Effect of budesonide treatment on gestagen-induced hyperbilirubinemia in a patient with alagille syndrome

Abstract

Multidrug-resistance protein (MRP2), which is involved in hepatobiliary transport of a wide variety of endogenous and exogenous compounds, might play an important role in drug-induced intrahepatic cholestasis. Animal studies have shown that dexamethasone treatment was able to counteract the drug-induced down-regulation of MRP2 expression (Gastroenterology 1999). A patient with Alagille syndrome (female, 30 years old) presented with typical clinical symptoms of hyperbilirubinemia six weeks after starting an oral contraception with levonorgestrel (30 [Jog daily). Although a therapy with ursodeoxycholic acid (15 mg/kg daily) was initiated, total bilirubin and conjugated bilirubin rose up to a maximum of 55.5 mg/dL and 46.4 mg/dL, respectively. Six days later, hyperbilirubinemia was nearly unchanged (total bilirubin: 53.1 mg/dL, conjugated bilirubin: 43.2 mg/dL). At this time point a therapy with budesonide (3x3 mg daily), a corticosteroid having low systemic bioavailability, was started after the patient had given written informed consent. On budesonide, a rapid continuous decrease was observed (six days after starting budesonide treatment: total bilirubin at 32.1 mg/dL, conjugated bilirubin: 23.7 mg/dL). After eight days a slight increase of body weight due to water retention was observed and treated with diuretics. Nevertheless, the patient did not want to continue the therapy with budesonide, which was tapered over six days. Subsequently total bilirubin and conjugated bilirubin did not further drop (37.7 mg/dL and 29.5 mg/dL ten days after reducing budesonide). These results show that gestagen-induced hyperbilirubinemia may be affected by budesonide treatment in vivo. It may be speculated that budesonide like dexamethasone counteracts the drug-induced down-regulation of MRP2 expression.