Tratamiento de infección por virus hepatitis C con nuevos antivirales en pediatría: a propósito de un caso / Treatment of hepatitis C virus infection with new direct-acting antivirals agents in pediatrics. Case report

La infección por virus de la hepatitis C en pediatría se produce principalmente por transmisión vertical. La historia natural en niños consiste en alta tasa de eliminación espontánea, infección asintomática o cambios histológicos mínimos. Las complicaciones suelen observarse en la adolescencia o en la edad adulta. El tratamiento clásico con interferón pegilado y ribavirina presenta efectos adversos, es de duración prolongada y logra una respuesta virológica sostenida (RVS) en el 50 % de los pacientes con infección por genotipo 1. Los nuevos antivirales de acción directa se encuentran disponibles para su indicación a partir de los 12 años, con excelente tolerancia y alta tasa de RVS. Se sugiere conducta terapéutica expectante en pacientes asintomáticos hasta acceder a la medicación. Reportamos el caso de un adolescente con hepatitis C crónica sin cirrosis que recibió tratamiento durante 12 semanas con ledipasvir/sofosbuvir y se logró una RVS.

Hepatitis C virus infection in children occurs mainly through vertical transmission. The natural history at this age consists in a high rate of spontaneous clearance, asymptomatic infection, or minimal histological changes. Disease complications are commonly seen in adolescence or adulthood. The classic treatment with pegylated interferon and ribavirin presents adverse effects, prolonged duration and achieves sustained viral response (SVR) in 50 % of patients with genotype 1 infection (the most frequent). New direct-acting antiviral treatments have been available in recent years for their indication from 12 years of age with excellent tolerance and a high SVR rate. Expectant therapeutic behavior is suggested in asymptomatic patients until they can access to them. We report the case of an adolescent with chronic hepatitis C without cirrhosis who received 12 weeks treatment with ledipasvir/sofosbuvir, achieving SVR.

Perspectivas de tratamiento para COVID-19 (en progreso) / Treatment prospects for COVID-19 (in progress)

CONTEXTO: Debido a la contingencia por COVID-19 provocada por el nuevo coronavirus, SARS-CoV-2, en la actualidad hay una intensa investigación de alternativas terapéuticas que sean seguras y eficaces. (Hay registrados 2208 protocolos de estudios en ClinicalTrials.gov1). Con el propósito de conocer el panorama terapéutico actual contra COVID-19, se realizó una búsqueda exhaustiva de las alternativas que han demostrado cierta eficacia en esta infección, concluyendo que los estudios que se han realizado tienen limitaciones metodológicas. Se trata de estudios no controlados, con alta probabilidad de sesgos que comprometen la validez interna y externa, consideran evidencia indirecta o la experiencia de expertos ante esa emergencia sanitaria, por lo que toda recomendación derivada de estos documentos debe de tomarse con extrema cautela. El uso de esas alternativas debe considerar los riesgos y los beneficios en casos individuales, en una decisión compartida entre médicos, pacientes y familiares ya que la mayoría de la evidencia se considera de baja o muy baja calidad. A la fecha no existe tratamiento específico en contra de este virus. BÚSQUEDA REALIZADA: Inmunoglobulinas intravenosas: Las inmunoglobulinas intravenosas (IgIV) es un grupo de IgG obtenido de donantes sanos, expuestos a enfermedades infecciosas endémicas, vacunas y microorganismos ubicuos que participan en la producción de anticuerpos IgG contra diferentes microorganismos y sus productos. El uso de inmunoglobulina intravenosa se ha

Informe diário de evidências COVID-19: busca realizada em 29 de maio de 2020 / COVID-19 daily evidence report: search conducted on May 29, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 13 artigos e 13 protocolos.

Treatment of chronic hepatitis C in patients with chronic kidney disease with Sofosbuvir-basead regimes

ABSTRACT Background: To analyze the effectiveness and the safety of Sofosbuvir-based regimens to treat patients with chronic hepatitis C virus (HCV) infection and chronic kidney disease (CKD). Methods: A retrospective, observational study in patients with chronic HCV infection and CKD treated with Sofosbuvir-based regimens was performed. Liver fibrosis, comorbidities, HCV genotype and sustained virological resposnse (SVR) at 12th week post-treatment were evaluated. Kidney function was accessed by serum creatinine and glomerular filtration rate (GFR). The assumed level of significance was 5 %. Results: Thirty-five patients were treated. The mean age was 52.1 ± 10.9 years, 19 (54.3 %) were women, 32 (91.4 %) were already kidney transplanted and 3 (8.6 %) were on hemodialysis. The SVR by intention to treat was 88.6 %. The mean GFR was 65.8 ± 28.6 and 63.7 ± 28.3 ml/min pre- and post-treatment respectively (p > 0.05). Treatment was interrupted in 1 (2.85 %) patient due to anemia and in 2 (5.7 %) due to loss of kidney function. Conclusion: Sofosbuvir-based regimens are effective to treat HCV in patients with CKD. In patients with mild CKD this type of therapy seems to be safe.

