Gilbert's syndrome--a frequent cause of unconjugated hyperbilirubinemia in children after orthotopic liver transplantation.

Gilbert's syndrome is one major cause for unconjugated hyperbilirubinemia in healthy individuals with the prevalence being approximately 3.2-8.6%. It is caused by a mutation in the promoter region of the UGT1A1-gene with a prolonged TAA-repeat coding for the enzyme bilirubin UDP-glucuronosyltransferase (A(TA)(7) TAA allele). After OLT, Gilbert's disease of the transplanted liver can cause unconjugated hyperbilirubinemia. Therefore, we looked for the presence of A(TA)(7) TAA alleles in pediatric liver transplant recipients with unconjugated hyperbilirubinemia. Laboratory results of 106 pediatric liver transplant recipients (aged 0-17 yr) were evaluated for elevated total bilirubin over 2.0 mg/dL (conjugated bilirubin <30%). In these patients, DNA of the liver graft was extracted from paraffin-embedded liver biopsy samples formerly taken for diagnostic reasons. The DNA was analyzed for A(TA)(7) TAA alleles in the promoter region of the UGT1A1-gene. In 4 of 106 pediatric liver transplant recipients we found unconjugated hyperbilirubinemia with total bilirubin above 2.0 mg/dL (conjugated bilirubin <30%). The analysis of the promoter region of the UGT1A1-gene of the liver grafts showed three homozygous A(TA)(7) TAA alleles (homozygous Gilbert's syndrome) and one heterozygous A(TA)(7) TAA allele (heterozygous Gilbert's syndrome). This study shows that pediatric liver transplant recipients with unconjugated hyperbilirubinemia are very likely to have received a liver graft from a donor with Gilbert's syndrome.