Zhu Xiao-Feng, Lu Li-Xia, Wang Ying, Xu Kong-Wen, Li Da-Jiang, Zhu Xia, Liu Li, Liu Cong, Wang Jin-Rong, Tang Hong, Wang Li-Chun
Epidemiology Department,West China School of public Health, Sichuan University, Chengdu, China.
Hepat Mon. 2011 Dec;11(12):980-5. doi: 10.5812/kowsar.1735143x.4203. Epub 2011 Dec 20.
Antiviral treatment with nucleoside analogs has been used for chronic hepatitis B (CHB). Each kind of nucleoside analog has its own characteristics and suitability for patients. Telbivudine (LdT, brand name: Sebivo, Beijing Novartis Pharma Ltd) is the newest nucleoside analog, with strong and rapid viral suppression. However, its resistance rate is relatively high during long-term application, due to low genetic barriers to resistance. So, it is necessary to increase the effect and reduce resistance with effective management, according to baseline factors and early on-treatment responses.
To reveal possible predictive factors of the effect of telbivudine (LdT) treatment on naïve HBeAg-positive chronic hepatitis B (CHB) patients to optimize treatment.
A total 71 naïve chronic hepatitis B (CHB) patients who met the inclusion criteria were enrolled. All patients were treated with LdT 600 mg Qd for at least 52 weeks. Multiple logistic regression analyses were done to investigate the predictive values of baseline factors and responses at Week 24.
The reduction in hepatitis virus B (HBV) DNA level was 6.44 ± 2.38 lg copies/mL at Week 52 compared with baseline. The complete virus response (CVR), biochemical response (BR), serological response (SR), and drug resistance (DR) were 61.99%, 77.46%, 35.21%, and 8.45% respectively. By multiple regression analysis, baseline alanine aminotransferase (ALT) levels significantly affected CVR (P = 0.024, OR = 1.008), and baseline ALT and baseline HBV DNA levels were independent compact factors of SR (P = 0.012, OR = 1.007; P = 0.001, OR = 0.423). The differences in CVR, SR, and DR in patients with ALT > 120 Iu/mL compared with patients with ALT ≤ 120 Iu/mL were statistically significant. The differences in SR in patients with HBV DNA > 107 copies/mL compared with patients with HBV DNA ≤ 107 copies/mL were statistically significant. Additionally, CVR, BR, and SR were differed significantly between patients with HBV DNA lower than 300 copies/mL at Week 24 and patients with HBV DNA higher than 300 copies/mL (P = 0.000, P = 0.0016, and P = 0.000, respectively).
There were more responders among naïve HBeAg-positive chronic hepatitis B patients with lower HBV DNA levels (especially lower than 107 copies/mL) and higher ALT values (especially higher than 120 Iu/mL at baseline) to LdT treatment. Adjustments for treatment strategy should be considered if HBV DNA > 300 copies/mL at Week 24 is observed.
核苷类似物抗病毒治疗已用于慢性乙型肝炎（CHB）。每种核苷类似物都有其自身特点及对患者的适用性。替比夫定（LdT，商品名：素比伏，北京诺华制药有限公司）是最新的核苷类似物，具有强效且快速的病毒抑制作用。然而，由于其耐药的基因屏障较低，长期应用时耐药率相对较高。因此，根据基线因素和治疗早期反应进行有效管理以提高疗效并降低耐药性很有必要。
揭示替比夫定（LdT）治疗初治HBeAg阳性慢性乙型肝炎（CHB）患者疗效的可能预测因素，以优化治疗。
共纳入71例符合纳入标准的初治慢性乙型肝炎（CHB）患者。所有患者接受LdT 600 mg每日1次治疗至少52周。进行多因素逻辑回归分析以研究基线因素及第24周反应的预测价值。
与基线相比，第52周时乙肝病毒（HBV）DNA水平下降了6.44±2.38 lg拷贝/mL。完全病毒学应答（CVR）、生化应答（BR）、血清学应答（SR）和耐药（DR）分别为61.99%、77.46%、35.21%和8.45%。通过多因素回归分析，基线丙氨酸氨基转移酶（ALT）水平显著影响CVR（P = 0.024，OR = 1.008），且基线ALT和基线HBV DNA水平是SR的独立影响因素（P = 0.012，OR = 1.007；P = 0.001，OR = 0.423）。ALT>120 Iu/mL的患者与ALT≤120 Iu/mL的患者相比，CVR、SR和DR的差异具有统计学意义。HBV DNA>107拷贝/mL的患者与HBV DNA≤107拷贝/mL的患者相比，SR的差异具有统计学意义。此外，第24周时HBV DNA低于300拷贝/mL的患者与高于300拷贝/mL的患者相比，CVR、BR和SR有显著差异（分别为P = 0.000、P = 0.0016和P = 0.000）。
初治HBeAg阳性慢性乙型肝炎患者中，HBV DNA水平较低（尤其是低于107拷贝/mL）且ALT值较高（尤其是基线时高于120 Iu/mL）的患者对LdT治疗的应答者更多。如果在第24周观察到HBV DNA>300拷贝/mL，则应考虑调整治疗策略。
