Análise crítica da política de alocação de órgãos para transplante de fígado no Brasil

Liver transplantation is now the standard treatment for end-stage liver disease. Given the shortage of liver donors and the progressively higher number of patients waiting for transplantation, improvements in patient selection and optimization of timing for transplantation are needed. Several solutions have been suggested, including increasing the donor pool; a fair policy for allocation, not permitting variables such as age, gender, and race, or third-party payer status to play any role; and knowledge of the natural history of each liver disease for which transplantation is offered. To observe ethical rules and distributive justice (guarantee to every citizen the same opportunity to get an organ), the "sickest first" policy must be used. Studies have demonstrated that death has no relationship with waiting time, but rather with the severity of liver disease at the time of inclusion. Thus, waiting time is no longer part of the United Network for Organ Sharing distribution criteria. Waiting time only differentiates between equally severely diseased patients. The authors have analyzed the waiting list mortality and 1-year survival for patients of the State of São Paulo, from July 1997 through January 2001. Only the chronological criterion was used. According to "Secretaria de Estado da Saúde de São Paulo" data, among all waiting list deaths, 82.2% occurred within the first year, and 37.6% within the first 3 months following inclusion. The allocation of livers based on waiting time is neither fair nor ethical, impairs distributive justice and human rights, and does not occur in any other part of the world.Transplante hepático é tratamento de escolha para pacientes portadores de doença hepática em fase terminal. Pela escassez de órgãos e número crescente de receptores, seleção dos candidatos e otimização do momento do procedimento são necessários. Estratégias foram apontadas: aumento do número de doadores; política justa impossibilitando que idade, sexo, raça, condição financeira façam diferença; conhecimento da história natural de cada doença hepática para a qual o trans plante hepático é indicado. Para obedecer aos princípios da ética médica e de justiça distributiva (garantia a todo cidadão a mesma oportunidade de obter um enxerto), é necessário estabelecer critérios de gravidade. Estudos (Institute of Medicine e Freeman e col.) demonstraram que tempo de lista não tem relação direta com o número de óbitos e sim com a gravidade dos pacientes no momento da inscrição. Assim, nos EUA, o tempo de lista foi retirado no cálculo para alocação, servindo apenas para diferenciar pacientes igualmente graves. Mortalidade em lista de espera bem como sobrevida de um ano no Estado de São Paulo, onde a alocação obedece critério cronológico rígido desde 1997, foram analisados. Dados da Secretaria de Estado da Saúde de São Paulo, no período de julho de 1997 a janeiro de 2001, dentre os óbitos em lista, 82.2% ocorreram dentro do 1º ano de lista, sendo 37,6% nos primeiros 3 meses após a inclusão

Peginterferon alfa-2a (40KD) (PEGASYS®) plus ribavirin (COPEGUS®) in retreatment of chronic hepatitis C patients, nonresponders and relapsers to previous conventional interferon plus ribavirin therapy

Peginterferon alfa plus ribavirin is currently the treatment of choice for chronic hepatitis C. Peginterferon alfa-2a (40KD) plus ribavirin has given an overall sustained virological response of 18% in F3/F4 previous nonresponder US patients. We evaluated the effectiveness of peginterferon alfa-2a (40KD) plus ribavirin in Brazilian patients who were relapsers or nonresponders to previous interferon-based therapy. One-hundred-thirty-four patients with biopsy-proven chronic hepatitis C, HCV RNA positive, elevated ALT and who were either relapsers (n=37) or nonresponders (n=97) to at least 24 weeks of conventional interferon/ribavirin therapy were retreated with peginterferon alfa-2a (40KD) 180mg/qw and ribavirin 800mg bid for 48 weeks. Efficacy was assessed as virological response (defined as undetectable HCV RNA) at the end of treatment (EoT) and at the end of follow-up (SVR - Sustained Virological Response). Safety assessments consisted of clinical and laboratory evaluations. In the patient sample, 72% were genotype 1 and 34% were cirrhotic. In an intention-to-treat analysis, relapser patients showed 78% EoT response and 51% SVR. Nonresponders showed 57% EoT response and 26% SVR. Positive predictive factors of SVR were non-1 genotype and relapser state. Six percent of the patients interrupted treatment because of adverse events and 45% had dose reduction (mainly associated with leucopenia and anemia). Brazilian patient relapsers and nonresponders to conventional interferon and ribavirin treatment can achieve a sustained virological response when retreated with peginterferon alfa-2a (40KD) and ribavirin. The safety profile is similar to that of naive patients.Federal University of São PauloSanta Casa de Misericórdia Gastroenterology ServiceFederal University of ParáFederal University of Juiz de ForaSão Paulo University Medical School of Ribeirão PretoEmílio Ribas InstituteFederal University of Minas GeraisMedical School of São José do Rio PretoFederal University of AlagoasFederal University of Santa CatarinaFederal University of BahiaTropical Medicine FundationOswaldo Cruz HospitalFederal University of ParaíbaRocheUNIFESPSciEL

Pharmacoeconomics applied to chronic hepatitis C

Life expectancy has increased over the last century as it had never been before. This is the result of a combination of many favorable variables such as level of education, improved socio-economic environment and development of medicine. However, new improvements demand heavy investment. Thus, the incorporation of medical technology became a health and economic issue. The pharmacoeconomic knowledge field is being developed to help in the analysis of medical costs and patient needs. The applies to hepatitic C, a common and chronic worldwide disease. In this article, the authors describe the rational behind this type of health economic analysis and review a hepatitis C model. Overall, in a non-Brazilian scenario, it was demonstrated that peginterferon alfa-2a (40KD) is cost effective in the treatment of HCV disease

