to carry out pathogenetic therapy most effectively, to reduce the duration and volume of therapeutic measures, to improve the prognosis of the disease, to stabilize the condition of patients, and to achieve compensation of the disease. The use of ACE inhibitors and β-adrenoblockers in CAH and LC, reliably correcting disturbances of hepatic blood flow, central hemodynamics, and systemic microcirculation in a short time, produces a good clinical effect, reduces the period of temporary disability, and lowers the cost of treatment.

Main propositions presented for defense

1. In patients with chronic active hepatitis and liver cirrhosis, reliable disturbances of hepatic blood flow, central hemodynamics, and microcirculation are observed with the formation, on the whole, of a hyperkinetic hemodynamic syndrome.

2. The hemodynamic disturbances discovered correlate with the main clinical manifestations of CAH and LC, as well as with biochemical and functional disturbances, and require their timely and adequate correction.

3. For the correction of hemodynamic disturbances (portal-hepatic blood flow, central hemodynamics, systemic microcirculation), schemes of treatment have been proposed, which, alongside traditional therapy, have included drugs of different groups correcting disturbances of hemodynamic homeostasis: enalapril, nitrosorbide, and propranolol.

4. A comparative analysis of the effectiveness of enalapril, nitrosorbide, and propranolol has made it possible to identify the most optimal agents and schemes of their administration in a differentiated manner for patients with chronic active hepatitis and liver cirrhosis. In this case, nitrosorbide aggravates, whereas enalapril and propranolol reduce the severity of the hyperkinetic syndrome in these patients.