A high frequency of Gilbert syndrome (UGT1A1*28/*28) and associated hyperbilirubinemia but not cholelithiasis in adolescent and adult north Indian patients with transfusion-dependent β-thalassemia

被引：0
作者：
Oshan Shrestha
Alka Rani Khadwal
Manphool Singhal
Amita Trehan
Deepak Bansal
Richa Jain
Arnab Pal
Jasbir Kaur Hira
Sanjeev Chhabra
Pankaj Malhotra
Reena Das
Prashant Sharma
机构：
[1] Postgraduate Institute of Medical Education and Research (PGIMER),Pathology Group of Departments
[2] PGIMER,Department of Internal Medicine, Adult Clinical Hematology Unit
[3] PGIMER,Department of Radiodiagnosis and Imaging
[4] PGIMER,Department of Pediatric Medicine, Pediatric Hematology/Oncology Unit
[5] PGIMER,Department of Biochemistry
[6] PGIMER,Department of Hematology
来源：
Annals of Hematology | 2020年 / 99卷
关键词：
Bilirubin; Gallstones; Gilbert syndrome; Jaundice; Liver disease; Thalassemia;
D O I：
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摘要：
Hyperbilirubinemia and pigment gallstones are frequent complications in transfusion-dependent β-thalassemia (TDβT) patients. Bilirubin production and clearance are determined by genetic as well as environmental variables like ineffective erythropoiesis, hemolysis, infection-induced hepatic injury, and drug- or iron-related toxicities. We studied the frequency of the Gilbert syndrome (GS), a common hereditary cause of hyperbilirubinemia in 102 TDβT patients aged 13–43 years (median 26 years). Total and unconjugated hyperbilirubinemia were frequent (81.4% and 84.3% patients respectively). Twenty (19.6%) patients showed total bilirubin > 3.0 mg/dL; 53 (51.9%) had an elevation of either alanine or aspartate aminotransferase, or alkaline phosphatase liver enzymes. Nineteen (18.6% of the 92 tested) were positive for hepatitis B or C, or HIV. The mean total and unconjugated bilirubin levels and AST, ALT, and ALP levels in patients positive for hepatitis B or C were not significantly different from negative cases. Eighteen patients (17.7%) had GS: homozygous (TA)7/7 UGT1A1 promoter motif (the *28/*28 genotype), 48 (47.1%) were heterozygous (TA)6/7. Total + unconjugated bilirubin rose significantly with the (TA)7 allele dose. Fourteen (13.7%) patients had gallstones. There was no significant difference in total/unconjugated bilirubin in patients with/without gallstones and no significant differences in frequencies of gallstones within the three UGT1A1 genotypes. This largest study in Indian TDβT patients suggests that GS should be excluded in TDβT cases where jaundice remains unexplained after treatable causes like infections, chelator toxicity, or transfusion-related hemolysis are excluded. GS was not associated with gallstones, possibly due to a lower incidence of cholelithiasis overall, a younger age cohort, or other environmental factors.
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页码：2019 / 2026
页数：7
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