Made available in DSpace on 2014-08-13T14:50:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-03-01Bitstream added on 2014-08-13T18:00:57Z : No. of bitstreams: 1 000750018.pdf: 2505036 bytes, checksum: 21a2b97761cc91543524e6c8614262f1 (MD5) / Os portadores de hepatite C crônica são pacientes que necessitam de um tratamento complexo que abrange um conjunto de técnicas e habilidades a serem desenvolvidas e mantidas ao longo de todo esse período. Dentre as estratégias utilizadas para melhorar a adesão, pesquisas têm apontado a importância de ações educativas para informar e orientar os pacientes acerca da doença e do tratamento. O estudo tem delineamento com pré e pós-teste, e objetiva identificar o nível de conhecimento do paciente sobre a hepatite C e o tratamento antes e após intervenção educativa; e, avaliar junto aos participantes a adequação do conteúdo do manual educativo. Foram utilizados instrumentos para a coleta de dados como o roteiro de entrevista, um teste para avaliar o nível de conhecimento sobre a doença e um inventário para identificar as condutas de adesão relativas à terapêutica. Após a avaliação do conhecimento prévio sobre a doença no início do tratamento, foi feita a intervenção educativa que utilizava um manual educativo para ampliar a visão dos participantes acerca da doença e do tratamento. Em um segundo momento, 12 semanas após o início do tratamento, foi reaplicado um teste de conhecimentos sobre o tratamento e um roteiro de avaliação do manual educativo, além de um inventário de adesão ao tratamento. Após 12 semanas desta aplicação foram avaliadas as fichas clínicas dos participantes, para analisarmos a aderência ao tratamento até a 24ª semana. Participaram desta pesquisa 70 portadores de hepatite C crônica que nunca foram submetidos ao tratamento com medicações antivirais. Da amostra de 70 participantes, 90% aumentaram seu conhecimento prévio sobre aspectos de sua doença após a apresentação do manual educativo, 80% da amostra aderiu ao tratamento até a 24ª semana de tratamento e o manual educativo teve excelente aceitação em 70% dos participantes. O estudo aponta para a importância de se ... / Individuals with chronic hepatitis C require complex treatment which involves a set of techniques and skills to be developed and maintained throughout this period. Among the strategies used to improve adherence, research has pointed to the importance of an education program to inform and educate patients about the disease and treatment. The study aims to identify the patient's knowledge about hepatitis C and treatment before and after the educational intervention, and, with participants evaluating the adequacy of the content of the educational manual. Instruments were used to collect data as structured interview, a test to assess the level of knowledge about the disease and an inventory to identify behaviors related to therapeutic adherence. After evaluation of prior knowledge about the disease at baseline, was made the educational intervention that used a manual education to expand the vision of the participants about the disease and treatment. In a second moment, 12 weeks after initiation of treatment was reapplied a knowledge test on the treatment and evaluation of a structured educational manual, plus an inventory of treatment adherence. After 12 weeks of this application we evaluated the medical records of the participants, to analyze adherence to treatment until week 24. In this study participated 70 patients with chronic hepatitis C who were never subjected to treatment with antiviral medications. Sample of 70 participants, 90% increased their prior knowledge about aspects of their disease after the presentation of educational handbook, 80% of the sample adhered to treatment by week 24 of treatment and educational manual had excellent acceptance by 70% of participants. The study points to the importance of using specific graphic materials in health education actions and signals the need for further research and interventions that promote strategies that favor the management of the disease

