Interferon-α action in cytokine profile in eosinophilic nasal polyp cultures / Ação do interferon-α sobre o perfil de citocinas em culturas de pólipos nasais eosinofílicos

Abstract Introduction Chronic rhinosinusitis is currently classified into two types: chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps. In the West, approximately 80% of chronic rhinosinusitis with nasal polyps cases are characterized by a predominantly eosinophilic cell infiltrate and a Th2 cytokine pattern. Objective To evaluate the effect of Interferon-α on cytokine levels of the eosinophilic nasal polyp cell culture supernatant. Methods Cell cultures were performed based on nasal polypoid tissue samples collected from 13 patients with eosinophilic chronic rhinosinusitis with nasal polyps. Polyps were considered eosinophilic according to the histopathological examination. Cell cultures were stimulated with 3000 IU of interferon-α. Before and after the stimulus, concentrations of Interferon-γ, tumor necrosis factor αand IL 2, 4, 6 and 10, using cytometric bead array, were assessed. Results Cell samples from eosinophilic nasal polyps from 13 patients were included in the study. Twenty-four hours after interferon-α stimulation, eosinophilic nasal polyp culture supernatants showed significantly decreased IL-4 concentrations and increase in interferon-γ, IL-10 and IL-6 concentrations compared to controls. There were no significant differences in tumor necrosis factor -α and IL-2 concentrations. Conclusion We demonstrated that interferon-α in vitro alters the pattern of cytokines in cell cultures of eosinophilic nasal polyps. Analysis of these alterations suggests that interferon-α promotes a rebalancing of inflammatory profiles in cell cultures, favoring the expression of Th1 and regulatory cytokines over Th2 cytokines.

Resumo Introdução A rinossinusite crônica, atualmente, é classificada em dois tipos: Rinossinusite Crônica sem Pólipos Nasais (RSCsPN) e Rinossinusite Crônica com Pólipos Nasais (RSCcPN). No Ocidente, cerca de 80% dos casos de RSCcPN caracterizam-se por um infiltrado celular predominantemente eosinofílico e um padrão de citocinas Th2. Objetivo Avaliar o efeito do Interferon-alpha nos níveis de citocinas do sobrenadante de culturas celulares de pólipos nasais eosinofílicos. Método Foram feitas culturas celulares a partir de amostras de tecido polipoide nasal coletadas de 13 pacientes com RSCcPN eosinofílica. Os pólipos eram considerados eosinofílicos segundo exame histopatológico. As culturas celulares foram estimuladas com 3000 UI de IFN-α. Antes e após tal estímulo, foram avaliadas, no sobrenadante das culturas celulares, as concentrações do Interferon-γ (IFN-γ), do Fator de Necrose Tumoral alfa (TNF-α) e das Interleucinas (IL) 2, 4, 6 e 10, usou-se o Cytometric Bead Array. Resultados Foram incluídas no estudo amostras celulares dos pólipos nasais eosinofílicos de 13 pacientes. Vinte e quatro horas após o estímulo com IFN-α, os sobrenadantes das culturas dos pólipos nasais eosinofílicos apresentaram, de forma significante, diminuição da concentração de IL-4 e aumento das concentrações de IFN-γ, IL-10 e IL-6, em relação ao controle. Não houve diferença significante nas concentrações de TNF-α e IL-2. Conclusão Demonstramos que o IFN-α, in vitro, altera o padrão de citocinas nas culturas celulares de pólipos nasais eosinofílicos. A análise do conjunto dessas alterações sugere que o IFN-α promove, nas culturas celulares, um rebalanceamento dos perfis inflamatórios, favorece a expressão de citocinas Th1 e regulatórias, em detrimento de citocinas do padrão Th2.

Interleukin-6 and Interferon-α Levels in Gingival Crevicular Fluid in HIV-1 Patients with Chronic Periodontitis / Niveles de Interleukin-6 e Interferon-α de Fluido Crevicular Gingival en Pacientes VIH-1 con Periodontitis Crónica

ABSTRACT: The influence of cytokine on the progression of chronic periodontitis in human immunodeficiency virus (HIV) patients is still controversial and poorly investigated. This study aimed to analyze and compare IL-6 and IFN-α levels in the gingival crevicular fluid of HIV-1-positive and HIV-1-negative patients with chronic periodontitis and different grades of tissue destruction and inflammation. Samples from the gingival crevicular sulcus were obtained from 35 HIV-1-positive individuals with chronic periodontitis and 35 seronegative patients with chronic periodontitis. Probing depth and clinical attachment level, as well as the results of the Enzyme-Linked Immunosorbent Assay for confirmation of patient diagnostics, were evaluated. Statistical analyses were performed using Student t, Mann-Whitney and Spearman tests. IL-6 levels were significantly lower, while IFN-α levels were significantly higher in HIV-1 patients. Clinical attachment level was directly associated with IFN-α levels in HIV-1 carriers, connected to probing depth in these patients. Clinical data in association with gingival crevicular fluid cytokine levels may reveal a localized immunological response pattern, which may contribute to the understanding of periodontitis pathogenesis in HIV-1 carriers.

