三年替诺治疗表面抗原下降和HBV DNA抑制模式

StephenW

Patterns of hepatitis B surface antigen decline and HBV DNA suppression in Asian treatment-experienced chronic hepatitis B patients after three years of tenofovir treatment

    Wai-Kay Seto a,
    Kevin Liu a,
    Danny Ka-Ho Wong a, b,
    James Fung a, b,
    Fung-Yu Huang a,
    Ivan Fan-Ngai Hung a,
    Ching-Lung Lai a, b,
    Man-Fung Yuen a, b, Corresponding author contact information, E-mail the corresponding author

    a Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hong Kong
    b State Key Laboratory for Liver Research, the University of Hong Kong, Queen Mary Hospital, Hong Kong

Abstract
Background

Patterns of serum hepatitis B surface antigen (HBsAg) decline during nucleos(t)ide analogue (NA) therapy have not been well-investigated.
Methods

We determined the cumulative serologic, virologic and biochemical outcomes of 142 Asian CHB patients, with at least 6 months exposure to other NAs, receiving tenofovir with or without lamivudine for up to 3 years. Liver biochemistry, serum HBV DNA and HBsAg levels were determined at baseline, 6 months and yearly from years 1 to 3.
Results

142, 123 (86.6%) and 70 (49.3%) CHB patients were followed up for 1, 2, and 3 years respectively. Two phases of HBsAg decline were observed. Patients with baseline HBsAg ⩾3 log IU/mL, when compared to patients with baseline HBsAg <3 log IU/mL, had a greater median rate of HBsAg reduction through 3 years of treatment (0.155 and 0.039 log IU/mL/year respectively, p<0.001). Among patients with 3 years of follow-up, there was a significantly greater median rate of HBsAg reduction during the first year when compared to the second and third years (0.220, 0.136 and 0.081 log IU/mL/year respectively, p<0.001). HBeAg status, HBV genotype and concomitant lamivudine therapy were not important determinants of HBsAg kinetics (all p>0.05). The 3-year cumulative virologic suppression rate was 93.3%, with no cases of resistance detected.
Conclusion

Serum HBsAg levels in NA-experienced patients receiving tenofovir demonstrated a variable pattern of decline, with slower rates of reduction noted in patients with lower baseline HBsAg levels, and could explain the rarity of HBsAg seroclearance during NA therapy. (ClinicalTrials.gov Identifier NCT01728935).

StephenW

血清乙型肝炎表面抗原（HBsAg）跌幅在核苷（酸）类似物（NA）治疗的模式还没有得到很好的调查。
方法

我们确定了累计142亚洲慢性乙肝患者的血清学，病毒学和生化结果，至少6个月暴露于其他NAS，​​接受替诺福韦或拉米夫定治疗长达3年。测定肝功能，血清HBV DNA和HBsAg水平在基线，6个月，每年从1到3年。
结果

142，123（86.6％）和70（49.3％）CHB患者随访分别为1，2，3年。对HBsAg下降两个阶段进行观察。患者基线HBsAg的⩾3日志IU / mL的患者与基线相比，当乙肝表面抗原<3日志IU / mL时，有较大的通过3年的治疗乙肝表面抗原降低率中位数（日志IU /毫升/年分别为0.155和0.039， P <0.001）。用3年的随访的患者中，有一个显着更大的中位数在第一年时的HBsAg减少率相比，第二年和第三年（0.220，0.136和0.081日志IU /毫升/年，P <0.001） 。 HBeAg状态，HBV基因型和随之而来的拉米夫定治疗乙肝表面抗原动力学的重要决定因素（P> 0.05）。 3年累计病毒学抑制率为93.3％，无一例检测电阻。
结论

NA经验的患者接受替诺福韦的血清HBsAg水平显示一个变量的下降格局，与速度较慢患者用较低的基线HBsAg水平减少注意到，可以解释的罕见NA治疗过程中的乙肝表面抗原转阴。 （ClinicalTrials.gov标识符NCT01728935）

StephenW

ClinicalTrials.gov Identifier NCT01728935)
Tenofovir in Asian Chronic Hepatitis B Patients
Purpose

Tenofovir (TDF) has been demonstrated to have potency antiviral against the hepatitis B virus (HBV) in various multiple-centre trials, with no cases of resistance encountered. However, its efficacy and resistance profile in the Asian population, which constitute the majority of chronic hepatitis B (CHB) patients, is unknown. Compared to other nucleoside analogues, TDF has been associated with relatively high rates of hepatitis B surface antigen (HBsAg) seroclearance. It would be interested to see if this could be reproduced. The investigators plan to report the serologic and virologic results of our 140 nucleoside analogue-experienced patients who were commenced on TDF.

