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Role of host-dependent factors in prediction of antiviral treatment response in chronic hepatitis C
Fraňková, Soňa ; Jirsa, Milan (advisor) ; Brůha, Radan (referee) ; Plíšek, Stanislav (referee)
Soňa Fraňková: Role of host-dependent factors in prediction of antiviral treatment response in chronic hepatitis C Abstract Hepatitis C virus infection represents a leading cause of liver disease in western countries. The primary goal of HCV therapy is elimination of the virus, i.e. sustained virological response (SVR) achievement. Genetic factors have long been suspected of playing a crucial role in determining response to IFN-α-based therapies, but pretreatment predictors of response were only poorly defined and did not allow personalization of therapy. The aim of the thesis is to describe the role of host-dependent factors in prediction of antiviral treatment response in chronic hepatitis C in specific groups of patients. First, we focused on the role of the IFNG -764G/C promoter variant in SVR achievement. We did not prove that this variant predicted SVR in Czech HCV-infected individuals. Next, we focused on the role of IL28B and IFNL4 in HCV-infected patients: we confirmed that the IL28B rs12979860 CC genotype slows down the progression of liver fibrosis in chronic HCV infection and that IFNL4 ss469415590 TT|ΔG genotyping does not bring a better prediction of treatment success than IL28B rs12979860 in the Czech population. Third, we assessed prediction of treatment response in HCV positive liver...
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Motives and forms of travelling
Fraňková, Soňa ; Půtová, Barbora (referee) ; Junek, Marek (referee)
Motives and forms of travelling, Fraňková Soňa The author's work analyzes three basic motives that lead to travel and subsequently introduces in more detail travel's four institutionalized forms and how these forms are realized. The three basic motives discussed by the author include; escape, instruction, and necessity. In addition, the forms are introduced as ways to implement these themes. The first distinctive modes of travel is described as pilgriming and trips for sacredness. The second form is romantic meandering which is the conscious act of leaving one's home in Romantic times. The third form discussed is wandering which through one realizes escape, instruction, and necessity. Finally, the last option is hiking. All these forms are presented in terms of theirhistorical development and specifics that are inherent within. An integral part of the work is also the comparison of these forms with an emphasis on their interaction.
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The role of oxidative stress in hepatocarcinogenesis.
Kubíčková, Kristýna ; Vítek, Libor (advisor) ; Zelenka, Jaroslav (referee) ; Fraňková, Soňa (referee)
This thesis focuses on the importance of heme catabolic pathway in hepatic carcinogenesis. Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumour. It is primarily caused by hepatic cirrhosis or chronic viral hepatitis. Hepatic carcinogenesis is associated with increased oxidative stress. Thus, our study aimed to assess the expression of the genes involved in the homeostasis of oxidative stress in patients with HCC. The study was performed on patients with primary HCC (n = 29) and control subjects (n = 11), gene expressions of heme oxygenase 1 (HMOX1), biliverdin reductase A/B (BLVRA/B), endothelial growth factor (VEGFA), NADPH oxidase 2 (NOX2) and p22phox were analyzed in the liver tissue; the identical gene expressions were analyzed in peripheral blood leukocytes (PBL) in HCC patients (n = 32) and in healthy controls (n = 27). Expression of BLVRA in liver tissue and PBL was significantly increased in cancer patients, as was NOX2 expression in PBL. Expression of VEGFA in liver tissue and PBL was significantly decreased in cancer patients. The expression of the other genes studied did not differ between HCC patients and controls. These data are consistent with the results of our previous study on patients with chronic hepatitis C, in which BLVRA expression was also...