Made available in DSpace on 2014-06-11T19:23:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-13Bitstream added on 2014-06-13T18:09:51Z : No. of bitstreams: 1 goncalves_dr_me_arafcf.pdf: 324378 bytes, checksum: 840054353218c4ea795f2d940d1164fe (MD5) / A infecção pelo vírus da hepatite C é um problema de saúde pública, por atingir cerca de 3% da população mundial, e evoluir para a cronicidade em 80% dos casos. A hepatite C crônica é uma doença inflamatória do fígado que desencadeia complicações hepáticas, podendo desenvolver o carcinoma hepatocelular, interfere também no metabolismo de lipídeos, aumenta o risco de desenvolvimento de resistência à insulina e estímulo de diversos processos inflamatórios. Por isso, tem sido sugerida a utilização de compostos com propriedades hipolipidêmicas, antioxidantes e anti-inflamatórias em portadores crônicos de hepatite C crônica, a fim de reduzir os efeitos deletérios causados pela doença. O suco de laranja de polpa vermelha é fonte de compostos bioativos como a vitamina C, o licopeno e as flavanonas cítricas, naringina e hesperidina, os quais são protetores das membranas lipídicas e da ação dos radicais livres. Diante da presença de compostos hipolipidêmicos, antioxidantes e anti-inflamatórios no suco de laranja vermelha, este poderia ser um alimento de consumo regular por indivíduos com hepatite C crônica / nfection by the hepatitis C virus is a public health problem, by attain around 3% of the world population, and evolve to chronicity in 80% of cases. Chronic hepatitis C is an inflammatory disease of the liver that triggers hepatic complications that may develop a hepatocellular carcinoma, also interferes in the metabolism of lipids increases the risk of developing insulin resistance and stimulation of various inflammatory processes. Therefore, it has been suggested to use compounds with hypolipidemic, antioxidants and anti-inflammatory properties in chronic carriers of hepatitis C, in order to reduce the deleterious effects caused by the disease. Orange juice of red pulp is a source of bioactive compounds like vitamin C, lycopene and citrus flavanones, hesperidin and naringin, which are protectors of lipid membranes and the action of free radicals. In the presence of hypolipidemic compounds, antioxidants and anti-inflammatory in red orange juice, this could be a regular food consumption by individuals with chronic HCV infection

Made available in DSpace on 2014-06-11T19:23:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-03-11Bitstream added on 2014-06-13T19:50:30Z : No. of bitstreams: 1 manjate_da_me_arafcf.pdf: 904109 bytes, checksum: 93344d2596a14d27effae840c502b0f8 (MD5) / Ministério da Ciência, Tecnologia e Inovação (Mcti) / Universidade Estadual Paulista (UNESP) / O vírus da hepatite C é um agente infeccioso responsável pela inflamação do fígado e cuja progressão leva a hepatite C podendo produzir complicações como a cirrose, insuficiência hepática e hepatocarcinoma. A infecção pelo VHC progride com inflamação, provocando danos no parênquima hepático, no metabolismo de nutrientes neste órgão, aumento de espécies reativas de oxigênio e à diminuição das concentrações plasmáticas de antioxidantes. Este processo favorece a persistência da replicação viral e a cronicidade podendo levar à ineficiência da resposta imune e agravamento do quadro clínico do paciente. A vitamina C plasmática atua na primeira linha de defesa do organismo inativando as espécies reativas de oxigênio e protegendo os constituintes celulares contra possíveis danos, pois estimula a produção do interferon e citocinas antiinflamatórias, proliferação dos linfócitos T, aumento da atividade anti-apoptótica, entre outras. Uma das principais fontes de vitamina C na dieta humana são as frutas cítricas, em especial o suco de laranja. O objetivo deste estudo foi avaliar o estado nutricional, bioquímico e oxidativo de pacientes com hepatite C crônica. Os pacientes ingeriram 500 mL/dia de suco de laranja durante 8 semanas. No início e final do protocolo proposto foram realizadas avaliações dietéticas, antropométricas, bioquímicas e do estresse oxidativo. Os resultados mostraram que a ingestão regular de suco de laranja não alterou as variáveis antropométricas mas reduziu algumas variáveis bioquímicas, sendo o colesterol total, LDL-c, insulina, destacando-se a redução da proteína C reativa, que houve aumento da capacidade antioxidante e redução da peroxidação lipídica no soro dos pacientes. Pelos resultados observa- se que a ingestão do suco de laranja pode contribuir positivamente para redução do processo inflamatório e do... / Hepatitis C virus is an agent responsible for liver inflammation and the progression can leads to hepatitis C and complications such as cirrhosis, liver failure and hepatocellular carcinoma.VHC infection progresses to inflammation, causing damage in the liver parenchyma, metabolism of nutrients, increase reactive oxygen species and decrease plasma concentration of antioxidants. This process favors the persistence of viral replication and chronic liver disease and lead to inefficiency of the immune response and aggravation of the clinical status of the patients. The plasma vitamin c acts as the first line of defense by inactivation reactive oxygen species and protecting cellular components potential damage and stimulates the production of interferon and anti-inflammatory cytokines, proliferation of T linphocytes increase of anti-apoptotic among others. The