RESUMEN: La influencia de la citocina en la progresión de la periodontitis crónica en pacientes con el virus de la inmunodeficiencia humana (VIH) sigue siendo controvertida y poco investigada. Este estudio tuvo como objetivo analizar y comparar los niveles de interleuquina-6 (IL6) e interferón-α (IFN-α) en el líquido crevicular gingival de pacientes VIH-1-positivos y VIH-1-negativos con periodontitis crónica y diferentes grados de destrucción e inflamación tisular. Se obtuvieron muestras del surco crevicular gingival de 35 individuos VIH-1 positivos con periodontitis crónica y 35 pacientes seronegativos con periodontitis crónica. Se evaluaron la profundidad de sondeo y el nivel de inserción clínica, así como los resultados del Ensayo Inmunoabsorbente Ligado a Enzimas para la confirmación del diagnóstico del paciente. Los análisis estadísticos se realizaron utilizando pruebas t de Student, Mann-Whitney y Spearman. Los niveles de IL-6 fueron significativamente más bajos, mientras que los niveles de IFN-a fueron significativamente más altos en los pacientes con VIH-1. El nivel de inserción clínica se asoció directamente con los niveles de IFN-α en los portadores del VIH1, conectados a la profundidad del sondaje en estos pacientes. Los datos clínicos en asociación con los niveles de citoquinas de los fluidos creviculares gingivales pueden revelar un patrón de respuesta inmunológica localizado, que puede contribuir a la comprensión de la patogénesis de la periodontitis en los portadores del VIH-1.

First-wave protease inhibitors for hepatitis C genotype 1 treatment: a real-life experience in Brazilian patients

Abstract INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.

Impact of alcohol consumption among patients in hepatitis C virus treatment / Impacto do consumo alcoólico entre pacientes em tratamento da hepatite C

ABSTRACT BACKGROUND: Recent studies have questioned the recommendation of abstinence from alcohol for at least 6 months for alcoholic patients to be treated for hepatitis C. OBJECTIVE: The present study aimed to assess the impact of alcohol consumption among patients undergoing hepatitis C treatment. METHODS: In this cross-sectional study, 121 patients [78 (64.5%) men; 28-70 years] were evaluated. They were divided as follows: patients who consumed <12 g of ethanol/day throughout life (Group 1), 12-59 g/day (Group 2) and ≥60 g/day (Group 3). Patients were treated with pegyla­ted-interferon plus ribavirin. RESULTS: These three groups could not be distinguished in terms of the severity of liver fibrosis and frequency of HCV genotype-1 infection. In Group 3, treatment discontinuation (32.4%) was higher than in the Group 1 (9.4%) or Group 2 (0%), it was higher among patients who drank during treatment (66.7% vs 21.4%) and among those who had not been abstinent for at least 6 months (72.7% vs 15.4%). Moderate alcohol drinkers showed good adherence and did not discontinue the treatment. The frequencies of sustained viral response among patients in Group 3 (44.4%) were similar to those in Group 1 (61%) and Group 2 (68.4%). CONCLUSION: Heavy drinkers more often discontinued treatment for hepatitis C, but those that received this treatment had acceptable sustained viral response rates. These results suggest that heavy drinkers should not be systematically excluded from the treatment, but they should be monitored to avoid drinking and abandoning treatment, mainly those who have not been abstinent for at least 6 months.

