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1.
PLoS One ; 13(7): e0199941, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29990371

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection is the major cause of end-stage liver disease (LD) worldwide. The aim of this study was to assess sustained virological response (SVR) rates in a real-world cohort of patients with HCV infection treated with interferon-free direct antiviral agents (DAA). PATIENTS AND METHODS: All patients with genotypes 1, 2 or 3 HCV infection who started interferon-free treatment at a university hospital from December 2015 through July 2017 were included. The primary outcome was SVR at post-treatment week 12 by intention-to-treat (ITT) and modified ITT (mITT) analysis. RESULTS: Five hundred twenty seven patients were enrolled, 51.6% with cirrhosis. Most patients received sofosbuvir + daclatasvir + ribavirin (60.7%) and sofosbuvir + simeprevir (25.6%). Overall SVR rates were 90.5% for ITT and 96% for mITT. SVR rates were higher in non-cirrhotic (94.2% in ITT and 96.8% in mITT) versus cirrhotic patients (87.1% in ITT and 95.2% in mITT). In ITT and mITT assessments, SVR rates were higher in patients with Child-Pugh A (n = 222, 88.7% and 95.7%, respectively) versus Child-Pugh B or C (n = 40, 80% and 90%, respectively); SVR rates were higher in patients with genotype 1 (n = 405, 92.1% and 98.2%), followed by genotype 2 (n = 13, 84.6% and 92.7%) and genotype 3 (n = 109, 84.4% and 88.4%). Lower comorbidity index (p = 0.0014) and absence of cirrhosis (p = 0.0071) were associated with SVR. Among cirrhotic patients, lower Model for End-Stage Liver Disease (p = 0.0258), higher albumin (p = 0.0015), and higher glomerular filtration rate (p = 0.0366) were related to SVR. Twenty-two cirrhotic patients (8%) had clinical liver decompensation during treatment. Complications of advanced LD were responsible for discontinuation of treatment and death in 12 and 7 patients, respectively. CONCLUSION: Treatment with all-oral DAA achieved high SVR rates, particularly in patients without cirrhosis and few comorbidities. Advanced LD is associated to poor outcome, such as treatment failure and death.


Assuntos
Antivirais/administração & dosagem , Antivirais/uso terapêutico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/complicações , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Estudos de Coortes , Comorbidade , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Hepatite C Crônica/epidemiologia , Humanos , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Segurança , Falha de Tratamento , Resultado do Tratamento
2.
Eur J Gastroenterol Hepatol ; 30(8): 959-966, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29727388

RESUMO

BACKGROUND AND OBJECTIVE: Controlled attenuation parameter (CAP) diagnostic performance for steatosis grading has been controversial and considerable observer-related variability in liver biopsy has been reported. This is a subanalysis of a larger chronic hepatitis C study on noninvasive fibrosis staging. MATERIALS AND METHODS: Patients were prospectively enrolled for paired liver biopsy and transient elastography. Biopsy fragments were subjected to digital morphometric steatosis quantification. Associated patient and technical factors, including a newly described elastogram quality score, were evaluated. RESULTS: A total of 312 patients were included in the final analysis. The mean liver stiffness was 8.7±2.1 kPa. Morphometry showed S0 in 19.2% of patients, S1 in 28.5%, S2 in 31.1%, and S3 in 21.2%. CAP showed S0 in 11.2% of patients, S1 in 26.6%, S2 in 56.7%, and S3 in 5.4%. Spearman coefficient showed a positive and independent correlation between CAP and morphometric analysis (r=0.48, P<0.05), except for distinguishing S1 and S2 (P=0.11). Area under the receiver operating characteristic curves for the presence or absence of steatosis was 0.944; differentiation between levels I, II, and III were 0.776, 0.812, and 0.879. Elastogram quality independently predicted accuracy [odds ratio (OR): 6.95, 95% confidence interval (95%CI): 4.45-9.06 as well as CAP interquartile range OR: 2.81, 95%CI: 1.67-3.99] and liver stiffness (OR: 0.78, 95%CI: 0.51-0.80). CONCLUSION: We present an external validation for CAP against the objective steatosis quantification provided by digital morphometry. Fairly good performance indicators were found, except for S1 versus S2 differentiation. Variability and higher liver stiffness were associated with lower performance. Achieving higher quality measurements, however, overcame such limitations with excellent accuracy.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/patologia , Hepatite C Crônica/diagnóstico por imagem , Hepatite C Crônica/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Adulto , Área Sob a Curva , Biópsia , Distribuição de Qui-Quadrado , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
3.
Eur J Gastroenterol Hepatol ; 29(10): 1149-1154, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28800033