greatest sources of vitamin C in the human diet are citrus fruits, especially orange juice. This study is aimed to evaluate the nutritional, biochemical and oxidative status of patients with chronic hepatitis C infection. The patients ingested 500 mL/Day of orange juice for eight weeks. At the beginning and end of the study were avaluated dietary, anthropometric, biochemical and marcs of oxidative stress. The study showed that regular intake of orange juice did not change the nutritional status, reduced some biochemical variables, and increased the antioxidant capacity and decrease lipid peroxidation in the serum of the patients. This study summarizes that the ingestion of orange juice can contribute positively to reduce inflammation oxidative stress have effect to hypocholesterolemic effect to chronic hepatitis C patients

Resumo: O vírus da hepatite C é um agente infeccioso responsável pela inflamação do fígado e cuja progressão leva a hepatite C podendo produzir complicações como a cirrose, insuficiência hepática e hepatocarcinoma. A infecção pelo VHC progride com inflamação, provocando danos no parênquima hepático, no metabolismo de nutrientes neste órgão, aumento de espécies reativas de oxigênio e à diminuição das concentrações plasmáticas de antioxidantes. Este processo favorece a persistência da replicação viral e a cronicidade podendo levar à ineficiência da resposta imune e agravamento do quadro clínico do paciente. A vitamina C plasmática atua na primeira linha de defesa do organismo inativando as espécies reativas de oxigênio e protegendo os constituintes celulares contra possíveis danos, pois estimula a produção do interferon e citocinas antiinflamatórias, proliferação dos linfócitos T, aumento da atividade anti-apoptótica, entre outras. Uma das principais fontes de vitamina C na dieta humana são as frutas cítricas, em especial o suco de laranja. O objetivo deste estudo foi avaliar o estado nutricional, bioquímico e oxidativo de pacientes com hepatite C crônica. Os pacientes ingeriram 500 mL/dia de suco de laranja durante 8 semanas. No início e final do protocolo proposto foram realizadas avaliações dietéticas, antropométricas, bioquímicas e do estresse oxidativo. Os resultados mostraram que a ingestão regular de suco de laranja não alterou as variáveis antropométricas mas reduziu algumas variáveis bioquímicas, sendo o colesterol total, LDL-c, insulina, destacando-se a redução da proteína C reativa, que houve aumento da capacidade antioxidante e redução da peroxidação lipídica no soro dos pacientes. Pelos resultados observa- se que a ingestão do suco de laranja pode contribuir positivamente para redução do processo inflamatório e do ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Hepatitis C virus is an agent responsible for liver inflammation and the progression can leads to hepatitis C and complications such as cirrhosis, liver failure and hepatocellular carcinoma.VHC infection progresses to inflammation, causing damage in the liver parenchyma, metabolism of nutrients, increase reactive oxygen species and decrease plasma concentration of antioxidants. This process favors the persistence of viral replication and chronic liver disease and lead to inefficiency of the immune response and aggravation of the clinical status of the patients. The plasma vitamin c acts as the first line of defense by inactivation reactive oxygen species and protecting cellular components potential damage and stimulates the production of interferon and anti-inflammatory cytokines, proliferation of T linphocytes increase of anti-apoptotic among others. The greatest sources of vitamin C in the human diet are citrus fruits, especially orange juice. This study is aimed to evaluate the nutritional, biochemical and oxidative status of patients with chronic hepatitis C infection. The patients ingested 500 mL/Day of orange juice for eight weeks. At the beginning and end of the study were avaluated dietary, anthropometric, biochemical and marcs of oxidative stress. The study showed that regular intake of orange juice did not change the nutritional status, reduced some biochemical variables, and increased the antioxidant capacity and decrease lipid peroxidation in the serum of the patients. This study summarizes that the ingestion of orange juice can contribute positively to reduce inflammation oxidative stress have effect to hypocholesterolemic effect to chronic hepatitis C patients / Orientador: Thais Borges César / Coorientador: João Bosco Faria / Banca: Paulo Inácio da Costa / Banca: Ellen Cristini Freitas / Mestre

