RESUMO
SUMMARY OBJECTIVE The recent development of direct-acting antiviral agents (DAAs) has dramatically changed the treatment of chronic hepatitis C, and interferon-based regimes have become a poor treatment choice in clinical practice. Today DAAs offer shorter, well-tolerated, highly effective curative therapies. This study aimed to evaluate the effectiveness and safety of DAAs in patients with end-stage renal disease and HCV genotype 1 infection in real clinical practice. METHODS Thirty-six patients who attended our clinic, were diagnosed with chronic hepatitis C (CHC), undergoing hemodialysis, and fulfilled the criteria of age >18 years, genotype 1 infection, with a detectable HCV RNA level were considered for the study. Patients with GT1a infection received OBV/PTV/r plus DSV plus RBV for 12 weeks; GT1b infected patients received this regimen without RBV for 12 weeks. RESULTS The study was conducted on 33 patients. The mean age was 52.30 ±13.77 years, and 70 % of them were male. By the fourth week of treatment, HCV RNA levels decreased below 15 IU/ml in all patients. Sustained virologic response (SVR) 12 rate was 100%. Nine patients had side effects during treatment. Of the patients with side effects, 89.9% were in group 1a and 11.1% in group 1b. CONCLUSION In this study, treatment with OBV/PTV/r and DSV with or without RBV resulted in high rates of sustained virologic response in HCV GT1-infected patients with end-stage renal disease (ESRD). SVR was achieved in all patients with few side effects.
RESUMO O recente desenvolvimento de agentes antivirais de ação direta (DAAs) mudou drasticamente o tratamento da hepatite C crônica, e os regimes livres de interferon tornaram-se pobres escolhas para tratamento na prática clínica. Hoje os DAAs oferecem terapias curativas mais curtas, bem toleradas e altamente eficazes. O objetivo deste estudo foi avaliar a eficácia e segurança dos DAAs em pacientes com doença renal em estágio terminal e infecção pelo genótipo 1 do HCV na prática clínica real. MÉTODOS Trinta e seis pacientes, que se inscreveram em nossa clínica com diagnóstico de hepatite C crônica (CHC), inclusive no programa de hemodiálise, e preencheram os critérios de idade >18 anos, foram considerados para infecção pelo genótipo 1 com nível detectável de RNA do HCV. Os pacientes com infecção por GT1a receberam OBV/PTV/r mais DSV mais RBV por 12 semanas. Os pacientes infectados com GT1b receberam este regime sem RBV por 12 semanas. RESULTADOS O estudo foi realizado em 33 pacientes. A idade média foi de 52,30±13,77 anos e 70% deles eram do sexo masculino. Na semana 4 do tratamento, os níveis de ARN do VHC diminuíram para menos de 15 UI/ml em todos os pacientes. A taxa de resposta virológica sustentada (RVS) 12 foi de 100%. Nove pacientes apresentaram efeitos colaterais durante o tratamento. Dos pacientes com efeitos colaterais, 89,9% estavam no grupo 1a e 11,1% no grupo 1b. CONCLUSÃO Neste estudo, o tratamento com OBV/PTV/r e DSV com ou sem RBV resultou em altas taxas de resposta virológica sustentada em pacientes infectados pelo VGC GT1 com doença renal em estágio final (ESRD). A RVS foi alcançada em todos os pacientes com poucos efeitos colaterais.
Assuntos
Humanos , Masculino , Feminino , Adulto , Idoso , Adulto Jovem , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Falência Renal Crônica/virologia , Ribavirina/uso terapêutico , Sulfonamidas/uso terapêutico , Fatores de Tempo , Uracila/análogos & derivados , Uracila/uso terapêutico , RNA Viral/sangue , Carbamatos/uso terapêutico , Resultado do Tratamento , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Estatísticas não Paramétricas , Ritonavir/uso terapêutico , Hepatite C Crônica/virologia , Compostos Macrocíclicos/uso terapêutico , Quimioterapia Combinada , Resposta Viral Sustentada , Genótipo , Anilidas/uso terapêutico , Pessoa de Meia-IdadeRESUMO
Objetivos: La terapia ideal para la hepatitis crónica C consiste en el uso de drogas antivirales de acción directa (DAA). En el Perú la experiencia en vida real con DAA no se conoce, por lo que el objetivo del presente estudio es reportar la alta eficacia terapéutica con estos esquemas. Material y métodos: Mediante correo electrónico se invitó a participar a través de una encuesta a médicos hepatólogos a nivel nacional. Se incluyeron los datos de 4 médicos. Los resultados fueron analizados con estadística descriptiva. Resultados: Se incluyeron 63 pacientes, la edad promedio fue 59 años, varones fueron 49,21%, cirrosis estuvo presente en el 49,21% (31/63), 34,92% había sido no respondedor a terapia con PEGIFN/RBV. El Genotipo 1 estuvo presente en 93,65% de casos, siendo el 1a el predominante (58,73%). Solo hubo dos casos de genotipo 2 y uno de genotipo 3. Se utilizaron 10 esquemas de combinación con DAA, siendo los más eficaces, Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/ Ribavirina y Sofosbuvir/Simeprevir, en todos ellos se logró Respuesta Viral Sostenida (RVS) de 100%. Con los otros 7 esquemas la RVS fue menor a 90% o solo se había incluido uno o dos pacientes. La tolerancia a la terapia fue adecuada y todos los pacientes culminaron la terapia. Conclusiones: En vida real los esquemas de terapia antiviral para hepatitis C con DAA tienen alta eficacia y seguridad. Las mejores respuestas se obtuvieron con Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina y Sofosbuvir/Simeprevir. Esta data puede ser útil para considerar estrategias de tratamiento con el enfoque de salud pública.
