The activity of uridine-diphosphoglucuronosyl transferase 1 (UGT1) may influence the concentration of serum bilirubin. Because UGT1 is too labile to be measured with classical biochemical methods, we analysed the whole UGT1A1 gene in 290 healthy Taiwanese adults by using the polymerase chain reaction method, and investigated the relationship between UGT1A1 genotypes and serum bilirubin levels. The results showed that slightly more than 50% of the subjects had one or more variant sites in UGT1A1 gene. The most common variant was A(TA)6TAA/A(TA)7TAA (6/7) in the promoter area, followed by heterozygous variation within the coding region, compound heterozygous and homozygous variations. Among the four variant sites within the coding region, 211 G to A was the predominate one, 1091 C to T was a novel variation, and 686 C to A was associated with 6/7. Subjects with 6/7 or heterozygous variation within the coding region or compound heterozygous (plus one homozygous) variation had significantly higher bilirubin levels than those with wild UGT1A1 gene. When the 290 subjects were stratified into six groups according to their serum bilirubin concentrations, the bilirubin levels were correlated well to the frequencies of variant UGT1A1 gene. Our results show that there is a strong association between UGT1A1 gene and bilirubin levels in healthy Taiwanese adults. The occurrence of A(TA)7TAA allele was relatively rare and the variation rate within the coding region was much higher in Taiwanese compared to that in Caucasians.
Patients dually infected with hepatitis C virus (HCV)/hepatitis B virus (HBV) have a higher risk of developing advanced liver disease or hepatocellular carcinoma compared with monoinfected patients. Yet, there is a similar rate of sustained virologic response (SVR) after peginterferon alfa-2a and ribavirin combination therapy in these patients compared with HCVmonoinfected patients and a high hepatitis B surface antigen (HBsAg) seroclearance rate. The durability of hepatitis C and B clearance in coinfected patients was investigated in a 5-year follow-up study. Patients with active HCV genotype 1, both HBV-coinfected (n 5 97) and HBVmonoinfected (n 5 110), underwent 48-week combination therapy with peginterferon alfa-2a plus ribavirin. In patients with active HCV genotype 2 or 3, both HBV-coinfected (n 5 64) and monoinfected (n 5 50) patients underwent 24-week combination therapy. A total of 295 (91.9%) patients completed treatment and 24 weeks posttreatment follow-up; 264 (89.5%) patients agreed to receive additional follow-up for up to 5 years after the end of treatment. After a median follow-up of 4.6 6 1.0 years, six of the 232 patients achieving SVR developed HCV RNA reappearance, including five HCV genotype 1/HBV-coinfected patients and one HCV genotype 2/3-monoinfected patient. Subgenomic analysis of the HCV core gene indicated that five patients developed delayed recurrence of HCV infection. Overall, the cumulative recurrence rate of HCV infection was 2.3% (0.4%/year; 95% confidence interval [CI], 0.9%-5.5%). The cumulative HBsAg seroclearance rate was 30.0% (95% CI, 21.5%-42.0%); with 33.1% (95% CI, 21.8%-50.1%) in the 48-week combination therapy group and 24.3% (95% CI, 13.7%-42.9%) in the 24-week therapy group. Conclusion: Peginterferon alfa-2a and ribavirin therapy provides good HCV SVR durability and a high accumulative HBsAg seroclearance rate in patients who are coinfected with HCV and HBV. (HEPATOLOGY 2013;57:2135-2142
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