Gilbert's syndrome disclosed during the treatment of hematological malignancies

Abstract

Gilbert's syndrome (GS) is a benign, familial condition characterized by recurrent asymptomatic non-hemolytic low-grade indirect hyper-bilirubinemia. Conditions related to fasting, stress or co-morbidity might reveal the disease in asymptomatic individuals. Seven patients who were treated for a hematological malignancy were identified with reversible indirect hyper-bilirubinemia. Liver function tests in all of them, including bilirubin levels were normal before the therapeutic maneuver, which was the delivery of combined chemotherapy in three cases and a bone marrow transplantation in four (three allografts and one autograft). Bilirubin levels returned to normal in all five patients following treatment. GS should not be overlooked in individuals exposed to these treatments who develop hyperbilirubinemia and jaundice.

Allogeneic hematopoietic stem cell transplantation for acute leukemia with Gilbert's syndrome

“…Among these cases, just like ours, non-hemolytic low-grade indirect hyperbilirubinemia after chemotherapy occurred repeatedly, but it did not effect the treatment of hematologic malignancies. In clinical practice, hyperbilirubinemia is suggestive of hemolysis, drug-induced liver damage or other conditions, but GS is not very frequently considered [2]. In our case, we initially attributed hyperbilirubinemia to drug-induced liver damage in the first two cycles of chemotherapy.…”

“…With mild symptoms and reversible indirect hyperbilirubinemia, most cases of GS remain undiagnosed and they may become evident after exercise, stress, drug administration, prolonged fasting or inter-current diseases [2]. Several drugs have been reported to induce hyperbilirubinemia to GS patients, such as paracetamol, nilotinib, and pazopanib [3,4].…”

“…Ruiz-Arguelles GJ, et al [2] reported seven cases of acute leukemia with coexisting GS, of which 3 patients accepted chemotherapy alone, 3 cases treated by allo-HSCT and one received auto-PBSCT. All seven patients developed indirect hyperbilirubinemia during the course of their treatment.…”

Recurrent Isolated Hyperbilirubinemia From Drug‐Induced Impaired Hepatic Bilirubin Uptake

“…Alick Feng, 1 Maen Masadeh, 1,2 and Arvind R. Murali 1,2 D rug-induced liver injury (DILI) is a common side effect of chemotherapy resulting in jaundice, elevated aminotransferases, and increases in alkaline phosphatase and/or gamma glutamyl transferase. We report a presentation of recurrent, isolated indirect hyperbilirubinemia secondary to cytarabine-based chemotherapy.…”

Rapid molecular diagnosis of the Gilbert's syndrome-associated exon 1 mutation within the UGT1A1 gene

“…Gilbert's syndrome is the most commonly inherited disorder of bilirubin metabolism, affecting 3-12% of the general population, and presents as mild unconjugated hyperbilirubinemia of around 1-5 mg/dL that becomes clinically apparent only during fasting, physical exercise, stress, intercurrent infections, or menstruation (Bosma et al, 1995;Monaghan et al, 1996;Borlak et al, 2000;Ruiz-Argüelles et al, 2005;Costa et al, 2006). The genetic variants of the uridine 5'-diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene, specifically in the TATA-box of the promoter region, might reduce the transcription activity of the gene and UGT1A1 enzyme concentration, to ultimately affect conjugation (hepatic glucuronidation) capacity, which results in Gilbert's syndrome (Bosma et al, 1995;Monaghan et al, 1996;Raijmakers et al, 2000;Hsieh et al, 2007).…”