RESUMO
BACKGROUND: Adherence is important for therapy of chronic diseases, but has still not been well studied in real life in chronic hepatitis C. AIMS: To assess adherence to hepatitis C combination therapy in routine clinical practice and to identify factors associated with imperfect adherence. METHODS: This cohort study included unselected chronic hepatitis C patients initiating peginterferon α-2b plus ribavirin. 100% adherence was defined by taking all the prescribed doses of both drugs for the full initially intended duration, as declared by the patient or believed by the physician. Quality of life was assessed using the short-form health survey (SF-36) questionnaire. RESULTS: 1860 patients were analysed, including 72% treatment-naive, 36% genotype 2/3, 23% psychiatric, 44% drug addicts and 3% human immunodeficiency virus (HIV)-positive patients. Early treatment discontinuation occurred in 30% of patients. Overall, 38% of patients reported 100% adherence. Patient- and physician-reported adherences were discordant, with a 20-30% overestimation by physicians. HIV co-infection [odds ratio (OR) 2.52, 95% confidence interval (CI) 1.36-4.67], no drug use during follow-up (2.37, 1.30-4.31), genotype 3 (1.55, 1.20-2.00) and treatment-naive (1.32, 1.03-1.69) were associated with 100% adherence. Quality of life worsened during treatment but returned to baseline after the end of treatment. CONCLUSIONS: Imperfect adherence to combination therapy is common in routine patients. Adherence is markedly overestimated by physicians and is associated with some patient's baseline characteristics. Knowledge of these factors might help identify patients who are most in need of intervention and plan more frequent and accurate follow-up.
Assuntos
Hepatite C/tratamento farmacológico , Cooperação do Paciente/estatística & dados numéricos , Qualidade de Vida , Estudos de Coortes , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Observação , Polietilenoglicóis/uso terapêutico , Estudos Prospectivos , Proteínas Recombinantes , Ribavirina/uso terapêutico , Estatísticas não Paramétricas , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The efficacy of a maintenance therapy in non-responder patients with chronic hepatitis C has been essentially evaluated by histological semiquantitative scores. AIM: The aim was to evaluate the efficiency of 2 years of treatment with peginterferon alpha-2a vs alpha-tocopherol in these patients by histology, morphometry and blood markers of fibrosis. METHOD: Hundred and five HCV patients with a Metavir fibrosis score > or = 2 were randomized to receive peginterferon alpha-2a 180 microg/week (PEG) (n=55) or alpha-tocopherol (TOCO) 1000 mg/day (n=50) for 96 weeks. The primary endpoint was improvement or stabilization of the Metavir fibrosis score by biopsy performed at week 96. Secondary endpoints included a quantitative assessment of fibrosis by morphometry and changes in blood markers of fibrosis. RESULTS: There was no difference at baseline between PEG and TOCO according to the metavir (83.3 vs 86.8%, P=0.751) stage. The median fibrosis rate, measured with morphometry was 2.72 and 2.86% at day 0, and 3.66 and 2.82% at week 96, in the PEG and TOCO groups (P=0.90) respectively. However, the percentage of patients with metavir activity grade improvement was significantly higher in the PEG group vs the TOCO group (52.8 vs 23.7%, P=0.016). Non-invasive markers analysis did not show any significant change in both groups. CONCLUSION: Long-term therapy with peginterferon alpha-2a did not reduce liver fibrosis degree assessed by morphometry and blood tests as compared with alpha-tocopherol. Blood tests could be useful to assess liver fibrosis changes in clinical trials.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Cirrose Hepática/prevenção & controle , Fígado/efeitos dos fármacos , Polietilenoglicóis/uso terapêutico , alfa-Tocoferol/uso terapêutico , Adulto , Antivirais/efeitos adversos , Biomarcadores/sangue , Biópsia , Progressão da Doença , Feminino , França , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Fígado/patologia , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Valor Preditivo dos Testes , RNA Viral/sangue , Proteínas Recombinantes , Fatores de Tempo , Resultado do Tratamento , alfa-Tocoferol/efeitos adversosRESUMO
AIM: To evaluate the impact of therapeutic education on adherence to antiviral treatment and sustained virological response (SVR) in a real-life setting in genotype 2/3 hepatitis C, as there are few adherence data in genotype 2/3 infection, even from randomized trials. METHODS: This prospective survey included genotype 2/3 patients who received peg-interferon alfa-2b and ribavirin. There was no intervention. Adherence was self-reported over the past 4 wk (peg-interferon) or 7 d (ribavirin). Adherence to bitherapy was defined as adherence to the two drugs for >or= 20 wk. SVR was defined as undetectable RNA >or= 12 wk after the end of treatment. RESULTS: 370/674 patients received education during the first 3 mo of treatment. After 6 mo, adherence to bitherapy was higher in educated patients (61% vs 47%, P = 0.01). Adherence to peg-interferon was 78% vs 69% (P = 0.06). Adherence to ribavirin was 70% vs 56% (P = 0.006). The SVR (77% vs 70%, P = 0.05) and relapse (10% vs 16%, P = 0.09) rates tended to be improved. After adjustment for baseline differences, education improved adherence [Odds ratio (OR) 1.58, P = 0.04] but not the SVR (OR 1.54, P = 0.06). CONCLUSION: In genotype 2/3 patients, therapeutic education helped maintain real-life adherence to bitherapy.