Detailed Description:

Recent multi-center trials have shown tenofovir disoprovil fumarate (TDF) demonstrating potent antiviral efficacy in both nucleoside-naive and -experienced chronic hepatitis B (CHB) patients. At present, there has been no identifiable amino acid substitutions associated with resistance to TDF.

Since TDF and adefovir (ADV), another licensed drug for CHB, belong to same molecular group, acyclic phosphonate, there had been various studies investigating the efficacy of TDF in ADV-resistant patients. The efficacy of tenofovir in this group of patients is conflicting. While several studies have shown TDF achieving similar viral suppression when compared to CHB patients without ADV-resistance , another study found that patients with the signature ADV mutations of rtA181V/T and /or rtN236T responded suboptimally to TDF. For all published studies, the number of patients with documented genotypic resistance to adefovir is actually small (n = 17-40), and therefore, further studies in this area are required.

Another interesting point to note was the relatively high rate of hepatitis B surface antigen (HBsAg) seroclearance found in patients taking TDF. The cumulative rate of HBsAg seroclearance up in hepatitis B e antigen (HBeAg)-positive was 10% after 4 years . However, the same study did not find any HBeAg-negative patients achieving HBsAg seroclearance. In addition, studies on TDF were mainly performed in Caucasian patients, the majority being genotypes A and D. A preliminary study performed in Asian patients, predominantly genotypes B and C, did not discover any cases of HBsAg seroclearance . Given the majority of the CHB population is found in Asia, further studies are needed to clarify if HBsAg seroclearance by nucleoside / nucleotide analogues is potentially achievable using TDF.


Enrollment:     141
Study Start Date:     April 2008
Estimated Study Completion Date:     March 2013
Primary Completion Date:     November 2012 (Final data collection date for primary outcome measure)

StephenW

ClinicalTrials.gov标识符NCT01728935）
替诺福韦在亚洲慢性乙型肝炎患者
目的

替诺福韦（TDF）已被证明有效价抗B型肝炎病毒（HBV）的各种多中心临床试验中，没有遇到的阻力。然而，其疗效和电阻档在亚洲人群中，慢性乙型肝炎（CHB）患者占多数，还是个未知数。其他核苷类似物相比，TDF已与乙肝表面抗原（HBsAg）转阴率相对较高。这将是感兴趣，看是否可以再现。研究者计划报告的血清学和病毒学的结果，我们的140个核苷类似物经验的患者开始TDF。

详细说明：

最近的多中心临床试验表明替诺福韦TDF）：富马酸disoprovil（展示了强大的抗病毒在核苷初治经验丰富的慢性乙型肝炎（CHB）患者的疗效。目前，已经与耐TDF没有可识别的氨基酸替换。

由于TDF和阿德福韦（ADV），另一间持牌药物为慢性乙型肝炎，属于相同的分子团，无环膦，曾有过各种各样的研究调查TDF ADV耐药患者的疗效。替诺福韦在这组患者的疗效是相互矛盾的。虽然一些研究表明TDF实现了类似的病毒抑制CHB患者相比没有ADV-阻力，另一项研究发现，患者ADV突变的rtA181V / T和/或rtN236T签名不理想的TDF。所有发表的研究报告，记载基因型耐药阿德福韦的患者数量实际上是小组（n = 17-40），因此，需要进一步在这方面的研究。

另一个有趣的一点需要注意的是乙肝表面抗原（HBsAg）转阴发现患者服用TDF率比较高。 4年后的累积率，乙肝表面抗原转阴，乙肝e抗原（HBeAg）阳性率为10％。然而，同样的研究并没有发现任何HBeAg阴性患者实现乙肝表面抗原转阴。此外，TDF的研究主要在白人患者中，多数是基因型A和D在亚洲患者中进行的初步研究，主要是基因型B和C，没有发现任何情况下，乙肝表面抗原转阴。鉴于CHB人口的大多数是在亚洲发现的，还需要进一步研究，以澄清，如果乙肝表面抗原转阴核苷/核苷酸类似物，使用TDF是可能实现的。


招生：141
研究开始日期：2008年4月
估计研究完成日期：2013年3月
完成日期：2012年11月（主要转归指标的最终数据收集日期）

咬牙硬挺

第二篇文章说阿德福韦耐药的患者服用替诺效果不太好是吗

StephenW

咬牙硬挺 发表于 2013-6-25 11:05
第二篇文章说阿德福韦耐药的患者服用替诺效果不太好是吗

是.