A modeling study of the effect of fasting on bilirubin kinetics in Gilbert's syndrome

The mechanism of fasting hyperbilirubinemia (FH) is not fully understood. We investigated basal bilirubin kinetics in 20 Gilbert's patients and in 7 healthy volunteers. The study was repeated in seven of these Gilbert's patients after 48-h fasting. A two-compartment model proved to be adequate for interpreting crystalline bilirubin kinetics in these individuals. The parameters of bilirubin kinetics were estimated by employing a maximum likelihood parameter estimation technique. Consistency of the model and uniqueness of the estimated parameter values (from the covariance matrix) were shown. Our results confirmed previous observations regarding impaired bilirubin kinetics in Gilbert's patients as compared to controls. The main results obtained from kinetic studies in Gilbert's patients after fasting were i) no modification in the bilirubin clearance, and ii) a more than twice increase of bilirubin turnover. These data indicate that FH is related to an increased bilirubin production (mainly intrahepatic). Furthermore, evidence arises from this study that the bilirubin tolerance test is a useful diagnostic test for Gilbert's syndrome.