Objective: The ideal therapy for chronic hepatitis C is the use of direct acting antivirals (DAA). In Peru there is no data in this aspect, in that sense it is necessary to report real life experience with these drugs. Material and methods: A digital survey was sent through e-mail to hepatologists, and the data of four is considered in this study. Statistical analysis was descriptive. Results: We included 63 patients, mean age was 59 years, 49.21% were male, cirrhosis was present in 49.21%, and 34.92% was non-responder to PEGIFN and Ribavirin. Genotype 1 was present in 93.65%, and subtype 1a was 58.73%, there were only 2 cases with Gt 2 and one with Gt 3. There were 10 different DAA combinations used, and the most effective were Sofosbuvir/ Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir, in all these cases the Sustained Viral Response (SVR) was 100%. The other combinations had SVR < 90% or only 1-2 patients included. All patients tolerated treatments and no serious adverse events occurred. Conclusions: In real life antiviral treatment for hepatitis C with AAD is effective and well tolerated. The best SVR was obtained with Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir. This report may be useful to consider treatment strategies with focus in public health.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Antivirais/administração & dosagem , Peru , Resultado do Tratamento , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Avaliação de Medicamentos , Quimioterapia Combinada , Genótipo , Cirrose Hepática/etiologia , Cirrose Hepática/patologiaRESUMO
Abstract INTRODUCTION: HPA polymorphism has been associated with HCV presence and fibrosis progression in chronic hepatitis C. However, it is unknown if there is an association between HPA-1 polymorphism and hepatocellular carcinoma (HCC). Therefore, this study aimed to evaluate HPA-1 polymorphism in the presence of HCC. METHODS: PCR-SSP was used to perform HPA genotyping on 76 HCV-infected patients. RESULTS: There was no association between patients with and without HCC. There was significant difference in HPA-1 genotypic frequency distribution between HCC and F1/F2 fibrosis degree. CONCLUSIONS: The HPA-1a/1b polymorphism appears to be more associated with liver damage progression than with HCC presence.
Assuntos
Humanos , Masculino , Feminino , Antígenos de Plaquetas Humanas/genética , Carcinoma Hepatocelular/virologia , Hepatite C Crônica/genética , Neoplasias Hepáticas/virologia , Prognóstico , Marcadores Genéticos , Reação em Cadeia da Polimerase , Fatores de Risco , Carcinoma Hepatocelular/genética , Progressão da Doença , Hepatite C Crônica/virologia , Genótipo , Neoplasias Hepáticas/genética , Pessoa de Meia-IdadeRESUMO
ABSTRACT BACKGROUND: Chronic hepatitis C (CHC) can progress to cirrhosis and its complications as hepatocellular carcinoma, leading to morbidity and mortality. To know the profile of patients with CHC virus is fundamental to optimize management. OBJECTIVE: To describe the profile of patients with CHC in a public health program in Southern Brazil. METHODS: A retrospective study was carried out in patients with CHC who underwent treatment against hepatitis C virus in a dispensation and pharmaceutical assistance center of the Public Health Department of the State of Rio Grande do Sul, South Brazil. All medical records of patients attended between December/2015 and December/2016 were evaluated. RESULTS: A total of 1,431 records of patients with CHC were evaluated. Males were the most prevalent (802; 56%) patients. The mean age was 58.6±9.9 years, ranging from 18 to 89 years. Genotype 1 was the most frequent (866;60.5%) of the patients. Ninety (6.3%) patients were transplanted from a solid organ, and of these, 73 (5.1%) were transplanted from the liver. The fibrosis evaluation was performed in 1,300 (90.8%) patients. Of these, 566 (39.6%) were evaluated through liver biopsy. Regarding the degree of fibrosis, 779 (54.4%) presented fibrosis grade 4 (cirrhosis). The genotype 3 was the most associated with fibrosis grade 4, and genotype 1 was associated with high viral load. CONCLUSION: The present study made possible the evaluation of the characteristics of patients with CHC in a public health program in South Brazil. There was a predominance of CHC in males, and the mean age was 59 years. They presented a predominance of genotype 1, higher viral load in patients with genotype 1 and greater degree of fibrosis in patients with genotype 3.