RESUMO

AIM: The aim of this study was to determine risk factors for premature treatment discontinuation among patients with hepatitis C and advanced fibrosis with advanced fibrosis treated with interferon (IFN)-free direct antiviral agents (DAA)-based therapy. PATIENTS AND METHODS: We included all patients with chronic hepatitis C virus infection and advanced liver fibrosis in whom treatment was initiated with IFN-free DAA therapy at a university hospital from December 2015 through June 2016. We prospectively collected data from medical records using standardized questionnaires and evaluated them using Epi Info 7.1.2.0. The primary outcome was treatment interruption and associated factors. RESULTS: In total, 214 patients were included in this study; 180 patients were treated with sofosbuvir (SOF)+daclatasvir±ribavirin (RBV), 31 received SOF+simeprevir±RBV, and three were treated with SOF+RBV. Treatment discontinuation rate was 8.9% (19 patients) and cirrhotic decompensation was the main reason [8 (42.1%)]. Among patients with Child B or C cirrhosis (31), 10 (32.2%) prematurely interrupted treatment. The risk factors for treatment discontinuation in univariate analysis were older age (P=0.0252), higher comorbidity index (P=0.0078), higher model for end-stage liver disease (P<0.0001), higher fibrosis index based on the 4 factores (P=0.0122), and lower hemoglobin (P=0.0185) at baseline. Multivariate analysis showed that older age (odds ratio: 1.1, 95% confidence interval: 1.02-1.19) and higher model for end-stage liver disease (odds ratio: 1.27, 95% confidence interval: 1.03-1.56) were associated with premature treatment interruption. CONCLUSION: Older age and advanced liver disease were related to treatment interruption. Identification of risk factors associated with treatment discontinuation is important to recognize patients who should be followed up closely during treatment, ando those whom possibly may not benefit from immediate DAA treatment or should be followed up closely during treatment.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/virologia , Adulto , Fatores Etários , Idoso , Antivirais/efeitos adversos , Distribuição de Qui-Quadrado , Progressão da Doença , Esquema de Medicação , Quimioterapia Combinada , Feminino , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hospitais Universitários , Humanos , Cirrose Hepática/diagnóstico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Fatores de Risco , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento
4.
Hepatology ; 57(4): 1325-32, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23315914

RESUMO

UNLABELLED: Chronic infection with the hepatitis C virus (HCV) is a leading cause of global morbidity and mortality. Although recent advances in antiviral therapy have led to significant improvements in treatment response rates, only a minority of infected patients are treated. Multiple barriers may impede the delivery of HCV therapy. The aim of this study was to identify perceived barriers to care, knowledge, and opinions among a global sample of HCV treatment providers. An international, multidisciplinary survey of HCV treatment providers was conducted. Each physician responded to a series of 214 questions concerning his or her practice characteristics, opinions regarding the state of HCV care, knowledge regarding HCV treatment, and perception of treatment barriers. A total of 697 physicians from 29 countries completed the survey. Overall, physicians viewed patient-level barriers as most significant, including fear of side effects and concerns regarding treatment duration and cost. There were distinct regional variations, with Central and Eastern European physicians citing government barriers as most important. In Latin America, the Middle East, and Africa, payer-level barriers, including lack of treatment coverage, were prominent. Overall, the perception of barriers was strongly associated with physician knowledge, experience, and region of origin, with the fewest barriers reported by Nordic physicians and the most reported by Middle Eastern and African physicians. Globally, physicians demonstrated deficits in basic treatment principles, including the role of viral kinetics and the management of treatment nonresponders. Two thirds of surveyed physicians believed that patients do not have adequate access to providers in their community. CONCLUSION: Barriers to HCV treatment vary globally, though patient-level factors are viewed as most significant by treating physicians. Efforts to improve awareness, education, and specialist availability are needed.


Assuntos
Antivirais/uso terapêutico , Atenção à Saúde , Saúde Global , Conhecimentos, Atitudes e Prática em Saúde , Hepatite C/tratamento farmacológico , Médicos/psicologia , Coleta de Dados , Custos de Cuidados de Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Cooperação Internacional , Cooperação do Paciente , Percepção
5.
Braz J Infect Dis ; 16(3): 232-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22729189