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Efficacy and treatment adherence to therapy of chronic HCV infection in people who inject drugs
Jandová, Zuzana ; Gabrhelík, Roman (advisor) ; Věchetová, Sonja (referee) ; Fraňková, Soňa (referee)
Backgrounds: Intravenous drug use represents the main route of transmission of hepatitis C virus infection (HCV). IVDU represent approximately 75-100% of newly diagnosed cases of HCV. IVDU have traditionally been considered as difficult-to-treat, owing to a low treatment adherence. The presumed low adherence to care in IVDU represent nowadays the barrier to therapy with direct-acting antivirals (DAA). Aims: The aim of the thesis was to assess efficacy of therapy of HCV with DAA and adherence to therapy in patients with history of IVDU. Comparing the results with the group of patients without IVDU, we would support the fact that the treatment efficacy in the IVDU group is high and that the utilisation of financial resources is effective. Methods: All consecutive patients who started DAA anti-HCV therapy at the Department of Hepatogastroenterology of Institute for Clinical and Experimental Medicine from 1st January 2017 to 6th August 2018 were included. The patients were divided into two groups: individuals with history of IVDU (IVDU, N = 101) and control group (Controls, N = 177), without IVDU in the past. The patients' data were obtained from patients medical charts during treatment and follow-up. Results: IVDU group achieved an SVR12 of 98% (vs. 98% in controls, N. S.). Two IVDU patients who were...
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Role of host-dependent factors in prediction of antiviral treatment response in chronic hepatitis C
Fraňková, Soňa ; Jirsa, Milan (advisor) ; Brůha, Radan (referee) ; Plíšek, Stanislav (referee)
Soňa Fraňková: Role of host-dependent factors in prediction of antiviral treatment response in chronic hepatitis C Abstract Hepatitis C virus infection represents a leading cause of liver disease in western countries. The primary goal of HCV therapy is elimination of the virus, i.e. sustained virological response (SVR) achievement. Genetic factors have long been suspected of playing a crucial role in determining response to IFN-α-based therapies, but pretreatment predictors of response were only poorly defined and did not allow personalization of therapy. The aim of the thesis is to describe the role of host-dependent factors in prediction of antiviral treatment response in chronic hepatitis C in specific groups of patients. First, we focused on the role of the IFNG -764G/C promoter variant in SVR achievement. We did not prove that this variant predicted SVR in Czech HCV-infected individuals. Next, we focused on the role of IL28B and IFNL4 in HCV-infected patients: we confirmed that the IL28B rs12979860 CC genotype slows down the progression of liver fibrosis in chronic HCV infection and that IFNL4 ss469415590 TT|ΔG genotyping does not bring a better prediction of treatment success than IL28B rs12979860 in the Czech population. Third, we assessed prediction of treatment response in HCV positive liver...
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Motives and forms of travelling
Fraňková, Soňa ; Půtová, Barbora (referee) ; Junek, Marek (referee)
Motives and forms of travelling, Fraňková Soňa The author's work analyzes three basic motives that lead to travel and subsequently introduces in more detail travel's four institutionalized forms and how these forms are realized. The three basic motives discussed by the author include; escape, instruction, and necessity. In addition, the forms are introduced as ways to implement these themes. The first distinctive modes of travel is described as pilgriming and trips for sacredness. The second form is romantic meandering which is the conscious act of leaving one's home in Romantic times. The third form discussed is wandering which through one realizes escape, instruction, and necessity. Finally, the last option is hiking. All these forms are presented in terms of theirhistorical development and specifics that are inherent within. An integral part of the work is also the comparison of these forms with an emphasis on their interaction.
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Pilgriming, wandering and hiking (culturological comparative approach)
Fraňková, Soňa ; Czumalo, Vladimír (advisor) ; Půtová, Barbora (referee)
This core work is a mutual comparison approach, which relates to the internal character and motives of the three specific forms of travel: pilgrimage, wandering and hiking. They are presented in chronological order, with an emphasis on comparison, resources, development and continuity of individual approaches. Regarded as the basic motive of these three ways which one sets out of the home; the author considers the human need for change, a desire for knowledge and an escape from everyday life, which are presented in more detail. In addition, being discussed is the concept of looking at these forms of travel as a kind of ritual transition when a person away from their normal environment becomes an individual that is on the border, detached from his past and his future already changed thanks to the newly acquired experiences and expertise - a man who returns is never the same. Pilgrimage, wandering and hiking are presented as activities in which by their own way often enable an individual to abandon everyday life. The level and manner of this work are expressed via a culturally and historical contingent and subject to further transformation. The oldest and most important form of travel is pilgrimage, which is the starting point for the other two forms mentioned. Pilgrimage gradually provides a platform for...
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