Abstract：
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.
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.
摘要：
目的：研究替比夫定磷酸化酶激酶基因变异和替比夫定血药浓度与慢性乙型肝炎患者肌酸激酶升高的相关性。
方法：在中国慢性乙型肝炎患者中进行了一项观察性研究，接受每日一次600mg替比夫定治疗。服用替比夫定后12h采用超高效液相色谱-串联质谱和位于RRM2B的SNP测定血浆浓度,通过MALDI-TOF质谱检测TK2和NME4。所有统计分析均使用R4.3.1进行，所有图形均由Origin2023b绘制，P值<0.05被认为具有统计学意义。
结果：共招募了140名接受替比夫定治疗的患者，中位血浆浓度为952.49（781.07-1238.98）ng/mL。血浆浓度值与肌酸激酶升高的等级成正比，区分3/4级CK升高的最佳替比夫定血浆浓度阈值为1336.61ng/mL。多因素分析显示血浆浓度和rs3826160是替比夫定诱导肌酸激酶升高的独立危险因素。rs3826160中具有TC和CC基因型的患者不仅肌酸激酶升高的发生率更高，而且血浆浓度也高于TT基因型携带者。
结论：rs3826160中具有TC和CC基因型的慢性乙型肝炎患者具有高的替比夫定血浆浓度，有升高的肌酸激酶的风险。
方法：在中国慢性乙型肝炎患者中进行了一项观察性研究，接受每日一次600mg替比夫定治疗。服用替比夫定后12h采用超高效液相色谱-串联质谱和位于RRM2B的SNP测定血浆浓度,通过MALDI-TOF质谱检测TK2和NME4。所有统计分析均使用R4.3.1进行，所有图形均由Origin2023b绘制，P值<0.05被认为具有统计学意义。
结果：共招募了140名接受替比夫定治疗的患者，中位血浆浓度为952.49（781.07-1238.98）ng/mL。血浆浓度值与肌酸激酶升高的等级成正比，区分3/4级CK升高的最佳替比夫定血浆浓度阈值为1336.61ng/mL。多因素分析显示血浆浓度和rs3826160是替比夫定诱导肌酸激酶升高的独立危险因素。rs3826160中具有TC和CC基因型的患者不仅肌酸激酶升高的发生率更高，而且血浆浓度也高于TT基因型携带者。
结论：rs3826160中具有TC和CC基因型的慢性乙型肝炎患者具有高的替比夫定血浆浓度，有升高的肌酸激酶的风险。
