A infecção crônica pelo vírus da hepatite C (HCV) é importante fator de risco para o desenvolvimento de cirrose hepática e de carcinoma hepatocelular. A evolução para formas mais graves está relacionada a fatores ligados ao vírus, ao hospedeiro e à resposta imune. O objetivo deste estudo foi avaliar a associação entre os polimorfismos do gene HLA-E, a expressão da molécula HLA-E e a gravidade da doença hepática pelo HCV. Foram incluídos 112 pacientes com hepatite C crônica e avaliados parâmetros clínicos, bioquímicos e histológicos (esteatose, atividade inflamatória e fibrose hepática). A variabilidade do gene HLA-E foi avaliada por sequenciamento de Sanger, e a expressão hepática da molécula, por imunoistoquímica. Para comparação da expressão hepática da molécula HLA-E e da variabilidade do gene HLA-E, foram usados dois grupos controles de indivíduos sem hepatopatia da mesma região geográfica. A imunoistoquímica para HLA-E identificou expressão da molécula nos hepatócitos e nas células de Kupffer. A expressão de HLAE em hepatócitos e células de Kupffer foi encontrada em 56,3% e 43,8% dos pacientes com HCV e em 20% e 10% nos controles (P = 0,008 e 0,02), respectivamente. Foi identificado que o percentual de pacientes do sexo masculino, com expressão moderada de HLA-E em células de Kupffer, foi maior em relação aos pacientes do sexo feminino (22,8% x 7,3%; P = 0,03). As amostras de fígado classificadas como esteatose, atividade necroinflamatória e fibrose graves apresentaram maior grau de expressão de HLA-E em células de Kupffer e hepatócitos, com associação linear significativa. Na análise multivariada, as variáveis que influenciaram significativamente a gravidade da doença foram a expressão da molécula HLA-E nos hepatócitos, a idade avançada e o índice de massa corporal maior que 25. Foram identificados 14 haplótipos diferentes do gene HLA-E, quatro deles ainda não descritos na literatura. A frequência do alelo HLA-E*01:01:01:03 foi menor no grupo de pacientes, quando comparada ao controle (P = 0,0001). O alelo HLA-E*01:03:05 associou-se a maior probabilidade (OR = 4,69) de expressão da molécula HLA-E, na célula de Kupffer (P = 0,046). O genótipo TT do polimorfismo +424 T/C (rs1059510) associou-se a menor probabilidade (OR = 0,06) de expressão da molécula HLA-E, na célula de Kupffer, em relação à ausência de expressão (P=0,009), a menor probabilidade (OR = 0,22) de atividade inflamatória moderada/grave em relação à leve (P = 0,047) e esteve associado a menor probabilidade (OR = 0,17) de fibrose hepática moderada/grave em relação à fibrose leve (P = 0,049). Os resultados do presente estudo sugerem que a pesquisa de fatores imunogenéticos, como a expressão hepática da molécula HLA-E e a identificação da variabilidade genética do HLA-E, pode ter aplicabilidade no manejo clínico dos pacientes, uma vez que auxilia na discriminação daqueles com maior risco de atingir formas avançadas da hepatite C crônica. / Chronic hepatitis C is an important risk factor for the development of cirrhosis and hepatocellular carcinoma. The severity of liver disease can be influenced by factors related to the virus, the host and the immune response. The aim of this study was to evaluate the association between HLA-E gene polymorphisms, HLA-E molecule expression and HCV liver disease severity. We included 112 patients with chronic hepatitis C and evaluated clinical, biochemical and histological parameters (steatosis, inflammatory activity and liver fibrosis). The variability of the HLA-E gene was assessed by Sanger sequencing and liver HLA-E expression by immunohistochemistry. Two control groups of individuals without hepatopathy from the same geographical region were used to compare the HLA-E expression and the gene variability. Immunohistochemistry for HLA-E showed positivity in hepatocyte and Kupffer cell. HLA-E positivity in hepatocytes and Kupffer cells