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CNAA / Theses / 2018 / June /

Chronic viral hepatitis B and C in children: clinical-immunological peculiarities and optimization of the antiviral therapy


Author: Raba Tatiana
Degree:doctor habilitat of medicine
Speciality: 14.00.10 - Infections Diseases
Year:2018
Scientific consultants: Vlada-Tatiana Dumbrava
doctor habilitat, professor, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
Victor Pântea
doctor habilitat, professor, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
Institution: Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova

Status

The thesis was presented on the 28 June, 2018
Approved by NCAA on the 23 November, 2018

Abstract

Adobe PDF document – 1.06 Mb / in romanian

Thesis

CZU 616.36-002.2-053.2-08(043)

Adobe PDF document 9.59 Mb / in romanian
215 pages

Keywords

viral hepatitis B and C, children, immunity, antiviral drugs. Field of the study: infection disease, pediatric hepatology

Summary

The volume and structure of the thesis: introduction, 5 chapters, the main conclusions and recommendations, bibliography of 198 sources, the main body of the text 215, 20 tables, 65 figures, 17 appendix. The results were published in 42 scientific papers. Keywords: viral hepatitis B and C, children, immunity, antiviral drugs.

Field of the study: infection disease, pediatric hepatology. Purpose of the thesis: To establish the ethiopathogenetic, clinico-immunological and evolutive peculiarities of the different clinical forms of the chronic viral hepatitis B and C in children, monitoring the evolution of the chronic process, determining the risk factors of chronicity and progression of the different clinical forms, developing of the early diagnostics algorithms, optimization of the antiviral treatment in chronic infected children.

The study objectives: Study of the clinical and evolutive peculiarities of CVHB and CVHC in children related on age, gender, duration of illness and clinical forms, estimation of the baseline clinical syndromes of HVCB and HVCC depending on the viral etiology and the activity of the chronic liver disease in children of different ages. Assessment of cellular and humoral immune status in CVHB and CVHC patients of different ages according to VHB or VHC viremic load and activity of the hepatic inflammatory process and elucidation of new and immunological aspects regarding the pathogenesis of CVHB and CVHC depending on the clinical form and the activity of the disease. Analysis of the correlations between the paraclinical parameters and the phase of the viral replication and the activity of the chronic liver inflammatory process. Highlighting instrumental changes in patients with CVHB and CVHC in children according to the activity of the chronic liver inflammatory process. Analysis of interrelations between the activity of the viral process and the chronic liver inflammatory process. Determination of differential diagnostic criteria between different forms of CVHB and CVHC according to clinical data in children of different age. Optimization and assessing the efficacy of interferon therapy in CVHB and CVHC in children of different age depending on the activity of the chronic liver inflammatory process.

Estimation of efficacy of locally produced pacovirin with immunomodulatory, antiviral, antioxidant, interferon-like action, compared to hepatoprotective treatment. Elaboration of diagnostic algorithm for CVHB and CVHC patients of different ages. Fulfillment of the antiviral and non-viral treatment algorithm of patients with CVHB and CVHC depending on viremia and liver function.

Scientific novelty: For the first time, a new vision of approaching cellular immunity, especially CD3 lymphocytes and its subpopulations by the monoclonal antibodies, was proposed as an important criterion depending on the degree of liver fibrosis and activity of the liver inflammatory process in CVHB and CVHC in children. For the first time in the Republic of Moldova and worldwide, was used a locally remedy pacovirin as an alternative method of antiviral treatment in CVHB and CVHC in children. Long-term monitoring criteria have been developed for CVHB and CVHC children undergoing antiviral treatment. New research directions: Implications of cellular immunity and proinflammatory cytokines in CVHB and CVHC pathogenesis were elucidated, interrelation between the viral and inflammatory process and the principles of antiviral treatment with interferon and pacovirin as an alternative method were optimized.

Theoretical and applicative value: is complementary with the etiopathogenetic vision of CVHB and CVHC in children, differential diagnostic criteria and selection of patients for antiviral treatment have been developed. A timetable has been developed for the monitoring of children with CVHB and CVHC undergoing antiviral therapy depending on the cellular immune status and the activity of the inflammatory process. Implementation of the scientific results: the scientific results obtained were used in the didactic process and in medical practice (contributed by 3 national programs for control of viral hepatitis B, C, D and antiviral treatment).