HEPATITIS C IN CHILDHOOD CANCER SURVIVORS

该建议的广泛、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、纵向自然病史研究。本研究的具体目的是：(1)收集儿童时期因输血感染HCV的儿童癌症幸存者队列，(2)建立肝硬化、慢性活动性肝炎、纤维化、肝脏失代偿、肝癌、肝细胞癌和其他HCV相关肝脏后遗症的预测模型。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，该队列的研究应促进对临床显著肝病患者易感因素的理解。到目前为止，1962年至1992年7月在St. Jude儿童研究医院接受输血的3767例患者中，有1441例（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；这些患者中有59人已入组，其余51人可能有资格参加HCV自然史的纵向研究。根据我们目前筛选的队列中HCV感染的流行程度，我们估计293例输血但未经检测的患者将呈HCV血清阳性。在对预期生存率和研究参与率进行调整后，我们估计我们将在一项前瞻性流行病学研究中招募268名HCV血清阳性癌症幸存者。由于本提案的最终目的是确定该队列中进展为临床显著肝脏疾病的风险，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。

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.