PB2283 TREATMENT OF GILBERT SYNDROME COMPLICATED BY BLOOD DISEASES: A SERIES OF CASE REPORTS
Authors: Xu R. , Cui X. , Huang N. , Xu J. , Dong X. 
Published: June 2019

Background:

Gilbert syndrome is a mild, hereditary unconjugated hyperbilirubinemia without liver dysfunction or hemolytic anemia. It is caused by defects in the UGT1A1 gene and is one of the most prevalent congenital metabolic disorders found clinically in 3‐10% of the population.Unfortunately, some patients with blood system diseases also have Gilbert syndrome. Therefore, it is crucial to diagnose Gilbert syndrome and treat the high bilirubin levels, especially for patients who require chemotherapy or targeted drugs.

Aims:

To investigate the clinical characteristics and treatment of patients with Gilbert syndrome complicated by blood diseases.

Methods:

Peripheral blood samples were obtained from patients with Gilbert syndrome complicated by diverse blood diseases. The UGT1A1 gene was tested via sequencing before treatment; bilirubin and phenobarbitone tests were also conducted prior to treatment. Patients were then treated for their primary disease and given ursodeoxycholic acid (UDCA) either with or without phenobarbitone.

Results:

For patient 1(Fig. 1A), we used ursodeoxycholic acid (UDCA; 250 mg p.o. bid) to control the patient's bilirubin level while administering ATG and Cyclosporin A. After UDCA treatment was initiated, the total bilirubin and unconjugated bilirubin concentrations were approximately 43.8 μmol/l and 37.6 μmol/l, respectively. After the patient completed his ATG treatment, UDCA (250 mg p.o. qd or bid) and Cyclosporin A were used to control his bilirubin and aplastic anemia levels, respectively.For patient 2(Fig. 1B) who was confirmed to have Gilbert syndrome complicated with chronic myelogenous leukemia. Imatinib was used to control his CML, and UDCA (250 mg p.o. qd or bid) was used to control his bilirubin levels. After 1 month of treatment, he showed a hematologic response (CHR: WBC, 4.39∗109/l; PLT, 280∗109/l; basophilic granulocytes, 0.03∗109/l) without splenomegaly. After the first 3 months, he showed an optimal response according to the European Leukemia Net recommendations[5] (BCR‐ABL1/ABL1 7.23%, IS BCR/ABL1/ABL1 5.78% (ABL1 copies: 250100); Ph+ 10%). After the first 6 months, he still has an optimal response (BCR‐ABL1/ABL1 0.4%, IS BCR/ABL1/ABL1 0.32% (ABL1 copies: 237100); Ph+ 0%). At the end of 6 month treatment, the patient's total bilirubin and unconjugated bilirubin concentrations were approximately 35 μmol/l and 30 μmol/l, respectively.For the patient 3(Fig. 1C) who had high bilirubin levels complicated with chronic aplastic anemia, phenobarbitone (25 mg p.o. per day) combined with UDCA was used to control the bilirubin levels. After 1 month of treatment, his total bilirubin level decreased to 71.6 μmol/l. He was then treated with Cyclosporin A (100 mg p.o. bid) combined with phenobarbitone (12.5 mg p.o. per day) and UDCA (250 mg p.o. tid).

Summary/Conclusion:

These results indicate that Gilbert syndrome should be addressed when treating blood diseases. Furthermore, our results suggest that UDCA can reduce the bilirubin concentration in these patients with lower levels of bilirubin. But for patients with higher levels of bilirubin (higher than 100 μmol/l), however, UDCA is not as effective, and phenobarbitone should be added to the treatment, especially in patients requiring urgent treatment.

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