RESUMO CONTEXTO: Estudos recentes têm questionado a recomendação de abstinência do álcool por pelo menos 6 meses para pacientes alcoolistas serem tratados para hepatite C. OBJETIVO: Este estudo objetivou avaliar o impacto do consumo de álcool entre pacientes submetidos ao tratamento para a hepatite C. MÉTODOS: Neste estudo transversal, avaliou-se 121 pacientes [78 (64,5%) homens; 28-70 anos). Eles foram divididos em três grupos: pacientes que consumiam <12 g de etanol/dia na vida (Grupo 1); 12-59 g/dia (Grupo 2) e ≥60 g/dia (Grupo 3). Pacientes foram tratados com interfe­ron-peguilado mais ribavirina. RESULTADOS: Os três grupos não puderam ser distinguidos em relação à gravidade da fibrose hepática e das frequências de infecção pelo genótipo-1 do HCV. No Grupo 3, descontinuação do tratamento (32,4%) foi maior do que no Grupo 1 (9,4%) ou Grupo 2 (0%), foi maior entre pacientes que beberam durante o tratamento (66,7% vs 21,4%) e entre aqueles que não estavam em abstinência por pelo menos 6 meses (72,7% vs 15,4%). Pacientes do Grupo 2 tiveram boa aderência e não descontinuaram o tratamento. As frequências de resposta virológica sustentada entre pacientes do Grupo-3 (44,4%) foi semelhante àquelas do Grupo 1 (61%) e do Grupo 2 (68,4%). CONCLUSÃO: Bebedores pesados mais frequentemente descontinuaram o tratamento da hepatite C, mas aqueles que foram tratados tiveram aceitáveis taxas de resposta virológica sustentada. Esses resultados sugerem que bebedores pesados não deveriam ser sistematicamente excluídos do tratamento, mas sim serem monitorados para evitar beber e abandonar o tratamento, principalmente aqueles que não estão abstinentes por pelo menos 6 meses.

Cúrcuma em combinação com os regimes de terapia tríplice melhora o estresse oxidativo e as alterações histopatológicas em gastrite crônica associada à infecçäo por Helicobacter pylori / Curcumin in combination with triple therapy regimes ameliorates oxidative stress and histopathologic changes in chronic gastritis-associated helicobacter pylori infection

ABSTRACT BACKGROUND Helicobacter pylori (H. pylori) gastric infection is a main cause of inflammatory changes and gastric cancers. OBJECTIVE The aim of this study was finding the effects of curcumin on oxidative stress and histological changes in chronic gastritis associated with H. pylori. METHODS In a randomized clinical trial, patients were divided into two groups: a standard triple therapy group and triple therapy with curcumin group. Endoscopic and histological examinations were measured for all patients before and after 8 weeks. RESULTS Triple therapy with curcumin treatment group significantly decreased malondialdehyde markers, glutathione peroxides and increased total antioxidant capacity of the gastric mucosa at the end of study compared to baseline and triple regimen groups. In addition, the oxidative damage to DNA was significantly decreased in triple therapy with curcumin group at the end of study compared to baseline and compared to triple therapy (P<0.05 for both). Triple therapy group in combination with Curcumin significantly decreased all active, chronic and endoscopic inflammation scores of patients compared to the baseline and triple therapy group (P<0.05 for both). The eradication rate by triple therapy + curcumin was significantly increased compared to triple therapy alone (P<0.05). CONCLUSION Curcumin can be a useful supplement to improve chronic inflammation and prevention of carcinogenic changes in patients with chronic gastritis associated by H. pylori.

RESUMO CONTEXTO A infecção gástrica pelo Helicobacter pylori (H. pylori) é principal causa de alterações inflamatórias e de câncer gástrico. OBJETIVO O objetivo deste estudo foi encontrar os efeitos da cúrcuma no estresse oxidativo e as alterações histológicas na gastrite crônica associada ao H. pylori. MÉTODOS Em um estudo randomizado clínico experimental, pacientes foram divididos em dois grupos: um grupo de terapia tríplice padrão e outro com terapia tríplice com e cúrcuma. Exames endoscópicos e histológicos foram analisados para todos os pacientes antes e depois de 8 semanas de tratamento. RESULTADOS A terapia tríplice com grupo de tratamento de cúrcuma diminuiu significativamente os marcadores de malondialdeído, de peróxidos de glutationa, com aumento da capacidade antioxidante total da mucosa gástrica ao final do estudo em comparação com grupos de regime basal e tríplice. Além disso, o dano oxidativo ao DNA diminuiu significativamente em terapia tríplice com grupo de cúrcuma no final do estudo em comparação com a linha de base e comparado à terapia tríplice (P<0,05 para ambos). No grupo de terapia tríplice em combinação com cúrcuma houve diminuição significativa de todas os escores ativos de inflamação crônica e endoscópica dos pacientes em relação ao grupo de terapia de base e tríplice (P<0,05 para ambos). A taxa de erradicação por terapia tríplice + cúrcuma aumentou significativamente em relação à terapia tríplice isolada (P<0,05). CONCLUSÃO A cúrcuma pode ser um complemento útil para melhorar a inflamação crônica e prevenção de alterações cancerígenas em pacientes com gastrite crônica associada ao H.pylori.

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.

