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.
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。