Incidence of Atazanavir-associated Hyperbilirubinemia in Korean HIV Patients: 30 Months Follow-up Results in a Population with Low UDP-glucuronosyltransferase1A1*28 Allele Frequency

Hyperbilirubinemia is frequently observed in Caucasian HIV patients treated with atazanavir. UDP-glucuronosyltransferase 1A1 polymorphism, UGT1A1*28, which is associated with atazanavir-induced hyperbilirubinemia, is less common in Asians than in Caucasians. However, little is known about the incidence of atazanavir-associated hyperbilirubinemia in Asian populations. Our objective was to investigate the incidence of and tolerability of atazanavir-associated hyperbilirubinemia in Korean HIV patients. The prevalence and cumulative incidence of atazanavir-associated hyperbilirubinemia and UGT1A1*28 allele frequency was investigated in 190 Korean HIV-infected patients treated with atazanavir 400 mg per day. The UGT1A1*28 were examined by direct sequencing of DNA from peripheral whole blood. The UGT1A1*28 allele frequency was 11%. The cumulative incidence of any grade of hyperbilirubinemia was 77%, 89%, 98%, and 100%, at 3, 12, 24, and 30 months, respectively. The cumulative incidence of severe (grade 3-4) hyperbilirubinemia was 21%, 41%, 66%, and 75%, at 3, 12, 24, and 30 months, respectively. However, the point prevalence of severe hyperbilirubinemia did not increase with time and remained around 25%. Our data suggest that atazanavir-associated hyperbilirubinemia is common but transient in a population with low UGT1A1*28 allele frequency.

Genetic polymorphism of uridine-diphosphoglucuronosyl transferase 1A7 gene in chronic viral hepatitis and hepatocellular carcinoma

Hepatocellular Carcinoma [HCC] is the most common cause of primary liver neoplasm and the fourth most frequent type of cancer worldwide causing one million deaths per year. Genetic polymorphisms of UDP-glucuronosyltransferases [UGTs], which detoxifies endogenous and environmental carcinogen, have been reported to be associated with HCC. The present study aimed to elucidate the role of UGT1A7 SNP [622 T-C] in the pathogenesis of Hepatocellular Carcinoma [HCC] and whether this polymorphism is associated with elevated bilirubin level or not. This study was conducted on 22 patients with HCC, 25 patients with chronic viral hepatitis B and/ or C and 16 apparently healthy controls. All subjects underwent laboratory tests for Liver and Kidney functions, serological markers [HBV and HCV] and serum AFP as a tumor marker, Genomic DNA from the blood was analyzed for UGT1A7 polymorphism using PCR-RFLP. The prevalence of HCV infection was higher in HCC group compared to other groups. AFP-level significantly increased in HCC than in viral hepatitis and control [p<0.0005]. A statistically significant increase was found in the frequency of risky genotypes [TC, CC] in HCC group as compared to the protective genotype [TT] [P<0.01]. UGT1A7 T allele and C allele were designated as H [high activity] and L [low activity] alleles, respectively. A statistically significant increase was found in frequency of L allele in HCC group [54%] as compared to control group [25%] p=0.03. On the other hand, the H allele showed statistically significant decrease in HCC group [46%] compared to control group [75%] p=0.03. Increase in total bilirubin level in cases harboring UGT 1A7 Polymorphism compared to wild genotype [p<0.01] was observed demonstrating its role in the pathogenesis of hyperbilirubineamia. The UGT1A7 polymorphism was associated with elevated bilirubin level and may play a role in the pathogenesis of HCC