Evaluation of hepatocellular function by way of receptor‐mediated uptake of a technetium‐99m—labeled asialoglycoprotein analog

Abstract

We have developed a quantitative functional imaging study of the liver using a radiolabeled asialoglycoprotein analog, Tc‐galactosyl‐neoglycoalbumin. Heart and liver time‐activity data can be transformed by automated kinetic analysis into asialoglycoprotein hepatocyte receptor concentration. Twenty‐eight healthy controls, 46 patients with noncholestatic chronic liver injury and 11 patients with primary biliary cirrhosis were studied. Liver function was also assessed by Pugh modified‐Child‐Turcotte criteria, 14C‐aminopyrine breath test and indocyanine green clearance (24 patients). Results: (a) In normal controls with a Child‐Turcotte criteria score of 5, receptor concentration ranged from 0.63 to 1.19 μmol/L, with a mean 0.83 ± 2 S.D. 0.06 μmol/L, which was significantly higher (p < 0.001) than that of the patient group (mean receptor concentration = 0.44 ± 2 S.D. 0.04 μmol/L). In cirrhotic patients with Child‐Turcotte criteria score of 5, the mean receptor concentration was 0.60 ± 2 S.D. 0.07 μmol/L, which was significantly lower than controls (p < 0.01). In end‐stage cirrhosis (Child‐Turcotte criteria score 11 to 15), a group in which patients died or required orthotopic liver transplantation within 1 yr, the mean receptor concentration was 0.35 ± 2 S.D. to 0.07 μmol/L. The sensitivity and specificity for receptor concentration in relation to liver disease, with values above 0.65 μmol/L being normal, were 0.96 and 0.88, respectively. Receptor concentration correlated well with Child‐Turcotte criteria score (r = 0.78, p = <0.001), with aminopyrine breath test (r = 0.75, p = <0.001) and with indocyanine green clearance (r = 0.88, p = <0.001). (b) Among 11 primary biliary cirrhosis patients, ten had Child‐Turcotte criteria score of 5. Receptor concentration and aminopyrine breath test values were lower in primary biliary cirrhosis patients with liver biopsy histological stage III‐IV than I‐II, although the numbers were too small for statistical analysis. We conclude that determination of receptor concentration, a rapid and bilirubin‐independent method of quantitating hepatocellular function, correlates well with Child‐Turcotte criteria score, aminopyrine breath test and indocyanine green clearance. This could prove valuable in evaluating the extent and the progression of liver disease and the impact of newer therapies in retarding chronic cholestatic and viral liver injury. Long‐term studies are needed to confirm this speculation. (Hepatology 1994;20:917–923). Copyright © 1994 American Association for the Study of Liver Diseases