Influência da Resposta inflamatória na Resposta virológica sustentada em pacientes com Hepatite C Crônica genótipo 1 durante o tratamento antiviral com terapia tripla

Detalhes bibliográficos
Autor(a) principal: Winckler, Fernanda Cristina [UNESP]
Data de Publicação: 2016
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://hdl.handle.net/11449/144991
Resumo: Hepatitis C is an infectious disease which becomes chronic in about 85% of infected people who can develop cirrhosis and hepatocellular carcinoma. Antiviral therapy isn’t effective in many patients, especially when these patients are genotype 1 and have advanced fibrosis, the inflammatory response also plays a role on sustained virological response (SVR) during treatment with Pegylated (PegIFN) plus Ribavirin (RBV). The aim of this study was evaluate the influence of the inflammatory response by cells and cytocines/chemokines on the virologic response of the patients under antiviral treatment with triple therapy. We included patients with HCV RNA+, naive, genotype 1, both male and female and with advanced fibrosis F3 (n=6); F4 (n=21) for triple treatment regimen. Patients had their samples collected and analyzed at weeks 0 and 12 of treatment and the following parameters were analyzed: IL- 2, IL-4, IL-6, IL-8, IL-10, IL-17A, TNF-α, IFN-γ RANTES, MCP-1, MIG, IP-10 by flow cytometry (CBA method). Control group of 15 healthy volunteers and 27 patients, who were separated into GI (SVR) and G2 (not SRV), were included, the SVR rate was 63%. Patients with chronic hepatitis C had higher circulating levels of IP10, MCP-1, MIG, RANTES, IL-8 and IL-6 compared with healthy volunteers, when G1xG2 were compared, levels of RANTES (p=0,040 and IL-6 (n=0,02) were associated with a SVR at week 0 and its levels were lower in G1; at week 12, levels of RANTES (p=0,04) and IL-8 (p=0,01) were associated with a SVR and its levels were higher in G2. The comparison between weeks 0 and 12 showed that, in G1, the IL6 levels (p = 0.02) and MCP-1 (p = 0.001) were associated with the treatment and in G2, the parameters associated with the treatment were RANTES (p = 0.05) and MCP-1 (p = 0.01). The results suggest that the cytocine IL-6 and chemokine RANTES are associated with SVR at week 0. At week 12, RANTES as well as IL-8 influence in SVR during antiviral therapy in triple regimen. When weeks 0 and 12 in patients SVR are compared, the cytocine IL-6 is associated with treatment. In non-SVR patients, RANTES is associated with treatment and MCP-1 is associated with independent treatment of the patient's response.
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spelling Influência da Resposta inflamatória na Resposta virológica sustentada em pacientes com Hepatite C Crônica genótipo 1 durante o tratamento antiviral com terapia triplaInfluence of inflamatory response on sustained virological response in pa ents with chronic Hepa s C genotype 1 during an viral treatment with triple therapyHepatitis CInflammatory responseSustained virological responseTreatmentHepatite CResposta inflamatóriaResposta virológicaTratamentoHepatitis C is an infectious disease which becomes chronic in about 85% of infected people who can develop cirrhosis and hepatocellular carcinoma. Antiviral therapy isn’t effective in many patients, especially when these patients are genotype 1 and have advanced fibrosis, the inflammatory response also plays a role on sustained virological response (SVR) during treatment with Pegylated (PegIFN) plus Ribavirin (RBV). The aim of this study was evaluate the influence of the inflammatory response by cells and cytocines/chemokines on the virologic response of the patients under antiviral treatment with triple therapy. We included patients with HCV RNA+, naive, genotype 1, both male and female and with advanced fibrosis F3 (n=6); F4 (n=21) for triple treatment regimen. Patients had their samples collected and analyzed at weeks 0 and 12 of treatment and the following parameters were analyzed: IL- 2, IL-4, IL-6, IL-8, IL-10, IL-17A, TNF-α, IFN-γ RANTES, MCP-1, MIG, IP-10 by flow cytometry (CBA method). Control group of 15 healthy volunteers and 27 patients, who were separated into GI (SVR) and G2 (not SRV), were included, the SVR rate was 63%. Patients with chronic hepatitis C had higher circulating levels of IP10, MCP-1, MIG, RANTES, IL-8 and IL-6 compared with healthy volunteers, when G1xG2 were compared, levels of RANTES (p=0,040 and IL-6 (n=0,02) were associated