Significance of UGT1A1*28 Genotype in Patients with Advanced Liver Injury Caused by Chronic Hepatitis C

Abstract

SummaryBackground:Chronic hepatitis C (CHC) is a significant cause of liver related morbidity and mortality worldwide. The role of genetics in the host response to hepatitis C virus is not elucidated. Genetic variations inUGT1A1gene are the most common cause of hereditary unconjugated hyperbilirubinemia-Gilbert syndrome. This is the first study investigating the association ofUGT1A1TA repeats promoter genotypes with the degree of liver injury, viremia and biochemical markers in CHC patients with advanced liver injury and late virological relapse.Methods:Genetic testing ofUGT1A1TA repeats promoter genotypes was performed in 42 CHC patients with advanced fibrosis and cirrhosis who achieved sustained virological response and 42 healthy blood donors. CHC patients were evaluated for clinical findings, laboratory tests and imaging.Results:UGT1A1*28 genotype (7/7 TA repeats) was observed in 23.8% CHC patients and 16.7% healthy controls with no significant difference in genotype frequencies (p=0.49). Pretreatment levels of ferritin and bilirubin were associated with the presence ofUGT1A1*28genotype, indicating its potential as a predictive marker. However, in our study, there was no correlation ofUGT1A1*28genotype with the degree of fibrosis or viremia. During antiviral treatment, dose reductions and treatment interruptions, as well as treatment success and occurrence of late virological relapse were not related to the presence ofUGT1A1*28genotype in CHC patients with severe liver injury.Conclusions:Frequencies ofUGT1A1*28genotype are high in both Serbian CHC patients and healthy subjects. The presence ofUGT1A1*28genotype was not associated with ribavirin-related adverse effects and had no effect on long term outcome in CHC patients.

IL-28B genotypes as predictors of long-term outcome in patients with hepatitis C-related severe liver injury

“…Our results differ, due to the size and specificity of our patient group and partially selection/inclusion criteria, as we included only patients who had achieved SVR, with HCV genotypes other than genotype 1 (genotypes 2 and 3 were also present), as well as differences in genotyping methods. These advantageous frequencies of favourable genotypes in our study may also explain very high treatment success rates in Serbia approximately 79.7% of end of treatment response (EOT) and 70.5% SVR (60.7% in genotype 1 HCV infection) [16,17].…”

“…undetectable HCV RNA 6 months after the completion of antiviral treatment) and gave informed consent for participation. The exclusion criteria for study group were: age (subjects younger than 16 Genomic DNA was extracted from peripheral blood samples of the patients using a QIAamp DNA Blood Mini Kit (Qiagen, Hilden, Germany). The detection of three SNPs near the IL28B gene, rs12979860, rs12980275 and rs8099917, was performed using sequence specific primerpolymerase chain reaction (SSP-PCR), as previously described [10].…”