RESUMO CONTEXTO: A hepatite crônica C (HCC) pode evoluir para cirrose e suas complicações como carcinoma hepatocelular, acarretando morbimortalidade. Conhecer o perfil dos pacientes portadores do vírus da HCC é fundamental para o melhor manejo do tratamento. OBJETIVO: Descrever o perfil dos pacientes portadores de HCC em um programa de saúde pública do sul do Brasil. MÉTODOS: Foi realizado um estudo retrospectivo onde foram incluídos os pacientes com HCC que realizaram o tratamento contra o vírus C em um polo de dispensação e assistência farmacêutica da Secretaria Estadual da Saúde do Estado do Rio Grande do Sul, Brasil. Foram avaliados todos os prontuários dos pacientes tratados entre dezembro/2015 e dezembro/2016. RESULTADOS: Foram avaliados 1.431 registros de pacientes portadores de HCC. O sexo masculino foi o mais prevalente (802; 56%) pacientes. A idade média dos pacientes foi de 58,6±9,9 anos, com variação de 18 a 89 anos. O genótipo 1 foi o mais frequente, em 866 (60,5%) dos pacientes. Noventa (6,3%) pacientes eram transplantados de órgão sólido, sendo que 73 (5,1%) eram transplantados de fígado. A avaliação de fibrose foi realizada em 1.300 (90,8%) pacientes. Dentre estes, 566 (39,6%) foram avaliados através de biópsia hepática. Em relação ao grau de fibrose, 779 (54,4%) apresentavam fibrose grau 4 (cirrose). Os genótipos foram analisados em relação aos diferentes graus de fibrose, sendo observado que o genótipo 3 está associado com o grau 4 de fibrose. O genótipo 1 está associado com alta carga viral. CONCLUSÃO: O presente estudo possibilitou a avaliação do perfil dos pacientes portadores de HCC em um programa de saúde pública do Brasil. Houve uma predominância de HCC no sexo masculino, e a média de idade foi de 59 anos. Apresentam um predomínio do genótipo 1, maior carga viral nos pacientes portadores do genótipo 1 e maior grau de fibrose nos portadores de genótipo 3.
Assuntos
Humanos , Masculino , Feminino , Adulto , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Hepatite C Crônica/epidemiologia , Índice de Gravidade de Doença , Brasil/epidemiologia , Saúde Pública , Estudos Retrospectivos , Progressão da Doença , Carga Viral , Hepatite C Crônica/virologia , Genótipo , Pessoa de Meia-IdadeRESUMO
Abstract INTRODUCTION This study reports the genotype prevalence of hepatitis C virus (HCV) in Pará, Brazil. METHODS: A retrospective cross-sectional study was conducted on 344 plasma samples sent to the Lacen-Pará for diagnostics by molecular techniques. RESULTS: HCV genotypes identified in the different regions of Pará were 1b (47.7%), 3 (23.3%), 1a (18%), and 2 (4.4%). Genotype 1 occurred in 41.6% of men and 30.8% of women in the 18-86-year-old group. CONCLUSIONS: Genotype 1 is the most predominant in Pará, which reinforces the idea of its relationship with late-diagnosed chronic infection.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Hepacivirus/genética , Hepatite C Crônica/epidemiologia , Brasil/epidemiologia , RNA Viral/genética , Prevalência , Estudos Transversais , Estudos Retrospectivos , Hepatite C Crônica/virologia , Genótipo , Pessoa de Meia-IdadeRESUMO
ABSTRACT BACKGROUND: Insulin resistance and diabetes mellitus are common extrahepatic manifestations of chronic hepatitis C (HCV). Insulin resistance assessed by HOMA-IR is associated with low rates of sustained virological response, especially in HCV genotype 1 positive patients treated with peginterferon/ribavirin. The effect of insulin resistance on sustained virologic response in HCV genotype 3 positive patients who were treated with peginterferon/ribavirin still remains unclear. OBJECTIVE: To evaluate the impact of insulin resistance on sustained virological response in HCV genotype 3 patients treated with peginterferon/ribavirin. METHODS: A retrospective multicenter study was performed to evaluate the impact of insulin resistance on sustained virological response in non-diabetic HCV genotype 3 positive patients treated with peginterferon and ribavirin. A total of 200 HCV genotype 3 positive patients were enrolled in the study. All patients were non-diabetic. Each patient had a HOMA-IR value measured before the initiation of HCV treatment with peginterferon/ribavirin. The treatment duration was at least 24 weeks. The HOMA-IR cut-off was defined in the study as ≥2.5 due to the coefficient of correlation with sustained virological response of 0.202 (P=0.004). RESULTS: Univariate analysis showed that age, aspartate aminotransferase, platelets, stage of fibrosis and HOMA-IR were predictors of sustained virological response. However multivariate analysis showed advanced fibrosis [OR=2.01 (95%CI: 0.986-4.119) P=0.05] and age [OR=1.06 (95%CI: 1.022-1.110) P=0.002] as negative predictors of sustained virological response. CONCLUSION: In this retrospective multicenter study of non-diabetic HCV genotype 3 positive patients, insulin resistance was not associated with the sustained virological response in patients who were treated with peginterferon/ribavirin.