Hematological and dermatological adverse events during hepatitis C treatment with peg-interferon and ribavirin / Eventos adversos hematológicos e dermatológicos durante o tratamento da hepatite C com interferon peguilado e ribavirina

Objective: To evaluate frequency and impact of adverse events, mainly the hematological and dermatological ones, on sustained virological response, and compliance to hepatitis C treatment. Methods: Patients were treated according to the guidelines of the Brazilian Ministry of Health. Variables associated with hematological and dermatological adverse events were: age, gender, stage of fibrosis, type of Pegylated interferon, dose reductions, temporary discontinuation and early interruption of treatment. Results: Two hundred and twenty two patients were studied (58% females; age 49±11 years). Dose reductions, temporary interruptions, and early discontinuations were observed in 21%, 8% and 9.5% of patients, respectively. The main adverse events were hematological (anemia, neutropenia and thrombocytopenia) and dermatological (pruritus and alopecia). Anemia (Hemoglobin <10g/dL) was associated with female gender (p<0.001), advanced fibrosis (p=0.047) and dose reductions (p<0.001); neutropenia with advanced fibrosis (p=0.003) and temporary discontinuation (p=0.002); thrombocytopenia with advanced fibrosis (p<0.001) and pegylated interferon α2a (p=0.05). Pruritus and alopecia were associated to female gender (p=0.008 and p=0.02) and treatment interruption (p=0.029 and p=0.02).Conclusion: Hematological and dermatological adverse events are frequent in hepatitis C patients treated with pegylated interferon and ribavirin. However, despite frequent dose reductions and interruptions, these adverse events did not affect the sustained virological response.

Objetivo: Avaliar a frequência e o impacto de eventos adversos, principalmente hematológicos e dermatológicos, na resposta virológica sustentada e na aderência ao tratamento para hepatite C. Métodos: Os pacientes foram tratados de acordo com diretriz do Ministério da Saúde. Variáveis associadas com eventos adversos hematológicos e dermatológicos foram: idade, sexo, grau de fibrose, tipo de interferon peguilado, reduções de dose, descontinuação temporária e interrupção precoce do tratamento. Resultados: Foram estudados 232 pacientes (58% mulheres; idade 49±11 anos). Reduções de dose, interrupções temporárias e descontinuações precoces foram observadas em 21%, 8% e 9,5% dos pacientes, respectivamente. Os principais eventos adversos foram hematológicos (anemia, neutropenia e plaquetopenia) e dermatológicos (prurido e alopecia). Anemia (hemoglobina <10g/dL) se associou a sexo feminino (p<0,001), fibrose avançada (p=0,047) e reduções de doses (p<0,001); neutropenia com fibrose avançada (p=0,003) e interrupção temporária (p=0,002); plaquetopenia com fibrose avançada (p<0,001) e interferon peguilado α2a (p=0,05). Prurido e alopecia se associaram ao sexo feminino (p=0,008 e p=0,02) e interrupção do tratamento (p=0,029 e p=0,02). Conclusão: Eventos adversos hematológicos e dermatológicos foram frequentes em pacientes tratados com interferon peguilado e ribavirina. Entretanto, a despeito de frequentes reduções de dose e interrupções, estes eventos adversos não afetaram a resposta virológica sustentada.

Predictors of early treatment discontinuation and severe anemia in a Brazilian cohort of hepatitis C patients treated with first-generation protease inhibitors

The aim of this study was to determine risk factors for adverse events (AE)-related treatment discontinuation and severe anemia among patients with chronic hepatitis C virus (HCV) genotype 1 infection, treated with first-generation protease inhibitor (PI)-based therapy. We included all patients who initiated treatment with PI-based therapy at a Brazilian university hospital between November 2013 and December 2014. We prospectively collected data from medical records using standardized questionnaires and used Epi Info 6.0 for analysis. Severe anemia was defined as hemoglobin ≤8.5 mg/dL. We included 203 patients: 132 treated with telaprevir (TVR) and 71 treated with boceprevir (BOC). AE-related treatment discontinuation rate was 19.2% and anemia was the main reason (38.5%). Risk factors for treatment discontinuation were higher comorbidity index (OR=1.85, CI=1.05-3.25) for BOC, and higher bilirubin count (OR=1.02, CI=1.01-1.04) and lower BMI (OR=0.98, CI=0.96-0.99) for TVR. Severe anemia occurred in 35 (17.2%) patients. Risk factors for this outcome were lower estimated glomerular filtration rate (eGFR; OR=0.95, CI=0.91-0.98) for patients treated with TVR, and higher comorbidity index (OR=2.21, CI=1.04-4.67) and ribavirin dosage (OR=0.84, CI=0.72-0.99) for those treated with BOC. Fifty-five (57.3%) patients treated with TVR and 15 (27.3%) patients treated with BOC achieved sustained virological response (SVR). Among patients who received TVR and interrupted treatment due to AE (n=19), only 26.3% (n=5) achieved SVR (P=0.003). Higher number of comorbidities, lower eGFR and advanced liver disease are associated with severe anemia and early treatment cessation, which may compromise SVR achievement.