Clinical and epidemiological profile of HCV genotype 3 patients in southern Brazil

Introduction: Despite the emergence of new treatments for HCV genotype 3 (HCV G3), there is still a lack of data about this particular subgroup in Brazil. Our objective was to describe clinical and sociodemographic variables and treatment profile of HCV G3 Brazilian patients. Methods: This was a descriptive, retrospective study, performed in a specialized center for HCV treatment in the South Region of Brazil. Medical records of patients diagnosed with HCV G3 were reviewed to collect clinical, sociodemographic, and treatment information. Results: Participants included total of 564 patients, with a mean age of 59.3 years (SD = 10.5). Cirrhosis was present in 54.4% of patients. The most common coexisting conditions were systemic arterial hypertension (36.6%) and diabetes mellitus (30%). Regarding treatment, 25.2% of the patients were treatment-naïve and 74.8% were currently under treatment (11.6%) or had received a previous treatment (87%). The most frequent ongoing treatment was sofosbuvir + daclatasvir (± ribavirin) (87.8%). Of the 388 patients who had at least one previous treatment, 67% achieved sustained virologic response in the last treatment. Caucasian / white, non-obese, transplanted patients, those with longer time since diagnosis and with cirrhosis were more likely to receive treatment, according to multivariate analysis. Patients with hepatocellular carcinoma were 64.1% less likely to be on treatment during the study period than those without this condition; patients with chronic kidney disease were 2.91-fold more likely to have an interruption of treatment than those without this condition. Conclusion: This study describes a large sample of Brazilian patients with HCV G3. Treatment patterns were mainly influenced by the presence of HCV complications and comorbidities.(AU)

Zika Vírus na gestação / Zika Virus in pregnancy

A infecção congênita pelo zika vírus (ZIKV) tornou-se uma pandemia em meados de 2015 e é considerada uma emergência em saúde pública de interesse mundial, no que tange à prevalência, transmissão e possíveis sequelas neurológicas fetais. O artigo busca realizar uma revisão sobre a infecção do ZIKV na gestação e suas consequências para o feto. Realizada revisão a partir de estudos qualitativo, retrospectivo e documental, baseando-se em levantamento de produções científicas publicadas entre 2016 e 2018. Por meio da estratégia de busca, localizou-se 194 artigos, dos quais 28 foram selecionados para redação final. Conclui-se que as alterações ultrassonográficas, advindas de infecção no primeiro e segundo trimestre, são devidas à ação viral direta, efeito de imunoglobulinas e alterações na placentação. As alterações fetais são sobretudo as neurológicas, cardíacas e oftalmológicas. Gestantes com infecção comprovada, ou suspeitada, devem ser acompanhadas até o parto. Os investimentos em medicamentos e vacinas devem ser continuados.(AU)

Congenital zika virus (ZIKV) infection has become pandemic by mid-2015 and is considered a public health emergency of global concern with regard to prevalence, transmission and possible fetal neurological sequelae. The article aims to review the ZIKV infection in pregnancy and its consequences for the fetus. A review was carried out based on a qualitative, retrospective and documental studies, based on a survey of scientific productions published between 2016 and 2018. Through the search strategy, 194 articles were found, of which 28 were selected for final writing. It is concluded that ultrasonographic changes, due to infection in the first and second trimester, are due to direct viral action, immunoglobulins effect and changes in placentation. Fetal alterations are especially those neurological, cardiac and ophthalmologic. Pregnant women with proven or suspected infection should be followed up until delivery. Investments in drugs and vaccines should be continued.(AU)

Effectiveness of chronic hepatitis C treatment with direct-acting antivirals in the Public Health System in Brazil

