Search

Background. Uridine diphosphate-glucuronosyltransferase-1A1 deficiency, causing Gilbert’s syndrome, has been attributed to two extra (TA) bases in the TATAA-box of the promoter region of its gene, where the A(TA)6TAA allele corresponds to the normal gene and A(TA)7TAA corresponds to a gene with reduced expression. Our aim was to determine whether isolated hyperbilirubinemia in liver transplant recipients was due to Gilbert’s syndrome acquired through the liver allograft. Methods. From 305 patients followed in our Liver Transplant Clinic, five patients with isolated unconjugated hyperbilirubinemia in the absence of hemolysis, recurrent viral hepatitis, and biliary tract pathology were identified; 10 other post-orthotopic liver transplantion patients with normal liver chemistry tests were randomly selected as a control group. DNA was extracted from paraffin-embedded liver allograft tissue and peripheral lymphocytes and was genotyped for the TA repeat at the uridine diphosphate glucononosyltransferase-1A1 promoter region by polymerase chain reaction and acrylamide gel electrophoresis. Homozygosity for the (TA)7 allele was considered diagnostic of Gilbert’s syndrome. Results. The mean serum total bilirubin level of the study patients was 2.28 mg/dl (range 1.8 ‐3.0), consisting predominantly of the unconjugated form; that of the control patients was 0.76 mg/dl (range 0.4 ‐1.1). The liver tissue from all five patients in the study group possessed the homozygous A(TA)7TAA genotype that was not observed in their lymphocytes. None of the liver tissue from the control patients demonstrated homozygosity for the A(TA)7TAA allele. Conclusion. Uridine diphosphate-glucuronosyltransferase-1A1 deficiency, causing Gilbert’s syndrome, may be carried by the donor liver and present with isolated unconjugated hyperbilirubinemia in liver transplant recipients. Gilbert’s syndrome is a common cause of inherited benign, unconjugated hyperbilirubinemia that occurs in the absence of overt hemolysis, other liver chemistry test (LCT) abnormalities and structural liver disease. It is clinically apparent in 2‐13% of the general population (1‐3), and occurs more frequently in males than in females (4, 5). In these patients, a deficiency in bilirubin glucuronidation due to decreased bilirubin uridine diphosphate (UDP)-glucuronosyl-transferase 1A1 (UGT-1A1) activity exists (6, 7). In majority of patients, the genetic basis of Gilbert’s syndrome has been linked to an extra base-pair (TA) in the upstream promoter region of the gene for bilirubin UGT-1A1 located on chromosome two. Whereas the A(TA) 6TAA promoter sequence corresponds to the wild-type or normal gene, patients with Gilbert’s syndrome are homozygous for the A(TA) 7TAA sequence (2, 5, 8). The longer TATAA element results in reduced expression of the UGT-1A1 enzyme, leading to decreased bilirubin conjugation and excretion, and hyperbilirubinemia (5).