RESUMO

BACKGROUND: Pegylated interferon (Peg-IFN) and standard interferon (IFN) play a significant role in the treatment of hepatitis C virus (HCV) infection. Biosimilar standard IFN is widely available in Brazil for the treatment of HCV infection genotypes 2 or 3, but its efficacy compared to Peg-IFN is unknown. OBJECTIVE: To compare the sustained virological response (SVR) rates following treatment with biosimilar standard IFN plus ribavirin (RBV) versus Peg-IFN plus RBV in patients with HCV genotypes 2 or 3 infection. METHODS: A retrospective cohort study was conducted in patients with HCV genotypes 2 or 3 infection treated with biosimilar standard IFN plus RBV or with Peg-IFN plus RBV. SVR rates of the two treatments were compared. RESULTS: From January 2005 to December 2010, 172 patients with a mean age of 44 +/- 9.3 years were included. There were eight (4.7%) patients with HCV genotype 2 infections. One hundred fourteen (66.3%) were treated with biosimilar standard IFN plus RBV, whist 58 (33.7%) patients were treated with Peg-IFN plus RBV. Between the two groups, there were no significant differences regarding age, gender, glucose level, platelet count, hepatic necroinflammatory grade, and hepatic fibrosis stage. Overall, 59.3% (102/172) patients had SVR. In patients treated with Peg-IFN plus RBV, 79.3% (46/58) had SVR compared to 49.1% (56/114) among those treated with biosimilar standard IFN plus RBV (p = 0.0001). CONCLUSION: In patients with HCV genotypes 2 or 3 infection, a higher SVR was observed in patients receiving Peg-IFN plus RBV related to patients treated with biosimilar standard IFN plus RBV.


Assuntos
Antivirais/administração & dosagem , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Interferons/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Adolescente , Adulto , Idoso , Estudos de Coortes , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , Proteínas Recombinantes/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento , Carga Viral , Adulto Jovem
6.
Liver Int ; 31 Suppl 2: 18-29, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21651701

RESUMO

BACKGROUND AND AIM: The purpose of the present investigation is to provide an analysis of previous works on the epidemiology of the hepatitis C virus (HCV) infection from six countries throughout Latin America, to forecast the future HCV prevalence trends in Argentina, Brazil, Mexico and Puerto Rico, and to outline deficiencies in available data, highlighting the need for further research. METHODS: Data references were identified through indexed journals and non-indexed sources. Overall, 1080 articles were reviewed and 150 were selected based on their relevance to this work. When multiple data sources were available for a key assumption, a systematic process using multi-objective decision analysis (MODA) was used to select the most appropriate sources. When data were missing, analogues were used. Data from other countries with similar risk factors and/or population compositions were used as a proxy to help predict the future trends in prevalence. RESULTS: The review indicates that the dominant genotype is type 1. HCV prevalence in the analysed countries ranges from 1 to 2.3%. The Latin American countries have been very proactive in screening their blood supplies, thus minimizing the risk of transmission through transfusion. This suggests that other risk factors are set to play a major role in continued new infections. The number of diagnosed and treated patients is low, thereby increasing the burden of complications such as liver cirrhosis or hepatocellular carcinoma. The HCV prevalence, according to our modelling is steady or increasing and the number of infected individuals will increase. CONCLUSIONS: The results herein reported should provide a foundation for informed planning efforts to tackle hepatitis.


Assuntos
Epidemias , Hepatite C/epidemiologia , Previsões , Genótipo , Hepacivirus/genética , Hepatite C/diagnóstico , Hepatite C/prevenção & controle , Hepatite C/terapia , Hepatite C/transmissão , Humanos , América Latina/epidemiologia , Prevalência , Medição de Risco , Fatores de Risco , Fatores de Tempo
7.
J Hepatol ; 54(2): 227-35, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21056496

RESUMO

BACKGROUND & AIMS: EPIC-3 is a prospective, international study that has demonstrated the efficacy of PEG-IFN alfa-2b plus weight-based ribavirin in patients with chronic hepatitis C and significant fibrosis who previously failed any interferon-alfa/ribavirin therapy. The aim of the present study was to assess FibroTest (FT), a validated non-invasive marker of fibrosis in treatment-naive patients, as a possible alternative to biopsy as the baseline predictor of subsequent early virologic (EVR) and sustained virologic response (SVR) in previously treated patients. METHODS: Of 2312 patients enrolled, 1459 had an available baseline FT, biopsy, and complete data. Uni- (UV) and multi-variable (MV) analyses were performed using FT and biopsy. RESULTS: Baseline characteristics were similar as in the overall population; METAVIR stage: 28% F2, 29% F3, and 43% F4, previous relapsers 29%, previous PEG-IFN regimen 41%, high baseline viral load (BVL) 64%. 506 patients (35%) had undetectable HCV-RNA at TW12 (TW12neg), with 58% achieving SVR. The accuracy of FT was similar to that in naive patients: AUROC curve for the diagnosis of F4 vs F2=0.80 (p<0.00001). Five baseline factors were associated (p<0.001) with SVR in UV and MV analyses (odds ratio: UV/MV): fibrosis stage estimated using FT (4.5/5.9) or biopsy (1.5/1.6), genotype 2/3 (4.5/5.1), BVL (1.5/1.3), prior relapse (1.6/1.6), previous treatment with non-PEG-IFN (2.6/2.0). These same factors were associated (p ≤ 0.001) with EVR. Among patients TW12neg, two independent factors remained highly predictive of SVR by MV analysis (p ≤ 0.001): genotype 2/3 (odds ratio=2.9), fibrosis estimated with FT (4.3) or by biopsy (1.5). CONCLUSIONS: FibroTest at baseline is a possible non-invasive alternative to biopsy for the prediction of EVR at 12 weeks and SVR, in patients with previous failures and advanced fibrosis, retreated with PEG-IFN alfa-2b and ribavirin.