ABSTRACT Introduction Chronic hepatitis C virus infection is one of the major causes of cirrhosis, hepatocellular carcinoma and liver transplantation. Treatment using direct-acting antivirals has revolutionized the treatment of hepatitis C virus, increasing long-term prognosis after cure. The goal of the present study was to evaluate the effectiveness of direct-acting antivirals in a Public Health System in southern Brazil. Methods A retrospective study evaluated all patients with chronic hepatitis C virus infection who underwent treatment at one center of the Public Health Department of the State of Rio Grande do Sul - Brazil, according to the Brazilian Clinical Protocol and Therapeutic Guidelines. The effectiveness was assessed in terms sustained virological response 12 weeks after the end of treatment. Results A total of 1002 patients who were treated for chronic hepatitis C virus infection were evaluated. The mean age was 58.6 years, 557 patients (55.6%) were male and 550 (54.9%) were cirrhotic. Overall sustained virological response was observed in 936 (93.4%) patients. There was a difference in sustained virological response rate varied according to sex, 91.6% in men and 95.7% in women (p= 0.009), length of treatment in genotype 1, 92.7% with 12 weeks and 99.1 with 24 weeks (p= 0.040), and genotype, 94.7% in genotype 1, 91.7% in genotype 2, and 91.4% in genotype 3 (p= 0.047). Conclusion The treatment of chronic hepatitis C virus infection for genotypes 1, 2 or 3 with the therapeutic regimens established by the Brazilian guidelines showed high rates of SVR, even in cirrhotic patients.

Ledipasvir associado a sofosbuvir para o tratamento de pacientes adultos com hepatite C crônica infectados por vírus de genótipo 1 / Ledipasvir associated with sofosbuvir for the treatment of adult patients with chronic hepatitis C infected with genotype 1 virus

CONTEXTO: O objetivo do presente relatório é analisar as evidências científicas apresentadas pelo demandante no que diz respeito à associação entre ledipasvir e sofosbuvir (LDV/SOF) ser eficaz e segura para tratamento da hepatite C crônica, de acordo com desfechos como SVR12 (Resposta Virológica Sustentada - do inglês - Sustained Virological Response 12 weeks after the end of treatment) e 24, frequência de eventos adversos e descontinuação do tratamento pelos mesmos, visando avaliar a sua incorporação no SUS. TECNOLOGIA: Ledipasvir/sofosbuvir (Harvoni®). INDICAÇÃO: Pacientes adultos com infecção crônica pelo vírus da hepatite C (HCV ­ do inglês: Hepatitis C Virus), genótipo 1. PERGUNTA: O uso de ledipasvir/sofosbuvir (LDV/SOF) é eficaz, seguro e custo-efetivo em pacientes com infecção crônica pelo HCV genótipo 1, quando comparado a outras opções atualmente disponíveis no SUS para o tratamento? EVIDÊNCIAS CIENTÍFICAS: Foram incluídos 28 estudos avaliando a tecnologia LDV/SOF em pacientes com HCV GT 1. As evidências encontradas apresentaram qualidade baixa a moderada para eficácia e baixa a muito baixa para segurança, sendo a maioria de não inferioridade e/ou superioridade à taxa histórica de resposta ao tratamento e apontam para uma eficácia superior a 90,0% na maioria dos estudos. Dessa forma, os resultados encontrados para LDV/SOF apresentaram semelhança quanto à eficácia terapêutica quando comparados a outros antivirais disponíveis atualmente no SUS. Quanto ao perfil de segurança, os eventos adversos (EA) mais comumente relatados foram diarreia, náuseas, fadiga e cefaleia. Por fim, observou-se que a associação de LDV/SOF à ribavirina pode levar ao aumento de EA quando comparado à LDV/SOF apenas. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: O demandante conduziu uma avaliação de custo-minimização, cujo modelo foi considerado adequado. Os custos considerados na análise foram restritos aos de aquisição dos diferentes medicamentos. O demandante propôs o valor de U$ 3.690,00 para a incorporação do tratamento com LDV/SOF. Foram considerados 65.000 tratamentos para Hepatite C, sendo o número de pacientes elegíveis para o tratamento com LDV/SOF de 41.600 pacientes. Considerou-se um Market Share de 30%. Assumiu-se dois cenários, um com todos os pacientes utilizando as alternativas terapêuticas de maior preço e o outro com as de menor preço. Dessa forma, com a incorporação de LDV/SOF no SUS, estima-se uma economia entre 60 e 80 milhões de reais no primeiro ano após a sua incorporação e não os 142 a 380 milhões apresentados pelo demandante. Em um horizonte temporal de cinco anos, o impacto orçamentário incremental seria uma economia entre 303 e 400 milhões. CONSIDERAÇÕES FINAIS: Os estudos incluídos neste relatório demonstram que o tratamento com LDV/SOF resultou em taxas de SVR12 altas, a maioria acima de 90%. Tanto a eficácia/efetividade, quanto o perfil de segurança se mostraram semelhantes aos dos demais medicamentos já incorporados no SUS. A avaliação econômica demonstrou que o tratamento com LDV/SOF poderá representar uma economia de 60 a 80 milhões de reais no primeiro ano de incorporação, comparado aos tratamentos atualmente disponíveis. RECOMENDAÇÃO INICIAL DA CONITEC: Na 63ª reunião ordinária da CONITEC em 1º de fevereiro de 2018 a Comissão decidiu por unanimidade emitir a recomendação inicial para a incorporação ao SUS da associação entre sofosbuvir 400 mg e ledipasvir 90 mg em comprimido único para o tratamento de hepatite C crônica em adultos causada exclusivamente pelo genótipo 1 do vírus. CONSULTA PÚBLICA: A consulta pública nº 10/2018 foi realizada entre os dias 24/02/2018 e 05/03/2018. Foram recebidas 29 contribuições, sendo 6 pelo formulário para contribuições técnico-científicas e 23 pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. Após apreciação das contribuições encaminhadas pela consulta pública, o plenário da CONITEC entendeu que não houve argumentação suficiente para alterar sua recomendação inicial, mantendo-se a recomendação favorável à incorporação da associação dos antivirais sofosbuvir e ledipasvir para o tratamento de hepatite C crônica em adultos infectados pelo genótipo 1 do vírus. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da CONITEC presentes na 64ª reunião ordinária, no dia 08 de março de 2018, deliberaram, por unanimidade, por recomendar a incorporação ao SUS da associação dos antivirais sofosbuvir e ledipasvir para o tratamento de hepatite C crônica em adultos infectados pelo genótipo 1 do vírus. Foi assinado o registro de deliberação n° 345/2018 pela incorporação da tecnologia. DECISÃO: Incorporar o ledipasvir associado a sofosbuvir para o tratamento de pacientes adultos com hepatite C crônica infectados por vírus de genótipo 1, conforme Protocolo Clínico e Diretrizes Terapêuticas no âmbito do Sistema Único de Saúde - SUS, dada pela Portaria nº 12, publicada no DOU nº 51, do dia 15 de março de 2018, seção 1, pág. 59.(AU)