Assuntos
Antivirais/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Adesão à Medicação , Educação de Pacientes como Assunto , Ribavirina/uso terapêutico , Adulto , Quimioterapia Combinada , Feminino , França , Genótipo , Pesquisas sobre Atenção à Saúde , Hepacivirus/genética , Hepatite C Crônica/genética , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polietilenoglicóis , Estudos Prospectivos , RNA Viral/sangue , Proteínas Recombinantes , Medição de Risco , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
Opiate substitution treatments radically changed the care management of HCV among drug user patients. Thanks to substitution, it is possible to treat HCV among these patients even with ongoing drug abuse. Overall, in terms of response to treatment, observance, adverse side effects and premature interruptions of treatment, the results are comparable with those observed among non drug addict patients. It is advisable nevertheless to create specific conditions which favour this total care management. The non-invasive fibrosis tests largely improve access to care as compared to liver biopsy. A multidisciplinary team is essential in addressing the associated problem of addiction, hepatitis C and psychiatric co-morbidities. HCV prevails strongly among patients in centres for drug users. These structures are particularly adapted to the management of HCV with the assistance of multidisciplinary teams and access to the non-invasive tests.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/complicações , Humanos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/virologia , Transtornos Mentais/complicações , Antagonistas de Entorpecentes/uso terapêutico , Equipe de Assistência ao Paciente , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Recusa do Paciente ao Tratamento , UltrassonografiaRESUMO
OBJECTIVE: To study management practices in the French health care system for antiviral-naïve patients with chronic hepatitis C virus (HCV) infection. METHODS AND PATIENTS: Two groups of general practitioners, group I (special training and experience in drug addiction) and group II (other general practitioners) enrolled untreated HCV positive patients and noted management practices for a 12-month period. RESULTS: Among 4660 enrolled patients, 2038 enrolled by 462 general practitioners in group I and 1756 enrolled by 588 general practitioners in group II were retained for analysis. These patients were adults, aged 42+/-14 years, who were naïve to antiviral treatment. The male/female ratio was 1: 7. Ten percent were coinfected with HIV, 12% had excessive alcohol intake, and 61% were current drug users, 75% of whom (45% of the total population) were taking replacement therapy. Minimal hepatic lesions (stage
Assuntos
Atenção à Saúde , Hepatite C Crônica/terapia , Adulto , Alcoolismo/complicações , Antivirais/uso terapêutico , Medicina de Família e Comunidade , Feminino , Seguimentos , França , Soropositividade para HIV/complicações , Acessibilidade aos Serviços de Saúde , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/classificação , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Estudos Prospectivos , Encaminhamento e Consulta , Fatores Sexuais , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Resultado do TratamentoRESUMO
BACKGROUND: Hepatitis C antiviral therapies have significant psychiatric side effects. It is therefore believed that they might exacerbate mental illness in patients with pre-existing psychiatric disorders, resulting in poor adherence and response to antiviral treatment. We aimed to assess adherence to treatment, virological outcomes and mental safety in psychiatric patients, compared with non-psychiatric patients, treated for hepatitis C. METHODS: A cohort study involved unselected hepatitis C patients on scheduled therapy with pegylated interferon-alpha2b and ribavirin, between 2002 and 2005 in France, and followed-up until 6 months after the end of treatment. Virological response was reported by the physician according to standard definitions and adverse events were monitored. Adherence to treatment was assessed by patient report. RESULTS: Among 1,860 patients, 403 (22%) had pre-existing psychiatric disorders, mostly depressive and anxiety disorders. Strict adherence was similar in psychiatric and non-psychiatric patients (35% versus 39%; P=0.20) as was the rate of sustained virological response (52% versus 51%; P=0.75). Conversely the rate of mental adverse events was higher in psychiatric patients (78% versus 57%; P<0.001). Baseline characteristics independently associated with the risk of later mental adverse events were history of depression, initial pegylated interferon-alpha2b dose and female gender. CONCLUSIONS: Antiviral therapy in hepatitis C patients with associated psychiatric disease appears as effective as in other patients but results in a higher rate of mental adverse events, emphasizing the need for close monitoring of these psychiatric patients.
