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- Title
Creatine kinase elevation in chronic hepatitis B patients with telbivudine therapy: influence of telbivudine plasma concentration and single nucleotide polymorphisms of TK2, RRM2B, and NME4.
- Authors
He, Tianye; Chen, Bicui; Li, Yaqun; Song, Yun; Wu, Jian; Xiong, Biyu; Wang, Bin; Long, Jianfei
- Abstract
Purpose: To study the correlations of genetic variants of telbivudine phosphorylase kinases and telbivudine plasma concentration with creatine kinase elevation in chronic hepatitis B patients who received telbivudine. Methods: An observational study was performed in China chronic hepatitis B patients receiving telbivudine therapy at 600 mg once daily. Plasma concentration was measured 12 h after taking telbivudine using ultra-performance liquid chromatography–tandem mass spectrometry and SNPs located in RRM2B, TK2, and NME4 was detected by MALDI-TOF mass spectrometry. All statistical analyses were performed with R 4.3.1 and all graphs were drawn by Origin 2023b and P value < 0.05 was considered statistically significant. Results: A total of 140 patients receiving telbivudine therapy were recruited with a median plasma concentration of 952.49 (781.07–1238.98) ng/mL. The value of plasma concentration was proportional to the grade of creatine kinase elevation and the best telbivudine plasma concentration threshold to discriminate the grade 3/4 CK elevation was 1336.61 ng/mL. Multivariate analysis revealed that plasma concentration and rs3826160 were the independent risk factor of telbivudine-induced creatine kinase elevation. Patients with TC and CC genotype in rs3826160 not only had a higher incidence of creatine kinase elevation but also a higher plasma concentration than TT genotype carriers. Conclusion: Chronic hepatitis B patients with TC and CC genotype in rs3826160 have high telbivudine plasma concentration are at risk of elevated creatine kinase.
- Subjects
NUCLEOSIDES; HIGH performance liquid chromatography; RESEARCH funding; SCIENTIFIC observation; CHRONIC hepatitis B; DESCRIPTIVE statistics; MULTIVARIATE analysis; CREATINE kinase; ANTIVIRAL agents; MASS spectrometry; TRANSFERASES; DATA analysis software; SINGLE nucleotide polymorphisms; GENOTYPES
- Publication
European Journal of Clinical Pharmacology, 2024, Vol 80, Issue 7, p1029
- ISSN
0031-6970
- Publication type
Article
- DOI
10.1007/s00228-024-03674-w