Methodological limitations of the use of intrinsic hepatic clearance of ICG as a measure of liver cell function

Abstract Negligible extra-hepatic elimination of indocyanine green (ICG) makes it well suited as a liver test substance. The liver blood flow rate ( Q ) is estimated from concentration measurements in peripheral ( A ) and hepatic venous ( V ) blood during a constant ICG infusion rate (Inf), as Q = Inf/( A – V ). Intrinsic hepatic clearance of ICG, Cli = Inf/((A – V)/In( A/V )), is interesting because it should give a flow-independent quantitative estimate of liver cell function, utilizing the same concentration measurements. The present study was aimed to investigate possible limitations involved in the estimation and use of Cli of ICG in 41 liver patients and 20 controls. Time-dependence was studied by means of two successive 40-min infusion periods (with no significant change in Q ). Cli of ICG decreased 6% per hour ± 3% (mean ± SD, n = 6, P < 0·01) due to a small but significant increase of the concentrations during the infusion period. Flow-dependence was studied by measurements before and after an increment of flow of on average 51%, induced by the intake of a meal. This caused no significant change in Cli of ICG ( P > 0·5, n = 5, Student's paired t -test). The intrinsic hepatic clearance of ICG was on average 0·75 ± 0·26 1 plasma min^-1 (± SD, n = 20) in controls and 0·39 ± 0·18 1 plasma min^-1 in liver patients ( n = 41), P < 0·001. It was positively correlated to the galactose elimination capacity, although the scatter was large ( P < 0·05, n = 56). This might be due to the fact that Cli depends both on liver cell function and on intra-hepatic vascular shunting of blood.