Assuntos
Antivirais/efeitos adversos , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Interferon-alfa/efeitos adversos , Transtornos Mentais/induzido quimicamente , Transtornos Mentais/complicações , Polietilenoglicóis/efeitos adversos , Ribavirina/efeitos adversos , Adulto , Antivirais/uso terapêutico , Estudos de Coortes , Quimioterapia Combinada , Feminino , França/epidemiologia , Hepatite C/epidemiologia , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Masculino , Adesão à Medicação , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Qualidade de Vida , Proteínas Recombinantes , Ribavirina/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: Injection drug users are often excluded from hepatitis C virus (HCV) treatment. This study compares sustained virological response, adherence, and quality of life in patients with or without a history of illicit drug use in routine clinical practice. METHODS: This is a post-hoc analysis of a prospective, observational study conducted in 1860 patients who received peginterferon alpha-2b/ribavirin combination therapy. Nondrug users (NDUs) were defined as patients without a history of drug addiction; former drug users (FDUs) as patients who had stopped using illicit drugs or opioid maintenance therapy and active drug users (ADUs) as patients using illicit drugs or on opioid maintenance therapy. Virological response, adherence, and the health-related quality of life were assessed by the measure of HCV RNA in the serum, self-report and 36-item short-form health survey Questionnaire, respectively. RESULTS: The analyzed population included 1038 (56%) NDUs, 578 (31%) FDUs, and 244 (13%) ADUs. About 85% of ADUs were on opioid maintenance therapy and 25% used illicit drugs. Although ADUs had a more chaotic lifestyle and more psychiatric disorders, sustained virological response of ADUs (58%) did not differ from that of NDUs (49%) and FDUs (51%) (P=0.133). Adherence rates were 39% in NDUs and FDUs, and 37% in ADUs (P=0.883). Health-related quality of life was improved in the three groups after the end of treatment. CONCLUSION: Our study suggests that HCV therapy in ADUs on opioid maintenance therapy is as effective as in other HCV patients. The effectiveness of HCV therapy in illicit drug users needs to be evaluated in further studies.
Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/complicações , Analgésicos Opioides/administração & dosagem , Estudos de Coortes , Quimioterapia Combinada , Interferon alfa-2 , Adesão à Medicação , Estudos Prospectivos , Qualidade de Vida , Proteínas Recombinantes , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Inquéritos e Questionários , Resultado do TratamentoAssuntos
Hepatite C Crônica/complicações , Hepatite C Crônica/terapia , Educação de Pacientes como Assunto , Pacientes/psicologia , Alcoolismo/complicações , Aconselhamento , Infecções por HIV/complicações , Hemofilia A/complicações , Hepatite C Crônica/psicologia , Humanos , Transplante de Fígado , Obesidade/complicações , Relações Médico-Paciente , Diálise Renal , Transtornos Relacionados ao Uso de Substâncias/complicaçõesRESUMO
BACKGROUND & AIMS: Pegylated interferon alfa-ribavirin combination is the standard treatment for chronic hepatitis C, but the mechanisms by which ribavirin enhances the rate of sustained hepatitis C virus (HCV) eradication remain unknown. We aimed to investigate the role of ribavirin in HCV clearance during therapy and to evaluate the consequences of ribavirin discontinuation in patients infected with genotype 1 hepatitis C who cleared HCV RNA at week 24. METHODS: A total of 516 patients were treated with pegylated interferon alfa-2a, 180 microg/wk, plus ribavirin, 800 mg/day. Seventy percent were RNA negative at week 24. They were randomized to continue with the combination or receive pegylated interferon alone. RESULTS: Responders at week 24 who stopped ribavirin had a significantly higher rate of breakthroughs during, and relapses after, therapy (sustained virologic response, 52.8% vs 68.2%; P = .004), but their side-effect profile and quality of life tended to improve. Multiple logistic regression analysis in the pegylated interferon alfa monotherapy group allowed identification of responders at week 24 who could stop ribavirin without losing their chance of a sustained virologic response, based on baseline viral load and age. Forty-eight weeks of ribavirin may not be needed when HCV RNA is undetectable at week 2. CONCLUSIONS: We made 3 conclusions from this study. First, ribavirin primarily acts by sustaining the virologic response to pegylated interferon alfa; second, ribavirin must be administered for the full treatment duration in most genotype 1-infected patients who respond; third, baseline parameters may help identify patients who could discontinue ribavirin or reduce the dose without losing their chance of success.