Skliar A. Clinical and prognostic value of immunological and microecological indicators in patients with acute hepatitis B

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0419U003439

Applicant for

Specialization

  • 14.03.08 - Імунологія та алергологія

25-06-2019

Specialized Academic Board

Д 64.618.01

State Institution "I.Mechnikov Institute of Microbiology and Immunology National Academy of Medical Sciences of Ukraine"

Essay

Object of study: acute hepatitis B in varying degrees of severity in the dynamics of the disease. The purpose of the research: to improve the diagnostic and therapeutic tactics and to develop additional criteria for predicting the course of HBV infection based on the study of clinical and immunological, molecular genetic and microbiological indicators. Methods of research: general-clinical (examination of patients with acute hepatitis B), laboratory (biochemical analysis of blood, coagulogram), immuno-enzyme and molecular genetic (markers of HBV infection), immunological (study of the state of cellular and humoral immunity, content of cytokines), microbiological (microbiocenosis content of the colon of the large intestine), instrumental (ultrasound of the abdominal cavity), mathematical and statistical. Equipment: immune enzyme analyzer Stat Fax 303-Plus, manufacturer of "Awareness Technology inc." USA. The dissertation is devoted to the study of the nature of primary non-specific defense, humoral immunity factors, immune response mediators and peculiarities of dysbiotic disorders in patients with acute hepatitis B (HBV) in different periods of the course and depending on the severity of the disease. The study has shown the role of complex analysis of indices of innate cellular, humoral immunity, dynamics of cytokine network levels in the evaluation of the body's response to HBV infection, and prediction of the consequences of the disease. The peculiarity of the immune response in patients with HBV is a specific imbalance of primary cellular defense and activation of humoral immunity, accompanied by hyperproduction of immune mediators. Immune disorders in HBV differ significantly in patients with mild to moderate severity in different clinical periods of the disease. A characteristic feature of patients with mild severity in the icteric period of HBV is the enhanced activation of phagocytic system, which is manifested by the increase in activated neutrophils, and their absorbing capacity in contrast to patients with moderate severity, who were shown to have a reduced intensity of phagocytosis of neutrophils with an increase in the phagocytic count of neutrophils. Regardless of the severity, phagocytic activity of the monocytes is suppressed by an unstable absorbing function. It has been established that the early criteria for the progression of HBV infection with the development of prolonged course are a decrease in the phagocytic index of neutrophils (PIN) 30, PIN-60 and PIN-180 by 10,0-40.0 %, phagocytic index of monocytes (PIM) 30, PIM-60 and PIM-180 by more than 50.0 %; hyperproduction of IL-8 in blood serum (by more than 9.6 times), increased TNF-α levels (by 2.3 times), and IFN-γ (within reference values), as well as Candida spp. contamination of the colon in concentration >10⁴colony forming units (CFU) in 1 g and detection of IgG titers to Candida spp. in blood serum. In the period of reconvalescence, adverse prognostic criteria are the presence of HBV, HBsAg, HBeAg DNA in the blood and/or the absence of anti-HBs, anti-HBe, and anti-HBc IgG, and increased titre of IgG to Candida spp. by more than 4 times. The criterion for an adequate immune response that leads to self-limitation of HBV is an increase of PIN-30, PIN-60, PIN-180 and PIM-60 in the blood of patients to reference values or higher; a significant increase in levels of TNF-α (more than 6.4-fold) and IFN-γ (more than 3.5-fold) and an increase in the concentration of IL-8 (more than 4.3-fold) from the upper limit of reference values in blood serum, as well as the absence of contamination of the colon with Candida spp. in the concentration >10⁴ CFU/g and IgG titers to Candida spp. In the period of reconvalescence, there are no HBV, HBeAg DNA and anti-HBs, anti-HBe and anti-HBc IgG are detected in the blood. Taking into account the detected impairments of immunological balance, dysbiotic changes in the biotope of the large intestine have been substantiated by the improvement of pathogenic therapy, with the inclusion of bifidum and lactobacillus to the complex treatment of patients with HBV. The degree of implementation: 6 acts of implementation, 1 patent. Sphere (industry) of use: health (medicine: immunology, infectious diseases).

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