were found in 56.3% and 43.8% of HCV patients and in 20% and 10% in the controls (P = 0.008 and 0.02), respectively. We found that the percentage of male patients with moderate HLA-E expression in Kupffer cells was higher than in females (22.8% vs. 7.3%, P = 0.03). The liver samples classified as severe fibrosis, necroinflammatory activity and steatosis presented greater expression of HLA-E on Kupffer cells and hepatocytes. There was a positive linear association between HLA-E expression and severity of liver damage (P<0.05). In the multivariate analysis, the variables that significantly influenced the severity of the disease were HLA-E molecule expression in hepatocytes, advanced age and body mass index greater than 25. Fourteen different HLA-E haplotypes were identified, four of them not yet described in the literature. The frequency of the HLA-E * 01: 01: 01: 03 allele was lower in the group of patients than in the control group (P = 0.0001). The HLA-E * 01: 03: 05 allele was associated with increased likelihood (OR = 4.69) of HLA-E expression in the Kupffer cell (P = 0.046). The TT genotype of the +424 T / C polymorphism (rs1059510) was associated with a lower probability (OR = 0.06) of HLA-E expression in the Kupffer cell in relation to the absence of its expression (P = 0.009), was associated with a lower probability (OR=0,22) of moderate/severe necroinflammatory activity in relation to the mild inflammatory activity (P=0,047) and was associated with a lower probability (OR = 0.17) of moderate / severe hepatic fibrosis in relation to mild fibrosis (P = 0.049). The results of the present study suggest that the study for immunogenic factors such as HLA-E liver expression and the identification of certain polymorphisms and alleles of the HLA-E gene may have applicability in the clinical management of patients since it aids in discrimination of those at greatest risk of reaching advanced forms of chronic hepatitis C.

A infecção crônica pelo vírus da hepatite C (HCV) é importante fator de risco para o desenvolvimento de cirrose hepática e de carcinoma hepatocelular. A evolução para formas mais graves está relacionada a fatores ligados ao vírus, ao hospedeiro e à resposta imune. O objetivo deste estudo foi avaliar a associação entre os polimorfismos do gene HLA-E, a expressão da molécula HLA-E e a gravidade da doença hepática pelo HCV. Foram incluídos 112 pacientes com hepatite C crônica e avaliados parâmetros clínicos, bioquímicos e histológicos (esteatose, atividade inflamatória e fibrose hepática). A variabilidade do gene HLA-E foi avaliada por sequenciamento de Sanger, e a expressão hepática da molécula, por imunoistoquímica. Para comparação da expressão hepática da molécula HLA-E e da variabilidade do gene HLA-E, foram usados dois grupos controles de indivíduos sem hepatopatia da mesma região geográfica. A imunoistoquímica para HLA-E identificou expressão da molécula nos hepatócitos e nas células de Kupffer. A expressão de HLAE em hepatócitos e células de Kupffer foi encontrada em 56,3% e 43,8% dos pacientes com HCV e em 20% e 10% nos controles (P = 0,008 e 0,02), respectivamente. Foi identificado que o percentual de pacientes do sexo masculino, com expressão moderada de HLA-E em células de Kupffer, foi maior em relação aos pacientes do sexo feminino (22,8% x 7,3%; P = 0,03). As amostras de fígado classificadas como esteatose, atividade necroinflamatória e fibrose graves apresentaram maior grau de expressão de HLA-E em células de Kupffer e hepatócitos, com associação linear significativa. Na análise multivariada, as variáveis que influenciaram significativamente a gravidade da doença foram a expressão da molécula HLA-E nos hepatócitos, a idade avançada e o índice de massa corporal maior que 25. Foram identificados 14 haplótipos diferentes do gene HLA-E, quatro deles ainda não descritos na literatura. A frequência do alelo