Qualitative versus quantitative PCR in establishing response to chronic hepatitis C treatment with sofosbuvir

Objective: To determine the change in rapid virological response for chronic hepatitis C by qualitative PCR testing after treatment with sofosbuvir

Study Design: A descriptive study

Place and Duration of Study: Memon Medical Institute Hospital, Karachi, from January to September 2016

Methodology: The study population consisted of patients above 18 years, till 80 years of age, of both genders, having chronic infection with HCV. Patients included were treatment-naive, non-responders or relapsers; and among these categories, both cirrhotic and non-cirrhotic patients were included. Initially, genotyping and quantitative PCR test was done, one at the start of treatment then at 4 weeks that is till rapid virological response [RVR] was elicited. Qualitative testing was compared by Chi-square with quantitative assays simultaneously to check sensitivity by qualitative testing

Results: Out of 106 patients, the mean age of the patients was 46.40 +/- 14 years. There were 39 [36.8%] males and 67 [63.2%] females. One hundred [94.3%] were infected with genotype 3. One hundred and five [99.05%] patients responded to sofosbuvir with successful achievement of RVR after 4 weeks. One patient did not achieve RVR [0.94%]. The sensitivity of qualitative test was 99%

Conclusion: Qualitative analysis is a cost-effective and sensitive method in patients treated with sofosbuvir for confirming RVR, especially in developing countries where patients are self-paying with significant financial constraints

Tratamiento exitoso con los nuevos antivirales de acción directa en paciente infectado con el virus de la hepatitis C con fibrosis avanzada y dos recaídas previas: Reporte de caso / Successful treatment with new direct acting antiviral in an infected patient with hepatitis C virus with advanced liver fibrosis in a treatment experienced patient: Case report

El tratamiento del virus de la hepatitis C ha presentado grandes cambios en los últimos años. El esquema base utilizado era Interferón Pegylado y Ribavirina, con el que se lograba respuesta viral sostenida (RVS) de alrededor del 50%. Con la adición de los inhibidores de proteasa Telaprevir y Boceprevir al esquema "esqueleto" de Interferon Pegylado y Ribavirina, la tasa de RVS mejoró hasta valores cercanos a 70%; sin embargo, ocurren efectos colaterales importantes y difícil adherencia. Los nuevos antivirales de acción directa (AAD) (inhibidores de la polimerasa NS5A y NS5B), tienen altas tasas de RVS alcanzando valores mayores de 95% en los diferentes genotipos, en pacientes que recibieron tratamiento previo o no, incluyendo cirróticos. Se presenta el caso de un paciente que recibió dos esquemas terapéuticos previos y con fibrosis hepática avanzada que presentó RVS al ser tratado con los nuevos AAD (Sofosbuvir y Ledipasvir). (AU)

