UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenib.

Purpose: To report a single case of uridine glucuronosyltransferase 1A1 (UGT1A1) polymorphism and hyperbilirubinemia in a patient who received sorafenib.

Methods: A 63-year-old man with cirrhosis was diagnosed with hepatocellular carcinoma. His cirrhosis was categorized as Child-Pugh A, total bilirubin concentration was 24 micromol/L (normal range <20 micromol/L). The patient was enrolled in a phase I trial combination study of cyclophosphamide and doxorubicin combined with sorafenib.

Results: After a single infusion of doxorubicin and cyclophosphamide and 7 days of sorafenib, he presented with an elevated bilirubin concentration (48 micromol/L). Unconjugated bilirubin was 38 micromol/L and conjugated was 10 micromol/L. The patient was found to have one mutant allele (UGT1A1*28).

Conclusions: The isolated increase in serum bilirubin levels in our patient was probably due to sorafenib-induced UGT1A1 inhibition that manifested itself due both to the patient having one UGT1A1*28 allele and the presence of underlying liver disease. Bilirubin elevations in patients treated with sorafenib could indicate progression or drug toxicity; hence, these possibilities need to be ruled out. We would suggest that when patients develop hyperbilirubinemia while taking sorafenib for any indication, consideration be given to obtaining a fractionation of bilirubin and consideration of UGT1A1 genotyping in order to exclude a Gilbert's syndrome as possible reason for the hyperbilrubinemia. Further studies are warranted to analyze the impact of sorafenib treatment on unconjugated bilirubin blood levels in patients with Gilbert's syndrome.