HLA-E*01:01:01:03 foi menor no grupo de pacientes, quando comparada ao controle (P = 0,0001). O alelo HLA-E*01:03:05 associou-se a maior probabilidade (OR = 4,69) de expressão da molécula HLA-E, na célula de Kupffer (P = 0,046). O genótipo TT do polimorfismo +424 T/C (rs1059510) associou-se a menor probabilidade (OR = 0,06) de expressão da molécula HLA-E, na célula de Kupffer, em relação à ausência de expressão (P=0,009), a menor probabilidade (OR = 0,22) de atividade inflamatória moderada/grave em relação à leve (P = 0,047) e esteve associado a menor probabilidade (OR = 0,17) de fibrose hepática moderada/grave em relação à fibrose leve (P = 0,049). Os resultados do presente estudo sugerem que a pesquisa de fatores imunogenéticos, como a expressão hepática da molécula HLA-E e a identificação da variabilidade genética do HLA-E, pode ter aplicabilidade no manejo clínico dos pacientes, uma vez que auxilia na discriminação daqueles com maior risco de atingir formas avançadas da hepatite C crônica. / Chronic hepatitis C is an important risk factor for the development of cirrhosis and hepatocellular carcinoma. The severity of liver disease can be influenced by factors related to the virus, the host and the immune response. The aim of this study was to evaluate the association between HLA-E gene polymorphisms, HLA-E molecule expression and HCV liver disease severity. We included 112 patients with chronic hepatitis C and evaluated clinical, biochemical and histological parameters (steatosis, inflammatory activity and liver fibrosis). The variability of the HLA-E gene was assessed by Sanger sequencing and liver HLA-E expression by immunohistochemistry. Two control groups of individuals without hepatopathy from the same geographical region were used to compare the HLA-E expression and the gene variability. Immunohistochemistry for HLA-E showed positivity in hepatocyte and Kupffer cell. HLA-E positivity in hepatocytes and Kupffer cells were found in 56.3% and 43.8% of HCV patients and in 20% and 10% in the controls (P = 0.008 and 0.02), respectively. We found that the percentage of male patients with moderate HLA-E expression in Kupffer cells was higher than in females (22.8% vs. 7.3%, P = 0.03). The liver samples classified as severe fibrosis, necroinflammatory activity and steatosis presented greater expression of HLA-E on Kupffer cells and hepatocytes. There was a positive linear association between HLA-E expression and severity of liver damage (P<0.05). In the multivariate analysis, the variables that significantly influenced the severity of the disease were HLA-E molecule expression in hepatocytes, advanced age and body mass index greater than 25. Fourteen different HLA-E haplotypes were identified, four of them not yet described in the literature. The frequency of the HLA-E * 01: 01: 01: 03 allele was lower in the group of patients than in the control group (P = 0.0001). The HLA-E * 01: 03: 05 allele was associated with increased likelihood (OR = 4.69) of HLA-E expression in the Kupffer cell (P = 0.046). The TT genotype of the +424 T / C polymorphism (rs1059510) was associated with a lower probability (OR = 0.06) of HLA-E expression in the Kupffer cell in relation to the absence of its expression (P = 0.009), was associated with a lower probability (OR=0,22) of moderate/severe necroinflammatory activity in relation to the mild inflammatory activity (P=0,047) and was associated with a lower probability (OR = 0.17) of moderate / severe hepatic fibrosis in relation to mild fibrosis (P = 0.049). The results of the present study suggest that the study for immunogenic factors such as HLA-E liver expression and the identification of certain polymorphisms and alleles of the HLA-E gene may have applicability in the clinical management of patients since it aids in discrimination of those at greatest risk of reaching advanced forms of chronic hepatitis C.