The treatment of hepatitis C virus utilized was Pegylated Interferon and Ribavirin, achieving a sustained virological response (SVR) of about 50 %. With the addition of the first-generation protease inhibitors Telaprevir and Boceprevir to the Pegylated Interferon/Ribavirin backbone the SVR rates rose up to approximately 70%, but with important side effects and a difficult adherence. The new direct acting antivirals (NS5A and NS5B polymerase inhibitors) improved SVR rates to 95 % or greater in the different genotypes, in the treatment-naive and treatment experienced patients including patients with cirrhosis. We report the case of a patient with advanced fibrotic stage, who failed to respond to 2 regimens and was subsequently treated with Ledipasvir/Sofosbuvir and achieved virogical cure. (AU)

Curing Chronic Hepatitis C: A Cost Comparison of the Combination Simeprevir Plus Sofosbuvir vs. Protease-Inhibitor-Based Triple Therapy

ABSTRACT Introduction. Interferon-free, multi-direct acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection is highly effective and well tolerated, but costly. To gain perspective on the evolving economics of HCV therapy, we compared the cost per cure of a multi-DAA regimen with the prior standard of triple therapy. Material and methods. Patients infected with HCV genotype 1 who were treated through the University of Colorado Hepatology Clinic between May 2011 and December 2014 comprised the study population. The multi-DAA regimen of simeprevir plus sofosbuvir (SMV/SOF) was compared to the triple therapy regimen consisting of peginterferon and ribavirin, with either boceprevir or telaprevir (TT). Sustained-virologic response (SVR) rates, total costs per treatment and adverse events were recorded. Total cost per SVR were compared for the two treatments, controlling for patient demographics and clinical characteristics. Results. One hundred eighty-three patients received SMV/SOF (n = 70) or TT (n = 113). Patients receiving SMV/SOF were older, more treatment experienced, and had a higher stage of fibrosis. SVRs were 86% and 59%, average total costs per patient were $152,775 and $95,943, and average total costs per SVR were $178,237 vs. $161,813.49 for SMV/SOF and TT groups, respectively. Medication costs accounted for 98% of SMV/SOF and 85% of TT treatment costs. Conclusion. The high cure rate of multi-DAA treatment of HCV is offset by the high costs of the DAAs, such that the cost per cure from TT to multi-DAA therapy has been relatively constant. In order to cure more patients, either additional financial resources will need to be allocated to the treatment of HCV or drug costs will need to be reduced.

Ampliação do tempo de tratamento HCV - genótipo 3 com cirrose, para 24 semanas / Extended treatment time HCV - genotype 3 with cirrhosis for 24 weeks