Reativação de leishmaniose durante tratamento de hepatite b crônica com alfainterferona 2b / Leishmaniasis reactivation during treatment of chronic hepatitis B with interferon alpha 2b - case report

Descreve-se aqui um caso de reativação de leishmaniose cutaneomucosa durante o tratamento com alfainterferona 2b (IFN) para hepatite B crônica (HBV). Relato do caso: Paciente masculino, 52 anos, natural da Bahia, procedente de São Paulo onde vivia há 30 anos, encaminhado por HBV. Na história epidemiológica, referiu-se a uma viagem há cinco anos para Porto Seguro-BA, sem apresentar outros fatores de risco. No exame físico para admissão, não havia evidências de doença hepática crônica. Sorologias pré-tratamento: HBsAg e HBeAg positivos, biópsia A0F0 (Metavir). Foi submetido a tratamento com IFN 5 milhões de UI/dia por 24 semanas. No final, apresentava-se HBV DNA detectável, sem soroconversão de HBeAg, porém evoluiu no quarto mês de tratamento com perda ponderal de 10 kg, astenia, sinais e sintomas de sinusite sem melhora clínica após antibioticoterapia. Foi encaminhado para a otorrinolaringologia com rouquidão persistente, destruição de septo nasal, com áreas de crostas, necrose local, alargamento nasal e lesão em palato mole, cuja biópsia mostrou processo inflamatório granulomatoso com necrose caseosa, sugestivo de leishmaniose. Sorologia para leishmaniose IgG 1/80 (IFI) e intradermorreação de Montenegro de 30 mm. Indicado antimoniato de meglumina IV por 30 dias, obteve melhora da rouquidão e das lesões de palato. Conclusão: O quadro clínico sugere reativação da leishmaniose induzida pelo IFN. Acredita-se que este seja o primeiro relato na literatura de reativação de leishmaniose muco-cutânea por uso de IFN, semelhantemente ao que ocorre com a tuberculose. Screening para leishmaniose deve ser realizado em paciente de região endêmica no pré-tratamento com IFN diante da possibilidade de reativação de infecção latente

PEGYLATED INTERFERON AND RIBAVIRIN FOR TREATMENT OF RECURRENT HEPATITIS C AFTER LIVER TRANSPLANTATION: a single-liver transplant center experience in Brazil / Interferon peguilado e ribavirina no tratamento da recorrência da hepatite C após transplante hepático: experiência de um centro de transplante hepático no Brasil

BackgroundTreatment of hepatitis C virus infection in post-transplantation patients is a challenge due to poor tolerance and low success rates.ObjectiveTo determine the response rate to pegylated interferon and ribavirin in post-liver transplant patients with hepatitis C recurrence.MethodsBetween 18 May 2002 and 18 December 2011, 601 patients underwent liver transplantation at our service (Hospital Universitário Walter Cantídio, University of Ceará), 176 (29.2%) of whom were hepatitis C virus positive. Forty received antiviral therapy and were included in this cohort study. Twenty-eight (70%) completed the treatment protocol, which consisted of pegylated interferon and ribavirin for 48 weeks.ResultsThe sustained virological response rate was 55% according to intention-to-treat analysis. Recipient age and exposure to antiviral drugs prior to liver transplantation were associated with sustained virological response in the multivariate analysis. Patients were followed for 57 months on the average. Survival at 1 and 5 years was 100% in responders, versus 100% and 78%, respectively, in non-responders.ConclusionSustained virological response rates were satisfactory in our series of liver transplantation patients, and decreased with increasing recipient age. Non-exposure to antiviral drugs prior to liver transplantation was positively associated with sustained virological response. The overall survival of responders and non-responders was similar.

ContextoO tratamento da infecção do vírus da hepatite C pós-transplante é um desafio devido à baixa tolerância dos pacientes e às baixas taxas de resposta.ObjetivoDeterminar a taxa de resposta ao interferon peguilado e ribavirina no tratamento da recorrência da hepatite C após transplante de fígado.MétodosEntre 18 de maio de 2002 e 18 de dezembro de 2011, 601 pacientes realizaram transplante hepático no Hospital Universitário Walter Cantídio, 176 (29,2%) desses eram infectados pelo vírus da hepatite C. Quarenta pacientes receberam terapia antiviral e foram incluídos nesse estudo. Vinte e sete (70%) completaram o protocolo de tratamento, que consistia de interferon peguilado e ribavirina por 48 semanas.ResultadosA taxa de resposta virológica sustentada foi de 55% de acordo com a análise por intenção de tratar. A idade dos receptores e a exposição prévia ao transplante de antivirais foram fatores associados com a resposta virológica sustentada na análise multivariada. Pacientes foram acompanhados por 57 meses em média. A sobrevida em 1 e 5 anos foi de 100% em respondedores, enquanto que em não respondedores foi de 100% e 78% respectivamente.ConclusãoA resposta virológica sustentada foi satisfatória na série de pacientes transplantados e diminuiu com o aumento da idade. A não exposição prévia ao transplante a drogas antivirais teve impacto positivo na chance de resposta virológica sustentada. A sobrevida global foi similar em respondedores e não respondedores.

