Chronic hepatitis C: hepatic iron content does not correlate with response to antiviral therapy

The complex interaction between hepatitis C virus infection, iron homeostasis and the response to antiviral treatment remains controversial. The aim of this study was to evaluate the influence of hepatic iron concentration (HIC) on the sustained virological response (SVR) to antiviral therapy in patients with chronic hepatitis C. A total of 50 patients who underwent pretreatment liver biopsy with assessment of HIC by graphite furnace atomic absorption spectroscopy and were subsequently submitted to antiviral treatment with interferon/peginterferon and ribavirin were included in the study. Patients with alcoholism, history of multiple blood transfusion, chronic kidney disease, hemolytic anemia and parenteral iron therapy were excluded. The iron related markers and HIC were compared between those who achieved an SVR and non-responders (NR) patients. The mean age was 45.7 years and the proportion of patients' gender was not different between SVR and NR patients. The median serum iron was 138 and 134 µg/dL (p = 0.9), the median serum ferritin was 152.5 and 179.5 ng/mL (p = 0.87) and the median HIC was 9.9 and 8.2 µmol/g dry tissue (p = 0.51), for SVR and NR patients, respectively. Thus, hepatic iron concentration, determined by a reliable quantitative method, was not a negative predictive factor of SVR in patients with chronic hepatitis C presenting mild to moderate hepatic iron accumulation.A complexa interação entre infecção pelo vírus da hepatite C, homeostase do ferro e resposta ao tratamento antiviral permanece controversa. O objetivo deste estudo foi avaliar a influência da concentração hepática de ferro (CHF) na resposta virológica sustentada (RVS) à terapia antiviral na hepatite C crônica. Foram incluídos 50 pacientes que foram submetidos à biopsia hepática pré-tratamento com determinação da CHF por espectrofotometria de absorção atômica com forno de grafite e tratados posteriormente com interferon/peginterferon e ribavirina. Pacientes com alcoolismo, história de múltiplas transfusões sanguíneas, doença renal crônica, anemia hemolítica e terapia com ferro parenteral foram excluídos. O perfil de ferro sérico e a CHF foram comparados entre aqueles que atingiram RVS e os não-respondedores (NR). A média de idade dos pacientes foi 45,7 anos e não houve diferença na proporção de homens e mulheres entre os grupos RVS e NR. A mediana do ferro sérico foi 138 and 134 µg/dL (p = 0.9), a mediana da ferritina sérica foi 152,5 e 179,5 ng/mL (p = 0,87) e a CHF mediana foi 9,9 e 8,2 µmol/g de tecido seco (p = 0,51), para pacientes com RVS e NR, respectivamente. Concluindo, a concentração hepática de ferro, determinada por um método quantitativo confiável, não foi um fator preditivo negativo de RVS em pacientes com hepatite C crônica e acúmulo de ferro hepático leve a moderado

Hepatic iron concentration in chronic hepatitis C: relationship with hepatic stellate cell activation and response to antiviral therapy