RESUMO CONTEXTO: A resistência insulínica e o diabetes mellitus são frequentes manifestações extra-hepáticas da hepatite C crônica. A resistência insulínica medida pelo HOMA-IR está associada a uma baixa taxa de resposta virológica sustentada, principalmente em pacientes portadores de hepatite C crônica genótipo 1 tratados com peginterferon/ribavirina. Em relação aos pacientes portadores de hepatite C crônica genótipo 3 tratados com peginterferon/ribavirina, a influência da resistência insulínica na resposta virológica sustentada ainda não está esclarecida. OBJETIVO: Avaliar a influência da resistência insulínica na resposta virológica sustentada em pacientes portadores de hepatite C crônica genótipo 3. MÉTODOS: Estudo multicêntrico retrospectivo foi realizado para avaliar a influência da resistência insulínica na resposta virológica sustentada em pacientes não-diabéticos portadores de hepatite C crônica genótipo 3 tratados com peginterferon/ribavirina. Um total de 200 pacientes portadores de hepatite C crônica genótipo 3 foi incluído no estudo. Todos os pacientes eram não diabéticos e apresentavam medida de HOMA-IR antes do início do tratamento da hepatite C crônica com peginterferon/ribavirina. A duração do tratamento foi de pelo menos 24 semanas. O cut-off de HOMA-IR foi definido para este estudo como ≥2,5 devido ao coeficiente de correlação com a resposta virológica sustentada de 0,202 (P=0,004). RESULTADOS: Na análise univariada, idade, aspartato aminotransferase, plaquetas, grau de fibrose e HOMA-IR foram preditores de resposta virológica sustentada. No entanto, na análise multivariada, apenas fibrose avançada [OR=2,01 (95%IC: 0,986-4,119) P=0,05] e idade [OR=1,06 (95%IC: 1,022-1,110) P=0,002] estavam relacionados como preditores negativo de resposta virológica sustentada. CONCLUSÃO: Neste estudo multicêntrico, retrospectivo, em pacientes não diabéticos portadores de hepatite C genótipo 3, a resistência insulínica não estava associada à resposta virológica sustentada em pacientes tratados com peginterferon/ribavirina.
Assuntos
Humanos , Masculino , Feminino , Antivirais/uso terapêutico , Ribavirina/uso terapêutico , Resistência à Insulina/fisiologia , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Estudos Retrospectivos , Interferon-alfa/uso terapêutico , Carga Viral , Hepatite C Crônica/virologia , Quimioterapia Combinada , Genótipo , Homeostase/fisiologiaRESUMO
Abstract INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.
Assuntos
Humanos , Masculino , Feminino , Adulto , Idoso , Antivirais/administração & dosagem , Inibidores de Proteases/administração & dosagem , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Oligopeptídeos/efeitos adversos , Antivirais/efeitos adversos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Inibidores de Proteases/efeitos adversos , Ribavirina/administração & dosagem , Ribavirina/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Prolina/administração & dosagem , Prolina/análogos & derivados , Prolina/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Interferon alfa-2 , Genótipo , Pessoa de Meia-IdadeRESUMO
ABSTRACT Background and aims: Hepatitis E virus infection in patients with underlying chronic liver disease is associated with liver decompensation and increased lethality. The seroprevalence of hepatitis E virus in patients with chronic hepatitis C in Brazil is unknown. This study aims to estimate the seroprevalence of hepatitis E virus in patients with chronic hepatitis C and to describe associated risk factors. Methods: A total of 618 patients chronically infected with hepatitis C virus from three reference centers of São Paulo, Brazil were included. Presence of anti-HEV IgG was assessed by enzyme-linked immunosorbent assay (WANTAI HEV-IgG ELISA). Results: Out of the 618 patients tested, 10.2% turned out positive for anti-HEV IgG (95% CI 8.0-12.8%). Higher seroprevalence was found independently associated with age over 60 years (OR = 2.04; p = 0.02) and previous contact with pigs (OR = 1.99; p = 0.03). Conclusions: Patients with chronic hepatitis C are under risk of hepatitis E virus superinfection in São Paulo. Contact with pigs is a risk factor for the infection, suggesting a possible zoonosis with oral transmission.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/imunologia , Hepatite E/epidemiologia , Hepatite C Crônica/epidemiologia , Brasil/epidemiologia , Imunoglobulina G/sangue , Estudos Soroepidemiológicos , Hepatite C Crônica/virologiaRESUMO
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.
Assuntos
Humanos , Masculino , Feminino , Adulto , Idoso , Inibidores de Proteases/administração & dosagem , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Ribavirina/administração & dosagem , Prolina/administração & dosagem , Prolina/análogos & derivados , Protocolos Clínicos , Interferons/administração & dosagem , Resultado do Tratamento , Hepatite C Crônica/virologia , Quimioterapia Combinada , Resposta Viral Sustentada , Genótipo , Pessoa de Meia-IdadeRESUMO
Abstract Hepatitis C is a worldwide endemic disease. However, hepatitis C virus genotype 4 (HCV GT-4) has rarely been reported in Brazil. HCV GT-4 demonstrates high sustained virological response (SVR). Here, we report the case of a 62-year-old HCV GT-4 positive woman complaining of a headache, nausea, and arthralgia. The patient was treated according to the protocol for genotype 4 (12 weeks administration of 400mg sofosbuvir and 60mg daclatasvir daily) and achieved SVR. Although this is not an Amazonas autochthonous case, the presence of genotype 4 is rarely reported in the region.
Assuntos
Humanos , Feminino , Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Sofosbuvir/administração & dosagem , Imidazóis/administração & dosagem , Resultado do Tratamento , Hepacivirus/genética , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Quimioterapia Combinada , Resposta Viral Sustentada , Genótipo , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Antivirais/administração & dosagem , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Inibidores de Proteases/administração & dosagem , Brasil , Estudos Transversais , Genótipo , Hepatite C Crônica/virologia , Interferon-alfa/administração & dosagem , Oligopeptídeos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Prolina/administração & dosagem , Prolina/análogos & derivados , Proteínas Recombinantes/administração & dosagem , RNA Viral/genética , Resultado do TratamentoRESUMO
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.
