QUANTITATIVE ASSESSMENT OF HEPATIC FUNCTION IN CHRONIC HCV (QLFT)

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。长期使用PEG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。常规肝脏检查（血清胆红素、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、碱性磷酸酶）不定量肝功能，仅评估是否存在肝胆损伤。我们假设，肝功能定量检测将比标准生化指标更有用，并且比临床终点更敏感，以评估肝功能障碍的程度和进展。在科罗拉多大学、弗吉尼亚医学院和加州大学欧文分校参加HALT C试验的患者将被邀请参加。需要所有受试者签署本研究专用的知情同意书。受试者将在基线以及维持治疗方案的第2年和第4年接受肝功能定量评估。将通过清除技术和定量肝脾扫描测量肝功能。清除研究中使用的供试化合物包括：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）。定量放射闪烁成像（SPECT肝-脾扫描）将用于测量灌注肝质量。供试化合物将经口（2 H4-胆酸盐、咖啡因、安替比林）和静脉（13 C-胆酸盐、半乳糖、利多卡因）给药。还将进行定量肝脾扫描（SPECT）。这些研究的磁带/计算机文件将以电子方式传输或邮寄至分析计算机构（UCI）。本试验生成的数据将由新英格兰研究所（NERI）管理和分析，NERI是一家单独资助的数据协调中心（DCC）。所有用于定量肝功能的研究均为连续变量，并将使用标准报告表报告给数据协调中心。基线研究的结果将通过每项肝功能指标（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、MEGX 15 min、胆酸盐kelim iv、胆酸盐Vd iv、胆酸盐Cliv、胆酸盐Clpo、胆酸盐SF和灌注肝质量）的平均值、中位数、分布和置信区间进行表征。将使用每项检测的中位值将患者样本分为两组，以分析检测预测临床进展的能力。将比较各种检测的预测值，并通过对连续自变量（定量检测）与二项因变量（发生或不发生临床失代偿）进行多变量分析，进行定量检测在预测结局方面的相互作用。

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).