RESUMO
BACKGROUND AND AIM: Ledipasvir with sofosbuvir (LED/SOF) for the treatment of patients infected with genotype 1 hepatitis C virus can be used with or without ribavirin (RBV). RBV is well known to promote significant adverse events (AE). The aim of this study was to compare the efficacy and safety of treatment with LED/SOF, with or without RBV, in patients infected with hepatitis C virus genotype 1. METHODS: We performed a systematic review followed by a pairwise meta-analysis including randomized controlled trials that reported efficacy (rapid virological response, sustained virological response at 4 and 12 weeks post-treatment (SVR4 and 12), and viral relapse) and safety outcomes (any AE, serious AE, discontinuation owing to AE, anemia, and rash). It was performed a subgroup analysis evaluating the SVR12 including only cirrhotic patients. Results were reported as risk ratios (RR) and with 95% confidence intervals (95% CI). RESULTS: Seven randomized controlled trials were analyzed. LED/SOF with RBV showed a worse safety profile when compared with LED/SOF without RBV for the following outcomes: any AE (RR 0.56 [95% CI 0.46-0.69]), anemia (RR 0.08 [95% CI 0.04-0.17]), and rash (RR 0.35 [95% CI 0.19-0.65]). No significant differences were observed regarding serious AE, rapid virological response, SVR4, SVR12, or viral relapse. The subgroup analysis did not show significant differences between either treatment groups. CONCLUSION: Administration of LED/SOF + RBV to treatment-naïve patients with or without cirrhosis, and non-cirrhotic treatment-experienced patients, did not promote significant additional benefits. Furthermore, it is still unclear whether cirrhotic treatment-experienced patients could benefit from combined therapy.
Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Bases de Dados Bibliográficas , Quimioterapia Combinada , Fluorenos/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ribavirina/efeitos adversos , Sofosbuvir/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVE: Wilson's disease (WD) is an inborn error of metabolism caused by abnormalities of the copper-transporting protein encoding gene ATP7B. In this study, we examined ATP7B for mutations in a group of patients living in southern Brazil. METHODS: 36 WD subjects were studied and classified according to their clinical and epidemiological data. In 23 subjects the ATP7B gene was analyzed. RESULTS: Fourteen distinct mutations were detected in at least one of the alleles. The c.3207C>A substitution at exon 14 was the most common mutation (allelic frequency=37.1%) followed by the c.3402delC at exon 15 (allelic frequency=11.4%). The mutations c.2018-2030del13 at exon 7 and c.4093InsT at exon 20 are being reported for the first time. CONCLUSION: The c.3207C>A substitution at exon 14, was the most common mutation, with an allelic frequency of 37.1%. This mutation is the most common mutation described in Europe.
Assuntos
Adenosina Trifosfatases/genética , Proteínas de Transporte de Cátions/genética , Estudos de Associação Genética , Degeneração Hepatolenticular/genética , Mutação/genética , Adolescente , Adulto , Criança , ATPases Transportadoras de Cobre , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: Wilson's disease (WD) is an inborn error of metabolism caused by abnormalities of the copper-transporting protein encoding gene ATP7B. In this study, we examined ATP7B for mutations in a group of patients living in southern Brazil. METHODS: 36 WD subjects were studied and classified according to their clinical and epidemiological data. In 23 subjects the ATP7B gene was analyzed. RESULTS: Fourteen distinct mutations were detected in at least one of the alleles. The c.3207C>A substitution at exon 14 was the most common mutation (allelic frequency=37.1%) followed by the c.3402delC at exon 15 (allelic frequency=11.4%). The mutations c.2018-2030del13 at exon 7 and c.4093InsT at exon 20 are being reported for the first time. CONCLUSION: The c.3207C>A substitution at exon 14, was the most common mutation, with an allelic frequency of 37.1%. This mutation is the most common mutation described in Europe. .
OBJETIVO: A doença de Wilson (DW) é um erro inato do metabolismo causado por abnormalidades no gene ATP7B, que codifica uma proteína transportadora de cobre. Neste estudo, avaliamos as mutações do gene ATP7B em um grupo de pacientes do sul do Brasil. MÉTODOS: Foram estudados 36 pacientes com DW e classificados do ponto de vista clínico e epidemiológico. Em 23 pacientes, o gene ATP7B foi analisado. RESULTADOS: A substituição c.3207C>A no éxon 14 foi a mutação mais comum seguida pela mutação c.3402delC no éxon 15 . A mutação c.2018-2030del13 no éxon 7 e a c.4093InsT no éxon 20 são relatadas pela primeira vez na literatura. CONCLUSÃO: A mutação do gene ATP7B, com a substituição c.3207C>A no éxon 14 foi a mais frequente. Esta mutação é a mais comumente encontrada em pacientes europeus. .