There are multiple immune mechanisms identified for persistence of hepatitis B virus (HBV) infection. This thesis considers the vital role that inhibitory receptors play in contributing to impairment of the adaptive immune system in chronic hepatitis B (CHB), and the potential role they play in the innate immune system, focusing on the inhibitory receptor leucocyte-associated immunoglobulin-like receptor (LAIR)-1. The unique aspect of this work is that for the first time LAIR-1 expression has been investigated on natural killer (NK) cells in CHB. Our striking findings of increased LAIR-1 expression on peripheral NK cells in CHB and an inverse correlation between expression and effector function suggest this inhibitory receptor could have a potential role in exhaustion of NK cells in CHB. We therefore additionally explored the expression of LAIR-1 on circulating NK cells from patients with hepatocellular carcinoma (HCC) and non-alcoholic fatty liver disease (NAFLD). The particular relevance of LAIR-1 to liver disease is that one of its major ligands is collagen. We demonstrated a downregulation of LAIR-1 expression on intrahepatic NK cells, which we postulate might occur following repetitive engagement with abundant collagen within the liver. In line with this, intrahepatic NK cells with a liver-resident (CXCR6+) phenotype had even lower LAIR-1 expression than liver infiltrating (non-resident, CXCR6-) NK cells. Furthermore, preliminary experiments display attenuation of the cytotoxic degranulation capacity (CD107a) by circulating NK cells from CHB patients upon exposure to plate-bound collagen. We demonstrate differential expression of LAIR-1 on NK cells in viral hepatitis, HCC and NAFLD and between peripheral and intrahepatic NK cells. Preliminary experiments demonstrate a role in inhibiting NK cell function suggesting this as a novel therapeutic target to harness the capacity of NK cells to control chronic infection and cancer.

Viral hepatitis - knowledge of upper grade high school students This thesis is focused on the issue of all types of viral hepatitis. The work is divided into two large units. The first part is theoretical and provides a comprehensive overview of all types of viral hepatitis in general. It deals in detail with each type separately; it describes its characteristics, what causes it, its epidemiology, course, diagnosis, treatment and prevention. The empirical part investigates the level of knowledge of students of third and fourth grade of high schools from a quantitative survey. It includes pedagogical research, whose task was to determine what knowledge students had acquired during compulsory education, and it also includes evaluation of this research.

Background and aims: This interdisciplinary thesis was designed to deepen understanding of the co-morbidity of anxiety and depression with chronic diseases of the digestive tract, and inflammatory bowel disease (IBD) in particular. The first part of the thesis aimed to explore the prevalence of psychological problems in IBD compared to irritable bowel syndrome (IBS) and chronic hepatitis C (HCV) groups. It also explored the relationship between the number of co-morbid functional gastrointestinal disorders and the severity of psychological problems in IBD and IBS. It also aimed to determine whether there is a relationship between psychological problems and the response to standard medical treatment/physical outcomes in patients with IBD, IBS and HCV. Furthermore, it aimed to explore whether disclosure of the psychological status of depressed and/or anxious IBD patients to their gastroenterologists influences doctors’ behaviour and affects patients’ responses to treatment/physical outcomes. The second part of the thesis aimed to investigate the potential role of antidepressants in IBD and to determine the feasibility of future randomised controlled trials on the role of antidepressants in IBD. Methods: Overall, a cohort of 139 outpatients (64 IBD, 41 HCV, and 34 IBS) and 18 gastroenterologists participated in the six studies comprising this thesis. A mixed methods design was applied. Two cross-sectional studies, an observational cohort prospective management study, a randomised controlled trial, a systematic review and an exploratory interview study were conducted. Differences between the groups for continuous variables were assesed with one way analysis of variance (ANOVA) and independent samples ttests. Differences in categorical variables were assessed with contingency tables with the Chi-Square test and the Fisher’s Exact Test. Propsective analyses were conducted with repeated measures ANOVA, logistic regression and Poisson regression. Qualitative data were analysed using content analysis. Results: Overall, 42% of participants were anxious and 19% were depressed. Participants with HCV had higher levels of psychological impairment compared with the IBS, the IBD group and the general population (p<0.05). Those IBD participants with fewer co-morbid functional disorders had better physical quality of life than participants with a greater number of these disorders (p=0.025). Moreover, depression/anxiety at baseline did not explain medical outcomes after 12 months in this cohort of patients with chronic diseases of the digestive tract. Doctors’ knowledge of patients’ psychological status was found to have no impact on IBD patients’ outcomes after 12 months. However, interestingly, the level of anxiety in IBD participants significantly dropped between the baseline and nine months indicating a possible benefit from participating in the study. In the literature review, insufficient evidence was found to conclude that antidepressants are efficacious for treatment of psychological co-morbidities or somatic complaints in IBD. However, the qualitative interview study indicated a potential positive impact of treatment with antidepressants on coping with disease symptoms and general wellbeing in patients with IBD. Conclusion: The thesis confirms that there is a significant burden of psychological co-morbidity in patients with chronic gastroenterological diseases. Interdisciplinary approaches to the management of these diseases are therefore warranted in Australian gastroenterology clinics. Anxiety targeted interventions and research in this setting are urgently needed, especially with respect to patients with HCV. Larger studies exploring the gastroenterologists’ role in treatment of co-morbid psychological problems in their patients are recommended. Longer prospective studies on homogenous samples of patients are also needed to clarify the nature of the relationship between psychological problems and relapse of somatic symptoms. Finally, randomised controlled trials exploring the efficacy of antidepressants in IBD are warranted. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1321006 / Thesis (Ph.D.) -- University of Adelaide, School of Population Health and Clinical Practice, 2008

No description available.