with a SVR at week 0 and its levels were lower in G1; at week 12, levels of RANTES (p=0,04) and IL-8 (p=0,01) were associated with a SVR and its levels were higher in G2. The comparison between weeks 0 and 12 showed that, in G1, the IL6 levels (p = 0.02) and MCP-1 (p = 0.001) were associated with the treatment and in G2, the parameters associated with the treatment were RANTES (p = 0.05) and MCP-1 (p = 0.01). The results suggest that the cytocine IL-6 and chemokine RANTES are associated with SVR at week 0. At week 12, RANTES as well as IL-8 influence in SVR during antiviral therapy in triple regimen. When weeks 0 and 12 in patients SVR are compared, the cytocine IL-6 is associated with treatment. In non-SVR patients, RANTES is associated with treatment and MCP-1 is associated with independent treatment of the patient's response.A hepatite C é uma doença infecciosa que torna-se crônica em cerca de 85% dos infectados que poderão desenvolver cirrose e carcinoma hepato celular. O tratamento antiviral em muitos dos pacientes não é eficaz, principalmente quando estes portam o genótipo 1 e fibrose avançada, a resposta inflamatória também desempenha seu papel sobre a resposta virológica sustentada (RVS) durante o tratamento com Interferon Peguilado (PegIFN) associado a Ribavirina (RBV). Nesse estudo nosso objetivo principal foi avaliar a influência da resposta inflamatória através de células e citocinas/quimiocinas sobre a resposta virológica do paciente em tratamento antiviral com terapia tripla. Incluimos pacientes com RNA VHC+, nunca tratados (naive), portadores do genótipo 1, ambos os sexos e com fibrose avançada F3 (n=6); F4 (n=21) candidatos ao tratamento em regime triplo. Os pacientes tiveram suas amostras coletadas e analizadas nas semanas 0 e 12 do tratamento e os seguintes parâmetros foram analisados: IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, TNF-α, IFN-γ, RANTES, MCP-1, MIG, IP- 10, através de citometria de fluxo (método CBA). Foram incluídos 15 voluntários saudáveis (grupo controle) e 27 pacientes que foram separados em G1(RVS) e G2 (não RVS), a taxa de RVS foi de 63%. Os pacientes com hepatite C crônica tiveram os níveis circulantes de IP10, MCP-1, MIG, RANTES, IL-8 e IL-6 mais elevados quando comparados com voluntários saudáveis, quando comparados G1xG2 os níveis de RANTES (p=0,04) e IL-6 (p=0,02) foram associadas com a RVS na semana 0, seus níveis eram mais baixos em G1, na semana 12 os níveis de RANTES (p=0,04) e IL-8 (n=0,01) foram associados com a RVS, seus níveis são mais elevados em G2, a comparação entre as semanas 0 e 12 mostrou que em G1 os níveis de IL6 (p= 0,02) e MCP-1 (p=0,001) apresentam associação com o tratamento e em G2 os parâmetros associados ao tratamento foram RANTES (p=0,05) e MCP-1 (p=0,01). Os resultados sugerem que, a citocina IL-6 e a quimiocina RANTES estão associadas com a RVS na semana 0. Na semana 12, RANTES assim como IL-8 influenciam na RVS durante terapia antiviral em regime triplo. Quando comparado semana 0 e 12 em pacientes RVS, a citocina IL-6 está associada ao tratamento. Em pacientes não RVS, RANTES esta associada ao tratamento e MCP-1 está associada ao tratamento independente da resposta obtida.Universidade Estadual Paulista (Unesp)Silva, Giovanni Faria [UNESP]Golim, Marjorie de Assis [UNESP]Universidade Estadual Paulista (Unesp)Winckler, Fernanda Cristina [UNESP]2016-12-02T16:28:26Z2016-12-02T16:28:26Z2016-10-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/11449/14499100087654533004064079P5porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESP2023-12-02T06:18:38Zoai:repositorio.unesp.br:11449/144991Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-12-02T06:18:38Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Influência da Resposta inflamatória na Resposta virológica sustentada em pacientes com Hepatite C Crônica genótipo 1 durante o tratamento antiviral com terapia tripla
Influence of inflamatory response on sustained virological response in pa ents with chronic Hepa s C genotype 1 during an viral treatment with triple therapy
title Influência da Resposta inflamatória na Resposta virológica sustentada em pacientes com Hepatite C Crônica genótipo 1 durante o tratamento antiviral com terapia tripla
spellingShingle Influência da Resposta inflamatória na Resposta virológica sustentada em pacientes com Hepatite C Crônica genótipo 1 durante o tratamento antiviral com terapia tripla
Winckler, Fernanda Cristina [UNESP]
Hepatitis C