Tiroiditis no-autoinmunes / Non-autoimmune thyroiditis

El término tiroiditis comprende un grupo de enfermedades de la glándula tiroides caracterizado por la presencia de inflamación, abarcando entidades autoinmunes y no-autoinmunes. Pueden manifestarse como enfermedades agudas con dolor tiroideo severo (tiroiditis subaguda y tiroiditis infecciosas), y condiciones en las cuales la inflamación no es clínicamente evidente, cursando sin dolor y presentando disfunción tiroidea y/o bocio (tiroiditis inducida por fármacos y tiroiditis de Riedel). El objetivo de esta revisión es aportar un enfoque actualizado sobre las tiroiditis no-autoinmunes cubriendo sus aspectos clínicos, diagnósticos y terapéuticos.

The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.

Vivências e necessidades de saúde de homens no período pós-nascimento de um filho / Experiences and health needs of men in the period post-birth of a child / Experiencias y necesidades de salud de los hombres en el período post-nacimiento de un hijo

Esta pesquisa aborda percepções de homens sobre suas experiências e necessidades de saúde no pós-nascimento. Objetiva-se distinguir analiticamente, a partir de uma perspectiva de gênero, necessidades de saúde relativas ao evento, experimentadas, expressas e/ou negadas pelos homens. Trata-se de um estudo exploratório-descritivo, qualitativo, realizado em dois territórios de saúde de Cuiabá, Mato Grosso, mediante entrevista semiestruturada e análise temática dos dados. Participaram oito homens que vivenciavam o pós-nascimento de um filho. Estes manifestaram, sobretudo, a necessidade de provimento de segurança financeira à família, destacando também a necessidade de bem estar do filho, acessando o retorno afetivo que a experiência traz. Não se reconheciam com necessidades de saúde no pós-nascimento. O apoio dos serviços locais de saúde é importante para que os homens se percebam na vivência da paternidade e a sua relação com aspectos socioculturais, para que distingam necessidades próprias, valorizem o cuidado de si e adotem uma perspectiva equânime de gênero.

This research addresses men’s perceptions about their experiences and health needs in the post-birth period. The goal is to distinguish analytically and from a gender perspective the health needs related to the event, experienced, expressed and/or denied by men. This is an exploratory, descriptive and qualitative study carried out in two municipal health areas of Cuiabá, state of Mato Grosso, using a semi structured interview and thematic analysis of the data. The participants were eight men who were experiencing the post-birth period of a child. Above all, they expressed the need to provide financial security to the family, emphasizing also the need of their children’s well-being, with the affective return that this experience brings. They did not perceive themselves with health needs during the post-birth period. The support provided by local health services is important so that men can understand the experience of parenthood and its relationship with social and cultural aspects in order to distinguish their own needs, appreciate self-care, and adopt a gender equity perspective.

Esta investigación aborda las percepciones de hombres acerca de sus experiencias y necesidades de salud en el período postparto. El objetivo es distinguir analíticamente, desde una perspectiva de género, las necesidades de salud relacionadas al evento, experimentadas, expresadas y/o negadas por los hombres. Se trata de un estudio exploratorio, descriptivo y cualitativo llevado a cabo en dos áreas municipales de salud de Cuiabá, Estado de Mato Grosso, mediante entrevista semiestructurada y análisis temático de los datos. Participaron ocho hombres que experimentaban el período postparto de un hijo. Ellos expresaron, sobre todo, la necesidad de proveer seguridad económica a la familia, destacando también la necesidad del bienestar de los hijos, con el retorno afectivo que esa experiencia proporciona. No se reconocían con necesidades de salud en el período postparto. El apoyo de los servicios locales de salud es importante para que los hombres entiendan la experiencia de la paternidad y su relación con aspectos socioculturales, para que distingan las necesidades, valoren el cuidado de sí mismos y adopten una perspectiva de equidad de género.