Hepatitis C virus (HCV) is a leading cause of chronic liver disease. In the developed world, injection drug use (IDU) through sharing of infected needles and other paraphernalia remains the principal risk factor for HCV transmission. Effective but expensive treatment is now possible but there remains a pressing need for a vaccine. A proportion of people who inject drugs (PWIDs) remain uninfected despite HCV exposure from a long history of sharing needles and other paraphernalia. These cases are termed exposed but uninfected (EU) and test negative for both HCV antibodies and RNA and exhibit a phenotype of resistance to HCV infection. Improved understanding of the mechanisms that confer resistance in the EUs has the potential to aid development of an effective vaccine and novel therapeutic strategies. This thesis reports on the findings from 3 different strategies to identify characteristics of HCV resistance. I used urinary metabolomics, serum lipidomics and the study of adaptive and innate immune responses. Each of these methods has demonstrated clear differences between EU cases and healthy controls and/or spontaneous resolvers of HCV infection. Urinary metabolomics suggest a potential role of the gut microbiome, the serum lipidomics showed marked differences in lipid profiles in EU cases pointing towards a perturbed lipid/virus interaction, and the immune studies confirmed previous work identifying low level T cell responses in many EU cases but has also identified a marked upregulation of interferon alpha production to low dose viral RNA in EU cases utilising ELISA assay. In conclusion, this thesis reports data that identifies a number of new findings that provide insight into mechanisms of resistance to HCV infection. My findings suggest that the complex interplay between the virus and lipids together with an upregulated innate immune response may together help determine the outcome following HCV exposure. In summary, studies performed in this thesis have demonstrated that there are different pathways that define the EU phenotype. Despite being a heterogenous subgroup of PWIDs, the EUs are clearly distinct from a healthy control population.

Le virus de l'hépatite C (VHC) est une menace majeure avec plus de 130 millions de personnes infectées chaque année. Il constitue la principale cause de cancer du foie. Le VHC est un virus transmis par le sang soit au cours de consommation de drogue par voie intraveineuse soit lors de transfusions sanguines. Il s'adapte à l'environnement de l'hôte grâce à un taux de mutation élevé qui amoindrit l’efficacité des traitements. Le virus se multiplie rapidement dans l'hôte et crée ainsi une population de virus génétiquement hétérogènes, appelée quasi-espèces, qui peut ainsi répondre aux pressions sélectives liées au traitement. Les traitement antiviraux existants sont des tri-thérapies contenant des peg-interféron, de la ribavirine et des inhibiteurs de la protéine (PI). Les inhibiteurs comme la telaprevir ou la bocéprévir ciblent la région NS3 du génome en bloquant le mécanisme de réplication. Cependant, en raison de la nature dynamique des quasi-espèces, les séquences cibles sont variables et les inhibiteurs conçus pour se lier à une région génomique particulière sont rendus inefficaces.Nous analysons ces populations virales en utilisant les techniques modernes de séquençage et le pyroséquencage profond qui permet l’analyse à grande échelle des données génétiques. La technique “Amplicon Sequencing” permet de cibler des régions particulières du génome viral, comme les régions NS3 ou NS5B qui participent au mécanisme de réplication et qui sont des cibles pour les thérapies antivirales. Par rapport au séquençage Sanger, notre pipeline NGS permet d’appréhender l’hétérogénéité de la population virale au sein d’un hôte. Pour analyser les données NGS, nous avons implémenté un pipeline d’analyse bioinformatique qui a été automatisé avec eHive.Nous étudions des échantillons de VHC de 40 patients traités par trithérapie. Deux sources de cellules virales sont utilisées pour le séquençage: les cellules du plasma et les cellules mononuclées du sang périphérique. L'objectif est de vérifier si une analyse des mutations de la région génomique NS3 peut aider à prédire le résultat du traitement. Nous constatons que des mutations de résistance aux antiviraux se trouvent à la fois chez les individus qui ont répondu et qui n’ont pas répondu au traitement. Nous avons donc recherché d'autres signatures génétiques de l'échec du traitement. Nous constatons que l'hétérogénéité génétique est plus faible chez les individus qui répondent de manière favorable au traitement. Notre conclusion est que l'hétérogénéité virale est un facteur indépendant pour prédire la réponse à un traitement, en plus de la présence de mutations spécifiques dans les régions ciblées par le traitement.Les techniques NGS permettent également d’étudier l'évolution virale au sein d'un seul hôte. En utilisant de multiples