Estudo dos auto-anticorpos nas Hepatites virais crônicas B e C antes, durante e após tratamento com Interferon-alfa

This study was undertaken to investigate the presence of autoantibodies in patients with chronic viral hepatitis B and C, before, during and after interferon-alpha (IFN-alpha) therapy and to study their relation to dose and type of IFN-alpha and response to treatment. Fifty patients with chronic hepatitis were divided in two groups, a control-group of 21 patients (10 type B and 11 type C) who were followed for 6 months without treatment and an IFN-group consisting of 29 patients (8 type B and 21 type C) who received IFN therapy for 6 months. Serum samples were tested for a range of antibodies at the start of the study, during therapy and at the end of the 6 month period. Antibodies tested for included: antinuclear, smooth muscle, antimitochondrial, parietal cell and thyroid microsomal. Four (8%) of the total patient group had autoantibodies at the beginning of the study (two in each group). During the follow-up period no patient in the control group developed antibodies compared with 3 (11%) patients in the treatment group. Autoantibodies developed in patients treated with higher doses of IFN and were found in those patients who tended to show a poor response to IFN-therapy. Further studies are needed to establish the relationship between poor response to IFN-alpha and development of autoantibodies.Este estudo teve como objetivo avaliar a presença de auto-anticorpos em pacientes com hepatite crônica pelos vírus B e C, antes, durante e após tratamento com interferon-alfa (IFN-alfa), assim como estudar a relação destes anticorpos com o tipo de IFN, com a dose e com a resposta terapêutica. Cinqüenta pacientes com hepatite viral crônica foram divididos em 2 grupos: grupo-controle constituído por 21 pacientes (10 hepatites B e 11 hepatites C), que foram seguidos durante 6 meses sem tratamento e grupo-IFN constituído por 29 pacientes (8 hepatites B e 21 hepatites C), que receberam IFN-alfa durante 6 meses. Anticorpos antinúcleo, antimúsculo liso, antimitocôndria, anticélula parietal e antitireóide foram pesquisados em amostras de soro colhidas antes do início, durante e ao final do estudo. Quatro dos 50 pacientes (8%) apresentavam auto-anticorpos no início do estudo (2 em cada grupo). Durante o estudo nenhum paciente do grupo-controle desenvolveu auto-anticorpos, enquanto que 3 (11%) pacientes do grupo-IFN passaram a apresentá-los. Os auto-anticorpos ocorreram apenas em pacientes tratados com doses mais elevadas de IFN. Verificou-se ainda tendência à resposta desfavorável ao tratamento naqueles indivíduos que apresentaram ou desenvolveram auto-anticorpos. Assim, sugere-se que mais estudos sejam realizados para determinar se existe ou não relação entre resposta desfavorável e a presença ou o desenvolvimento de auto-anticorpos

Estudo dos auto-anticorpos nas Hepatites virais crônicas B e C antes, durante e após tratamento com Interferon-alfa

This study was undertaken to investigate the presence of autoantibodies in patients with chronic viral hepatitis B and C, before, during and after interferon-alpha (IFN-alpha) therapy and to study their relation to dose and type of IFN-alpha and response to treatment. Fifty patients with chronic hepatitis were divided in two groups, a control-group of 21 patients (10 type B and 11 type C) who were followed for 6 months without treatment and an IFN-group consisting of 29 patients (8 type B and 21 type C) who received IFN therapy for 6 months. Serum samples were tested for a range of antibodies at the start of the study, during therapy and at the end of the 6 month period. Antibodies tested for included: antinuclear, smooth muscle, antimitochondrial, parietal cell and thyroid microsomal. Four (8%) of the total patient group had autoantibodies at the beginning of the study (two in each group). During the follow-up period no patient in the control group developed antibodies compared with 3 (11%) patients in the treatment group. Autoantibodies developed in patients treated with higher doses of IFN and were found in those patients who tended to show a poor response to IFN-therapy. Further studies are needed to establish the relationship between poor response to IFN-alpha and development of autoantibodies.Este estudo teve como objetivo avaliar a presença de auto-anticorpos em pacientes com hepatite crônica pelos vírus B e C, antes, durante e após tratamento com interferon-alfa (IFN-alfa), assim como estudar a relação destes anticorpos com o tipo de IFN, com a dose e com a resposta terapêutica. Cinqüenta pacientes com hepatite viral crônica foram divididos em 2 grupos: grupo-controle constituído por 21 pacientes (10 hepatites B e 11 hepatites C), que foram seguidos durante 6 meses sem tratamento e grupo-IFN constituído por 29 pacientes (8 hepatites B e 21 hepatites C), que receberam IFN-alfa durante 6 meses. Anticorpos antinúcleo, antimúsculo liso, antimitocôndria, anticélula parietal e antitireóide foram pesquisados em amostras de soro colhidas antes do início, durante e ao final do estudo. Quatro dos 50 pacientes (8%) apresentavam auto-anticorpos no início do estudo (2 em cada grupo). Durante o estudo nenhum paciente do grupo-controle desenvolveu auto-anticorpos, enquanto que 3 (11%) pacientes do grupo-IFN passaram a apresentá-los. Os auto-anticorpos ocorreram apenas em pacientes tratados com doses mais elevadas de IFN. Verificou-se ainda tendência à resposta desfavorável ao tratamento naqueles indivíduos que apresentaram ou desenvolveram auto-anticorpos. Assim, sugere-se que mais estudos sejam realizados para determinar se existe ou não relação entre resposta desfavorável e a presença ou o desenvolvimento de auto-anticorpos