Sexual dysfunction and dissatisfaction in chronic hepatitis C patients

Introduction The prevalence of sexual dysfunction (SD) and dissatisfaction with sexual life (DSL) in patients with chronic hepatitis C virus infection (CHC) was jointly investigated via a thorough psychopathological analysis, which included dimensions such as fatigue, impulsiveness, psychiatric comorbidity, health-related quality of life (HRQL) and sociodemographic and clinical characteristics. Methods Male and female CHC patients from an outpatient referral center were assessed using the Brief Fatigue Inventory, the Barrat Impulsiveness Scale, the Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale, the Hamilton Anxiety Scale (HAM-A), and the World Health Organization Quality of Life Scale-Brief Version (WHOQOL-BREF). Structured psychiatric interviews were performed according to the Mini-International Neuropsychiatric Interview. SD was assessed based on specific items in the BDI (item 21) and the HAM-A (item 12). DSL was assessed based on a specific question in the WHOQOL-BREF (item 21). Multivariate analysis was performed according to an ordinal linear regression model in which SD and DSL were considered as outcome variables. Results SD was reported by 60 (57.1%) of the patients according to the results of the BDI and by 54 (51.4%) of the patients according to the results of the HAM-A. SD was associated with older age, female gender, viral genotype 2 or 3, interferon-α use, impulsiveness, depressive symptoms, antidepressant and benzodiazepine use, and lower HRQL. DSL was reported by 34 (32.4%) of the patients and was associated with depressive symptoms, anxiety symptoms, antidepressant use, and lower HRQL. Conclusions The prevalence of SD and DSL in CHC patients was high and was associated with factors, such as depressive symptoms and antidepressant use. Screening and managing these conditions represent significant steps toward improving medical assistance and the HRQL of CHC patients. .

Acute pancreatitis associated with boceprevir: a case report

Approximately 170 million people are infected with hepatitis C, and the sustained virological response rate to treatment with pegylated interferon and ribavirin is 30-50%. In an attempt to improve the chances of cure, boceprevir is being added to therapy, but it is associated with an increased incidence of adverse events. We herein report a case of acute pancreatitis developed during treatment with pegylated interferon, ribavirin and boceprevir. Boceprevir was the most likely cause of drug-associated pancreatitis after the most common causes were ruled out, since this adverse event had not occurred when the patient had previously been exposed to pegylated interferon and ribavirin and there was no recurrence of the episode of pancreatitis when these two drugs were reintroduced. Acute pancreatitis is a rare adverse event associated with boceprevir therapy, but a potentially fatal event. Sequential determination of pancreatic enzymes should be considered during hepatitis C treatment with boceprevir.

Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

Background: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. Methods: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. Conclusion: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment. .

Custo-efetividade da inclusão dos respondedores virológicos lentos no tratamento da hepatite C na presença da coinfecção com o HIV / Cost-effectiveness of hepatitis C treatment in slow virologic responders coinfected with HIV / Coste-efectividad del tratamiento de la hepatitis C en coinfectados con el VIH con respuesta virológica lenta

Evidências recentes demonstram que respondedores virológicos lentos podem se beneficiar com a extensão do tratamento antiviral. O estudo investigou a adoção desse protocolo diante da coinfecção VHC/HIV. O objetivo foi estudar a relação de custo/efetividade da terapêutica com peguinterferon associado à ribavirina em portadores do genótipo 1 do VHC coinfectados com o HIV, comparando-se a inclusão ou não de respondedores virológicos lentos. Simulou-se por meio de um modelo de Markov a progressão da doença hepática em uma coorte hipotética de mil homens, maiores de 40 anos, considerandose a perspectiva do Sistema Único de Saúde (SUS) e horizonte temporal de 30 anos. A extensão do tratamento para respondedores lentos resultou em uma razão incremental de custo efetividade de R$ 44.171/QALY, valor abaixo do limiar de aceitabilidade proposto pela Organização Mundial da Saúde. A análise de sensibilidade não modificou os resultados alcançados. A inclusão de indivíduos coinfectados VHC/HIV respondedores virológicos lentos no protocolo de tratamento apresenta-se como uma estratégia custo-efetiva para o SUS.

Recent evidence has demonstrated that slow responders may benefit from antiviral treatment in HCV/HIV coinfection. This study aimed to evaluate the cost-effectiveness of HCV treatment in individuals with genotype 1 coinfected with HIV, with peg-interferon in combination with ribavirin, compared to the inclusion (versus non-inclusion) of slow responders. A Markov model was developed that simulated the progression of liver disease in a hypothetical cohort of one thousand men over 40 years of age, considering the Brazilian Unified National Health System (SUS) perspective and a 30-year timeline. The extension of treatment to slow responders provided a 60% increase in the number of individuals who eliminated HCV and an incremental cost-effectiveness ratio of 44,171 BRL/QALY, below the acceptability threshold proposed by World Health Organization. Sensitivity analysis did not alter the results. The inclusion of HCV/ HIV-coinfected slow virologic responders in the treatment protocol is shown to be a cost-effective strategy for the SUS.

