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Portal–Systemic Shunts Reduce Asialoglycoprotein Receptor Density in Rats

Liver Transplant Program, Department of Surgery, Burns and Allen Research Institute, Cedars-Sinai Medical Center and University of California, Los Angeles; and Department of Radiology, University of California, San Diego, La Jolla, California

The clinical usefulness of quantitative functional imaging techniques that use asialoglycoprotein receptor (ASGP-R) binding is based on the correlation between ASGP-R density and hepatic functional reserve. Portal–systemic shunting (PSS) is common in patients with cirrhosis and portal hypertension—the same group that is most frequently considered for such imaging. PSS occurs spontaneously through collateral vessels and from the creation of surgical shunts or placement of transjugular intrahepatic portal-systemic shunts (TIPS). Understanding the physiologic relationship between PSS and ASGP-R activity may aid in the interpretation of quantitative clinical imaging. This study was conducted to determine the relationship between PSS and ASGP-R density in the absence of parenchymal disease. Methods: Sprague-Dawley rats with end-to-side portal-systemic shunts and sham-operated control rats were imaged with ^99mTc-diethylenetriaminepentaacetic acid galactosyl-neoglycoalbumin. Pharmacokinetic modeling of the liver and heart time–activity data was used to measure ASGP-R concentration, as well as hepatic plasma volume and flow. Results: The mean ASGP-R density (nmol/g of liver) was significantly decreased in the shunted rats. Blood ammonia was significantly elevated, whereas hepatic plasma flow, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase levels were unaltered. Liver histology was normal in both groups. Conclusion: A significant change in the ASGP-R density occurs with PSS in the absence of parenchymal disease. PSS appears to be an independent variable affecting ASGP-R activity. This could prove clinically important during interpretation of quantitative imaging from patients with varying degrees of PSS based on underlying disease or the presence of a surgical shunt or TIPS device.

Key Words: ^99mTc-diethylenetriaminepentaacetic acid galactosyl-neoglycoalbumin • hepatic blood flow • liver • quantitative functional imaging