Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus

Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.7595% CI 0.58-0.99p=0.045) and to early treatment interruption due to SAE (PR 0.3695% CI 0.20-0.68p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.0695% CI 1.02-1.10p<0.001) and occurrence of liver cirrhosis (PR 2.0695% CI 1.11-3.83p=0.022). In conclusion, Peg-IFN/RBV might represent an adequate treatment option, mainly in young patients without advanced liver disease or when the use of direct-action drugs is limited to specific patient groups.Univ Sul Santa Catarina, Fac Med, Dept Ciencias Biol & Saude & Ciencias Sociais Apl, Disciplina Doencas Infecciosas, Av Pedra Branca 25, BR-88137270 Palhoca, SC, BrazilUniv Fed Sao Paulo, Disciplina Infectol, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Div Gastroenterol & Hepatol, Sao Paulo, SP, BrazilUniv Fed Estado Rio de Janeiro, Dept Clin Med, Disciplina Gastroenterol, Rio De Janeiro, RJ, BrazilUniv Fed Espirito Santo, Serv Infectol, Vitoria, ES, SpainUniv Sao Paulo, Fac Med Ribeirao Preto, Div Gastroenterol, Ribeirao Preto, SP, BrazilInst Infectol Emilio Ribas, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Dept Doencas Infecciosas & Parasitarias, Sao Paulo, SP, BrazilSecretaria Estadual Saude, Unidade Mista Saude, Unimista 508 509, Brasilia, DF, BrazilUniv Sao Paulo, Inst Med Trop Sao Paulo, Lab Virol, LIM 52, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Disciplina Infectol, Sao Paulo, SP, BrazilWeb of Scienc

Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus

Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients; 70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.75; 95% CI 0.58-0.99; p=0.045) and to early treatment interruption due to SAE (PR 0.36; 95% CI 0.20-0.68; p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.06; 95% CI 1.02-1.10;

Efficacy and safety of glecaprevir/pibrentasvir in treatment-naïve adults with chronic hepatitis C virus genotypes 1–6 in Brazil

Introduction and objectives: Glecaprevir/pibrentasvir is a highly effective and well tolerated treatment for hepatitis C infection. Brazilian patients were not included in the original development studies for glecaprevir/pibrentasvir. This study aimed to assess safety and efficacy of glecaprevir/pibrentasvir in treatment-naïve Brazilian adults without cirrhosis or with compensated cirrhosis. Patients and methods: EXPEDITION-3 was a Phase 3, open-label, multicenter study in treatment-naïve Brazilian adults with hepatitis C infection genotype 1–6. Patients without cirrhosis (F2 or F3) or with compensated cirrhosis (F4) received 8 or 12 weeks of glecaprevir/pibrentasvir, respectively. The primary efficacy endpoint was the rate of sustained virologic response at post-treatment Week 12. Secondary endpoints were on-treatment virologic failure and relapse rates. Baseline polymorphisms were assessed in NS3 and NS5A. Adverse events and laboratory abnormalities were monitored. Results: 100 patients were enrolled, 75 received 8 weeks of treatment and 25 received 12 weeks; all patients completed treatment. Overall sustained virologic response at post-treatment Week 12 rate was high (98.0%; 98/100; 95% confidence interval: 93.0–99.4) and remained high regardless of baseline viral or host factors, including demographics, hepatitis C virus RNA levels, polymorphisms in NS3 and/or NS5A, genotype, and relevant comorbidities. 55% of patients reported ≥1 adverse event, the most common beingheadache (18.0%). Four patients reported serious adverse events; none were considered drug related orled to study drug discontinuation. No hepatic decompensations were observed.Conclusions: Glecaprevir/pibrentasvir was effective and well tolerated in treatment-naïve Brazilianpatients with hepatitis C infection without cirrhosis and with compensated cirrhosis

Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus

ABSTRACT Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients; 70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.75; 95% CI 0.58-0.99; p=0.045) and to early treatment interruption due to SAE (PR 0.36; 95% CI 0.20-0.68; p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.06; 95% CI 1.02-1.10; p<0.001) and occurrence of liver cirrhosis (PR 2.06; 95% CI 1.11-3.83; p=0.022). In conclusion, Peg-IFN/RBV might represent an adequate treatment option, mainly in young patients without advanced liver disease or when the use of direct-action drugs is limited to specific patient groups

