QUANTITATIVE ASSESSMENT OF HEPATIC FUNCTION IN CHRONIC HCV (QLFT)

慢性丙型肝炎肝功能的定量评估 (QLFT)

• 批准号: 7604372
• 负责人: Gregory Thomas Everson
• 金额: $ 1.31万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604372
• 关键词: Alanine Transaminase; Alkaline Phosphatase; Antipyrine; Ascites; Aspartate Transaminase; Bilirubin; Biochemical; Blood; Caffeine; California; Cholates; Chronic; Clinical; Colorado; Computer Retrieval of Information on Scientific Projects Database; Computers; Confidence Intervals; Consent; Data; Data Coordinating Center; Development; Encephalopathies; End Point; Enrollment; Functional disorder; Funding; Galactose; Grant; Hemorrhage; Hepatic; Hepatic Mass; Hepatobiliary; Injury; Institution; Interferons; Lidocaine; Liver; Liver Function Tests; Liver diseases; Mails; Maintenance; Measurement; Measures; Medical; Multivariate Analysis; New England; Outcome; Participant; Patients; Predictive Value; Prevention therapy; Reporting; Research; Research Institute; Research Personnel; Resources; Saliva; Sampling; Scanning; Serum; Source; Spleen; Standards of Weights and Measures; Techniques; Testing; Treatment Protocols; United States National Institutes of Health; Universities; Virginia; cholate; college; liver function; monoethylglycinexylidide; single photon emission computed tomography; stable isotope

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. Long-term use of PEG Interferon (maintenance treatment) may slow the progression of liver disease. Endpoints for effective therapy are prevention of clinical decompensation (ascites, variceal hemorrhage, and encephalopathy) and stabilization of liver function. Conventional liver tests (serum bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase) do not quantitate hepatic function but only assess the presence or absence of hepatobiliary injury. We hypothesize that quantitative tests of liver function will be more useful than standard biochemical measurements, and more sensitive than clinical endpoints for evaluating the degree and progression of hepatic dysfunction. Patients enrolled in the HALT C trial at the University of Colorado, Medical College of Virginia, and University of California, Irvine, will be invited to participate. A signed consent, specific for this study, will be required of all participants. Participants will undergo quantitative assessment of hepatic function at baseline, and at 2 and 4 years of the maintenance treatment protocol. Hepatic function will be measured by clearance techniques and quantitative liver-spleen scan. Test compounds used in clearance studies will include: cholate (dual stable isotopes, blood), lidocaine (MEGX, blood), antipyrine (saliva), caffeine (saliva), and galactose (blood). Quantitative radioscintigraphy (SPECT liver-spleen scan) will be used to measure perfused hepatic mass. Test compounds will be administered both orally (2H4-cholate, caffeine, antipyrine) and intravenously (13C-cholate, galactose, lidocaine). Quantitative Liver-Spleen Scan (SPECT) will also be performed. Tapes/computer files from these studies will be electronically transferred or mailed to the analytical computing facility (UCI). Data generated from this trial will be managed and analyzed by New England Research Institute (NERI), a separately funded data coordinating center (DCC). All of the studies done to quantitate hepatic function are continuous variables and will be reported to the Data Coordinating Center using standard report forms. The results of the baseline studies will be characterized by mean, median, distribution, and confidence intervals for each of the measures of hepatic function (caffeine kelim, antipyrine kelim, antipyrine Vd, antipyrine clearance, galactose elimination capacity, MEGX15min, cholate kelim iv, cholate Vd iv, cholate Cliv, cholate Clpo, cholate SF, and perfused hepatic mass). The median value for each test will be used to divide the patient sample into two groups for analysis of the ability of the test to predict clinical progression. The predictive value of the various tests will be compared and interaction between the quantitative tests in predicting outcome will be performed by multivariate analysis of the continuous independent variables (quantitative tests) against the binomial dependent variable (development or absence of clinical decompensation).

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。 长期使用聚乙二醇干扰素（维持治疗）可能会减缓肝病的进展。 有效治疗的终点是预防临床失代偿（腹水、静脉曲张出血和脑病）和稳定肝功能。 传统的肝脏检查（血清胆红素、丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶）不能定量肝功能，只能评估是否存在肝胆损伤。 我们假设肝功能的定量测试将比标准生化测量更有用，并且比评估肝功能障碍的程度和进展的临床终点更敏感。 科罗拉多大学、弗吉尼亚医学院和加州大学欧文分校参加 HALT C 试验的患者将受邀参加。 所有参与者都需要签署专门针对本研究的同意书。 参与者将在基线以及维持治疗方案 2 年和 4 年时接受肝功能定量评估。 将通过清除技术和定量肝脾扫描来测量肝功能。 清除研究中使用的测试化合物包括：胆酸盐（双稳定同位素，血液）、利多卡因（MEGX，血液）、安替比林（唾液）、咖啡因（唾液）和半乳糖（血液）。 定量放射闪烁扫描（SPECT 肝脾扫描）将用于测量灌注的肝脏质量。 测试化合物将口服（2H4-胆酸盐、咖啡因、安替比林）和静脉内（13C-胆酸盐、半乳糖、利多卡因）施用。 还将进行定量肝脾扫描 (SPECT)。 这些研究的磁带/计算机文件将通过电子方式传输或邮寄到分析计算设施（UCI）。 该试验生成的数据将由新英格兰研究所 (NERI) 管理和分析，该研究所是一个单独资助的数据协调中心 (DCC)。 所有定量肝功能的研究都是连续变量，并将使用标准报告表格报告给数据协调中心。 基线研究的结果将通过每个肝功能指标的平均值、中位数、分布和置信区间来表征（咖啡因 kelim、安替比林 kelim、安替比林 Vd、安替比林清除率、半乳糖消除能力、MEGX15min、胆酸盐 kelim iv、胆酸盐 Vd iv、胆酸盐 Cliv、胆酸盐 Clpo、胆酸盐 SF 和灌注肝肿块）。 每个测试的中值将用于将患者样本分为两组，以分析测试预测临床进展的能力。 将比较各种测试的预测值，并通过连续自变量（定量测试）与二项式因变量（临床失代偿的发生或不存在）的多变量分析来执行预测结果的定量测试之间的相互作用。