Background: The complex relationship between liver iron and fibrosis progression in chronic hepatitis C, possibly mediated by activation of hepatic stellate cells (HSC), as well as the impact of iron depositions on sustained virological response (SVR) to antiviral therapy remain inconclusive. Aims: To evaluate the relationship between hepatic iron concentration (HIC) and HSC activation and the influence of HIC on SVR. Patients and Methods: Patients with chronic hepatitis C and liver biopsy with tissue iron quantification by atomic absorption spectrophotometry were eligible for HSC measurement. Of these patients, those receiving ribavirin and interferon based therapy (24 or 48 weeks) were included for the assessment of the relationship between SVR and HIC. Fibrosis and necroinflammatory activity were classified according to the Brazilian Society of Pathology. Activated HSC measurement was carried out by immunohistochemical test with anti-smooth muscle ¥á-actin antibody; these cells were semiquantified according to the modified Schimitt-Graff et al. score, graded in the lobular (zone 1 and zones 2-3) and mesenchymal (portal tracts/fibrous septa) compartments. Spearman.s correlation coefficient was used to identify the association of HIC, activated HSC, necroinflammatory activity and fibrosis variables. HIC was compared in patients with and without SVR by Mann-Whitney and Fisher.s exact tests; p 800 ¥ìg/g reached statistical significance, p=0.04. Conclusions: HIC was not associated to greater HSC activation despite of the association of HSC activation with greater liver histological damage. In addition, HIC had a positive impact on SVR. Thus, in the context of physiological thresholds, there must be an optimal iron concentration range, which is beneficial for the host in relation with hepatitis C virus infection.Introducao: A complexa relacao entre ferro hepatico e progressao da fibrose na hepatite C cronica, possivelmente mediada pela ativacao de celulas estreladas hepaticas (CEH), bem como o impacto dos depositos de ferro sobre a taxa de resposta virologica sustentada (RVS) a terapia antiviral permanecem inconclusivos. Objetivos: Avaliar a relacao entre concentracao de ferro hepatico (CHF) e ativacao de CEH e a influencia da CFH sobre a taxa de RVS. Metodos: Foram elegiveis para estudo das CEH pacientes com hepatite C cronica e biopsia hepatica com quantificacao de ferro no tecido por espectrofotometria de absorcao atomica. Dentre estes pacientes, os que foram submetidos a terapia baseada em interferon e ribavirina (24 ou 48 semanas) foram incluidos para analise da relacao entre RVS e CFH. Fibrose e atividade necroinflamatoria foram graduadas segundo a Sociedade Brasileira de Patologia. Pesquisa de CEH ativadas foi realizada por exame imuno-histoquimico com anticorpo contra ƒ¿-actina de musculo liso; estas celulas foram semi-quantificadas de acordo com o escore de Schimitt-Graff et al. modificado, graduadas no compartimento lobular (zona 1 e zonas 2-3) e mesenquimal (espaco-porta/septos). Para identificar associacao entre as variaveis CFH, CEH ativadas, atividade necroinflamatoria e fibrose, utilizou-se o coeficiente de correlacao de Spearman. CFH foi comparada entre pacientes com e sem RVS, empregando-se os testes Mann-Whitney e exato de Fisher; p 800 ƒÊg/g alcancou significancia estatistica, p=0,04. Conclusoes: A CFH nao se associou a maior ativacao de CEH, a despeito da associacao desta ativacao com maior dano histologico hepatico. Alem disso, a CFH teve impacto positivo sobre a RVS. Assim, no contexto de limites fisiologicos, deve haver uma faixa otima de concentracao do ferro, que seja benefica para o hospedeiro na sua relacao com a infeccao pelo virus da hepatite C.TEDEBV UNIFESP: Teses e dissertaçõe

Einflussfaktoren auf die Staatsexamens-Ergebnisse brasilianischer Medizinstudierender

