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.

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.

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

Protocolo clínico e diretrizes terapêuticas para hepatite C e coinfecções / Clinical protocol and therapeutic guidelines for hepatitis C and coinfections

INTRODUÇÃO: As hepatites virais são uma das maiores causas de transplantes hepáticos no mundo - com destaque para a hepatite C (HCV), um agravo que hoje afeta mais de 185 milhões de pessoas em todos os continentes. Inicialmente denominada hepatite não-A não-B, a hepatite C foi elucidada apenas em 1989, com a identificação de seu agente etiológico. Desde então, a infecção pelo HCV adquiriu especial relevância entre as causas de doença hepática particularmente entre pacientes portadores do HIV em terapia antirretroviral, grupo que apresenta importante morbimortalidade para o agravo. A história natural do HCV é marcada pela evolução silenciosa: muitas vezes, a doença é diagnosticada décadas depois da infecção. Os sinais e sintomas são comuns às demais doenças parenquimatosas crônicas do fígado e costumam manifestar-se apenas em fases mais avançadas da doença. Estas características também afetam negativamente o diagnóstico da infecção, contribuindo para os números de portadores assintomáticos em todo o mundo. OBJETIVOS: O novo Protocolo Clínico e Diretrizes Terapêuticas para Hepatite C e Coinfecções tem como objetivo oferecer, no âmbito do SUS, uma estratégia custo-efetiva para o tratamento da hepatite C - com novas terapêuticas, acesso flexibilizado, menores índices de efeitos adversos e maior expectativa de cura. Esta proposta inovadora foi pautada também em uma ampla negociação de preços para alcançar a sustentabilidade e o acesso universal à assistência no SUS. O novo PCDT também apresenta uma proposta de cuidado integral ao paciente portador de hepatite viral, além de tratamentos que permitem melhor assistência e ampliação da capacidade do SUS. Assim, são objetivos desta publicação: -Estabelecer novas diretrizes terapêuticas nacionais e orientar os profissionais de saúde no manejo da hepatite C e coinfecções, visando estabelecer uma política baseada nas melhores evidências da literatura científica; -Promover assistência humanizada e especializada; -Buscar melhor qualidade na assistência e uso racional do arsenal terapêutico e demais insumos estratégicos; -Garantir melhores resultados em saúde pública e a sustentabilidade do acesso universal ao tratamento; -Reduzir a probabilidade de evolução para insuficiência hepática e câncer hepático. METODOLOGIA: Com o intuito de apresentar as melhores evidências científicas publicadas e as estratégias estabelecidas, realizou-se a revisão de protocolos internacionais (American Association for the Study of Liver Diseases, 2014; National Institute for Health and Care Excellence; The European Association for the Study of the Liver, 2015; Asian Pacific Association for the Study of the Liver, 2012; World Health Organization, 2014) e de literatura científica. As recomendações deste Protocolo Clínico e Diretrizes Terapêuticas para a Hepatite C e Coinfecções foram pesquisadas nas bases de dados MEDLINE, com o termo de busca "("Hepatitis C/drug therapy"[Mesh] OR "Hepatitis C/therapy"[Mesh])" e com os filtros "Clinical Conference, Clinical Trial (I, II, III, IV), Consensus Development Conference, Evaluation Studies, Guideline, Meta-Analysis, Multicenter Study, Practice Guideline, Randomized Controlled Trial, Review, Systematic Reviews" e "Humans" e data de publicação nos últimos cinco anos; e a base de dados LILACS, com o descritor "hepatite C". Esta busca resultou em 5.336 e 122 publicações, respectivamente. Complementou-se esta pesquisa com uma revisão sistemática realizada pelo Departamento de Gestão e Incorporação de Tecnologias em Saúde (DGITS/SCTIE/MS), que identificou as últimas evidências de estudos clínicos realizados com os medicamentos propostos neste documento. (Departamento de Gestão e Incorporação de Tecnologias no SUS, 2015) Bases de dados consultadas pelo DGITS/SCTIE/MS: MEDLINE, Cochrane Collaboration, DARE, Central, Clinicaltrials.gov e anais dos últimos eventos científicos internacionais em hepatites virais. CONSULTA PÚBLICA: A consulta pública para a aprovação do Protocolo Clínico e Diretrizes Terapêuticas para Hepatite C e Coinfecções foi realizada entre os dias 22 de junho e 01 de julho de 2015. Foram recebidas 53 contribuições durante a consulta pública. Somente são consideradas contribuições de consulta pública aquelas que foram encaminhadas no período estipulado em formulário próprio. As 53 contribuições foram analisadas pelo Departamento de DST, Aids e Hepatites Virais, responsável pelo programa/ação de que trata o protocolo e pelo Plenário da CONITEC, tendo sido agrupadas por tema. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na reunião do plenário do dia 02/07/2015 deliberaram, por unanimidade, recomendar a aprovação do Protocolo Clínico e Diretrizes Terapêuticas para Hepatite viral C crônica. DECISÃO: Portaria nº 37, de 24 de julho de 2015 - Torna pública a decisão de aprovar o Protocolo Clínico e Diretrizes Terapêuticas (PCDT) para Hepatite viral C crônica no âmbito do Sistema Único de Saúde - SUS.