CONTEXTO: A Organização Mundial da Saúde reconhece a epidemia de hepatites virais como um problema de saúde pública mundial. Vários esforços estão sendo realizados ao redor do planeta para promover estratégias e políticas de prevenção e controle das hepatites virais. Estima-se que a infecção pelo vírus da hepatite C (HCV) atinge mais de 100 milhões em todo o mundo. No Brasil, cerca de 1,4 a 1,7 milhões de pessoas encontram-se afetadas por esta infecção e apresentam o risco de desenvolver as complicações da doença (fibrose, cirrose, insuficiência hepática, hepatocarcinoma). Especificamente, genótipo 3 (GEN 3) constitui o segundo genótipo mais comum, o que corresponde a 30% de todos os casos de hepatite C crônica em todo o mundo. No Brasil e em toda a América Latina, a prevalência deste genótipo é alta. O Ministério da Saúde elaborou e disponibilizou, em julho de 2015, Protocolo Clínico e Diretrizes Terapêuticas (PCDT) para o tratamento da doença e o SUS faz a oferta de toda a linha de cuidado prevista no referido protocolo, que inclui além do diagnóstico, o tratamento por meio de medicamentos com associações entre antivirais de ação direta para todos os genótipos do vírus da hepatite C. No entanto, após um período de incorporação da nova terapia, os especialistas entendem como emergencial a ampliação do tempo de tratamento do paciente portador de hepatite C crônica, genótipo 3 com cirrose, para 24 Semanas, uma vez que o tratamento de 12 semanas não tem apresentado resultados favoráveis. TECNOLOGIA: Sofosbuvir + daclatasvir associado ou não a ribavirina. INDICAção: Pacientes portadores de hepatite C, genótipo 3 com cirrose hepática. a: "o tratamento utilizando sofosbuvir e daclatasvir, com ou sem ribavirina, por 24 semanas em pacientes com hepatite C crônica, genótipo 3 e com cirrose, apresenta maior eficácia quando comparado com o tratamento utilizando a mesma terapêutica no período de 12 semanas?" EVIDÊNCIAS CIENTÍFICAS: Após a realização das buscas, observou-se que, em estudos fase 3, a utilização de sofosbuvir + daclatasvir (com ou sem o uso da ribavirina) por 12 semanas, para o tratamento da hepatite C em pacientes cirróticos genótipo 3, proporciona taxas de sucesso terapêutico que variam de 25% a 68%. Em estudos de vida real, a utilização de sofosbuvir + daclatasvir (com ou sem o uso da ribavirina) por 24 semanas, para o tratamento da hepatite C em pacientes cirróticos genótipo 3, obteve taxas de 78% a 88% de sucesso terapêutico. Desta forma, as principais guias terapêuticas em todo o mundo passaram a recomendar a extensão de 24 semanas para pacientes com genótipo 3, cirróticos tratados com o esquema de sofosbuvir, associado ou não à ribavirina. : a ampliação do tempo de tratamento HCV ­ genótipo 3 com cirrose, para 24 semanas resultaria em um acréscimo de R$ 36.925.634,2113 no tratamento sem ribavirina e de R$ 36.925.681,2513 no tratamento com ribavirina. O impacto orçamentário ao final do triênio seria de R$ 110.776.902,6339 sem ribavirina e de R$ 110.777.043,7539 no tratamento com ribavirina. DISCUSSÃO: o resgate terapêutico de pacientes já tratados com os novos medicamentos de ação direta, compõem um dos maiores desafios terapêuticos da atualidade, pois, a maioria dos pacientes que falham a estes esquemas, apresentam variantes de resistência que comprometem a utilização de medicamentos da mesma classe. Esta preocupação aumenta quando se refere ao retratamento de cirróticos, que são os que mais falham e os que tem menos tempo para aguardar a aprovação de novas opções de resgate, ainda em investigação. Sendo assim, em pacientes com genótipo 3 e doença avançada é muito importante otimizar o esquema de tratamento no sentido de se diminuir a necessidade de retratamento. Desta forma, a recomendação atual, é que os esquemas terapêuticos sejam utilizados de forma mais otimizada possível, tornando-os mais eficazes no sentido de diminuir a chance de falha terapêutica. : recomendação preliminar favorável à ampliação do tempo de tratamento HCV ­ genótipo 3 com cirrose, para 24 semanas. A matéria será disponibilizada em Consulta Pública. CONSULTA PÚBLICA: A Consulta pública nº 43, de 20 de dezembro de 2016 publicada no Diário Oficial da União em 21 de dezembro de 2016 permaneceu aberta para contribuições no período de 22/12/2016 a 10/01/2017. Foram recebidas 10 respostas por meio do formulário destinado a contribuições técnico-científicas e 33 por meio do formulário para contribuições relativas a opiniões e experiências profissionais ou pessoais. O nível de concordância integral com a recomendação inicial da CONITEC foi de 100% para as contribuições técnicas, não se identificando fato novo que pudesse modificar a recomendação inicial favorável da comissão pela ampliação do tempo de tratamento ou que pudesse inviabilizar a análise apresentada nesse parecer. As experiências profissionais relatadas convergem com a proposta de ampliação do tempo de tratamento identificando o baixo aproveitamento, em termos de negativação viral, com o uso do esquema posológico de 12 semanas. RECOMENDAÇÃO FINAL: Aos 09 (nove) dias do mês de março de 2017 reuniu-se a Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde ­ CONITEC, regulamentada pelo Decreto nº 7.646, de 21 de dezembro de 2011, e os membros presentes deliberaram por unanimidade recomendar a ampliação do tempo de tratamento com sofosbuvir e daclatasvir de 12 para 24 semanas nos casos de Hepatite C genótipo 3 com cirrose hepática. DECISÃO: Ampliar o tempo de tratamento com sofosbuvir e daclastavir nos casos de hepatite C - genótipo 3 com cirrose hepática no âmbito do Sistema Único de Saúde - SUS, dada pela Portaria nº 18, publicada no DOU nº 77, do dia 24 de abril de 2017, seção 2, pág. 57.(AU)

Combination of Ledipasvir and Sofosbuvir for Treatment of Hepatitis C Virus Genotype 1 Infection: Systematic Review and Meta-Analysis

