Peginterferon alfa-2a (40KD) (PEGASYS®) plus ribavirin (COPEGUS®) in retreatment of chronic hepatitis C patients, nonresponders and relapsers to previous conventional interferon plus ribavirin therapy

Peginterferon alfa plus ribavirin is currently the treatment of choice for chronic hepatitis C. Peginterferon alfa-2a (40KD) plus ribavirin has given an overall sustained virological response of 18% in F3/F4 previous nonresponder US patients. We evaluated the effectiveness of peginterferon alfa-2a (40KD) plus ribavirin in Brazilian patients who were relapsers or nonresponders to previous interferon-based therapy. One-hundred-thirty-four patients with biopsy-proven chronic hepatitis C, HCV RNA positive, elevated ALT and who were either relapsers (n=37) or nonresponders (n=97) to at least 24 weeks of conventional interferon/ribavirin therapy were retreated with peginterferon alfa-2a (40KD) 180mg/qw and ribavirin 800mg bid for 48 weeks. Efficacy was assessed as virological response (defined as undetectable HCV RNA) at the end of treatment (EoT) and at the end of follow-up (SVR - Sustained Virological Response). Safety assessments consisted of clinical and laboratory evaluations. In the patient sample, 72% were genotype 1 and 34% were cirrhotic. In an intention-to-treat analysis, relapser patients showed 78% EoT response and 51% SVR. Nonresponders showed 57% EoT response and 26% SVR. Positive predictive factors of SVR were non-1 genotype and relapser state. Six percent of the patients interrupted treatment because of adverse events and 45% had dose reduction (mainly associated with leucopenia and anemia). Brazilian patient relapsers and nonresponders to conventional interferon and ribavirin treatment can achieve a sustained virological response when retreated with peginterferon alfa-2a (40KD) and ribavirin. The safety profile is similar to that of naive patients.Federal University of São PauloSanta Casa de Misericórdia Gastroenterology ServiceFederal University of ParáFederal University of Juiz de ForaSão Paulo University Medical School of Ribeirão PretoEmílio Ribas InstituteFederal University of Minas GeraisMedical School of São José do Rio PretoFederal University of AlagoasFederal University of Santa CatarinaFederal University of BahiaTropical Medicine FundationOswaldo Cruz HospitalFederal University of ParaíbaRocheUNIFESPSciEL

Estudo dos auto-anticorpos nas Hepatites virais crônicas B e C antes, durante e após tratamento com Interferon-alfa

This study was undertaken to investigate the presence of autoantibodies in patients with chronic viral hepatitis B and C, before, during and after interferon-alpha (IFN-alpha) therapy and to study their relation to dose and type of IFN-alpha and response to treatment. Fifty patients with chronic hepatitis were divided in two groups, a control-group of 21 patients (10 type B and 11 type C) who were followed for 6 months without treatment and an IFN-group consisting of 29 patients (8 type B and 21 type C) who received IFN therapy for 6 months. Serum samples were tested for a range of antibodies at the start of the study, during therapy and at the end of the 6 month period. Antibodies tested for included: antinuclear, smooth muscle, antimitochondrial, parietal cell and thyroid microsomal. Four (8%) of the total patient group had autoantibodies at the beginning of the study (two in each group). During the follow-up period no patient in the control group developed antibodies compared with 3 (11%) patients in the treatment group. Autoantibodies developed in patients treated with higher doses of IFN and were found in those patients who tended to show a poor response to IFN-therapy. Further studies are needed to establish the relationship between poor response to IFN-alpha and development of autoantibodies.Este estudo teve como objetivo avaliar a presença de auto-anticorpos em pacientes com hepatite crônica pelos vírus B e C, antes, durante e após tratamento com interferon-alfa (IFN-alfa), assim como estudar a relação destes anticorpos com o tipo de IFN, com a dose e com a resposta terapêutica. Cinqüenta pacientes com hepatite viral crônica foram divididos em 2 grupos: grupo-controle constituído por 21 pacientes (10 hepatites B e 11 hepatites C), que foram seguidos durante 6 meses sem tratamento e grupo-IFN constituído por 29 pacientes (8 hepatites B e 21 hepatites C), que receberam IFN-alfa durante 6 meses. Anticorpos antinúcleo, antimúsculo liso, antimitocôndria, anticélula parietal e antitireóide foram pesquisados em amostras de soro colhidas antes do início, durante e ao final do estudo. Quatro dos 50 pacientes (8%) apresentavam auto-anticorpos no início do estudo (2 em cada grupo). Durante o estudo nenhum paciente do grupo-controle desenvolveu auto-anticorpos, enquanto que 3 (11%) pacientes do grupo-IFN passaram a apresentá-los. Os auto-anticorpos ocorreram apenas em pacientes tratados com doses mais elevadas de IFN. Verificou-se ainda tendência à resposta desfavorável ao tratamento naqueles indivíduos que apresentaram ou desenvolveram auto-anticorpos. Assim, sugere-se que mais estudos sejam realizados para determinar se existe ou não relação entre resposta desfavorável e a presença ou o desenvolvimento de auto-anticorpos

