%0 Journal Article
%T 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.
%A He T
%A Chen B
%A Li Y
%A Song Y
%A Wu J
%A Xiong B
%A Wang B
%A Long J
%J Eur J Clin Pharmacol
%V 80
%N 7
%D 2024 Jul 19
%M 38502357
%F 3.064
%R 10.1007/s00228-024-03674-w
%X OBJECTIVE: 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.
CONCLUSIONS: Chronic hepatitis B patients with TC and CC genotype in rs3826160 have high telbivudine plasma concentration are at risk of elevated creatine kinase.