Assuntos
Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Adenosina Trifosfatases/genética , Proteínas de Transporte de Cátions/genética , Estudos de Associação Genética , Degeneração Hepatolenticular/genética , Mutação/genéticaRESUMO
BACKGROUND: Long-term data on the clinical follow-up and the treatment effectiveness of Wilson's disease are limited because of the low disease frequency. This study evaluated a retrospective cohort of Wilson's disease patients from southern Brazil during a 40-year follow-up period. METHODS: Thirty-six Wilson's disease patients, diagnosed from 1971 to 2010, were retrospectively evaluated according to their clinical presentation, epidemiological and social features, response to therapy and outcome. RESULTS: Examining the patients' continental origins showed that 74.5% had a European ancestor. The mean age at the initial symptom presentation was 23.3 ± 9.3 years, with a delay of 27.5 ± 41.9 months until definitive diagnosis. At presentation, hepatic symptoms were predominant (38.9%), followed by mixed symptoms (hepatic and neuropsychiatric) (30.6%) and neuropsychiatric symptoms (25%). Kayser-Fleischer rings were identified in 55.6% of patients, with a higher frequency among those patients with neuropsychiatric symptoms (77.8%). Eighteen patients developed neuropsychiatric features, most commonly cerebellar syndrome. Neuroradiological imaging abnormalities were observed in 72.2% of these patients. Chronic liver disease was detected in 68% of the patients with hepatic symptoms. 94.2% of all the patients were treated with D-penicillamine for a mean time of 129.9 ± 108.3 months. Other treatments included zinc salts, combined therapy and liver transplantation. After initiating therapy, 78.8% of the patients had a stable or improved outcome, and the overall survival rate was 90.1%. CONCLUSION: This study is the first retrospective description of a population of Wilson's disease patients of mainly European continental origin who live in southern Brazil. Wilson's disease is treatable if correctly diagnosed, and an adequate quality of life can be achieved, resulting in a long overall survival.
Assuntos
Degeneração Hepatolenticular/terapia , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Brasil/epidemiologia , Quelantes/uso terapêutico , Criança , Feminino , Seguimentos , Degeneração Hepatolenticular/epidemiologia , Degeneração Hepatolenticular/etnologia , Degeneração Hepatolenticular/patologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Penicilamina/uso terapêutico , Estudos Retrospectivos , Distribuição por Sexo , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Long-term data on the clinical follow-up and the treatment effectiveness of Wilson's disease are limited because of the low disease frequency. This study evaluated a retrospective cohort of Wilson's disease patients from southern Brazil during a 40-year follow-up period. METHODS: Thirty-six Wilson's disease patients, diagnosed from 1971 to 2010, were retrospectively evaluated according to their clinical presentation, epidemiological and social features, response to therapy and outcome. RESULTS: Examining the patients' continental origins showed that 74.5 percent had a European ancestor. The mean age at the initial symptom presentation was 23.3 ± 9.3 years, with a delay of 27.5 ± 41.9 months until definitive diagnosis. At presentation, hepatic symptoms were predominant (38.9 percent), followed by mixed symptoms (hepatic and neuropsychiatric) (30.6 percent) and neuropsychiatric symptoms (25 percent). Kayser-Fleischer rings were identified in 55.6 percent of patients, with a higher frequency among those patients with neuropsychiatric symptoms (77.8 percent). Eighteen patients developed neuropsychiatric features, most commonly cerebellar syndrome. Neuroradiological imaging abnormalities were observed in 72.2 percent of these patients. Chronic liver disease was detected in 68 percent of the patients with hepatic symptoms. 94.2 percent of all the patients were treated with D-penicillamine for a mean time of 129.9 ± 108.3 months. Other treatments included zinc salts, combined therapy and liver transplantation. After initiating therapy, 78.8 percent of the patients had a stable or improved outcome, and the overall survival rate was 90.1 percent. CONCLUSION: This study is the first retrospective description of a population of Wilson's disease patients of mainly European continental origin who live in southern Brazil. Wilson's disease is treatable if correctly diagnosed, and an adequate quality of life can be achieved, resulting in a long overall survival.