ABSTRACT Background and aim. The combination of Sofosbuvir (SOF) and Ledipasvir (LDV) has been lead to considerable enhancement of treatment of hepatitis C virus (HCV) genotype 1 infection. A meta-analysis of the currently available studies was undertaken with the aim to evaluate the antiviral efficacy of SOF/LDV therapy for 12 or 24 weeks with or without Ribavirin (RBV) in patients with HCV genotype 1 infection. Material and methods. In this meta-analysis, we searched databases including PubMed, Scopus, Science Direct and Web of Science using appropriate keywords. All papers which evaluated the efficacy of combination therapy of SOF/LDV with or without RBV for 12 or 24 weeks among patients with HCV genotype 1 infection were included. Results. The 20 published articles were assessed for eligibility and finally 10 articles pooling 2248 participants were included in this meta-analysis. Pooled SVR12 for four SOF/LDV regimens were 95% (95%CI = 93%-97%) for 12 weeks of treatment with SOF/LDV, 97% (95%CI = 95%-98%) for 24 weeks of treatment with SOF/LDV, 96% (95%CI = 94%-97%) for 12 weeks of treatment with SOF/ LDV/RBV and 98% (95%CI = 97%-99%) for 24 weeks of treatment with SOF/LDV/RBV. Only in treatment regimen of SOF/LDV for 12 weeks, cirrhosis had a significant effect on the SVR12 (OR = 0.21, 95%CI = 0.07-0.66). Furthermore, NS5A resistance-associated substitutions at baseline were associated with decrease in the rate of SVR (OR = 0.31, 95%CI = 0.2-0.5). Conclusions. The Interferon-free regimen of SOF/LDV for 12 or 24 weeks with or without RBV is highly effective for treatment of patients with HCV genotype 1 infection.

Rapid virological and End treatment response of patients treated with Sofosbuvir in Chronic Hepatitis C

Objective: To determine Rapid and End treatment response of patients treated with Sofosbuvir in Chronic Hepatitis C at tertiary care hospital

Methods: It was an observational study conducted at Memon Medical Institute from January 2016 to July 2017. The inclusion criteria for patients was 18 years of age or older, having chronic infection with HCV. Total=201 received sofosbuvir with or without interferon in our OPDs. Patients were categorized into Treatment naive, treatment experienced and decompensated chronic liver disease. Pregnant patients and those not willing to participate were excluded. Initially genotyping and Quantitative HCV RNA test was done

Results: A total of 201 subjects were included in the study with mean age of the patients was 46.22+/- 14.41 years. Of 201 patients, n= 131 [65.2%] chronic hepatitis C, compensated cirrhosis n= 47[23.4%], and with decompensated cirrhosis n=23[11.4%]. Most commonly genotype 3 n= 180 [89.6%] was present followed by genotype 1 n=9 [4.5%], genotype 2 n=1[0.5%], genotype 4 n=1[0.5%]

Of patients with genotype 3, 123 received dual therapy and 57 were given triple therapy. After one month of therapy HCV RNA by PCR, 200[99.5%] achieved RVR, 199[99%] achieved ETR and SVR achieved in 178[88.5%] while remaining 1 patient did not achieved RVR, 2 ETR and 12 patients did not achieved SVR and remaining 11 SVR lost follow up

Conclusion: Sofosbuvir has shown to be very effective and successful with achievement of virological response with little or no resistance in all genotypes mainly genotype 3 treated in our study population. The promising results of our study will aid in better outcomes and therefore help in eradication of the virus

Chronic hepatitis C treatment: a systematic review

Background: Chronic hepatitis C [CHC] infection affects almost 3% of the global population and can lead to cirrhosis, liver failure, and hepatocellular carcinoma in a significant number of those infected. Thus, there is a compelling need to develop and introduce new therapeutics with a direct-acting antiviral effect in order to target various stages of the HCV lifecycle for HCV eradication without concomitant interferon

Study Objective: to provide treatment recommendations for chronic HCV for specialists and generalists based on published evidence

Methods: A literature search of Web of Science, Scopus, Embase, Agricola, Cochrane Library, Cinahl Plus, Google Scholar, and Oaister was conducted from 1990 to 2016, records were filtered according to the Inclusion criteria and 27 hits were yielded

Results: Hepatitis C virus genotype 1 is more difficult to cure than genotype 2 or genotype 3. Patients with HCV genotype 1 should receive treatment with sofosbuvir + pegylated interferon + ribavirin because of the shorter duration of therapy and high rates of SVR [89%-90%]. Simeprevir + pegylated interferon + ribavirin is an alternative for patients with HCV genotype 1 [SVR, 79%-86%]. Patients with HCV genotypes 2 and 3 should receive therapy with sofosbuvir + ribavirin alone [SVR for genotype 2, 12 weeks' duration: 82%-93%; SVR for genotype 3, 24 weeks' duration, 80%-95%]. Patients with HIV-HCV coinfection and patients with compensated cirrhosis [ie, cirrhosis but preserved synthetic liver function] should receive the same treatment as HCV-monoinfected patients

