Interferon and ribavirin combination therapy are linked to severe indirect hyperbilirubinemia in patients with nt-211G &gt; A variant of UGT1A1 gene

Biziya, Nyam; Gidaagaya, Sarantuya; Namdag, Bira; Yang, Sien–Sing

doi:10.1016/j.jfma.2014.11.004

“…After pretreatment analysis of liver function tests and biochemical markers commonly used for diagnostic orientation in patients with CHC, we found significant associations of the bilirubin and ferritin levels with UGT1A1*28 genotype, similar to results by Piekuse L. et al (37) and de Souza et al (5). Hyper bilirubinemia caused by reduced UGT1A1 activity in patients with hepatitis C has been documented in reports of severe ribavirin-induced jaundice, after com mencing pegylated interferon and ribavirin therapy, suggesting usefulness of genotyping for UGT1A1*28 variant for the decision to continue therapy with ribavirin (38). Elevated bilirubin due to UGT1A1*28 variant can be a cause for exclusion of patients from clinical trials, as well as overestimation of liver disease prognostic scores (Child-Pugh and Model for End Stage Liver Disease-MELD) (39,40).…”

Section: Discussionsupporting

confidence: 89%

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

Jordovic¹,

Bojović²,

Simonovic-Babic³

et al. 2018

Journal of Medical Biochemistry

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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.

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“…After pretreatment analysis of liver function tests and biochemical markers commonly used for diagnostic orientation in patients with CHC, we found significant associations of the bilirubin and ferritin levels with UGT1A1 *28 genotype, similar to results by Piekuse L. et al (37) and de Souza et al (5). Hyper bilirubinemia caused by reduced UGT1A1 activity in patients with hepatitis C has been documented in reports of severe ribavirin-induced jaundice, after com mencing pegylated interferon and ribavirin therapy, suggesting usefulness of genotyping for UGT1A1 *28 variant for the decision to continue therapy with ribavirin (38). Elevated bilirubin due to UGT1A1 *28 variant can be a cause for exclusion of patients from clinical trials, as well as overestimation of liver disease prognostic scores (Child-Pugh and Model for End Stage Liver Disease-MELD) (39, 40).…”

Section: Discussionmentioning

confidence: 99%

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

Jordovic¹,

Bojović

²

,

Simonovic-Babic

³

et al. 2019

Journal of Medical Biochemistry

4

0

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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.

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Interferon/ribavirin

2016

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Interferon and ribavirin combination therapy are linked to severe indirect hyperbilirubinemia in patients with nt-211G > A variant of UGT1A1 gene

Cited by 3 publications

References 5 publications

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

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

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

Interferon/ribavirin

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