Background and aims: This interdisciplinary thesis was designed to deepen understanding of the co-morbidity of anxiety and depression with chronic diseases of the digestive tract, and inflammatory bowel disease (IBD) in particular. The first part of the thesis aimed to explore the prevalence of psychological problems in IBD compared to irritable bowel syndrome (IBS) and chronic hepatitis C (HCV) groups. It also explored the relationship between the number of co-morbid functional gastrointestinal disorders and the severity of psychological problems in IBD and IBS. It also aimed to determine whether there is a relationship between psychological problems and the response to standard medical treatment/physical outcomes in patients with IBD, IBS and HCV. Furthermore, it aimed to explore whether disclosure of the psychological status of depressed and/or anxious IBD patients to their gastroenterologists influences doctors’ behaviour and affects patients’ responses to treatment/physical outcomes. The second part of the thesis aimed to investigate the potential role of antidepressants in IBD and to determine the feasibility of future randomised controlled trials on the role of antidepressants in IBD. Methods: Overall, a cohort of 139 outpatients (64 IBD, 41 HCV, and 34 IBS) and 18 gastroenterologists participated in the six studies comprising this thesis. A mixed methods design was applied. Two cross-sectional studies, an observational cohort prospective management study, a randomised controlled trial, a systematic review and an exploratory interview study were conducted. Differences between the groups for continuous variables were assesed with one way analysis of variance (ANOVA) and independent samples ttests. Differences in categorical variables were assessed with contingency tables with the Chi-Square test and the Fisher’s Exact Test. Propsective analyses were conducted with repeated measures ANOVA, logistic regression and Poisson regression. Qualitative data were analysed using content analysis. Results: Overall, 42% of participants were anxious and 19% were depressed. Participants with HCV had higher levels of psychological impairment compared with the IBS, the IBD group and the general population (p<0.05). Those IBD participants with fewer co-morbid functional disorders had better physical quality of life than participants with a greater number of these disorders (p=0.025). Moreover, depression/anxiety at baseline did not explain medical outcomes after 12 months in this cohort of patients with chronic diseases of the digestive tract. Doctors’ knowledge of patients’ psychological status was found to have no impact on IBD patients’ outcomes after 12 months. However, interestingly, the level of anxiety in IBD participants significantly dropped between the baseline and nine months indicating a possible benefit from participating in the study. In the literature review, insufficient evidence was found to conclude that antidepressants are efficacious for treatment of psychological co-morbidities or somatic complaints in IBD. However, the qualitative interview study indicated a potential positive impact of treatment with antidepressants on coping with disease symptoms and general wellbeing in patients with IBD. Conclusion: The thesis confirms that there is a significant burden of psychological co-morbidity in patients with chronic gastroenterological diseases. Interdisciplinary approaches to the management of these diseases are therefore warranted in Australian gastroenterology clinics. Anxiety targeted interventions and research in this setting are urgently needed, especially with respect to patients with HCV. Larger studies exploring the gastroenterologists’ role in treatment of co-morbid psychological problems in their patients are recommended. Longer prospective studies on homogenous samples of patients are also needed to clarify the nature of the relationship between psychological problems and relapse of somatic symptoms. Finally, randomised controlled trials exploring the efficacy of antidepressants in IBD are warranted. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1321006 / Thesis (Ph.D.) -- University of Adelaide, School of Population Health and Clinical Practice, 2008

