4年恩替卡韦的疗效比较有NUC经验和没有经验台湾慢性乙肝

StephenW

A comparison of 4-year entecavir efficacy in nucleos(t)ide analog-naïve and -experienced adult Taiwanese chronic hepatitis B patients


    Chien-Hung Chen,
    Tsung-Hui Hu,
    Chao-Hung Hung,
    Sheng-Nan Lu,
    Jing-Houng Wang,
    Min-Hui Chang,
    Chi-Sin Changchien,
    Chuan-Mo Lee

Purpose

To compare the efficacy of entecavir (ETV) monotherapy up to 4 years in nucleos(t)ide analog (NA)-experienced and -naïve subjects.
Methods

One hundred sixty NA-experienced and 282 naïve chronic hepatitis B patients who were treated with ETV were enrolled. Of the 160 NA-experienced patients, 49 had prior lamivudine (LAM)-resistant mutants, 18 had resistant mutants to LAM followed by adefovir (ADV) after switching to ADV sequential therapy (LAM/ADV resistance), and 9 had prior ADV-resistant mutants. NA-resistant mutants were detected by line probe assay.
Results

Four years of ETV therapy resulted in virological response (VR, HBV DNA < 300 copies/ml), HBeAg seroconversion, and ETV-resistant mutants development in 98.2, 45.2, and <1 % of naïve patients, respectively. LAM- and ADV-experienced patients who never developed LAM-resistant mutants had similar VR and ETV-resistant mutant rates to NA-naïve patients. In contrast, prior LAM-resistant mutants were significantly associated with higher ETV-resistant mutants development and reduced VR rates. Patients with prior LAM-resistant mutants but not at baseline had a lower rate of ETV-resistant mutants compared to those with baseline LAM-resistant mutants [hazard ratio (HR): 0.58, 95 % confidence interval (CI): 0.35–0.95] and those who had LAM/ADV resistance (HR:0.16, 95 % CI:1.0.03–0.76). Early add-on ADV achieved VR in eight of nine patients with ETV-resistant mutants when HBV DNA was <2 × 105 copies/ml.
Conclusions

Entecavir was highly efficacious and low resistance in NA-naïve, LAM-, or ADV-experienced patients without LAM-resistant mutants. Patients with prior LAM-resistant mutants but not at baseline had lower ETV-resistant mutant rates compared to those with baseline LAM-resistant mutants or LAM/ADV resistance.

  

StephenW

方法

一百六十经验和NA- 282天真的慢性乙肝患者，恩替卡韦治疗的患者。 NA- 160经验的患者， 49之前有拉米夫定（ LAM ）耐药突变， 18 LAM耐药突变后，阿德福韦（ ADV ）切换到ADV序贯疗法（ LAM / ADV阻力的），和9的前ADV-耐药突变。 NA耐药突变检测线探针检测。
结果

四年ETV治疗导致病毒学应答（ VR ， HBV DNA < 300拷贝/ ml ） ， HBeAg血清学转换， ETV耐药突变发展， 98.2 ，45.2 ，和<1％的初治患者，分别。经验丰富的林和ADV从未开发LAM耐药突变的患者也有类似的VR和ETV- NA初治患者的耐药突变率。相比之下，前LAM耐药突变明显伴有较高的ETV耐药突变发展，减少VR率。前LAM耐药突变的患者，但不能达到基准ETV-耐药突变率较低相比，那些与基线LAM耐药突变[危险比（ HR ） ： 0.58， 95 ％可信区间（CI ） ： 0.35-0.95 ] LAM / ADV耐药（ HR ：0.16 ， 95％CI为:1.0.03 - 0 .76 ） 。提前ADV实现VR八九ETV-耐药突变时HBV DNA < 2× 105拷贝/ ml的患者。
结论

NA-天真，林，或ADV经验没有LAM耐药突变的患者，恩替卡韦是非常有效和低电阻。事先LAM耐药突变体，但不是在基线患者有较低的ETV耐药突变率比基线LAM耐药突变或LAM / ADV耐药