Assuntos
Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Cirrose Hepática/diagnóstico , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Alanina Transaminase/sangue , Biópsia , Quimioterapia Combinada , Fígado Gorduroso/diagnóstico , Feminino , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Proteínas Recombinantes
8.
Braz J Infect Dis ; 15(5): 449-56, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22230851

RESUMO

OBJECTIVE: The treatment of the chronic hepatitis C (HCV) with α-interferon is associated with thyroid dysfunction (TD). The aim of this study was to evaluate thyroid function outcome among patients with chronic HCV under treatment with conventional interferon (IFN) or peguilated interferon (PEG-IFN) in association with ribavirin. PATIENTS AND METHODS: We studied 293 patients with chronic HCV, submitted to drug therapy for 24 or 48 weeks. Initially, we evaluated FT4, TSH, TPOAb, TgAb, and continued to monitor FT4 and TSH every three months during therapy and six months thereafter. RESULTS: At baseline, TD prevalence was 6.82% (n = 20); 6.14% hypothyroidism; 0.68% hyperthyroidism. TPOAb was present in 5.46% of euthyroid patients. Out of 273 euthyroid patients at baseline, 19% developed TD: 17.2% hypothyroidism; 1.8% hyperthyroidism; 5.1% destructive thyroiditis (DT). 90% of TPOAb-positive patients at baseline developed hypothyroidism vs 14.5% of TPOAb-negative patients (p < 0.001). On average, TD occurred after 25.8 ± 15.5 weeks of treatment. 87.2% of patients who developed hypothyroidism did so during the first therapeutic cycle (p = 0.004; OR = 3.52; 95% CI = 1.36-9.65). Patients infected with genotype 1 virus were 2.13 times more likely to develop hypothyroidism (p = 0.036; 95% CI = 1.04-4.38). Hypothyroid and DT patients presented higher TSH levels before-treatment than patients who had remained euthyroid (p < 0.001; p = 0.002, respectively). DT patients presented lower qALT (p = 0.012) than euthyroid patients. CONCLUSION: Hypothyroidism was the most frequent TD, especially during the first cycle of α-interferon. Genotype 1 virus was associated with a risk two times higher for developing the illness. There was no need to interrupt or to change HCV treatment. Therefore, approximately 34% of TD was transient.


Assuntos
Antivirais/efeitos adversos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hipotireoidismo/induzido quimicamente , Interferon-alfa/efeitos adversos , Polietilenoglicóis/efeitos adversos , Ribavirina/efeitos adversos , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Autoanticorpos/sangue , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Hipertireoidismo/induzido quimicamente , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Estudos Prospectivos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Adulto Jovem
9.
BMC Infect Dis ; 10: 212, 2010 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-20646277

