Effectiveness of first-wave protease inhibitors in hepatitis C virus genotype 1 infection: a multicenter study in Brazil.

INTRODUCTION: In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated. METHODS: Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol. Treatment effectiveness was verified by using bivariate and multivariate analysis; p-values of < 0.05 were considered significant. RESULTS: Of 275 patients (64.7% men; average age, 57 years old), most (61.8%) were treatment-experienced; 53.9% had subgenotype 1a infection, 85.1% had advanced fibrosis, and 85.5% were treated with telaprevir. SVR was observed in 54.2%. Rapid virological response (RVR) was observed in 54.6% of patients (data available for 251 patients). Overall, 87.5% reported side effects and 42.5% did not complete treatment. Skin rash, severe infection, and death occurred in 17.8%, 2.5%, and death in 1.4% of cases, respectively. SVR was associated with treatment completion, RVR, and anemia. CONCLUSIONS: The effectiveness of hepatitis C virus triple therapy was lower than that reported in phase III clinical trials, possibly owing to the prioritized treatment of patients with advanced liver fibrosis. The high frequency of side effects and treatment interruptions observed supported the decision of the Brazilian authorities to suspend its use when safer and more effective drugs became available in 2015.

Effectiveness of first-wave protease inhibitors in hepatitis C virus genotype 1 infection: a multicenter study in Brazil

Abstract INTRODUCTION: In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated. METHODS: Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol. Treatment effectiveness was verified by using bivariate and multivariate analysis; p-values of < 0.05 were considered significant. RESULTS: Of 275 patients (64.7% men; average age, 57 years old), most (61.8%) were treatment-experienced; 53.9% had subgenotype 1a infection, 85.1% had advanced fibrosis, and 85.5% were treated with telaprevir. SVR was observed in 54.2%. Rapid virological response (RVR) was observed in 54.6% of patients (data available for 251 patients). Overall, 87.5% reported side effects and 42.5% did not complete treatment. Skin rash, severe infection, and death occurred in 17.8%, 2.5%, and death in 1.4% of cases, respectively. SVR was associated with treatment completion, RVR, and anemia. CONCLUSIONS: The effectiveness of hepatitis C virus triple therapy was lower than that reported in phase III clinical trials, possibly owing to the prioritized treatment of patients with advanced liver fibrosis. The high frequency of side effects and treatment interruptions observed supported the decision of the Brazilian authorities to suspend its use when safer and more effective drugs became available in 2015.

PEGYLATED INTERFERON AND RIBAVIRIN FOR TREATMENT OF RECURRENT HEPATITIS C AFTER LIVER TRANSPLANTATION: a single-liver transplant center experience in Brazil.

BACKGROUND: Treatment of hepatitis C virus infection in post-transplantation patients is a challenge due to poor tolerance and low success rates. OBJECTIVE: To determine the response rate to pegylated interferon and ribavirin in post-liver transplant patients with hepatitis C recurrence. METHODS: Between 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. RESULTS: The 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. CONCLUSION: Sustained 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.

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.

Evolução inesperada em um paciente com cirrose hepática, ascite refratária e peritonite bacteriana espontânea de repetição / Unexpected evolution in a patient with liver cirrhosis, refractory acite, and repeated spontaneous bacterial peritonitis

Introdução: A combinação de cirrose hepática, ascite refratária e peritonite bacteriana espontânea (PBE) de repetição tem prognostico ruim e alta mortalidade. O transplante hepático é a única terapeutica atualmente disponível para esses pacientes. O objetivo é decrever uma evolução inesperada, com sobrevida em longo prazo sem transplante hepático, em um paciente com cirrose alcoólica, ascite refratária e PBE de repetição. Descrição: Paciente masculinoa, 44 anos, com cirrose alcoólica, ascite refratária e PEB de repetição. Apresentava MELD 22 e CHILD c12. Nos 18 mese anteriores, havia sido internado 10 vezes devido principalmente a PBE e encefalopatia e havia realizado 56 paracenteses de alívio. Após um mês em lista de espera, o paciente foi admitdio para transplante. Entretanto, durante o procedimento não foi possível abordar a topografia hepatica, devido a multiplas aderências ao redor do fígado. Diante da impossibilidade técnica realizou-se apenas limpeza ampla da cavidade abdominal. Inesperadamente, mais de 50 meses após a tentativa do transplante, o paciente continua vivo, com MELD 17 e CHILD B8 atuais. Discussão: O transplante hepático talvez seja a única terapêutica curativa atualmente disponível em pacientes com cirrose avançada, PBE de repetição e ascite refratária. Contudo, este relato mostra uma evolução inesperada em um paciente com essas co-morbidades que, mesmo sem transplante, evolui bem, com sobreida em longo prazo.