The traveling salesman problem and its application to car sharing services

With a rapidly growing population across the globe and the ease of car ownership, the challenges of the individual transport vehicles is showing every day. Individual transport vehicles not only cause a lack of space, but they also produce air, noise and visual pollution. A soluction to the problem of city road saturation is car sharing. The purpose of the thesis is to explain the possible application of algorithms to transportation sharing services and its benefits. This research covers the history, evolution and derivations of these pathfinding algorithms. The objectives have been achieved through an extensive research on both pathfinding problems and algorithms. Some of the documents consulted were from the early 20th century, which provide an overview of the evolution of the pathfinding problems. The result is a comprehensive analysis on pathfinding algorithms and the derivations of the Traveling Salesman Problem. The reader will have a better understanding of the subject even with very little knowledge on programming. The thesis serves as an introduction to pathfinding problems for new programmers. With very basic programming skills, any reader will be able to replicate the algorithms explained in the thesis

EP-266 - CASO DE HEPATITE AGUDA PELO VÍRUS DA HEPATITE E EM SÃO PAULO: O PAPEL DA CARACTERIZAÇÃO GENÉTICA VIRAL NO ESTABELECIMENTO DA PROVÁVEL FONTE DE INFECÇÃO

Introdução: O vírus da Hepatite E (HEV) é responsável pelo desenvolvimento da hepatite E, e sua principal via de transmissão é fecal-oral. O genótipo 3 (HEV-3), zoonótico, está globalmente distribuído, sendo o consumo de carne suína mal cozida o principal fator de risco para infecção. No Brasil, o HEV está presente em suínos e produtos derivados, havendo ainda poucos relatos de infecção em humanos, embora os estudos sorológicos apontem para uma prevalência bem maior. A ausência de triagem rotineira dificulta a compreensão dessa infecção em nosso meio fazendo-se necessária a inclusão desse agente como hipótese diagnóstica nos casos de hepatite aguda sem etiologia definida. Resultados: Paciente masculino, 67 anos, deu entrada no Hospital das Clínicas da FMUSP com quadro de hepatite aguda apresentando os seguintes sintomas: náusea, dor abdominal, urina escura e fezes claras. Os níveis de enzimas hepáticas estavam elevados (AST = 2.616 U/L; ALT = 2.654 U/L), fosfatase alcalina de 256 U/l, gama-glutamil transpeptidase de 210 U/l e bilirrubina total de 11,6 mg/dL. A tomografia de abdome apresentou fígado de dimensões um pouco aumentadas, de contornos regulares, sem evidência de lesões focais. A infecção pelos vírus das hepatites A, B ou C foi descartada por ausência de marcadores sorológicos dessas infecções. Foi realizada a pesquisa do HEV por PCR em tempo real sendo o RNA viral detectado com carga viral de 222,44 U/ul, além disso a sorologia para pesquisa de anticorpos anti-HEV IgM e IgG foi reagente. O genoma dessa cepa de HEV foi caracterizado e o genótipo classificado como 3 subtipo f (HEV-3f). Na análise filogenética essa sequência viral agrupou-se com cepas do HEV detectadas em suínos da região Nordeste do Brasil. Conclusão: No Brasil até o presente momento apenas o genótipo 3 do HEV foi identificado infectando humanos e suínos. Curiosamente, o paciente infectado pelo HEV identificado neste estudo tinha um histórico de viagem recente para a cidade de Garanhuns - Pernambuco, onde foi relatada alta soroprevalência de HEV em suínos. A estreita relação filogenética do HEV isolado do paciente com cepas suínas isoladas no referido estado, em cidades próximas de onde o paciente esteve, sugere uma possível transmissão zoonótica do HEV nesta região. O estudo da diversidade genética do HEV é de grande relevância para o entendimento das vias de transmissão predominantes em nosso meio e para a avaliação da eficácia dos métodos moleculares utilizados para diagnóstico