RESUMO

BACKGROUND: More than 50% of hepatitis C viruses (HCV)-infected patients do not respond to the classical Interferon (IFN)/Ribavirin (RBV) combination therapy. The aim of this study was to evaluate the efficacy of retreatment with Peg-Interferon alpha-2b (PEG-IFN alpha-2b) plus RBV, in patients with HCV, genotypes 1 or 3, who were non-responders to the previous standard treatment with IFN/RBV. METHODS: In the period 2005-2007, a total of 238 HCV chronic patients were non-responders to previous treatment with IFN plus RBV. Of these 130 agreed to be retreated with PEG-IFN alpha-2b and participated in this evaluation (90 with genotype 1 HCV and 40 with genotype 3 HCV). Patients were retreated at assisted IFN application hubs in compliance with the country's public health system rules. They received subcutaneous PEG-IFN alpha-2b, 1.5 microg, once weekly, associated with RBV, through the oral route, with doses determined according to weight (1,000 mg if weight 75 kg). Patients with genotype 1 HCV were retreated for over 48 weeks and patients with genotype 3 HCV for over 24 weeks. HCV-RNA was tested by polymerase chain reaction (PCR) at baseline, at week 12, at the end of the treatment, and 6 months thereafter. The predictiveness of week 12 in the development of a sustained virologic response (SVR) was also evaluated. Patients with negative HCV-RNA at week 12 were considered as early virologic responders (EVR). RESULTS: EVR was observed in 25% of the patients with genotype 1 HCV and in 64% of the patients genotype 3 HCV (risk = 2.075 and p-value = 0.0414). SVR was observed in 22.2% of the patients with genotype 1 HCV and in 40% with genotype 3 HCV (intention-to-treat analysis). The positive predictive value (PPV) of the HCV-RNA testing at week 12, in order to obtain the SVR, was 65% for genotype 1 and 56% for genotype 3, and the negative predictive value (NPV) was 88% for genotype 1 and 89% for genotype 3. CONCLUSIONS: PEG-IFN alpha-2b plus weight-based ribavirin is effective in re-treating previous interferon-alpha plus RBV failure; 22.2% of the patients with genotype 1 HCV and 40% of patients with genotype 3 HCV achieved SVR.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Interferons/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Quimioterapia Combinada/métodos , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Proteínas Recombinantes , Retratamento/métodos , Resultado do Tratamento , Carga Viral
10.
Braz J Infect Dis ; 14(2): 193-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20563450

RESUMO

Hemodialysis patient with chronic HCV infection,who was started on monotherapy with interferon.Qualitative HCV RNA remained positive at 12 weeks of treatment; ribavirin was associated. HCV RNA was negative at week 24 and treatment was extended to 72 weeks. HCV RNA negative six months after treatment.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferons/administração & dosagem , Diálise Renal , Ribavirina/administração & dosagem , Adulto , Quimioterapia Combinada , Hepatite C Crônica/complicações , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , RNA Viral/análise , Resultado do Tratamento
11.
BMC Infect Dis ; 9: 149, 2009 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-19737394

RESUMO

BACKGROUND: Knowledge of HBV genotype is very important for clinical treatment. Studies have suggested possible pathogenic and therapeutic differences among HBV genotypes. The aim of this study was to determine HBV subtypes and genotypes in HBV-infected patients in our region (southeast Brazil) and to correlate results with clinical and histopathological data. METHODS: One hundred and thirty-nine HBsAg-positive patients were included in the study. All patients were anti-HCV and anti-HIV negative (64% male; mean age 42 +/- 14.5 years; range 7-80 years; 84% Caucasian) and were followed up at the University Hospital. A method for genotyping and subtyping HBV by partial HBsAg gene sequencing with primers common to all known genotypes was used. The viral load was measured by Amplicor Monitor assay (Roche). RESULTS: HBV genotype A was the most prevalent (55%), while genotypes C, D and F were found in 3%, 38% and 4% of HBV-infected patients, respectively. Among the patients infected by genotype A, 18.3% (14/76) were African descendents and, among the patients infected by genotype D, 11.3% (6/53) were also African descendents. In the four patients infected with genotype C, 2 were Asian descendents and 2 were Caucasians. All (7) genotype F infected patients were Caucasians. Seventy percent of our HBsAg-positive patients were HBeAg negative (62% genotypes A; 26.2% D; 7.1% C and 4.7%F). The viral load of HBV-DNA was about 5 times higher in HBeAg-positive than in HBeAg-negative patients. About 40% of these patients had alanine aminotransferase of up to 1.5 times the normal level. The mean stage of fibrosis in genotype A patients (2.8) was significantly higher than the mean stage of fibrosis in genotype D patients (2.0) (P = 0.0179). CONCLUSION: The genotypes encountered in our HBV-infected patients were apparently a consequence of the types of immigration that occurred in our region, where European and African descendents predominate. The HBeAg-negative status predominated, possibly due to the length of time of infection. The viral load in HBeAg-positive patients was higher than in HBeAg-negative individuals. The fibrosis grade in genotype A-infected patients was more advanced than genotype D-infected patients.


Assuntos
Antígenos E da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Criança , Feminino , Genótipo , Hepatite B/epidemiologia , Vírus da Hepatite B/classificação , Humanos , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Sequência de DNA , Adulto Jovem
12.
Gastroenterology ; 136(5): 1618-28.e2, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19208349