Diagnosis of spontaneous bacterial peritonitis in cirrhotic patients in northeastern Brazil by use of rapid urine-screening test.

CONTEXT AND OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication of cirrhotic patients with ascites. It has been proposed that the reagent strip for leukocyte esterase designed for the testing of urine (Combur test UX) could be a useful tool for diagnosing SPB. The aim of this study was to assess the sensitivity and specificity of urine test strips for diagnosing SBP in cirrhotic patients with ascites. DESIGN AND SETTING: Prospective study, at a university hospital in northeastern Brazil. METHODS: Forty-two unselected consecutive cirrhotic patients (32 males; mean age: 51.7 +/- years) were included, and a total of 100 paracenteses were performed. All ascitic fluid samples were analyzed using the reagent strip and cytology, neutrophils, lymphocyte count, appropriate biochemical tests and culturing. The strips were considered positive if the color became purple on a colorimetric scale. RESULTS: Nine patients were diagnosed with SBP using cytology (> 250 neutrophils/mm(3)), and the strips were positive for all these nine patients with SBP. In one sample, the strip was positive but the neutrophil count was less than 250 cells/mm(3). For 86 samples, both the strips and cytology were negative. At the threshold of 250 neutrophils/mm(3) in ascitic fluid, the sensitivity, specificity, positive predictive value and negative predictive value for the strips were respectively 100%, 98.9%, 92.3% and 100%. CONCLUSION: The Combur test UX urine screening test is a very sensitive and specific method for diagnosing SBP in cirrhotic patients with ascites.

Diagnosis of spontaneous bacterial peritonitis in cirrhotic patients in northeastern Brazil by use of rapid urine-screening test / Diagnóstico de peritonite bacteriana espontânea em pacientes cirróticos com o uso fita reagente para urinanálise no nordeste do Brasil

CONTEXT AND OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication of cirrhotic patients with ascites. It has been proposed that the reagent strip for leukocyte esterase designed for the testing of urine (Combur test® UX) could be a useful tool for diagnosing SPB. The aim of this study was to assess the sensitivity and specificity of urine test strips for diagnosing SBP in cirrhotic patients with ascites. DESIGN AND SETTING: Prospective study, at a university hospital in northeastern Brazil. METHODS: Forty-two unselected consecutive cirrhotic patients (32 males; mean age: 51.7 ± years) were included, and a total of 100 paracenteses were performed. All ascitic fluid samples were analyzed using the reagent strip and cytology, neutrophils, lymphocyte count, appropriate biochemical tests and culturing. The strips were considered positive if the color became purple on a colorimetric scale. RESULTS: Nine patients were diagnosed with SBP using cytology (> 250 neutrophils/mm³), and the strips were positive for all these nine patients with SBP. In one sample, the strip was positive but the neutrophil count was less than 250 cells/mm³. For 86 samples, both the strips and cytology were negative. At the threshold of 250 neutrophils/mm³ in ascitic fluid, the sensitivity, specificity, positive predictive value and negative predictive value for the strips were respectively 100 percent, 98.9 percent, 92.3 percent and 100 percent. CONCLUSION: The Combur test® UX urine screening test is a very sensitive and specific method for diagnosing SBP in cirrhotic patients with ascites.