temps d'échantillonnage, nous pouvons mesurer les caractéristiques de l'évolution de la population virale. Pour trois patients avec des échantillons viraux couvrant une période de 13 ans, nous avons utilisé la technique “Amplicon Sequencing“ pour les régions NS3 et NS5B. Des infections mixtes comprenant de multiples génotypes sont retrouvées chez deux patients. Nous avons montré qu’il existe de la structure de populations et des lignées divergentes de VHC au sein de chaque patient. Au cours du traitement, l'hétérogénéité génétique et la taille efficace de la population dans la région NS5B augmente fortement après le début du traitement. Ces résultats mettent en évidence un processus de sélection diversifiante suite au traitement qui augmente l'hétérogénéité génétique virale. Nous mettons ainsi en évidence un processus dit de balayage sélectif doux qui est observé pour la première fois chez des patients infectées par des génotypes multiples du virus VHC.Notre analyse NGS montre que l'hétérogénéité génétique du VHC est liée à l'échec ou à la réussite du traitement et que son évolution permet de mieux comprendre la façon dont les virus s'adaptent au traitement. / Hepatitis C virus (HCV) is a major threat to global health, with over 130 million annual infections. HCV is a blood borne virus transmitted primarily via intravenous drug use or hospital transfusions. It infects the liver cells and is the leading cause of liver cancer. It adapts to the host environment with a high mutation rate and can make efficient treatment very difficult. Due to poor replication proofreading, the virus multiplies rapidly in the host and creates a population of viruses which is genetically heterogeneous enough to escape selective pressures. This HCV population called quasispecies is found within and between infected hosts. Current antiviral treatment consists of a triple therapy of peg-Interferon, ribavirin and protein inhibitors (PI). PIs such as telaprevir, boceprevir target the NS3 region of the genome, blocking the replication mechanism. However due to the highly dynamic nature of the quasispecies, the target sequences are variable and PIs designed to bind to a particular genomic region are therefore rendered ineffective.We analyse viral populations of HCV using Next generation Sequencing (NGS) technologies and ultradeep pyrosequencing, which allow for rapid and large scale analysis of genetic data. Amplicon sequencing allows for targeting particular regions of the viral genome, such as the NS3 or NS5B which form a part of the replication mechanism and hence are targets for antiviral therapy. Compared to Sanger sequencing, our NGS pipeline ascertains viral population heterogeneity within a host. We implemented the bioinformatics workflow manually and in eHive as an automated pipeline.We study HCV samples from 40 patients treated with triple therapy. Two sources of the virus, plasma and peripheral blood mononuclear cells are used for sequencing. The main aim is to check if a baseline analysis of the NS3 genomic region can help to predict the outcome of the treatment. We find that antiviral resistance mutations are found in both responders and non-responders to the treatment. Since no correlation exists between observed mutations and failure of tri-therapy, we look for other genetic signatures of treatment failure. We find that genetic heterogeneity, calculated using Shannon’s entropy, is lower in responders. We conclude that the viral heterogeneity can be used as an independent factor to predict response to treatment, more than presence of specific mutations at baseline.NGS also enables large-scale studies of viral evolution within a single host. Using multiple sampling time points, we gain insights about viral evolutionary characteristics of HCV and responses to selective pressures during infection. For three patients with viral samples covering a period of 13 years, we perform amplicon sequencing on the NS3 and NS5B regions. Mixed infections comprising of multiple genotypes are found in two patients. We find considerable population structure and diverging HCV lineages within each patient. Over the course of treatment, genetic heterogeneity and effective population size in the NS5B regions increases sharply after treatment initiation compared to baseline. These results provide evidence of diversifying selection occurring post-treatment, acting on standing genetic variation resulting in high genetic heterogeneity. These are characteristics of a soft selective sweep, which is observed for the first time in chronic HCV patients infected with multiple genotypes.Our NGS analysis show that genetic heterogeneity in HCV is related to treatment failure and that its evolution provides insights about how viruses adapt to treatment.