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Hepatitis C is an infectious disease with an overall prevalence of 2.2% and Brazil 1.5%. Drug therapy consists of interferon α, peginterferon α and ribavirin. It is filled with aggressive treatment of adverse reactions, hence the importance of pharmacovigilance as an additional tool in monitoring the treatment and rational use of medicines. Thus, adverse reactions occurred in patients with chronic hepatitis C who were treated with peginterferon and ribavirin, were identified and quantified through a retrospective and observational study. The most prevalent reactions observed in 46 patients in the study, were: fatigue (84.8%), fever (82.6%), loss weight (80.4%), irritability (73.9%) and body pain (71.7%). Most reactions were classified as mild (95.1%), while like moderate, 4.5% and as serious, 0.4%. The adverse reactions caused the therapeutic management in 11 patients (23.9%) where it was, dose reduction for 7 patients (15.2%), temporary discontinuation of the treatment for 5 patients (10.9%) and permanent discontinuation for 3 patients (6.5%). Eleven potential drug interactions were identified in 9 patients (19.6 %), where the most frequent was among peginterferon α 2a and captopril (45.4%). Said that, it s noticed that the treatment for chronic hepatitis C is marked for many adverse reactions with variable severity, that may interfere on patient s quality of life or in compliance of the treatment and this may be exacerbated by potential drug interactions. Additionally we evaluated the pharmacovigilance system of the Hepatology service of the University Hospital of the Federal University of Sergipe of patients registered from January 2007 to July 2009. / A hepatite C é uma doença infecciosa, com prevalência global de 2,2% e no Brasil de 1,5%. A terapêutica medicamentosa é constituída pelo interferon α, peginterferon α e a ribavirina. É um tratamento agressivo repleto de reações adversas, daí a importância da farmacovigilância como ferramenta adicional no acompanhamento do tratamento e do uso racional dos medicamentos. Assim, Reações adversas ocorridas em pacientes com hepatite C crônica tratados com peginterferon e ribavirina foram identificadas, quantificadas e classificadas através de um estudo retrospectivo e observacional. As reações mais prevalentes observadas nos 46 pacientes do estudo foram: astenia (84,8%), febre (82,6%), perda de peso (80,4%), irritabilidade (73,9%) e dor no corpo (71,7%). A maior parte das reações foi classificada como leve (95,1%), enquanto que como moderada, 4,5% e como graves, 0,4%. As reações adversas acarretaram o remanejamento terapêutico de 9 pacientes (19,6%) nos quais houve, redução da dose para 7 (15,2%), interrupção temporária do tratamento para 5 (10,9%) e interrupção permanente para 3 pacientes (6,5%). Onze interações medicamentosas potenciais foram identificadas em 9 pacientes (19,6 %), nos quais a mais freqüente foi entre o peginterferon α 2a e o captopril (45,4%). Diante do exposto, observa-se que o tratamento para hepatite C crônica é marcado por várias reações adversas, de gravidade variável, que podem interferir na qualidade de vida do paciente ou no cumprimento do tratamento e que isto pode ser agravado pelas potenciais interações medicamentosas. Adicionalmente se avaliou o sistema de farmacovigilância do Ambulatório de Hepatologia do Hospital Universitário da Universidade Federal de Sergipe dos pacientes cadastrados de janeiro de 2007 a julho de 2009.