RESUMO

BACKGROUND & AIMS: Treatment with peginterferon alfa and ribavirin produces a sustained virologic response (SVR) in approximately 60% of hepatitis C virus (HCV)-infected patients. Alternate options are needed for patients who relapse or do not respond to therapy. METHODS: This prospective, international, multicenter, open-label study evaluated efficacy and safety of peginterferon alfa-2b (1.5 microg/kg/wk) plus weight-based ribavirin (800-1400 mg/day) in 2333 chronic HCV-infected patients with significant fibrosis/cirrhosis whose previous interferon alfa/ribavirin therapy failed. Patients with undetectable HCV-RNA at treatment week (TW) 12 received 48 weeks of therapy; patients with detectable HCV-RNA at TW12 could enter maintenance studies at TW18; 188 patients with low/detectable HCV-RNA at TW12 continued therapy at the investigator's request. RESULTS: Overall, 22% of the patients attained SVR (56% with undetectable HCV-RNA and 12% with low/detectable HCV-RNA at TW12). SVR was better in relapsers (38%) than nonresponders (14%), regardless of previous treatment, and in patients previously treated with interferon-alfa/ribavirin (25%) than peginterferon alfa-ribavirin (17%). Predictors of response in patients with undetectable HCV-RNA at TW12 were genotype (2/3 vs 1, respectively; odds ratio [OR] 2.4; P < .0001), fibrosis score (F2 vs F4; OR, 2.2; F3 vs F4; OR, 1.7; P < .0001), and baseline viral load (< or =600,000 vs >600,000 IU/mL; OR, 1.4; P = .0223). These factors plus previous treatment and response were overall predictors of SVR. Safety was similar among fibrosis groups. CONCLUSIONS: Peginterferon alfa-2b plus weight-based ribavirin is effective and safe in patients who failed interferon alfa/ribavirin therapy. Genotype, baseline viral load, and fibrosis stage were predictors of response.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Ribavirina/administração & dosagem , Quimioterapia Combinada , Feminino , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis , RNA Viral/sangue , Proteínas Recombinantes , Falha de Tratamento
13.
BMC Infect Dis ; 8: 164, 2008 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-19055835

RESUMO

BACKGROUND: The progression of liver disease in patients with chronic hepatitis C virus (HCV) infection is influenced by host and viral factors. Distinct clinical outcomes in patients infected with different HCV genotypes have been described in the literature. However, the association between specific HCV genotype and clinical outcome remains unclear. We set out to study the natural history of HCV genotype 1 and 3 infections in Campinas, São Paulo state, Brazil, focusing on epidemiological, clinical, biochemical, and histological characteristics. METHODS: Patients with HCV infection referred for treatment between January 2003 and December 2006 were included in this study. We collected epidemiological, clinical, and laboratorial data using standard forms. RESULTS: A total of 283 patients were included; genotype 1 was identified in 163 (57.6%) patients, genotype 3 in 112 (39.6%), genotype 2 in 7 (2.5%), and genotype 4 in 1 (0.35%). Patients with genotype 2 and 4 were excluded from analysis. Multivariate analysis showed that intravenous energetic drug, positive cryoglobulin, and cirrhosis were independently and significantly associated with HCV genotype 3 (p < 0.05). CONCLUSION: Genotype 3 currently seems to be associated with intravenous energetic drug, high frequency of cryoglobulinemia, and advanced liver disease in our region. Understanding the distribution of the different HCV genotypes can elucidate transmission of HCV and support optimal prevention strategies.


Assuntos
Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Adulto , Idoso , Brasil/epidemiologia , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/isolamento & purificação , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
14.
BMC Infect Dis ; 8: 5, 2008 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-18199334

RESUMO

BACKGROUND: Blood transfusion has always been an important route for Chagas Disease (CD) transmission. The high prevalence of CD in Latin America and its lifelong asymptomatic clinical picture pose a threat for the safety of the blood supply. The outcome of measures designed to improve transfusion safety can be assessed by evaluating the prevalence of CD among multitransfused patients METHODS: In order to assess the impact of CD control measures on the safety of the blood supply, an observational cross-sectional study was designed to determine the prevalence of CD in 351 highly transfused patients, in which vectorial transmission was excluded. This study compared patients that received transfusion products before (n = 230) and after (n = 121) 1997, when measures to control transfusion-transmitted CD were fully implemented in Brazil. RESULTS: The study group consisted of 351 patients exposed to high numbers of blood products during their lifetime (median number of units transfused = 51, range 10-2086). A higher prevalence of transfusion-transmitted CD (1.30%) was observed among multitransfused patients that received their first transfusion before 1997, compared with no cases of transfusion-transmitted CD among multitransfused patients transfused after that year. The magnitude of the exposure to blood products was similar among both groups (mean number of units transfused per year of exposure = 25.00 +/- 26.46 and 23.99 +/- 30.58 respectively; P = 0.75, Mann-Whitney test). CONCLUSION: Multiple initiatives aimed to control vector and parental transmission of CD can significantly decrease transfusion-transmitted CD in Brazil. Our data suggest that mandatory donor screening for CD represents the most important measure to interrupt transmission of CD by blood transfusions.