Assuntos
Humanos , Inibidores de Proteases/economia , Inibidores de Proteases/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/economia , Hepatite C Crônica/tratamento farmacológico , Simeprevir/economia , Simeprevir/uso terapêutico , Sofosbuvir/economia , Sofosbuvir/uso terapêutico , Ambulatório Hospitalar/economia , Inibidores de Proteases/efeitos adversos , Indução de Remissão , Colorado , Resultado do Tratamento , Análise Custo-Benefício , Hepacivirus/enzimologia , Hepacivirus/genética , Modelos Econômicos , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Quimioterapia Combinada , Simeprevir/efeitos adversos , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , GenótipoRESUMO
Abstract: Background. Daclatasvir and asunaprevir dual therapy is approved for the treatment of HCV genotype 1b infection in several countries. Aim. To evaluate the efficacy and safety of daclatasvir and asunaprevir dual therapy in Turkish patients. Material and methods. Sixty-one patients with HCV genotype 1b were enrolled in the Turkish early access program. Most of the patients were in difficult-to-treat category. Patients were visited at each 4 week throughout the follow-up period. Laboratory findings and adverse events were recorded at each visit. Results. Fifty-seven of 61 enrolled patients completed 24 weeks of treatment. Two patients died as a result of underlying diseases at 12-14th weeks of treatment. Two patients stopped the treatment early as a consequence of virological breakthrough, and 2 patients had viral relapse at the post-treatment follow-up. Overall SVR12 rates were 90% (55/61) and 93.2% (55/59) according to intention-to-treat (ITT) and per protocol (PP) analysis respectively. In ITT analysis, SVR12 was achieved by 93% (13/14) in relapsers, 80% (12/15) in interferon-ineligible patients and 91% (20/22) in previous nonresponder patients. SVR12 rates were 86.5% and 91.4% in patients with cirrhosis according to ITT and PP analysis respectively. SVR12 was 95.8% in non-cirrhosis group in both analysis. Patients with previous protease inhibitor experience had an SVR12 of 87.5%. Common adverse events developed in 28.8% of patients. There were no treatment related severe adverse event or grade-4 laboratory abnormality. Conclusions. Daclatasvir and asunaprevir dual therapy is found to be effective and safe in difficult-to-treat Turkish patients with HCV genotype 1b infection.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Antivirais/uso terapêutico , Sulfonamidas/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Acessibilidade aos Serviços de Saúde , Imidazóis/uso terapêutico , Isoquinolinas/uso terapêutico , Antivirais/economia , Antivirais/efeitos adversos , Sulfonamidas/economia , Sulfonamidas/efeitos adversos , Fatores de Tempo , Turquia , RNA Viral/genética , Avaliação de Programas e Projetos de Saúde , Resultado do Tratamento , Custos de Medicamentos , Análise Custo-Benefício , Hepacivirus/genética , Carga Viral , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/economia , Hepatite C Crônica/virologia , Quimioterapia Combinada , Genótipo , Acessibilidade aos Serviços de Saúde/economia , Imidazóis/economia , Imidazóis/efeitos adversos , Isoquinolinas/economia , Isoquinolinas/efeitos adversosRESUMO
Resumen Introducción: La infección crónica por el virus de la hepatitis C es un problema de salud pública y se estima que hay más de 180 millones de personas infectadas en el mundo. En Colombia no se conoce la epidemiología de la infección ni los genotipos virales más frecuentes. Objetivo. Describir los genotipos y subtipos del virus de la hepatitis C en pacientes colombianos infectados. Materiales y métodos: Se hizo un estudio descriptivo y retrospectivo de pruebas realizadas en dos laboratorios de referencia nacional, entre el 2003 y el 2015, mediante electroforesis en geles de poliacrilamida (Polyacrylamide Gel Electrophoresis, PAGE) o reacción en cadena de la polimerasa en tiempo real (quantitative PCR, qPCR). Resultados. Se estudiaron 1.538 aislamientos del virus de la hepatitis C de 1.527 pacientes con una edad promedio de 53 años, de los cuales 70 % tenía entre 40 y 70 años y 52 % eran mujeres. El 57 % de las pruebas se ordenaron en la ciudad de Bogotá, y el 80 % de los casos provenía de los departamentos de Cundinamarca, Valle y Atlántico. Se encontró el genotipo 1 en 88,6 % de los casos, distribuido así: subtipo 1b, 70 %, subtipo 1a, 13,5 %, y no determinado, 5,1 % de los casos; el genotipo 2 se encontró en el 5,4 % de los casos, el 3, en el 2 %, y el 4, en el 4 %. Se encontraron genotipos mixtos en 0,8 % de la muestra. Conclusión: El genotipo 1 del virus de la hepatitis C es el que circula con mayor frecuencia en el país, con predominio del subtipo 1b.
