Jia Ji-dong, Hou Jin-lin, Yin You-kuan, Xu Dao-zhen, Tan De-ming, Niu Jun-qi, Zhou Xia-qiu, Wang Yu-ming, Zhu Li-min, He Yong-wen, Ren Hong, Wan Mo-bin, Chen Cheng-wei, Wu Shan-ming, Chen Ya-gang, Xu Jia-zhang, Wang Qin-huan, Wei Lai, Ma Hong
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Zhonghua Gan Zang Bing Za Zhi. 2007 May;15(5):342-5.
To investigate the possibilities of an association between the degrees of HBV suppression with nucleoside treatments at week 24 and week 52 in hepatitis B patients and to find a useful predictor for treatment efficacy.
In this phase III, double-blind, multicenter trial, we compared the efficacy of telbivudine treatment with lamivudine treatment in 332 Chinese compensated chronic hepatitis B patients. The patients were randomly assigned to a daily 600 mg telbivudine treatment group or daily 100 mg lamivudine group for 24 weeks. They were then categorized into 4 groups according to their serum HBV DNA levels (copies/ml) at week 24: a PCR-undetectable group (< 300 copies/ml); a QL- < 10(3) copies/ml group; a 10(3)-<10(4) copies/ml group; and a > or = 10(4) copies/ml group. The treatments were continued as they previously had been for another 28 weeks and the patients serum HBV DNA levels were examined again.
At week 52, mean reductions of serum HBV DNA were significantly greater in the telbivudine-treated patients than in the lamivudine-treated group (6.2 log10 vs 5.4 log10, t = 3.6, P < 0.01). Viral resistance was twice as common in lamivudine-treated patients compared to those receiving telbivudine. Telbivudine was well-tolerated with an adverse event profile similar to that of lamivudine. The lower the HBV DNA level achieved at week 24, the higher HBV DNA non-detectable by PCR. ALT normalization and HBeAg seroconversion achieved at week 52, and viral resistance at week 48 decreased parallel to the degree of HBV DNA inhibition.
HBV DNA PCR-undetectable at week 24 in nucleoside-treated hepatitis B patients suggests a better efficacy at week 52 and lower viral resistance at week 48. The degree of suppression of HBV at week 24 may be used as a predictor of 1-year outcome.
探讨乙型肝炎患者接受核苷类治疗24周和52周时乙肝病毒（HBV）抑制程度与治疗效果之间存在关联的可能性，并寻找预测治疗效果的有用指标。
在这项III期双盲多中心试验中，我们比较了替比夫定与拉米夫定治疗332例中国代偿期慢性乙型肝炎患者的疗效。患者被随机分为每日600mg替比夫定治疗组或每日100mg拉米夫定组，治疗24周。然后根据他们在24周时的血清HBV DNA水平（拷贝/毫升）分为4组：PCR检测不到组（<300拷贝/毫升）；QL-<10³拷贝/毫升组；10³-<10⁴拷贝/毫升组；以及≥10⁴拷贝/毫升组。治疗按之前方案继续进行另外28周，并再次检测患者血清HBV DNA水平。
在52周时，替比夫定治疗患者的血清HBV DNA平均下降幅度显著大于拉米夫定治疗组（6.2 log₁₀对5.4 log₁₀，t = 3.6，P < 0.01）。拉米夫定治疗患者的病毒耐药率是接受替比夫定治疗患者的两倍。替比夫定耐受性良好，不良事件谱与拉米夫定相似。24周时达到的HBV DNA水平越低，PCR检测不到HBV DNA的比例越高。52周时谷丙转氨酶（ALT）正常化和HBeAg血清学转换以及48周时的病毒耐药率与HBV DNA抑制程度呈平行下降。
核苷类治疗的乙型肝炎患者在24周时HBV DNA PCR检测不到提示52周时疗效更好且48周时病毒耐药率更低。24周时HBV的抑制程度可作为1年治疗结局的预测指标。