Background: The Brazilian National Student Performance Examination - ENADE is an instrument used to measure the quality of undergraduate courses. The identification of factors that influence the result of this examination can contribute to providing support necessary to improve the quality of medical courses. The purpose of this work was to evaluate the factors that affect the National Student Performance Examination grades of Brazilian undergraduate medical programs. Methods: Factors that influenced the 2010 ENADE grades of 100 undergraduate medical programs were studied. Data collection was performed using public databases. Academic and healthcare infrastructure variables were investigated. The data analysis was based on the performance of the medical programs on the 2010 ENADE, whereby the programs were divided into two groups: ENADE 1-2 (unsatisfactory grade) versus ENADE 4-5 (satisfactory grade). Results: One hundred schools were included in this analysis. In the univariate analysis the university variables (p=0.037), public institution (p<0.001), lower number of openings per course (p=0.036), lower number of specialist professors (p=0.003) and higher number of doctors (p=0.010), strictu sensu post-graduation program (p<0.001), higher course lifetime (p<0.001) were associated to best results in ENADE. In the multivariate analysis of logistic binary regression four variables remained independently associated to a better performance in ENADE: public institution (OR 9.9; 95%CI 1.03 to 95.5), lower number of openings per course (OR 0.984; 95% CI 0.969 to 0.999), strictu sensu post-graduation program (OR 8.189; 95% CI 1.459 to 45.971) and longer course lifetime (OR 1.058; 95% CI 1.013 to 1.105). Conclusions: The satisfactory score of this evaluation (ENADE 4-5) was associated to the public administration category of higher degree institutions, lower number of openings offered per course, the presence of a strictu sensu and longer course lifetime.Hintergrund: Das nationale brasilianische Examen zur Erfassung der Studentischen Leistung - ENADE (Exame Nacional de Desempenho do Estudante) untersucht die Qualität medizinischer Grund- bzw. Bachelorstudienprogramme. Die Identifikation der Faktoren, die die Ergebnisse dieses Examens beeinflussen, kann dazu beitragen, die notwendige Unterstützung zur Verbesserung der Qualität medizinischer Ausbildungsprogramme bereitzustellen. Das Ziel dieser Arbeit war die Evaluation der Faktoren, die einen Einfluss auf die Ergebnisse brasilianischer Medizinstudierender im ENADE haben.Methoden: Untersucht wurden alle Faktoren, die 2010 die ENADE-Ergebnisse von 100 medizinischen Studiengängen bedingt haben. Die Daten wurden aus öffentlichen Datenbanken erhoben und im Hinblick auf strukturbezogene Variablen im Bereich des Hochschul- und Gesundheitswesens untersucht. Die Datenanalyse basiert auf den Ergebnissen der medizinischen Studienprogramme beim ENADE 2010, wobei die Studienprogramme in zwei Gruppen aufgeteilt wurden: ENADE 1-2 (Studienprogramme mit unbefriedigenden Ergebnissen) gegenüber ENADE 4-5 (Studienprogramme mit befriedigenden Ergebnissen). Ergebnisse: Die Analyse umfasste die Untersuchung von 100 Ausbildungsstätten. Bei der univariaten Analyse zeigte sich eine Korrelation zwischen besseren ENADE-Ergebnissen und den Variablen Universität (p=0,037), staatliche Ausbildungsstätte (p<0,001), geringes Anzahl an Studienplätzen (p=0,036), weniger Lehrende mit einem "Spezialisten"-Titel (Especializacao) (p=0,003) und mehr Lehrende mit einem Doktortitel (p=0,010), stricto sensu Post-Graduiertenprogramm (cursos de pós-graduação stricto sensu ) (p<0,001), sowie längeres Bestehen des Studienprogramms (p<0,001). Bei der multivariaten Analyse der binären logistischen Regression wurde gezeigt, dass vier Variablen lose mit besseren ENADE-Ergebnissen korrelieren: staatliche Ausbildungsstätte (OR 9,9; 95%CI 1,03 bis 95,5), geringes Angebot an Studienplätzen (OR 0,984; 95% CI 0,969 bis 0,999), stricto sensu Post-Graduiertenprogramm (cursos de pós-graduação stricto sensu ) (OR 8,189; 95% CI 1,459 bis 45,971) und längeres Bestehen des Studienprogramms (OR 1,058; 95% CI 1,013 bis 1,105). Schlussfolgerung: Das Erreichen eines befriedigenden Ergebnisses bei diesem Examen (ENADE 4-5) wurde mit der staatlichen Administration von Hochschulen, dem geringeren Angebot an Studienplätzen pro Studienprogramm, dem Angebot von stricto sensu Post-Graduiertenprogrammen sowie dem längeren Bestehen der Studienprogramme in Verbindung gebracht

Hepatite C crônica: concentração hepática de ferro não é correlacionada com a resposta ao tratamento antiviral