Abstract Introduction: Chronic hepatitis C virus infection is a worldwide public health problem; it has been estimated that over 180 million people are infected with this virus worldwide. Its precise incidence and prevalence (i.e., epidemiology) and the most frequent circulating genotypes in Colombia are unknown. Objective: To describe the hepatitis C virus (HCV) genotypes and subtypes in infected Colombian patients. Materials and methods: We recovered the data on 1,538 HCV isolates from 1,527 patients in two Colombian reference laboratories typed by PAGE or qPCR. Results: Patients' mean age was 53 years; 70% of them were 40 to 70 years old, and 52%, females; 57% of all tests were ordered in Bogotá and 80% of cases were from Cundinamarca, Valle and Atlántico departments. Genotype 1 was detected in 88.6% of cases, distributed as follows: 70% subtype 1b, 13.5% subtype 1a and 5.1%, undetermined subtypes. Genotype 2 was found in 5.4% of the patients, genotype 3 in 2% and genotype 4 in 4%. Mixed genotypes were found in 0.8% of the samples. Conclusion: Genotype 1 is the most common HCV genotype circulating in Colombia, and subtype 1b the most frequent.
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Humanos , Reação em Cadeia da Polimerase/métodos , Hepacivirus/imunologia , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Prevalência , Colômbia/epidemiologia , Hepacivirus/classificação , GenótipoRESUMO
ABSTRACT Background Due to the high prevalence of co-infection by hepatitis C virus (HCV) and human immunodeficiency virus (HIV) and the severity of these infections, the understanding of the biological mechanisms involved in these processes, including viral behavior and host genetic profile, is of great importance for patient treatment and for public health policies.Some single nucleotide polymorphisms (SNPs) in the human genome, such as the SNP rs1045642 (C3435T) in the MDR1 gene, have been reported to be associated to the sustained virological response (SVR) to HCV treatment in HCV-HIV co-infected patients. Objective The present study analyzes the MDR1 gene C3435T polymorphism in HCV-HIV co-infected patients. Methods A total of 99 HCV-HIV patients were included in the study. The DNA was extracted from blood samples, and the SNP rs1045642 was assessed by Real Time PCR (qPCR). Risk factors for acquiring the virus and the SVR after HCV treatment with pegylated interferon-alpha and ribavirin were also analyzed. Results Among the patients, 54 (54.5%) were male and 45 (45.5%) were female. The average age was 46.1±9.8 years. The SVR after HCV treatment was 40%. The frequencies of MDR1 genotypes CC, CT and TT were 28.3%, 47.5% and 24.2%, respectively. Allele frequencies were 52% for the C allele and 48% for the T allele. No association was found for SNP rs1045642 (C3435T) regarding response to treatment (P=0.308). Conclusion - In this study, the C3435T polymorphism in the MDR1 gene appears not to be associated with SVR in HCV-HIV co-infected individuals.
RESUMO Contexto Em virtude da elevada prevalência da coinfecção pelos vírus da hepatite C (HCV) e da imunodeficiência humana (HIV) e às inúmeras complicações que esses vírus acarretam, é fundamental o maior entendimento do comportamento biológico dos mesmos. O polimorfismo de nucleotídeo único rs1045642 C3435T do gene de resistência a múltiplas drogas MDR1, no qual ocorre modificação do códon ATC para ATT, parece estar relacionado à resposta virológica sustentada ao tratamento do HCV em coinfectados HCV-HIV. Objetivo Mapear o polimorfismo C3435T do gene MDR1 em pacientes coinfectados HCV-HIV e correlacionar com dados clínicos e laboratoriais. Métodos Foram analisados 99 pacientes coinfectados HCV-HIV. A identificação molecular do polimorfismo de nucleotídeo único rs1045642 do gene MDR1 foi realizada pela técnica de PCR em tempo real (qPCR) alelo-específico com primers e sondas específicos para a identificação desse polimorfismo. Fatores de risco para a aquisição do HCV e a resposta virológica sustentada ao tratamento do HCV com interferon-alfa peguilado e ribavirina foram analisados. Resultados Dentre os pacientes avaliados, 54 (54,5%) eram do gênero masculino e 45 (45,5%) do gênero feminino. A média de idade foi de 46,1 anos (±9,8). As frequências dos genótipos CC, CT e TT foram 28,3%, 47,5% e 24,2% respectivamente, e as frequências alélicas foram 52% para alelo C e 48% para alelo T. Não houve associação entre o gene MDR1 e a resposta virológica sustentada (P=0,308). Conclusão Neste estudo, o polimorfismo C3435T no gene MDR1 não apresentou associação com a resposta virológica sustentada ao tratamento em indivíduos coinfectados HCV-HIV.
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Humanos , Masculino , Feminino , Infecções por HIV/genética , Genes MDR , Hepatite C Crônica/genética , Polimorfismo de Nucleotídeo Único , Antivirais/uso terapêutico , Ribavirina/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Estudos Transversais , HIV , Interferon-alfa/uso terapêutico , Hepacivirus , Carga Viral , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Coinfecção/virologia , Reação em Cadeia da Polimerase em Tempo Real , Genótipo , Pessoa de Meia-IdadeRESUMO
La Organización Mundial de la Salud estima que aproximadamente 170 millones de personas están crónicamente infectadas por el virus de la hepatitis C (VHC). En este estudio se evaluó la presencia de anticuerpos contra el VHC en pacientes remitidos durante enero de 2010 a febrero de 2013, al Laboratorio Regional de Salud Pública del Hospital Universitario Antonio Patricio de Alcalá en Cumaná, Venezuela. La presencia de anticuerpos se hizo mediante dos ensayos de ELISA y se determinaron los genotipos circulantes a través de análisis filogenéticos de fragmentos de genoma viral amplificados por la región 5 no codificante (5NC) y región no estructural 5b (NS5b) usando la transcripción reversa y reacción en cadena de la polimerasa en dos rondas (RT-PCR). Se encontró una prevalencia de anticuerpos contra el VHC del 0,57 % (17/3005), siendo el grupo etario mayor de 41 años el más afectado (0,9 %). Un total de 16 muestras resultaron positivas para la presencia del ARN viral por RT-PCR en la región 5´NC (16/17, 94 %). El análisis filogenético de la región 5´NC permitió identificar la circulación del genotipo 2 y 1 y de un genotipo 3 y uno 4. Mediante análisis filogenéticos de la región NS5b, se observó la presencia de diversos subtipos dentro del genotipo 2 (2a, 2j y 2s), lo que concuerda con estudios anteriores que muestran que este genotipo es relativamente diverso en nuestro país.
