HEPATITIS C IN CHILDHOOD CANCER SURVIVORS

儿童癌症幸存者中的丙型肝炎

• 批准号: 6174412
• 负责人: MELISSA M HUDSON
• 金额: $ 30.36万
• 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/6174412
• 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。 该提案的具体目标是（1）收集儿童时期因输血感染丙肝病毒的儿童癌症幸存者队列，以及（2）开发肝硬化、慢性活动性肝炎、纤维化、肝脏失代偿、肝癌、肝细胞癌和其他丙肝相关肝脏后遗症后续发展的预测模型。 与其他慢性 HCV 感染组相比，该队列的独特之处在于这些患者在年轻时感染并接受免疫抑制或肝毒性治疗。 因此，该队列的研究应增进对使患者易患具有临床意义的肝病的临床危险因素的理解。 迄今为止，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 名患者中的 1,441 名（38.3%）已通过酶免疫印迹测定进行了 HCV 筛查。 其中，110 名（7.6%）患者可检测到 HCV 抗体；其中 59 名患者已入组，其余 51 名患者可能有资格参与 HCV 自然史的纵向研究。 根据我们目前筛选的队列中 HCV 感染的流行情况，我们估计 293 名接受过输血但未经检测的患者将出现 HCV 血清阳性。 在调整预期生存率和研究参与率后，我们估计将总共招募 268 名 HCV 血清阳性癌症幸存者参加前瞻性流行病学研究。 由于该提案的最终目的是确定该队列中进展为具有临床意义的肝病的风险，并阐明年龄、免疫抑制和肝毒性癌症治疗对慢性 HCV 感染结果的影响，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。