QUANTITATIVE ASSESSMENT OF HEPATIC FUNCTION IN CHRONIC HEPATITIS C

慢性丙型肝炎肝功能的定量评估

• 批准号: 7717010
• 负责人: Mitchell L Shiffman
• 金额: $ 2.01万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717010
• 关键词: Abdomen; Ancillary Study; Antiviral Therapy; Ascites; Blood; Blood Circulation; Brain; Caffeine; Catheters; Cessation of life; Chronic Hepatitis; Chronic Hepatitis C; Cirrhosis; Clinical; Computer Retrieval of Information on Scientific Projects Database; Degenerative Disorder; Diet; Disease Progression; Eating; Encephalopathies; End Point; Evaluation; Fibrosis; Funding; Grant; Hemorrhage; Hepatic; Hepatitis C; Hepatitis C virus; Histologic; Home environment; Hour; Institution; Interferons; Intravenous; Liquid substance; Liver; Liver Function Tests; Liver diseases; Maintenance; Maintenance Therapy; Malignant neoplasm of liver; Measurement; Measures; Patients; Pharmaceutical Preparations; Prevention; Research; Research Personnel; Resources; Ribavirin; Risk; Saliva; Sampling; Scanning; Score; Source; Staging; Standards of Weights and Measures; Testing; Time; United States National Institutes of Health; Upper arm; Veins; day; liver function; liver transplantation; response; single photon emission computed tomography

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. An evaluation of the usefulness of certain tests of the liver function and liver blood circulation; an ancillary study to the HALT-C trial. It is estimated that 8,000 to 10,000 patients in the U.S. died in 1998 and 30,000 will die annually by the year 2010, as a direct result of advanced liver disease from chronic hepatitis C (HCV). Patients with advanced histologic stages of hepatitis C, bridging fibrosis and cirrhosis, are at greatest risk of developing clinical evidence of hepatic decompensation, need for liver transplantation, liver cancer, and death from liver disease. The hypothesis for the National Institutes of Health Trial of HCV nonresponders with fibrosis or cirrhosis is that long-term use of antiviral therapy (maintenance treatment) will slow the progression of liver disease. In noncirrhotic patients who have significant fibrosis, effective maintenance therapy is expected to slow or stop histologic progression to cirrhosis. Standard endpoints for effective response to maintenance therapy in cirrhotic patients are prevention of clinical decompensation, (ascites [the accumulation of fluid in the abdomen], variceal hemorrhage[bleeding from enlarged veins], encephalopathy [degenerative diseases of the brain]), and stabilization of liver function as measured clinically by Childs-Turcott-Pugh (CTP) score. However, clinical endpoints are insensitive parameters of disease progression. HALT-C treatment is long-term therapy with interferon plus ribavirin. Testing will be done three times during this study. First, at baseline, before the beginning of the HALT-C medications, and two and four years after the first six months of treatment. Each testing period will be the same. Patients will be admitted to the CRC for one day. Diets will be caffeine free three days before and three days after the tests and there will be a pre-admit overnight fast. Saliva samples will be collected at home twice a day for two days after testing and then brought to the CRC. At the time of testing , there will be an intravenous catheter placed into the arm to draw blood and administer test compounds. Six saliva samples will be collected over three days. Three compounds will be given by vein and three will be given orally. Blood will be drawn to see how the liver clears these compounds. After the tests are complete, the patient will eat a normal meal. Two hours later a SPECT Scan will be done to allow measurement of hepatic function.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 评估某些肝功能和肝脏血液循环测试的有用性； HALT-C 试验的辅助研究。 据估计，1998 年美国有 8,000 至 10,000 名患者死亡，到 2010 年，每年将有 30,000 名患者死于慢性丙型肝炎 (HCV) 导致的晚期肝病。丙型肝炎组织学晚期、桥接纤维化和肝硬化患者出现肝功能失代偿临床证据、需要肝移植、肝癌和肝病死亡的风险最大。 美国国立卫生研究院对患有纤维化或肝硬化的丙肝无反应者进行的试验假设是，长期使用抗病毒治疗（维持治疗）将减缓肝病的进展。对于有明显纤维化的非肝硬化患者，有效的维持治疗有望减缓或阻止组织学进展为肝硬化。肝硬化患者维持治疗有效反应的标准终点是预防临床失代偿（腹水[腹部积液]、静脉曲张出血[静脉扩大出血]、脑病[大脑退行性疾病]），以及通过Childs-Turcott-Pugh (CTP)评分临床测量的肝功能稳定。然而，临床终点是疾病进展的不敏感参数。 HALT-C 治疗是干扰素加利巴韦林的长期治疗。本研究期间将进行三次测试。首先，在基线时，在开始 HALT-C 药物之前，以及在治疗的前六个月后两年和四年。每个测试周期都是相同的。患者将在 CRC 住院一天。检查前三天和检查后三天饮食中将不含咖啡因，并且入院前将禁食过夜。检测后，将在两天内每天在家采集两次唾液样本，然后带到 CRC。 测试时，将一根静脉导管插入手臂以抽血并施用测试化合物。将在三天内收集六份唾液样本。三种化合物将通过静脉给药，三种化合物将口服给药。将抽取血液来观察肝脏如何清除这些化合物。 检查完成后，患者将正常进食。两小时后将进行 SPECT 扫描以测量肝功能。