QUANTITATIVE ASSESSMENT OF HEPATIC FUNCTION IN CHRONIC HCV (QLFT)

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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).