The complex interaction between hepatitis C virus infection, iron homeostasis and the response to antiviral treatment remains controversial. The aim of this study was to evaluate the influence of hepatic iron concentration (HIC) on the sustained virological response (SVR) to antiviral therapy in patients with chronic hepatitis C. A total of 50 patients who underwent pretreatment liver biopsy with assessment of HIC by graphite furnace atomic absorption spectroscopy and were subsequently submitted to antiviral treatment with interferon/peginterferon and ribavirin were included in the study. Patients with alcoholism, history of multiple blood transfusion, chronic kidney disease, hemolytic anemia and parenteral iron therapy were excluded. The iron related markers and HIC were compared between those who achieved an SVR and non-responders (NR) patients. The mean age was 45.7 years and the proportion of patients' gender was not different between SVR and NR patients. The median serum iron was 138 and 134 µg/dL (p = 0.9), the median serum ferritin was 152.5 and 179.5 ng/mL (p = 0.87) and the median HIC was 9.9 and 8.2 µmol/g dry tissue (p = 0.51), for SVR and NR patients, respectively. Thus, hepatic iron concentration, determined by a reliable quantitative method, was not a negative predictive factor of SVR in patients with chronic hepatitis C presenting mild to moderate hepatic iron accumulation.A complexa interação entre infecção pelo vírus da hepatite C, homeostase do ferro e resposta ao tratamento antiviral permanece controversa. O objetivo deste estudo foi avaliar a influência da concentração hepática de ferro (CHF) na resposta virológica sustentada (RVS) à terapia antiviral na hepatite C crônica. Foram incluídos 50 pacientes que foram submetidos à biopsia hepática pré-tratamento com determinação da CHF por espectrofotometria de absorção atômica com forno de grafite e tratados posteriormente com interferon/peginterferon e ribavirina. Pacientes com alcoolismo, história de múltiplas transfusões sanguíneas, doença renal crônica, anemia hemolítica e terapia com ferro parenteral foram excluídos. O perfil de ferro sérico e a CHF foram comparados entre aqueles que atingiram RVS e os não-respondedores (NR). A média de idade dos pacientes foi 45,7 anos e não houve diferença na proporção de homens e mulheres entre os grupos RVS e NR. A mediana do ferro sérico foi 138 and 134 µg/dL (p = 0.9), a mediana da ferritina sérica foi 152,5 e 179,5 ng/mL (p = 0,87) e a CHF mediana foi 9,9 e 8,2 µmol/g de tecido seco (p = 0,51), para pacientes com RVS e NR, respectivamente. Concluindo, a concentração hepática de ferro, determinada por um método quantitativo confiável, não foi um fator preditivo negativo de RVS em pacientes com hepatite C crônica e acúmulo de ferro hepático leve a moderado.Federal University of São Paulo Hepatitis Section Division of GastroenterologyFederal University of São Paulo Department of PathologyUNIFESP, Hepatitis Section Division of GastroenterologyUNIFESP, Department of PathologySciEL

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

Is early virological response as predictive of the hepatitis C treatment response in dialysis patients as in non-uremic patients?

Objective: the aim of the present study was to determine whether hepatitis C virus (HCV) RNA present at week 12 is a good predictor of the response to interferon (IFN) monotherapy in hemodialysis patients with hepatitis C.Methods: Hemodialysis patients with hepatitis C who were treated between 1997 and 2008 with IFN monotherapy for 48 weeks without dose reduction were included. the predictive value of HCV RNA at week 12 for achieving a sustained virological response (SVR) was determined.Results: Forty patients (mean age 47 +/- 9 years; 75% males and 80% with genotype 1) were included. Septal fibrosis or cirrhosis was observed in 38% of these patients. Twelve (30%) of the 40 patients achieved SVR. HCV RNA was undetectable at week 12 in 68%. the positive predictive value of HCV RNA at week 12 was 45% and the negative predictive value was 100%.Conclusions: the presence of HCV RNA at week 12 had a high negative predictive value for SVR in hemodialysis patients with chronic hepatitis C treated with IFN for 48 weeks. Therefore, if HCV RNA is detected at week 12, treatment should be discontinued due to the low probability of a sustained response. (0 2012 International Society for Infectious Diseases. Published by Elsevier B.V. All rights reserved