Aprovados para o tratamento da hepatite C crônica (HCC) em 2011, os inibidores da protease (IPs) de primeira geração telaprevir (TVR) e boceprevir (BOC) representaram o início de uma nova era caracterizada pelo desenvolvimento de fármacos de ação direta contra o vírus da hepatite C (HCV). Os principais objetivos do presente trabalho foram descrever a efetividade e as incidências de eventos adversos ao uso de BOC ou TVR em esquema triplos com interferon peguilado (Peg-INF) e ribavirina (RBV), verificar a associação de fatores do hospedeiro e de fatores virais com a resposta virológica sustentada (RVS) e com a cirrose hepática (CH), além de realizar uma análise de custo-efetividade envolvendo a incorporação de TVR e BOC ao Sistema Único de Saúde (SUS). Foi realizado um estudo descritivo que incluiu pacientes cronicamente infectados pelo genótipo 1 do HCV cujo tratamento para HCC foi iniciado entre julho de 2013 e dezembro de 2015. Realizou-se ainda uma análise de custo-efetividade comparando as terapias triplas com a terapia dupla com RBV e Peg- INF alfa-2a. Foram incluídos 115 indivíduos, dos quais 58 (50,4%) tinham CH e 103 (89,6%) utilizaram TVR. A taxa de RVS global foi de 61,7% (62,1%, considerando TVR e 58,3%, considerando BOC). As análises bivariadas indicaram que ausência de CH, recidiva a tratamento prévio em relação a outros tipos de resposta, ausência de varizes de esôfago, presença dos alelos CC localizados no sítio rs12979860 do gene que codifica a interleucina-28 e razão entre o valor de aspartato aminotransferase (AST) pré-tratamento e o limite superior da normalidade menor que 3,0 são fatores associados com a RVS. A regressão logística evidenciou que o nível de AST e o tipo de resposta ao tratamento prévio seriam as variáveis mais fortemente associadas. Evidenciou-se ainda que valores maiores de transaminases estão associados ao diagnóstico de CH, sendo a alanina aminotransferase mais fortemente associada. Com relação às reações adversas a medicamentos, foi evidenciado que a inclusão de um dos IPs à terapia para HCC aumenta a incidência destas, com destaque para os eventos hematológicos que foram observados em quase 100,0% dos pacientes. Sobre a análise farmacoeconômica, os cálculos das razões de custo-efetividade, das razões de custoefetividade incremental e as análises de sensibilidade foram favoráveis à terapia dupla. As taxas de RVS foram superiores àquelas descritas nos estudos com terapia dupla e inferiores às taxas de efetividade encontradas nos principais estudos précomercialização com TVR ou BOC. Fatores relacionados à condição clínica do paciente infectado e ao seu sistema imune estão associados com a RVS aos IPs de primeira geração. As terapias triplas mostraram um perfil de segurança desfavorável em relação ao esquema com RBV e Peg-INF. O estudo sugeriu ainda que a incorporação de TVR ou BOC ao SUS não foi uma conduta custo-efetiva. / Approved for the treatment of chronic hepatitis C (CHC) in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC) were the beginning of a new era characterized by the development of direct action drugs against the hepatitis C virus (HCV). The main aims of the present study were to describe effectiveness and the incidence of adverse events to the use of BOC or TVR with pegylated interferon (Peg-INF) and ribavirin (RBV) in triple therapy, to verify the association of host factors and viral factors with sustained virological response (SVR) and with cirrhosis and to perform a cost-effectiveness analysis involving the incorporation of TVR and BOC to Brazilian Public Health System (BPHS). A descriptive study was carried out which included patients chronically infected with HCV genotype 1 whose treatment for CHC was started between July 2013 and December 2015. A cost-effectiveness analysis comparing triple therapies to a therapy with RBV and Peg-INF alpha-2a was also performed. A