The World Health Organization estimates that approximately 170 million people are chronically infected with hepatitis C virus (HCV). This study evaluated the presence of antibodies against HCV by two immunoassays. HCV genotypes were analyzed by phylogenetic analysis of viral genome fragments amplified from the 5 non-coding (5NC) region and non-structural region 5b (NS5b), using reverse transcription and nested polymerase chain reaction (RT-PCR), in patients referred from January 2010 to February 2013 to the Reference Laboratory of Public Health, University Hospital Antonio Patricio de Alcalá. The prevalence of anti-HCV antibodies was 0.57% (17/3005), being the group of patients older than 41 years the most affected (0.9%). A total of 16 samples were found positive for HCV RNA by RT-PCR in the 5NC region (16/17, 94%). Phylogenetic analysis of the 5´NC region allowed to identify the circulation of genotypes 2 and 1, and one genotype 3 and one 4. By phylogenetic analysis of the NS5b region, diverse subtypes of HCV genotype 2 were identified (2a, 2j and 2s). This finding is in accordance with previous studies that indicate that this genotype is relatively diverse in our country.
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Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Adulto Jovem , Hepacivirus/genética , Hepatite C Crônica/virologia , Filogenia , Venezuela , Saúde Pública , Genótipo , Hospitais UniversitáriosRESUMO
The aim of this study was to determine risk factors for adverse events (AE)-related treatment discontinuation and severe anemia among patients with chronic hepatitis C virus (HCV) genotype 1 infection, treated with first-generation protease inhibitor (PI)-based therapy. We included all patients who initiated treatment with PI-based therapy at a Brazilian university hospital between November 2013 and December 2014. We prospectively collected data from medical records using standardized questionnaires and used Epi Info 6.0 for analysis. Severe anemia was defined as hemoglobin ≤8.5 mg/dL. We included 203 patients: 132 treated with telaprevir (TVR) and 71 treated with boceprevir (BOC). AE-related treatment discontinuation rate was 19.2% and anemia was the main reason (38.5%). Risk factors for treatment discontinuation were higher comorbidity index (OR=1.85, CI=1.05-3.25) for BOC, and higher bilirubin count (OR=1.02, CI=1.01-1.04) and lower BMI (OR=0.98, CI=0.96-0.99) for TVR. Severe anemia occurred in 35 (17.2%) patients. Risk factors for this outcome were lower estimated glomerular filtration rate (eGFR; OR=0.95, CI=0.91-0.98) for patients treated with TVR, and higher comorbidity index (OR=2.21, CI=1.04-4.67) and ribavirin dosage (OR=0.84, CI=0.72-0.99) for those treated with BOC. Fifty-five (57.3%) patients treated with TVR and 15 (27.3%) patients treated with BOC achieved sustained virological response (SVR). Among patients who received TVR and interrupted treatment due to AE (n=19), only 26.3% (n=5) achieved SVR (P=0.003). Higher number of comorbidities, lower eGFR and advanced liver disease are associated with severe anemia and early treatment cessation, which may compromise SVR achievement.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Anemia/etiologia , Hepatite C Crônica/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Prolina/análogos & derivados , Inibidores de Proteases/administração & dosagem , Antivirais/administração & dosagem , Taxa de Filtração Glomerular , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Interferon-alfa/administração & dosagem , Modelos Logísticos , Oligopeptídeos/efeitos adversos , Polietilenoglicóis/administração & dosagem , Prolina/administração & dosagem , Prolina/efeitos adversos , Estudos Prospectivos , Inibidores de Proteases/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Ribavirina/administração & dosagem , Fatores de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Resposta Viral Sustentada , Fatores de Tempo , Falha de TratamentoRESUMO
Response-guided therapy is of limited use in developing countries because hepatitis C virus RNA detection by sensitive molecular methods is time- and labor-consuming and expen- sive. We evaluated early predictive efficacy of serum hepatitis C virus core antigen kinetics on sustained virologic response in patients with genotype 1 hepatitis C virus during pegylated interferon plus ribavirin treatment. For 478 patients recruited, hepatitis C virus RNAs were detected at baseline, and at weeks 4, 12, 24, 48, and 72 using Cobas TaqMan. Architect hepatitis C virus core antigen was performed at baseline, and weeks 4 and 12. Predictive values of hepatitis C virus core antigen on sustained virologic response were compared to hepatitis C virus RNA. In the first 12 weeks after treatment initiation the dynamic patterns of serum hepatitis C virus core antigen and hepatitis C virus RNA levels were similar in sustained virologic response, relapse, and null response patients groups. Although areas under the receiver operating characteristics curves of hepatitis C virus core antigen were lower than those of hepatitis C virus RNA at the same time points, modeling analysis showed that undetectable hepatitis C virus core antigen (rapid virological response based on hepatitis C virus core antigen) had similar positive predictive value on sustained virologic response to hepatitis C virus RNA at week 4 (90.4% vs 93.3%), and hepatitis C virus core antigen decrease greater than 1 log10 IU/mL (early virological response based on hepatitis C virus core antigen) had similar negative predictive value to hepatitis C virus RNA at week 12 (94.1% vs 95.Z%). Analysis on the validation group demonstrated a positive predictivevalue of 97.5% in rapid virological response based on hepatitis C virus core antigen and a negative predictive value of 100% in early virological response based on hepatitis C virus core antigen. In conclusion, hepatitis C virus core antigen is comparable to hepatitis C virus RNA in predicting sustained virologic response of chronic genotype 1 hepatitis C virus infected patients, and can be used to guide anti-hepatitis C virus treatment, especially in resource-limited areas.