Inflammatory response
Sustained virological response
Treatment
Hepatite C
Resposta inflamatória
Resposta virológica
Tratamento
title_short Influência da Resposta inflamatória na Resposta virológica sustentada em pacientes com Hepatite C Crônica genótipo 1 durante o tratamento antiviral com terapia tripla
title_full Influência da Resposta inflamatória na Resposta virológica sustentada em pacientes com Hepatite C Crônica genótipo 1 durante o tratamento antiviral com terapia tripla
title_fullStr Influência da Resposta inflamatória na Resposta virológica sustentada em pacientes com Hepatite C Crônica genótipo 1 durante o tratamento antiviral com terapia tripla
title_full_unstemmed Influência da Resposta inflamatória na Resposta virológica sustentada em pacientes com Hepatite C Crônica genótipo 1 durante o tratamento antiviral com terapia tripla
title_sort Influência da Resposta inflamatória na Resposta virológica sustentada em pacientes com Hepatite C Crônica genótipo 1 durante o tratamento antiviral com terapia tripla
author Winckler, Fernanda Cristina [UNESP]
author_facet Winckler, Fernanda Cristina [UNESP]
author_role author
dc.contributor.none.fl_str_mv Silva, Giovanni Faria [UNESP]
Golim, Marjorie de Assis [UNESP]
Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Winckler, Fernanda Cristina [UNESP]
dc.subject.por.fl_str_mv Hepatitis C
Inflammatory response
Sustained virological response
Treatment
Hepatite C
Resposta inflamatória
Resposta virológica
Tratamento
topic Hepatitis C
Inflammatory response
Sustained virological response
Treatment
Hepatite C
Resposta inflamatória
Resposta virológica
Tratamento
description Hepatitis C is an infectious disease which becomes chronic in about 85% of infected people who can develop cirrhosis and hepatocellular carcinoma. Antiviral therapy isn’t effective in many patients, especially when these patients are genotype 1 and have advanced fibrosis, the inflammatory response also plays a role on sustained virological response (SVR) during treatment with Pegylated (PegIFN) plus Ribavirin (RBV). The aim of this study was evaluate the influence of the inflammatory response by cells and cytocines/chemokines on the virologic response of the patients under antiviral treatment with triple therapy. We included patients with HCV RNA+, naive, genotype 1, both male and female and with advanced fibrosis F3 (n=6); F4 (n=21) for triple treatment regimen. Patients had their samples collected and analyzed at weeks 0 and 12 of treatment and the following parameters were analyzed: IL- 2, IL-4, IL-6, IL-8, IL-10, IL-17A, TNF-α, IFN-γ RANTES, MCP-1, MIG, IP-10 by flow cytometry (CBA method). Control group of 15 healthy volunteers and 27 patients, who were separated into GI (SVR) and G2 (not SRV), were included, the SVR rate was 63%. Patients with chronic hepatitis C had higher circulating levels of IP10, MCP-1, MIG, RANTES, IL-8 and IL-6 compared with healthy volunteers, when G1xG2 were compared, levels of RANTES (p=0,040 and IL-6 (n=0,02) were associated with a SVR at week 0 and its levels were lower in G1; at week 12, levels of RANTES (p=0,04) and IL-8 (p=0,01) were associated with a SVR and its levels were higher in G2. The comparison between weeks 0 and 12 showed that, in G1, the IL6 levels (p = 0.02) and MCP-1 (p = 0.001) were associated with the treatment and in G2, the parameters associated with the treatment were RANTES (p = 0.05) and MCP-1 (p = 0.01). The results suggest that the cytocine IL-6 and chemokine RANTES are associated with SVR at week 0. At week 12, RANTES as well as IL-8 influence in SVR during antiviral therapy in triple regimen. When weeks 0 and 12 in patients SVR are compared, the cytocine IL-6 is associated with treatment. In non-SVR patients, RANTES is associated with treatment and MCP-1 is associated with independent treatment of the patient's response.
publishDate 2016
dc.date.none.fl_str_mv 2016-12-02T16:28:26Z
2016-12-02T16:28:26Z
2016-10-19
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/11449/144991
000876545
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Universidade Estadual Paulista (Unesp)
publisher.none.fl_str_mv Universidade Estadual Paulista (Unesp)
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
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instname_str Universidade Estadual Paulista (UNESP)
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institution UNESP
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