total of 115 subjects were included, of which 58 (50,4 %) had cirrhosis and 103 (89,6 %) used TVR. The overall SVR rate was 61,7 % (62,1 %, considering TVR and 58,3 %, considering BOC). Bivariate analyzes indicated that absence of cirrhosis, relapse of previous treatment in relation to other types of response, absence of esophageal varices, presence of the CC alleles located at the site rs12979860 of the gene coding the interleukin-28 and ratio between the pre-treatment aspartate aminotransferase (AST) value and the upper limit of normality less than 3.0 are factors associated to SVR. The logistic regression showed that the level of AST and type of response to previous treatment would be as variables more strongly associated. It was also evidenced that higher values of transaminases are associated to the diagnosis of cirrhosis, being the alanine aminotransferase more strongly associated. In relation to the adverse drug reactions, it was evidenced that the inclusion of one of the PIs to the therapy for CHC increases the incidence of these, highlighting the hematological disorders that were observed in almost 100,0% of the patients. About the pharmacoeconomic analysis performed, the calculations of the cost-effectiveness ratios, incremental cost-effectiveness ratios and the sensitivity analyzes were favorable to the dual therapy. The SVR rates were higher than those described in most studies with dual therapy and lower than the rates of effectiveness found in the main premarketing studies with TVR or BOC. Factors related to the infected patients clinical condition and to their immune system are associated with SVR to the firstgeneration PIs. The triple therapies showed an unfavorable safety profile in relation to dual regimen with RBV and Peg-INF. The study also suggested that incorporation of TVR or BOC to BPHS was not a cost-effective conduct.

BACKGROUND: Rapid advances in the treatment of the hepatitis C virus (HCV) have been witnessed in clinical practice over the last five years. Pharmacological developments have ended the reliance on the drug interferon-α as a component of successful therapy, heralding the dawn of a new era in the fight against the disease. How this new era is being understood and experienced by those individuals living with the virus is currently unknown. METHODS: A purposive sample of 20 individuals participated in face-to-face semi-structured interviews exploring their experience of living with HCV. Eight of these participants were interviewed again following a period of interferon-free treatment. All interviews were conducted between June 2015 and March 2016. The interviews were transcribed verbatim and explored using thematic analysis, underpinned by social phenomenological theory. RESULTS: Analysis of the corpus of data resulted in three overarching themes entitled ‘positioning HCV', ‘beyond a physical burden' and ‘reconstructing uncertainty'. These themes offer original insight into how this new era of therapy is being realised by those living with the virus. The experience of interferon-free treatment was also explored through the narratives of those individuals who participated in a further post-treatment interview. Three further themes entitled ‘expectations and realisations', ‘an honour and a pleasure' and ‘treatment needs' encapsulate their experience. DISCUSSION: The findings from this study recontextualise the lived experience of HCV within a new era of treatment. In doing so, they expose social and emotional spheres of illness, and a perception of illness chronicity, which remain untouched by the treatment revolution. Further, this work emphasises how treatment inequalities fundamentally underpin multiple aspects of the daily lived experience, and are integral to how those living with HCV articulate the disease. The implications of this work challenge current HCV policy and clinical practice.