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Hepacivirus/imunologia , Antígenos da Hepatite C/imunologia , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Genótipo , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Valor Preditivo dos Testes , Curva ROC , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo , Proteínas do Core Viral/imunologiaRESUMO
Introduction: in Brazil, chronic hepatitis C in patients coinfected with the human immunodeficiency virus (HIV) is treated with pegylated interferon (Peg-IFN) and ribavirin (RBV). However, few studies have evaluated the effectiveness of this treatment in this particular population. The identification of the factors that predict sustained virological response (SVR) under current clinical practice would enable clinicians to more accurately estimate the probability of achieving an SVR and therefore utilize the appropriate therapeutics, especially in the era of direct-acting antiviral (DAA) agents. Aims: the primary aim of our study was to determine the SVR rate under current clinical practice. The secondary aims were as follows: (1) to determine the factors before and during treatment that predict SVR; and (2) to identify the causes of treatment interruption. Methods: within a cohort of HIV/hepatitis C virus (HCV)-coinfected patients in Brazil, we performed a retrospective analysis of those individuals treated with Peg-IFN and RBV. Results: among the 382 analyzed patients, SVR was observed in 118 [30.9% (95% confidence interval (CI): 26.3-35.8)], which included 25.9% (75/289) of the patients with genotypes 1 and 4 and 48.2% (41/85) of those with genotypes 2 and 3. After multivariate analyses the independent positive predictors for SVR after treatment for chronic hepatitis C with PegIFN and RBV were: absence of an AIDS-defining illness (p = 0.001), HCV viral load lower than 600,000 IU/mL at the onset of treatment (p = 0.003), higher liver enzyme levels (p = 0.039) at baseline, infection with genotypes 2 or 3 (p = 0.003), and no transient treatment interruption (p = 0.001). The treatment was interrupted in 25.6% (98/382) of the patients because of adverse events (11.3%, 43/382), virologic failure (7.8%, 30/382), and dropout (6.5%, 43/382). The main adverse events were cytopenia and psychiatric disorders. Conclusions: ...
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Antivirais/efeitos adversos , Estudos de Coortes , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Interferon-alfa/efeitos adversos , Polietilenoglicóis/efeitos adversos , Estudos Retrospectivos , RNA Viral , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Ribavirina/efeitos adversos , Resultado do Tratamento , Carga ViralRESUMO
Introduction: A population-based survey conducted in Brazilian capital cities found that only 16% of the population had ever been tested for hepatitis C. These data suggest that much of the Brazilian population with HCV infection remains undiagnosed. The distribution of age ranges at diagnosis and its association with the degree of hepatitis C are still unknown in Brazilian patients. Material and methods: Patients with HCV infection, diagnosed by HCV RNA (Amplicor-HCV, Roche), were included in the study. Patients with HBV or HIV coinfection, autoimmune diseases, or alcohol intake > 20 g/day were excluded. HCV genotyping was performed by sequence analysis, and viral load by quantitative RT-PCR (Amplicor, Roche). The METAVIR classification was used to assess structural liver injury. The Chi-square (χ2) test and student's t-test were used for between-group comparisons. Spearman's rank correlation coefficient were used for analysing the correlation between parameters. Results: A total of 525 charts were reviewed. Of the patients included, 49.5% were male, only 10% of the patients were aged less than 30 years; peak prevalence of HCV infection occurred in the 51-to-60 years age range. Genotype 1 accounted for 65.4% of the cases. Information on HCV subtype was obtained in 227 patients; 105 had subtype 1a and 122 had 1b. According to the degree of structural liver injury, 8.3% had F0, 23.4% F1, 19.8% F2, 11.9% F3, and 36.5% F4. Age at diagnosis of hepatitis correlated significantly with fibrosis (rs = 0.307, p < 0.001). The degree of fibrosis increased with advancing age. Only age at diagnosis and fasting blood glucose were independently associated with disease stage. Those patients with subtype 1a had higher prevalence of F2–F4 than those with subtype 1b. Conclusion: In Brazil, diagnosis of hepatitis C is more commonly established in older patients (age 45–60 years) with more advanced disease. Reassessment of strategies ...