Estudo dos auto-anticorpos nas Hepatites virais crônicas B e C antes, durante e após tratamento com Interferon-alfa

This study was undertaken to investigate the presence of autoantibodies in patients with chronic viral hepatitis B and C, before, during and after interferon-alpha (IFN-alpha) therapy and to study their relation to dose and type of IFN-alpha and response to treatment. Fifty patients with chronic hepatitis were divided in two groups, a control-group of 21 patients (10 type B and 11 type C) who were followed for 6 months without treatment and an IFN-group consisting of 29 patients (8 type B and 21 type C) who received IFN therapy for 6 months. Serum samples were tested for a range of antibodies at the start of the study, during therapy and at the end of the 6 month period. Antibodies tested for included: antinuclear, smooth muscle, antimitochondrial, parietal cell and thyroid microsomal. Four (8%) of the total patient group had autoantibodies at the beginning of the study (two in each group). During the follow-up period no patient in the control group developed antibodies compared with 3 (11%) patients in the treatment group. Autoantibodies developed in patients treated with higher doses of IFN and were found in those patients who tended to show a poor response to IFN-therapy. Further studies are needed to establish the relationship between poor response to IFN-alpha and development of autoantibodies.Este estudo teve como objetivo avaliar a presença de auto-anticorpos em pacientes com hepatite crônica pelos vírus B e C, antes, durante e após tratamento com interferon-alfa (IFN-alfa), assim como estudar a relação destes anticorpos com o tipo de IFN, com a dose e com a resposta terapêutica. Cinqüenta pacientes com hepatite viral crônica foram divididos em 2 grupos: grupo-controle constituído por 21 pacientes (10 hepatites B e 11 hepatites C), que foram seguidos durante 6 meses sem tratamento e grupo-IFN constituído por 29 pacientes (8 hepatites B e 21 hepatites C), que receberam IFN-alfa durante 6 meses. Anticorpos antinúcleo, antimúsculo liso, antimitocôndria, anticélula parietal e antitireóide foram pesquisados em amostras de soro colhidas antes do início, durante e ao final do estudo. Quatro dos 50 pacientes (8%) apresentavam auto-anticorpos no início do estudo (2 em cada grupo). Durante o estudo nenhum paciente do grupo-controle desenvolveu auto-anticorpos, enquanto que 3 (11%) pacientes do grupo-IFN passaram a apresentá-los. Os auto-anticorpos ocorreram apenas em pacientes tratados com doses mais elevadas de IFN. Verificou-se ainda tendência à resposta desfavorável ao tratamento naqueles indivíduos que apresentaram ou desenvolveram auto-anticorpos. Assim, sugere-se que mais estudos sejam realizados para determinar se existe ou não relação entre resposta desfavorável e a presença ou o desenvolvimento de auto-anticorpos

Direct antiviral therapy for treatment of hepatitis C: A real-world study from Brazil

Introduction and objectives: Direct antiviral agents (DAAs) including sofosbuvir (SOF), daclatasvir (DCV), simeprevir (SIM) and ombitasvir, paritaprevir and dasabuvir were introduced 2015 in Brazil for treatment of hepatitis C virus (HCV) infection. The aims of this study were to assess effectiveness and safety of HCV treatment with DAA in real-life world in a highly admixed population from Brazil. Materials and methods: All Brazilian reference centers for HCV treatment were invited to take part in a web-based registry, prospectively conducted by the Brazilian Society of Hepatology, to assess outcomes of HCV treatment in Brazil with DAAs. Data to be collected included demographics, disease severity and comorbidities, genotype (GT), viral load, DAA regimens, treatment side effects and sustained virological response (SVR). Results: 3939 patients (60% males, mean age 58 ± 10 years) throughout the country were evaluated. Most had advanced fibrosis or cirrhosis, GT1 and were treated with SOF/DCV or SOF/SIM. Overall SVR rates were higher than 95%. Subjects with decompensated cirrhosis, GT2 and GT3 have lower SVR rates of 85%, 90% and 91%, respectively. Cirrhosis and decompensated cirrhosis in GT1 and male sex and decompensated cirrhosis in GT3 were significantly associated with no SVR. Adverse events (AD) and serious AD occurred in 18% and 5% of those subjects, respectively, but less than 1% of patients required treatment discontinuation. Conclusion: SOF-based DAA regimens are effective and safe in the heterogeneous highly admixed Brazilian population and could remain an option for HCV treatment at least in low-income countries