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Introdução: Diabete Melito Pós-Transplante (DMPT) é considerado uma séria complicação do transplante de rim, podendo diminuir a sobrevida do enxerto e do paciente. O imunossupressor tacrolimo (TAC) pode aumentar o risco de desenvolvimento de DMPT. Objetivos: Estimar o risco de DMPT em pacientes tratados com TAC no Serviço de Transplante Renal da Irmandade da Santa Casa de Misericórdia de Porto Alegre, identificar os demais fatores de risco para o DMPT e suas conseqüências. Métodos: Foram analisados 413 pacientes sem diabetes prévia ao transplante, com 18 anos ou mais, tratados com TAC, ciclosporina (CsA) ou sirolimo (SIR), em uso de corticoterapia e com período de seguimento póstransplante maior de 6 meses. O estudo seguiu o modelo observacional–coorte retrospectivo. Os critérios da Associação Americana de Diabete foram utilizados para o diagnóstico de DMPT. Os dados foram coletados de prontuários. Resultados: Dos 413 pacientes analisados, 171(41,4%) receberam como imunossupressão inicial TAC, 221(53,5%) CsA e 21(5,1%) SIR. DMPT ocorreu em 20,6% dos pacientes da coorte (85 de 413). A mediana do tempo para o desenvolvimento de DMPT foi de 54 dias. A incidência cumulativa de DMPT foi de 24,6% e 17,2% para os grupos de tratamento TAC e CsA, respectivamente. Na análise por intenção de tratamento, o risco para o desenvolvimento de DMPT, ao comparar os grupos TAC vs. CsA foi de HR=1,563, (IC:95%=1,008–2,425), P=0,006. Pelo método de Kaplan-Meier, 78,9% dos pacientes em uso de TAC estavam livres de DMPT no mês 6 vs. 87,8% dos pacientes em uso de CsA (P= 0,044). Os demais fatores de risco independentes identificados foram: índice de massa corporal (IMC) pré-transplante (P<0,0001), idade do receptor (P<0,0001) e episódio de rejeição aguda (RA) (P=0,013). Não houve diferença estatística significativa para anti-HCV reagente do receptor. Em 3 anos, a sobrevida do enxerto, ao comparar os pacientes com diagnóstico de DMPT vs. ausência de DMPT foi de 85,5% e 93,3%, respectivamente (P=0,021) e a sobrevida do paciente foi de 88,9% e 96,7%, respectivamente (P=0,017). Conclusão: A incidência de DMPT está associada com o tipo de imunossupressão utilizada, idade do receptor, IMC pré-transplante e episódio de RA. DMPT é um importante fator de risco para perda do enxerto e mortalidade. Medidas para minimizar o risco dessa complicação devem ser tomadas, como a individualização da terapia imunossupressora. / Introduction: Post-transplant diabetes mellitus (PTDM) is considered a serious complication of kidney transplantation and may reduce the patient and graft survival. The immunosuppressive Tacrolimus (TAC) may increase the risk of developing PTDM. Purpose: To estimate the risk of PTDM in renal transplant recipients treated with TAC in our center, identify all risk factors for PTDM and its consequences. Methodology: We analyzed 413 patients without diabetes prior to transplantation, with age ≥ 18 years, who were treated with tacrolimus (TAC), cyclosporine (CyA) or sirolimus (SIR), under steroids therapy and with a follow-up post-transplant period more than 6 months. We performed a retrospective review – cohort study. PTDM was diagnosed according to American Diabetes Association guidelines. Data were collected from medical records. Results: We examined 413 renal allograft recipients, these, 171 (41.4%) received initial immunosuppresion with TAC, 221 (53.5%) CyA and 21 (5.1%) SIR. PTDM occurred in 20.6% of patients in the cohort (85 of 413). The median time to the development of PTDM was 54 days post transplant. The cumulative incidence of PTDM was 24.6% and 17.2% for groups TAC and CyA treatment, respectively. In the analysis by intention to treat, the proportion of patients receiving TAC who developed PTDM was significantly higher than patients receiving CyA (HR=1,563, (CI:95%=1,008–2,425), P=0,006. The Kaplan-Meier method showed that 78,9% patients taking TAC were free of PTDM at six months compared to 87,8% of patients taking CsA (P= 0.044). The other independent risk factors identified were: body mass index (BMI) (P<0,0001), recipient age (P<0,0001) and acute rejections episodes (AR) (P=0,013). There was no statistically significant difference for patients with hepatitis C. Three years actuarial graft survival was 85,5% in patients with PTDM compared with 93,3% for those without diabetes (P=0,021) and patient survival was 88,9% e 96,7%, respectively (P=0,017). Conclusions: The incidence of PTDM is associated with TAC use, the recipient age, BMI and acute rejections episodes. PTDM is an important risk factor for graft loss and mortality. Measures to minimize the risk of this complication should be taken, such as the individualization of immunosuppresive therapy.