Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3) and 50% (geno 3 type 1) were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

Distribution of hepatitis C virus genotypes among different exposure categories in the State of Pará, Brazilian Amazon / Distribuição dos genótipos do vírus da hepatite C em diferentes categorias de exposição no Estado do Pará, Amazônia Brasileira

INTRODUCTION: Epidemiological studies concerning HCV genotypic distribution in the Brazilian Amazon are scarce. Thus, this study determined the patterns of distribution of HCV genotypes among different exposure categories in the State of Pará, Brazilian Amazon. METHODS: A cross-sectional study was conducted on 312 HCV-infected individuals belonging to different categories of exposure, who were attended at the HEMOPA, CENPREN and a private hemodialysis clinic in Belém. They were tested for HCV antibodies using an immunoenzymatic test, RNA-HCV, using real-time PCR and HCV genotyping through phylogenetic analysis of the 5' UTR. The population groups were epidemiologically characterized according to data collected in a brief interview or medical consultation. RESULTS: Genotype 1 predominated in all the different categories of HCV exposure. HCV genotypic distribution among blood donors comprised genotypes 1 (94 percent) and 3 (6 percent). All patients with chronic hematologic diseases had HCV genotype 1. The genotypic distribution in illicit-drug users comprised genotypes 1 (59.6 percent) and 3 (40.4 percent). In patients under hemodialysis, genotypes 1 (90.1 percent), 2 (3.3 percent), and 3 (6.6 percent) were detected. Finally, the frequency of genotypes 1 and 3 was significantly different between the groups: BD and DU, PUH and DU, PUH and PCHD and PCHD and DU. CONCLUSIONS: The genotypic frequency and distribution of HCV in different categories of exposure in the State of Pará showed a predominance of genotype 1, regardless of the possible risk of infection.

INTRODUÇÃO: Estudos epidemiológicos sobre a distribuição genotípica do HCV na Amazônia Brasileira são escassos. Baseado nisto, determinamos o padrão de distribuição genotípica do HCV em diferentes categorias de exposição no Estado do Pará, Amazônia Brasileira. MÉTODOS: Estudo transversal foi realizado com 312 indivíduos infectados pelo HCV, pertencentes a diferentes categorias de exposição atendidas pelo HEMOPA, CENPREN e uma clínica privada de hemodiálise em Belém. Eles foram testados quanto à presença de anticorpos anti-HCV por teste imunoenzimático, RNA-HCV utilizando PCR em tempo real e genotipados através de análise filogenética da 5' UTR. Os grupos de populações foram caracterizados epidemiologicamente de acordo com dados coletados em breve entrevista ou consulta de prontuários médicos. RESULTADOS: Em todas as diferentes categorias de exposição ao HCV, foram encontrados predomínio do genótipo 1. A distribuição genotípica do HCV em doadores de sangue (BD) foi constituída pelos genótipos 1 (94 por cento) e 3 (6 por cento). Todos os pacientes com doenças hematológicas crônicas (PCHD) possuíam genótipo 1. A distribuição genotípica em usuários de drogas ilícitas (DU) foi constituída pelos genótipos 1 (59,6 por cento) e 3 (40,4 por cento). Em pacientes em hemodiálise (PUH) foram detectados os genótipos 1 (90,1 por cento), 2 (3,3 por cento) e 3 (6,6 por cento). Finalmente, a frequência entre os genótipos 1 e 3 foi significativamente diferente entre os grupos: BD e DU, PUH e DU, PUH e PCHD, e PCHD e DU. CONCLUSÕES: A frequência genotípica e distribuição de HCV em diferentes categorias de exposição no Estado do Pará mostraram predominância do genótipo 1, independentemente do possível risco de infecção.

Likely transmission of hepatitis C virus through sharing of cutting and perforating instruments in blood donors in the State of Pará, Northern Brazil / Possível transmissão do vírus da hepatite C por compartilhamento de materiais cortantes e perfurantes em doadores de sangue no Estado do Pará, Norte do Brasil

We determined the risk factors for HCV infection in blood donors in the State of Pará, Northern Brazil. We examined 256 blood donors seen at the Blood Bank of Pará State between 2004 and 2006. They were divided into two groups, depending on whether they were infected with HCV or not; 116 donors were infected with HCV, while the other 140 were free of infection. The HCV-RNA was detected by real-time PCR. All of the participants filled out a questionnaire about possible risk factors. The data were evaluated using simple and multiple logistic regressions. The main risk factors for HCV were found to be use of needles and syringes sterilized at home (OR = 4.55), invasive dental treatment (OR = 3.08), shared use of razors at home (OR = 1.99), sharing of disposable razors in barbershops, beauty salons, etc. (OR = 2.34), and sharing manicure and pedicure material (OR = 3.45). Local and regional health authorities should educate the public about sharing perforating and cutting materials at home, in barber/beauty shops, and in dental clinics as risk factors for HCV infection.

Nós determinamos os fatores de risco à infecção pelo HCV em doadores de sangue no Estado do Pará, Brasil. Foram analisados 256 doadores de sangue atendidos na Fundação HEMOPA de 2004 a 2006, sendo divididos em dois grupos: infectados e não-infectados. O diagnóstico foi realizado por PCR em tempo real. Todos os participantes responderam a questionário sobre possíveis fatores de risco, sendo a modelagem estatística feita por regressão logística simples e múltipla. Os fatores de risco à infecção foram: uso de agulhas e seringas de vidros esterilizadas em casa (OR = 4,55), realização de tratamento dentário invasivo (OR = 3,08), compartilhamento de lâminas em domicílio (OR = 1,99), compartilhamento de lâminas descartáveis em barbearias, salões de beleza (OR = 2,34), e compartilhamento de material de manicure e pedicure (OR = 3,45). As autoridades de saúde devem conscientizar a população sobre o compartilhamento de materiais perfuro-cortantes em domicílio, salões de beleza e consultórios dentários como fatores de risco à infecção.

Prevalence and genotyping of hepatitis C virus in blood donors in the state of Pará, Northern Brazil

Given the scarcity of epidemiological information on hepatitis C virus (HCV) infection in Northern Brazil, we determined the prevalence and genotypic frequency in blood donors in the state of Pará (PA). Blood samples from all of the blood donors at the Fundação HEMOPA (blood bank of PA) from 2004-2006 were screened for the presence of antibodies to anti-HCV and samples seroreactive to anti-HCV were further tested for HCV RNA using real-time PCR. In total, 116 HCV-RNA samples were genotyped, based on maximum likelihood phylogenetic analyses, using BioEdit, Modelgenerator, PHYML and FigTree software. The population consisted of 242,726 volunteers who donated blood from 2004-2006; the most common subgroup was males between the ages of 18-29 years old (37.30 percent). Within the whole group, 1,112 blood donors (0.46 percent) had indeterminate or positive serology; among these, 28.78 percent were males whose ages ranged from 18-29 years. A diagnosis of chronic HCV infection was confirmed for 304 donors (60.20 percent males; 66.45 percent were 30-49 years old), resulting in a prevalence of HCV RNA in 0.13 percent of the samples (304 of 242,726). HCV genotyping revealed a high frequency of genotype 1 (108/116) followed by genotype 3 (8/116). This study found HCV infection to be relatively infrequent in PA; genotype 1 was most commonly isolated. This information can help guide prevention and control policies aimed at efficient diagnosis and control measures.