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

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