[Foreign substances as indicators of liver function]

Abstract

The need to use xenobiotics to quantify liver function is based on the fact that the serum levels of endogenous tracers (such as transaminases, alkaline phosphatase, bilirubin and bile acids) cannot be interpreted in pharmacokinetic terms, since information is lacking on volume of distribution and on rate of synthesis and of disposition. Methods are now available which allow practically non-invasive estimation of (minimal) hepatic perfusion by indocyanine green fractional clearance, of portosystemic shunt flow by finger pulse photometry following nitroglycerin administration, of microsomal capacity by the aminopyrine breath test (ABT) or caffeine clearance, and of cytosolic function by galactose elimination capacity (GEC). Assessment of inherited hydroxylation deficiency of the debrisoquine type is best performed with dextromethorphan, and of the acetylator phenotype with sulfadimidine. Recently, caffeine clearance in saliva has been studied extensively in this laboratory, and, on the basis of a constant relationship between caffeine concentrations in serum and saliva, overnight clearance measurements (requiring a saliva sample at bedtime and upon arising following a single oral dose of caffeine) have been shown to be closely related to ABT or GEC. This approach, which has been successfully used in children, may represent the first simple and innocuous test for quantifying of hepatic function in the pediatric age group. The clinical utility of these clearance tests is to assess severity of disease (or genetically determined impairment of function), thus yielding important clues to prognosis.