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Chronic hepatitis C has been associated with non-organ-specific autoantibodies (NOSA) production. Despite of increasing number of researches about this subject, there is no agreement among the authors of which autoantibodies are produced during combinated therapy of interferon and ribavirin or the clinical relevance of NOSA in patientâs organism. Our aim was to evaluate the profile of NOSA in patients with chronic hepatitis C who attended to Walter CantÃdio Hospital (HUWC) and received combinated antiviral therapy (interferon-ribavirin). A total of 34 patients with hepatitis C were studied. Anti-nuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti-liver/kidney microsomal antibody type 1 (LKM-1) and anti-mitochondrial antibody (AMA) were detected by indirect immunofluorescence. The presence of NOSA was related to clinical and epidemiological variables and to the outcome of antiviral combination therapy with interferon-alfa and ribavirin. Patients were classified as nonresponders, relapsers or long-term responders depending on the outcome of treatment. In our study, before therapy, 23 patients were NOSA positive (SMA was detected in 6 patients, SMA and AMA in 10 and SMA, AMA and ANA in 7). On the 24th week of treatment, 24 patientes were NOSA positive (SMA was detected in 4 patients, SMA and AMA in 10, ANA and SMA in 1, ANA and AMA in 1 and SMA, AMA and ANA in 8). NOSA behavior did not show significant variation during treatment. The overall rate of long-term response was 26,5% (9/34). Long-term response occurred in 17,4% (4/23) of NOSA positive patients and 45,5% (5/11) of NOSA negative patients. Positivity of autoantibodies was not associated with gender, age, viral genotype or aminotransferase levels. In conclusion, ANA was the only NOSA associated with treatment outcome. The absence of NOSA might indicate a significantly higher chance for viral clearance in response to combination therapy for chronic hepatitis C infection. / A hepatite crÃnica pelo vÃrus C tem sido associada à produÃÃo de autoanticorpos nÃo-ÃrgÃo especÃficos (NOSA). Apesar do aumento do nÃmero de pesquisas nessa Ãrea, ainda nÃo existe um consenso entre quais autoanticorpos tÃm seus nÃveis elevados devido ao tratamento combinado de interferon e ribavirina, nem sua influÃncia no desfecho do mesmo ou a relevÃncia clÃnica da presenÃa desses autoanticorpos no organismo do pacientes. O objetivo do presente estudo foi avaliar o perfil de NOSA em pacientes com hepatite C crÃnica atendidos no Hospital UniversitÃrio Walter CantÃdio (HUWC) e submetidos à terapia combinada de interferon-alfa e ribavirina. Para isso, um total de 34 pacientes com hepatite C foram estudados. Os anticorpos anti-nuclear (FAN), anti-mÃsculo liso (SMA), anti-microssomal de fÃgado e rim do tipo 1 (LKM-1) e anti-mitocÃndria (AMA) foram detectados atravÃs de imunofluorescÃncia indireta. A presenÃa de NOSA foi relacionada a variÃveis clÃnicas e epidemiolÃgicas e à resposta ao tratamento. Os pacientes foram classificados, em relaÃÃo à resposta ao tratamento, como nÃo respondedores, recidivantes ou respondedores (resposta virolÃgica sustentada). Em nosso estudo, 23 pacientes foram NOSA reagentes (SMA foi detectado em 6 pacientes, SMA e AMA em 10 e SMA, AMA e FAN em 7). Na 24 semana de tratamento, 24 pacientes foram NOSA reagentes (SMA foi detectado em 4 pacientes, SMA e AMA em 10, FAN e SMA em 1, FAN e AMA em 1 e SMA, AMA e FAN em 8). A variaÃÃo dos tÃtulos dos autoanticorpos durante o tratamento nÃo foi significativa. O percentual total de respondedores foi de 26,5% (9/34). A resposta virolÃgica sustentada foi obtida por 17,4% (4/23) dos pacientes NOSA reagentes e 45,5% (5/11) dos pacientes nÃo reagentes para NOSA. A presenÃa de autoanticorpos nÃo foi associada a gÃnero, idade, genÃtipo viral ou nÃveis de transaminases. Conclui-se que o FAN foi o Ãnico NOSA significativamente associado à resposta à terapia. A ausÃncia de NOSA indica uma tendÃncia à resposta virolÃgica sustentada no tratamento da hepatite C crÃnica.