La evidencia reciente ha demostrado que los individuos con respuesta virológica lenta pueden beneficiarse de una extensión del tratamiento antiviral. El estudio investigó la adopción de este protocolo antes de la coinfección por VHC/HIV. El objetivo fue estudiar la relación coste-efectividad de la terapia con peginterferon asociado con ribavirina en pacientes con genotipo 1 del VHC, coinfectados por el HIV respondedores virológicos lentos. Se simula mediante un modelo de Markov la progresión de la enfermedad hepática en una cohorte hipotética de un millar de hombres, más de 40, teniendo en cuenta la perspectiva del Sistema Único de Salud (SUS) y un horizonte temporal de 30 años. El grado de tratamiento a los respondedores lentos dio lugar a un incremento de coste-efectividad de R$ 44.171/QALY, por debajo del umbral de aceptabilidad propuesto por la Organización Mundial de la Salud. El análisis de sensibilidad no modificó los resultados. La inclusión de los individuos coinfectados y con respuesta virológica lenta en el protocolo de tratamiento se presenta como una estrategia económica para el SUS.

Response to treatment in Brazilian patients with chronic hepatitis C is associated with a single-nucleotide polymorphism near the interleukin-28B gene

A single-nucleotide polymorphism (SNP) upstream of interleukin (IL)28B was recently identified as an important predictor of the outcome of chronic hepatitis C patients treated with pegylated interferon plus ribavirin (PEG-IFN/RBV). The aim of this study was to investigate the association between the IL28B gene polymorphism (rs12979860) and virological response in chronic hepatitis C patients. Brazilian patients (n = 263) who were infected with hepatitis C virus (HCV) genotype 1 and were receiving PEG-IFN/RBV were genotyped. Early virological response (EVR) (12 weeks), end-of-treatment response (EOTR) (48 weeks), sustained virological response (SVR) (72 weeks) and relapse were evaluated using conventional and quantitative polymerase chain reaction (PCR) assays. The frequency of the C allele in the population was 39%. Overall, 43% of patients experienced SVR. The IL28B CC genotype was significantly associated with higher treatment response rates and a lower relapse rate compared to the other genotypes [84% vs. 58% EVR, 92% vs. 63% EOTR, 76% vs. 38% SVR and 17% vs. 40% relapse rate in CC vs. other genotypes (CT and TT), respectively]. Thus, the IL28B genotype appears to be a strong predictor of SVR following PEG-IFN/RBV therapy in treatment-naïve Brazilian patients infected with HCV genotype 1. This study, together with similar research examining other SNPs, should help to define adequate protocols for the treatment of patients infected with HCV genotype 1, especially those with a poor prognosis.

Therapeutic effectiveness of biosimilar standard interferon versus pegylated interferon for chronic hepatitis C genotypes 2 or 3

BACKGROUND: Pegylated interferon (Peg-IFN) and standard interferon (IFN) play a significant role in the treatment of hepatitis C virus (HCV) infection. Biosimilar standard IFN is widely available in Brazil for the treatment of HCV infection genotypes 2 or 3, but its efficacy compared to Peg-IFN is unknown. OBJECTIVE: To compare the sustained virological response (SVR) rates following treatment with biosimilar standard IFN plus ribavirin (RBV) versus Peg-IFN plus RBV in patients with HCV genotypes 2 or 3 infection. METHODS: A retrospective cohort study was conducted in patients with HCV genotypes 2 or 3 infection treated with biosimilar standard IFN plus RBV or with Peg-IFN plus RBV. SVR rates of the two treatments were compared. RESULTS: From January 2005 to December 2010, 172 patients with a mean age of 44 +/- 9.3 years were included. There were eight (4.7%) patients with HCV genotype 2 infections. One hundred fourteen (66.3%) were treated with biosimilar standard IFN plus RBV, whist 58 (33.7%) patients were treated with Peg-IFN plus RBV. Between the two groups, there were no significant differences regarding age, gender, glucose level, platelet count, hepatic necroinflammatory grade, and hepatic fibrosis stage. Overall, 59.3% (102/172) patients had SVR. In patients treated with Peg-IFN plus RBV, 79.3% (46/58) had SVR compared to 49.1% (56/114) among those treated with biosimilar standard IFN plus RBV (p = 0.0001). CONCLUSION: In patients with HCV genotypes 2 or 3 infection, a higher SVR was observed in patients receiving Peg-IFN plus RBV related to patients treated with biosimilar standard IFN plus RBV.