We propose to continue to prospectively obtain comparisons of Tc-NGA estimates of hepatic functional capacity with quantitative functional values obtained from the 14C-aminopyrine breath test (ABT) to define the severity of liver disease. The ABT test has been found useful to assess liver function and provide a simple procedure for the quantitative assessment of microsomal and hepatocyte function in man. The test is more sensitive in detecting hepatocellular disease than standard liver function tests. The ABT is easy to perform, is non-invasive and will serve as a complement to other liver function tests. The ABT score is a reliable measure of histologic liver damage in viral hepatitis, severe hepatic necrosis from any cause, drug or viral, and in alcoholic liver disease. It also correlates well with histopathologic improvement in those conditions. Based on estimates of HBP concentration, Tc-NGA functional liver imaging should be of particular prognostic importance in diseases such as hepatic necrosis, chronic hepatitis and candidates for liver transplantation. It may serve a role in evaluating major medical or surgical therapies such as corticosteroid treatment and portal systemic shunting. We plan to examine the usefulness of Tc-NGA as a quantitative liver function test in three areas: 1) Determination of prognosis, 2) Evaluation of medical and surgical therapies, 3) Liver blood flow. All patients will have endogenous ligand assay from a serum sample. Various investigators have reported increased levels of circulating asialoglycoprotein in patients with liver disease. These values, however, are two orders of magnitude below our estimates of normal receptor concentration. Severe cirrhosis may depress [R] such that endogenous ligand may influence our receptor estimates. These values will be compared to the receptor estimates obtained from kinetic analysis. Although we have validated (see Progress Report) the in vivo receptor estimates using healthy pigs, correlation of in vitro and in vivo measurements in human disease will significantly contribute to the validation of Tc-NGA as a functional imaging agent for in vivo biochemistry. When possible we will also retrieve and assay liver biopsy samples for HBP concentration.
| Pimstone, N R; Stadalnik, R C; Vera, D R et al. (1994) Evaluation of hepatocellular function by way of receptor-mediated uptake of a technetium-99m-labeled asialoglycoprotein analog. Hepatology 20:917-23 |