Assuntos
Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Degeneração Hepatolenticular/terapia , Distribuição por Idade , Fatores Etários , Brasil/epidemiologia , Quelantes/uso terapêutico , Seguimentos , Degeneração Hepatolenticular/epidemiologia , Degeneração Hepatolenticular/etnologia , Degeneração Hepatolenticular/patologia , Fígado/patologia , Penicilamina/uso terapêutico , Estudos Retrospectivos , Distribuição por Sexo , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJETIVO: Conhecer a prevalência e as características epidemiológicas de pacientes com fibromialgia e infecção pelo vírus da hepatite C. MÉTODOS: oitenta e quatro pacientes com o vírus da hepatite C foram consecutivamente avaliados em um período de 6 meses. A prevalência da fibromialgia e as características da população foram avaliadas por anamnese, exame físico e revisões de prontuários. RESULTADOS: a síndrome de fibromialgia foi verificada em 12 pacientes (14,2 por cento), com 23 por cento das mulheres entrevistadas apresentando esse diagnóstico. A porcentagem entre homens também foi alta (8 por cento). Outro dado relevante foi a prevalência de alteração do sono encontrada no grupo de pacientes com o vírus da hepatite C, alcançando 50 por cento. Não houve relação entre a prevalência da fibromialgia e o tempo de doença hepática (média de 3,37 anos). Também não foi encontrada diferença no grau de comprometimento hepático (avaliado com ALT e biópsia hepática) entre os grupos com ou sem fibromialgia. CONCLUSÕES: a síndrome de fibromialgia teve grande prevalência neste estudo. A prevalência dessa doença em mulheres infectadas com o vírus da hepatite C foi de aproximadamente 25 por cento, índice elevado em relação à média mundial, mas compatível com a literatura. Embora não faça parte da investigação de rotina, especial atenção deve ser dada, durante a anamnese e exames físicos e laboratoriais, a pacientes com esse quadro. Futuros estudos trarão mais informações sobre essa associação e os mecanismos patogênicos da fibromialgia em pacientes infectados com o vírus da hepatite C.
Assuntos
Masculino , Feminino , Humanos , Síndrome de Fadiga Crônica , Fibromialgia , Hepacivirus , Hepatite C , Doenças Reumáticas , Transtornos do Sono-VigíliaRESUMO
Hepatitis C virus (HCV) infection is very common among hemodialysis (HD) patients. Transmission of Infection in this setting has been related to the number of blood transfusions, the duration of hemodialysis and to nosocomial transmission of virus in the dialysis unit. We conducted a study of 74 HD patients to determine the frequency of HCV at a single point in time (cross-sectional analysis), and to evaluate the association between HCV infection and patients' demographic, clinical and biochemical features. Serum samples were tested for anti-HCV antibodies using a third-generation enzyme-linked immunosorbent assay (ELISA). In the case of a positive result, third-generation recombinant immunoblot and HCV RNA detection by polymerase chain reaction (PCR) tests were performed. Collected data included the patient's age, gender, time on HD, number of blood transfusions and serum alanine aminotransferase (ALT) activity. Twenty-nine patients (29/74.4 percent) were found to be HCV positive using a third generation ELISA assay. From these 29 patients, 27 were also positive by recombinant immunoblot assay and 2 patients had indederminate results. In the subgroup of anti-HCV ELISA positive, 20 (69 percent) of the 29 patients had detectable HCV RNA. The HCV RNA positive patients had received more blood transfusions (15ñ3 vs.5ñ1 units of packed red blood cells, p<0.0001) and had been on HD for a longer period of time than the HCV RNA negative patients (65ñ32 vs.32ñ29 months, p<0.0001). Mean serum ALT levels were significantly higher in the HCV RNA positive group (30ñ18 vs.15ñ9,p<0.0001). We were unable to determine the most likely mode of transmission in our unit, but these results emphasize the need for strict adherence to blood collecting and handing precautions, careful attention to hygiene in the dialysis units, and sterilization of dialysis machines in order to properly combat this frequent infection.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Unidades Hospitalares de Hemodiálise , Hepatite C/epidemiologia , Hepatite C/virologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Controle de Infecções , PrevalênciaRESUMO
No período de 24 de setembro de 1991 a 31 de setembro de 1995 foram realizados 35 transplantes hepáticos no Hospital de Clínicas da Universidade Federal do Paraná. A idade dos pacientes variou de 6 a 57 anos, com média de 26 anos. As indicaçöes do procedimento foram bastante variáveis e as mais comuns foram a cirrose criptogenética, cirrose por hepatite autoimune, cirrose alcoólica por hepatite C. Trinta e quatro implantes foram realizados de 1 a 4 horas após a retirada do fígado do doador e um 12 horas após. O implante foi realizado com todo o fígado em 34 pacientes e com os segmentos I, II, III e IV em um paciente. As complicaçöes pós-operatórias mais frequentes foram a rejeiçäo celular, insuficiência renal aguda, síndrome da angústia respiratória do adulto e trombose da artéria hepática. Seis pacientes (17 por cento) foram a óbito durante a internaçäo hospitalar e sete (20 por cento) faleceram no pós-operatório tardio (seguimento de 1 a 48 meses). As causas de óbito foram múltiplas e a principal foi a infecçäo viral. A qualidade de vida após 6 meses de transplante é muito boa, com o paciente retornando às suas atividades normais
Assuntos
Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Hepatopatias , Cirrose Hepática , Rejeição de Enxerto , Transplante de Fígado , Hepatopatias/cirurgiaRESUMO
Transplante hepático é hoje uma forma aceita e bem sucedida de tratamento de doença hepática avançada. Há contudo desconhecimento de grande parcela da classe médica a respeito das suas indicaçöes e contra-indicaçöes, bem como aos resultados deste procedimento. Tem este trabalho o propósito de delinear as indicaçöes e contra-indicaçöes do transplante hepático