Portal-systemic shunting in patients with fibrosis or cirrhosis due to chronic hepatitis C: the minimal model for measuring cholate clearances and shunt

Abstract

Background: Measurement of portal inflow and portal-systemic shunt using cholate clearances could be useful in monitoring patients with liver disease.

Aim: To examine relationships of cholate clearances and shunt to cirrhosis and varices and to define minimal sampling requirements.

Methods: Five hundred forty-eight studies were performed in 282 patients enrolled in the Hepatitis C Antiviral Long-term Treatment to prevent Cirrhosis (HALT-C) trial. Stable, non-radioactive isotopes of cholate were administered intravenously and orally, clearances (Cl(iv) and Cl(oral)) were calculated from [dose/area under curve (AUC)] and cholate shunt from [(AUC(oral):AUC(iv)) x (Dose(iv):Dose(oral)) x 100%].

Results: Cholate Cl(oral) and cholate shunt correlated with prevalences of both cirrhosis and varices (P < 0.0001 for all). Peripheral venous sampling at 5, 20, 45, 60 and 90 min defined the minimal model. Linear regression of cholate shunt determined from five points within 90 min vs. the standard method of 14 points over 3 h yielded slope of 1.0 and intercept 0.5% (r(2) = 0.98, P < 0.0001). Results were identical in the 189 validation studies (slope 1.0, intercept 0.5%, r(2) = 0.99, P < 0.0001).

Conclusions: Cholate Cl(oral) and cholate shunt may be useful in monitoring patients with liver disease. The 5-point model enhances application of cholate Cl(oral) and cholate shunt in the non-invasive assessment of the portal circulation.