Conclusion: A growing body of evidence suggests that recently developed HCV combined treatment modalities have transformed chronic HCV into a routinely curable disease being relatively available and well tolerated,which can potentially reduce the need for liver transplantation and reduce HCV-related mortality. Treatment protocol for genotype1 is based on a combined regimen of Pegylated interferons with ribavirin and sofosbuvir or simeprevir while Sofosbuvir with ribavirin alone should be used to treat patients infected with HCV genotypes 2 and 3. Patients coinfected with human immunodefiency virus and HCV genotype 1 should be treated for HCV with pegylated interferons, ribavirin, and sofosbuvir by a physician with experience in treating this particular group of patients and familiar with potential drug interactions

Management of direct antiviral agent failures

The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). Most HCV patients treated with these drugs achieve viral elimination, but 1% to 15% fail to attain this objective. Treatment failures are usually related to relapse, and less often to on-treatment viral breakthrough. HCV drug resistant associated substitutions are detected in most patients who do not eliminate the virus. The risk of developing these variants depends on host- and virus-related factors, the properties of the drugs used, and the treatment strategies applied. Patients who carry Resistant Associated Substitutions (RASs) may not obtain benefits from treatment, and are at a risk of disease progression. Whether HCV RASs persist depends on their type: NS3-4A variants often disappear gradually after DAA therapy is stopped, whereas NS5A variants tend to persist for more than 2 years. The best way to prevent emergence of resistant variants is to eliminate the virus at the first treatment using highly potent DAAs with genetic barriers to resistance. For those who fail an NS5A inhibitor, deferral of treatment is recommended pending the availability of additional data if they do not have cirrhosis or reasons for urgent re-treatment. If re-treatment is needed, the most commonly used strategy is sofosbuvir as backbone therapy plus a drug from a class other than that previously used, for 24 weeks. Unless it is contraindicated, weight-based ribavirin should also be added. If available, nucleotide-based (eg, sofosbuvir) triple or quadruple DAA regimens may be considered. The optimal treatment for patients who fail an NS5A inhibitor and those with multidrug-resistant variants remains to be defined, and research efforts should continue to focus on treatment for these patients.

Renewed 2015 Clinical Practice Guidelines for Management of Hepatitis C by Korean Association for the Study of the Liver; What Has Been Changed? - Treatment of Chronic Hepatitis C Genotype 2 and 3 / 대한소화기학회지

Ever since direct-acting antiviral agents (DAA) have been approved and released into the world, numerous studies on the efficacy, adverse effects and drug-drug interactions of interferon-free DAA combination therapy have been studied and published. With all oral DAA therapy showing sustained virological response rate of 80-90% with minimal adverse events, HCV eradication has now become a realistic goal. DAA combination treatments were approved and adapted to practice in Korea in 2015, and Korean Association for the Study of the Liver (KASL) has revised the guideline based on the systematic approach that reflects evidence-based medicine and expert opinions. In this article, new recommendations for treatment of chronic HCV genotype 2 and 3 infected patients will be introduced base on KASL practice guidelines for management of hepatitis C that has been updated in 2015.

Renewed 2015 Clinical Practice Guidelines for Management of Hepatitis C by Korean Association for the Study of the Liver; What Has Been Changed? - Treatment of Chronic Hepatitis C Genotype 1 / 대한소화기학회지

The introduction of direct-acting antiviral agents (DAAs) has markedly improved the sustained virological response (SVR) rates in patients with chronic hepatitis C. Currently, four classes of DAAs targeting three HCV proteins (NS3, NS5A, and NS5B) have been approved for treatment in many countries. Since drugs show advantages and disadvantages, use of a combination of two or more DAAs with different targets or addition of ribavirin in a difficult-to-treat patient shows an SVR rate of ~90% after 12 weeks of treatment or expanded treatment for 24 weeks. Various types of DAA are awaiting approval which will improve the treatment of chronic hepatitis C virus genotype 1 infection. However, high costs, drug resistance and interactions between various drugs remain to be overcome. With further advances in the development of antiviral agents, it could be expected that in the near future, there will be DAAs that are affordable and cost effective, require shorter treatment duration, effective in a broad range of patients, and have less side effects and drug-drug interactions.