HEPATITIS C IN CHILDHOOD CANCER SURVIVORS

儿童癌症幸存者中的丙型肝炎

• 批准号: 6514468
• 负责人: MELISSA M HUDSON
• 金额: $ 23.11万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-15 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6514468
• 关键词: blood transfusion; chronic disease /disorder; clinical research; disease /disorder etiology; disease /disorder model; disease /disorder onset; disease /disorder proneness /risk; epidemiology; hepatitis C; histology; human subject; immunosuppression; liver disorder; long term survivor; longitudinal human study; model design /development; outcomes research; pathologic process; pediatric neoplasm /cancer; prognosis

The broad, long-term objective of this proposal is to conduct a prospective, longitudinal natural history study of hepatitis C (HCV) infection in a well-defined cohort of childhood cancer survivors. The specific aims of this proposal are (1) to assemble a cohort of survivors of childhood cancer who were infected with HCV by transfusion during childhood, and (2) to develop predictive models for the subsequent development of cirrhosis, chronic active hepatitis, fibrosis, liver decompensation, hepatoma, hepatocellular carcinoma, and other HCV-related hepatic sequelae. This cohort is unique in comparison with other groups with chronic HCV infection in that these patients acquired the infection when they were young and were receiving immunosuppressive or hepatotoxic therapy. Thus, studies of this cohort should advance the understanding of clinical risk factors that predispose patients to clinically significant liver disease. So far, 1,441 of 3,767 (38.3 percent) patients who received transfusions at St. Jude Children's Research Hospital between 1962 and July 1992 have been screened for HCV by enzyme immunoblot assay. Of these, 110 (7.6 percent) patients have detectable HCV antibodies; 59 of these patients have been enrolled, and the remaining 51 are potentially eligible for participation in a longitudinal study of the natural history of HCV. Based on the prevalence of HCV infection in our currently screened cohort, we estimate that 293 transfused, but untested patients will be HCV seropositive. After adjusting for the anticipated rates of survival and study participation, we estimate that we will enroll a total of 268 HCV seropositive cancer survivors in a prospective epidemiologic study. As the ultimate aims of this proposal are to define the risk of progression to clinically significant liver disease in this cohort and to elucidate the impact of age, immunosuppression, and hepatotoxic cancer therapy on the outcome of chronic HCV infection, the histologic findings of these study patients will be correlated with clinical, laboratory, and diagnostic imaging variables.

该提案的广泛、长期目标是在明确定义的儿童癌症幸存者队列中进行丙型肝炎（HCV）感染的前瞻性、纵向自然史研究。 该提案的具体目的是（1）收集一组在儿童时期通过输血感染HCV的儿童癌症幸存者，以及（2）开发肝硬化、慢性活动性肝炎、纤维化、肝失代偿、肝癌、肝细胞癌和其他HCV相关肝脏后遗症后续发展的预测模型。 该队列与其他慢性HCV感染组相比是独特的，因为这些患者在年轻时获得感染并接受免疫抑制或肝毒性治疗。 因此，该队列的研究应该促进对使患者易患临床显著肝病的临床风险因素的理解。 到目前为止，在1962年至1992年7月期间在圣裘德儿童研究医院接受输血的3,767名患者中，有1,441名（38.3%）通过酶免疫印迹法进行了HCV筛查。 其中，110例（7.6%）患者可检测到HCV抗体;其中59例患者已入组，其余51例可能有资格参与HCV自然史的纵向研究。 根据我们目前筛查队列中HCV感染的患病率，我们估计293例输血但未检测的患者将为HCV血清阳性。 在调整了预期的生存率和研究参与率后，我们估计我们将在前瞻性流行病学研究中招募总共268名HCV血清阳性癌症幸存者。 由于该提案的最终目的是确定该队列中进展为临床显著肝病的风险，并阐明年龄、免疫抑制和肝毒性癌症治疗对慢性HCV感染结局的影响，因此这些研究患者的组织学结果将与临床、实验室和诊断成像变量相关。