CONTEXTO E OBJETIVO: Peritonite bacteriana espontânea (PBE) é uma freqüente e grave complicação em pacientes cirróticos com ascite. Vem sendo proposto o uso de fitas reagente para esterase leucocitária, utilizadas para diagnóstico de infecção urinária, como instrumento para diagnosticar PBE. O objetivo deste estudo é avaliar a sensibilidade e a especificidade da fita reagente Combur Test® UX no diagnóstico de PBE em pacientes cirróticos com ascite. TIPO DE ESTUDO E LOCAL: Estudo prospectivo, realizado no Hospital Universitário Walter Cantídio, Fortaleza, Ceará, Brasil. MÉTODOS: Quarenta e dois pacientes consecutivos, não selecionados (32 homens, com média de idade de 51,7 ± anos) foram incluídos e um total de 100 paracenteses foram realizadas. O líquido ascítico foi avaliado pela fita reagente (Combur Test® UX), citologia, contagem de neutrófilos, linfócitos, testes bioquímicos e cultura. As fitas reagentes foram consideradas positivas se havia mudança na cor para roxo na escala colorimétrica fornecida pelo fabricante. RESULTADOS: Foram diagnosticados nove pacientes com PBE pela citologia (> 250 neutrófilos/mm³), estando a fita Combur Test® UX positiva em todos os nove pacientes. Em uma amostra o teste da fita foi positivo, embora a contagem de neutrófilos fosse < 250 células/mm³. Nas outras 86 amostras ambos os testes foram negativos. Tendo-se como ponto de corte 250 PMN/mm³ no líquido ascítico, a sensibilidade, a especificidade, o valor preditivo positivo e o valor preditivo negativo foram respectivamente 100 por cento, 98,9 por cento, 92,3 por cento e 100 por cento. CONCLUSÕES: Combur Test® UX (fita reagente para urinanálise) é um método sensível e específico para o diagnóstico de PBE em pacientes cirróticos com ascite.

Helicobacter pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy: an open randomized clinical trial.

BACKGROUND: Optimal anti-Helicobacter pylori treatment has not yet been established. AIM: To evaluate H. pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy in northeastern of Brazil. PATIENTS AND METHODS: One hundred and four patients with H. pylori infection, as determined by rapid urease testing and histology, were randomly assigned to receive either: lansoprazole (30 mg q.d.), tetracycline (500 mg q.i.d.), and furazolidone (200 mg t.i.d.) for 7 days (LTF; n = 52); or lansoprazole (30 mg b.i.d.) and amoxicillin (1 g b.i.d.) for 1 week, plus azithromycin (500 mg q.d.) for the first 3 days (LAAz; n = 52). H. pylori eradication was assessed 3 months following completion of therapy by means of rapid urease testing, histology and a 14C-urea breath test. RESULTS: H. pylori eradication was achieved in 46 of 52 (88.4%, 95% CI: 77.5%-95.1%) patients in LTF group and in 14 of 52 (26.9%, 95% CI: 16.2%-40,1%) patients in LAAz group. On a per-protocol analysis, eradication rates were 91.8% (95% CI: 81.4%-97.3%) and 28.5% (95% CI: 17.2%-42.3%), respectively in LTF and LAAz groups. CONCLUSION: The LAAz regimen yielded unacceptably low eradication rates. On the other hand, the LTF scheme represents a suitable alternative for H. pylori eradication.

Helicobacter pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy: an open randomized clinical trial

RACIONAL: Ainda não está estabelecida a melhor terapêutica anti-H. pylori. OBJETIVO: Avaliar a erradicação de H.pylori usando tetraciclina e furazolidona versus amoxicilina e azitromicina em terapia tríplice com lansoprazol no nordeste do Brasil. PACIENTES E MÉTODOS: Cento e quatro pacientes infectados por H. pylori, diagnosticado através do teste rápido da urease e histologia, foram selecionados aleatoriamente para receber: lansoprazol (30 mg q.d.), tetraciclina (500 mg q.i.d.), furazolidona (200 mg t.i.d.) por 7 dias (LTF; n = 52); ou lansoprazol (30 mg b.i.d.) e amoxicilina (1 g b.i.d.) por 1 semana, mais azitromicina (500 mg q.d.) nos primeiros 3 dias (LAAz; n = 52). A erradicação de H.pylori foi avaliada 3 meses após término da terapia através do teste da urease, histologia e teste respiratório usando uréia marcada com 14Carbono. RESULTADOS: A erradicação do H. pylori foi atingida em 46 de 52 (88.4%, 95% CI: 77.5%-95.1%) pacientes no grupo LTF e em 14 de 52 (26.9%, 95% CI: 16.2%-40,1%) pacientes no grupo LAAz. Na análise per-protocolo, a taxa de erradicação foi de 91.8% (95% CI: 81.4%-97.3%) e 28.5% (95% CI: 17.2%-42.3%), respectivamente no grupo de LTF e LAAz. CONCLUSÃO: O esquema com LAAz ofereceu taxas de erradicação inaceitáveis. Por outro lado, o esquema com LTF representa alternativa adequada para erradicação de H.pylori.