HEPATITIS C IN CHILDHOOD CANCER SURVIVORS

这项建议的广泛和长期目标是在明确界定的儿童癌症幸存者队列中进行丙型肝炎(丙型肝炎)感染的前瞻性、纵向自然历史研究。这项建议的具体目的是(1)收集在儿童时期通过输血感染丙型肝炎病毒的儿童癌症幸存者队列，(2)开发预测随后发展为肝硬变、慢性活动性肝炎、纤维化、肝脏失代偿、肝癌、肝细胞癌和其他与丙型肝炎病毒相关的肝脏后遗症的模型。与其他慢性丙型肝炎感染者相比，这个队列是独一无二的，因为这些患者在年轻时就感染了丙型肝炎，并接受了免疫抑制或肝毒治疗。因此，对这一队列的研究应该会促进对临床危险因素的理解，这些因素使患者容易患上临床上重要的肝病。到目前为止，在圣犹大儿童研究医院1962年至1992年7月间接受输血的3767名患者中，有1441名(38.3%)已通过酶免疫印迹试验对丙型肝炎病毒进行了筛查。在这些患者中，110名(7.6%)患者有可检测到的丙型肝炎病毒抗体；其中59名患者已被登记，其余51名患者可能有资格参加丙型肝炎病毒自然史的纵向研究。根据我们目前筛查的队列中丙型肝炎病毒感染的流行率，我们估计293名输血但未检测的患者将是丙型肝炎病毒血清阳性。在调整了预期的存活率和研究参与率后，我们估计我们将在前瞻性流行病学研究中招募总共268名丙型肝炎病毒血清阳性的癌症幸存者。由于这项建议的最终目的是确定在这一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丙型肝炎感染结局的影响，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。

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.