Assuntos
Doença de Chagas/epidemiologia , Doença de Chagas/transmissão , Testes Obrigatórios , Reação Transfusional , Adolescente , Adulto , Animais , Brasil/epidemiologia , Doença de Chagas/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos
16.
J Med Virol ; 78(10): 1296-303, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16927280

RESUMO

Hepatitis C virus subtype 3a (HCV-3a) originates from Asia and has spread widely among injecting drug users as well as other patient groups in industrialized countries. HCV subtype 3a infection remains highly prevalent and frequently transmitted in the population of intravenous drug users. The objective of this study was to understand better the mechanisms of the worldwide HCV-3a epidemics in drug users. Ninety-three sera from HCV-3a-infected IDUs from France, the United States, Brazil, Argentina, and Australia were studied. Phylogenetic analyses of the non-structural 5B region showed no specific clustering according to the continent of the patient's origin. Non-exclusive clusters of viral sequences from South America, Australia, and California were observed, but topologies were not supported by strong bootstrap values. The results suggest that HCV-3a has been transmitted from a common origin through a unique worldwide epidemic that rapidly spread among drug users. Regional transmission occurred in the recent past, leading to an embryonic genetic diversification of HCV-3a among local injecting drug user population.


Assuntos
Hepacivirus/genética , Hepatite C/epidemiologia , Epidemiologia Molecular , Abuso de Substâncias por Via Intravenosa/complicações , Argentina/epidemiologia , Austrália/epidemiologia , Brasil/epidemiologia , França/epidemiologia , Hepacivirus/classificação , Hepatite C/complicações , Humanos , RNA Viral/genética , Estados Unidos/epidemiologia , Proteínas não Estruturais Virais/genética
17.
Braz J Infect Dis ; 10(5): 311-6, 2006 10.
Artigo em Inglês | MEDLINE | ID: mdl-17293917

RESUMO

Combination therapy with pegylated interferon and ribavirin is considered the new standard therapy for naïve patients with chronic hepatitis C. We evaluated the efficacy and safety of treatment with weight-based peginterferon alpha-2b (1.5 mg/kg per week) plus ribavirin (800-1,200 mg/day) for 48 weeks in naïve, relapser and non-responder (to previous treatment with interferon plus ribavirin) patients with chronic hepatitis C. Sixty-seven naïve, 26 relapser and 40 non-responder patients were enrolled. The overall sustained virological response (SVR) for the intention-to-treat population was 54% for naïve, 62% for relapser and 38% for non-responder patients. In the naïve subgroup, SVR was significantly higher in patients with the non-1 genotype (67%) compared to those with genotype 1 (45%). In relapsers and non-responders, SVR was, respectively, 69% and 24% in patients with genotype 1 and 43% and 73% in those with genotype non-1. There were no significant differences in SVR rates among the three body weight ranges (<65 kg, 65-85 kg and >85 kg) in any of the subgroups. Early virological response (EVR) was reached by 78%, 81% and 58% of naïve, relapser and non-responder patients, respectively, and among those with EVR, 63%, 67% and 61%, respectively, subsequently achieved SVR. All of the non-responder patients who did not have EVR reached SVR. Treatment was discontinued in 13% of the patients, due to loss to follow-up, hematological abnormalities or depression.


Assuntos
Antivirais/administração & dosagem , Peso Corporal , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Ribavirina/administração & dosagem , Adolescente , Adulto , Idoso , Esquema de Medicação , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis , Estudos Prospectivos , RNA Viral/sangue , Proteínas Recombinantes , Resultado do Tratamento , Carga Viral
18.
J Hepatol ; 43(3): 425-33, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15990196

RESUMO

BACKGROUND/AIMS: Prediction of sustained virological response (SVR) during treatment would allow clinicians to identify patients most likely to benefit from therapy. METHODS: Retrospective analysis of data from 1121 adults with chronic hepatitis C treated for 48 weeks with peginterferon alfa-2a (40 KD) 180 microg/week plus placebo or ribavirin (1000/1200 mg/day), or interferon alfa-2b 3 MIU three times/week plus ribavirin in a randomized, multinational, study. RESULTS: 67% of patients treated with peginterferon alfa-2a (40 KD)/ribavirin with early virological responses (HCV RNA negative or > or = 2 log10 decrease) at week 12 had SVRs at week 72 (HCV RNA < 50 IU/mL). The negative predictive value (NPV) was 97%. The probability of an SVR increased with the rapidity of HCV RNA suppression. The highest SVR rates were achieved in patients with rapid virological responses at week 4, but the corresponding NPV (74%) is too low for a decision criterion. In patients with early virological responses by week 12, the SVR rate was approximately 20% lower in those who received <80% compared with patients who received > or = 80% of the planned ribavirin dose. CONCLUSIONS: Early, sustained suppression of HCV replication portends an SVR. Cessation of treatment may be contemplated in patients without a > or = 2 log10 reduction in HCV RNA after 12 weeks.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Interferon alfa-2 , Probabilidade , RNA Viral/análise , Proteínas Recombinantes , Estudos Retrospectivos , Resultado do Tratamento , Carga Viral
19.
J Clin Virol ; 34 Suppl 2: S27-32, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16461237

RESUMO

BACKGROUND: Transfusion-transmitted infections (TTI) continue to be a problem in many parts of the world, and multi-transfused patients (MTP) are at a particularly increased risk of TTI. OBJECTIVES: to estimate the prevalence of TTI among multi-transfused patients in Brazil, and to understand the epidemiological characteristics of TTI among these patients. STUDY DESIGN: cross-sectional study of 353 MTP, who were interviewed using a structured questionnaire and tested for serological markers of hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infection. RESULTS: the overall prevalence of HCV, HIV, HBV and co-infection among MTP were 16.7%, 1.7%, 0.8% and 1.7% respectively. A dose-effect relationship could be detected between the number of units transfused and HCV infection. Other non-transfusion related (NTR) risk factors for HCV did not confer any excess risk of HCV infection to MTP. CONCLUSIONS: HCV infection was the most prevalent TTI among MTP, and remains a major health problem for these patients. A dose-effect relationship could be detected between HCV and the number of units transfused. The implementation of measures such as donor education programs, standards for donor selection criteria, and of improved serological screening protocols, paralleled the decline in the prevalence of TTI, specially of HCV, observed in MTP, underscoring the importance of such measures for the reduction of the residual risk of TTI.


Assuntos
Anticorpos Anti-HIV/sangue , Infecções por HIV/epidemiologia , Infecções por HIV/etiologia , Anticorpos Anti-Hepatite B/sangue , Hepatite B/epidemiologia , Hepatite B/etiologia , Anticorpos Anti-Hepatite C/sangue , Hepatite C/epidemiologia , Hepatite C/etiologia , Reação Transfusional , Adulto , Brasil/epidemiologia , Comorbidade , Estudos Transversais , Transmissão de Doença Infecciosa , Feminino , Infecções por HIV/transmissão , Hepatite B/transmissão , Hepatite C/transmissão , Hospitais Universitários , Humanos , Masculino , Estudos Soroepidemiológicos , Inquéritos e Questionários
20.
Braz J Infect Dis ; 8(6): 431-9, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15880234

RESUMO

Occult hepatitis B virus (HBV) infections have been identified in patients with chronic hepatitis C virus (HCV) infection, although the clinical relevance of occult HBV infection remains controversial. We searched for serum HBV DNA in 106 HBsAg negative/anti-HBc positive patients with chronic HCV infection and in 150 blood donors HBsAg negative/anti-HBc positive/anti-HCV negative (control group) by nested-PCR. HCV genotyping was done in 98 patients and percutaneous needle liver biopsies were performed in 59 patients. Fifty-two patients were treated for HCV infection with interferon alone (n=4) or combined with ribavirin (n=48) during one year. At the end and 24 weeks after stopping therapy, they were tested for HCV-RNA to evaluate the sustained virological response (SVR). Among the 106 HCV-positive patients, 15 (14%) were HBV-DNA positive and among the 150 HCV-negative blood donors, 6 (4%) were HBV-DNA positive. Liver biopsy gave a diagnosis of liver cirrhosis in 2/10 (20%) of the HBV-DNA positive patients and in 6/49 (12%) of the HBV-DNA negative patients. The degree of liver fibrosis and portal inflammation was similar in HCV-infected patients HBV-DNA, irrespective of HBV-DNA status. SVR was obtained in 37.5% of the HBV-DNA positive patients and in 20.5% of the HBV-DNA negative patients; this difference was not significant. In conclusion, these data suggested that occult HBV infection, which occurs at a relatively high frequency among Brazilian HCV-infected patients, was not associated with more severe grades of inflammation, liver fibrosis or cirrhosis development and did not affect the SVR rates when the patients were treated with interferon or with interferon plus ribavirin.


Assuntos
Antivirais/uso terapêutico , Hepatite B/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Fígado/patologia , Ribavirina/uso terapêutico , Adulto , Biópsia por Agulha , Estudos de Casos e Controles , DNA Viral/análise , Quimioterapia Combinada , Feminino , Genótipo , Hepatite B/complicações , Hepatite B/patologia , Vírus da Hepatite B/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Humanos , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco
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