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标题: 在中国慢性乙型肝炎患者恩替卡韦抗病毒的作用一个五年的 [打印本页]

作者: StephenW 时间: 2016-7-2 16:12 标题: 在中国慢性乙型肝炎患者恩替卡韦抗病毒的作用一个五年的

Sci Rep. 2016 Jul 1;6:28779. doi: 10.1038/srep28779.
A five years study of antiviral effect of entecavir in Chinese chronic hepatitis B patients.Liu K1, Xiang X1, Bao R2, Chen R1, Liu Y1, Xie J1, Guo Q1, Bao S3, Xie Q1, Wang H1.
Author information

1Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
2Discipline of Anatomy and Histology, School of Medical Sciences and The Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia.
3Discipline of Pathology, School of Medical Sciences and The Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia.

AbstractEntecavir (ETV) is a potent viral replication inhibitor for chronic hepatitis B (CHB) patients. To investigate the efficacy of ETV in Chinese nucleos(t)ide(NA)-experienced CHB patients. Among 89 CHB patients with ETV monotherapy for ≥6 months, 33/89 (37%) or 56/89 (73%) were NA-naïve or NA-experienced. During a median follow-up of 5.75 years, all NA-naïve CHB patients achieved VR without genotypic ETV-resistance. However, VR was observed in 50/56 (~90%) of NA-experienced CHB patients during a median follow-up of 4.75 years. Antiviral efficacy was not reduced in patients with previous lamivudine (LAM) with/without LAM-resistance (HR 0.465; 95% CI 0.196-1.100; p > 0.05) (HR 0.472; 95% CI 0.205-1.091; p > 0.05). Patients with a primary treatment failure to adefovir (ADV) had a reduced probability of achieving VR compared to NA-naïve (HR 0.496; 95% CI 0.287-0.857; p < 0.01). Previous ADV-experienced patients with a partial VR (HR 1.253; 95% CI 0.429-3.665; p > 0.05) did not influence antiviral response to ETV. The antiviral efficacy of ETV is not influenced by previous treatment LAM with/without LAM-resistance. ETV may still be an option in ADV-experienced patients with a partial VR, but not advised in patients with a primary treatment failure to ADV.

PMID:27364728DOI:10.1038/srep28779

作者: StephenW 时间: 2016-7-2 16:12

。科学众议员2016年7月1日; 6：28779。 DOI：10.1038 / srep28779。
在中国慢性乙型肝炎患者恩替卡韦抗病毒的作用一个五年的研究。
刘K1，湘X1，宝R2，R1陈，刘Y1，谢J1，郭Q1，宝S3，谢Q1，H1王。
作者信息

传染病教研室，医学院瑞金医院，上海交通大学，上海，中国的学校。
解剖学和组织学，医学科学学院和博世研究所，悉尼大学，悉尼，2006年澳大利亚新南威尔士州的2Discipline。
病理3Discipline，医学科学学院和博世研究所，悉尼，悉尼，2006年澳大利亚新南威尔士州大学。

抽象

恩替卡韦（ETV）为慢性乙型肝炎（CHB）的患者的有力病毒复制抑制剂。为了研究ETV在中国的核苷（酸）IDE（NA）的疗效-experienced慢性乙肝患者。在89 CHB患者ETV单药治疗≥6个月，八十九分之三十三（37％）或56/89（73％）为NA-天真或NA-经验。在5.75年的中位随访，所有的NA初治慢性乙肝患者达到无VR ETV基因型耐药性。然而，在VR 50/56（〜90％）观察NA-经验CHB患者为4.75年的中位随访期间。抗病毒疗效不是在既往有拉米夫定（LAM）有/无LAM-性降低（HR 0.465; 95％CI 0.196-1.100; P> 0.05）（HR 0.472; 95％CI 0.205-1.091; P> 0.05）。与主治疗失败阿德福韦（ADV）的患者实现VR相比，NA-天真的可能性降低（HR 0.496; 95％CI 0.287-0.857; P <0.01）。上一页ADV经验的患者与部分VR（HR 1.253; 95％CI 0.429-3.665; P> 0.05）并没有影响到ETV抗病毒反应。 ETV的抗病毒疗效不受既往治疗LAM有/无LAM-性的影响。 ETV仍可能在ADV经验的患者具有部分VR一种选择，但在患者不建议用伯治疗失败ADV。

结论：
27364728
DOI：
10.1038 / srep28779
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作者: leechanlee 时间: 2016-7-3 05:53

结论是什么？

作者: StephenW 时间: 2016-7-3 15:59

回复 leechanlee 的帖子

在ADV治疗失败患者, 不建议用ETV.

作者: 别愁 时间: 2016-7-4 13:00

本帖最后由别愁于 2016-7-4 13:07 编辑

回复 StephenW 的帖子

"The antiviral efficacy of ETV is not influenced by previous treatment LAM with/without LAM-resistance."? 恩提抗病毒的效果不受早先用拉米的影响（不论是否拉米耐药过）——没提是否可以长期用

作者: 老王卖麻花 时间: 2016-7-4 13:19

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作者: 老王卖麻花 时间: 2016-7-4 13:42

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作者: zhujun 时间: 2016-7-4 13:48

老王卖麻花发表于 2016-7-4 13:42
The antiviral efficacy of ETV is not influenced by previous treatment LAM with/without LAM-resistanc ...

不管拉米是否耐药，恩替的抗病毒效果不受影响。

作者: zhujun 时间: 2016-7-4 13:51

同以前的用药推荐指南说法不同，靠谱吗？

作者: 别愁 时间: 2016-7-4 14:13

回复 zhujun 的帖子

看了原文，大概10个拉米耐药的病人中有3个5年里恩替也耐药了。用的都是1mg的量，结论还是一样的，只是比例好像低了一点。

作者: zhujun 时间: 2016-7-4 14:25

那就是拉米耐药，1毫克的恩替还可以混几年，不是以前说法是6-9个月。

作者: 别愁 时间: 2016-7-4 14:45

回复 zhujun 的帖子

运气好的话是可以顶上一阵子的。
那3个好像还是在开始用恩提时能检测出拉米耐药株的。

作者: zhujun 时间: 2016-7-4 15:03

回复别愁的帖子

“大概10个拉米耐药的病人中有3个5年里恩替也耐药了”，不是10个拉米都耐药了吗？

作者: 老王卖麻花 时间: 2016-7-4 15:28

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作者: StephenW 时间: 2016-7-4 15:37

别愁发表于 2016-7-4 13:00
回复 StephenW 的帖子

"The antiviral efficacy of ETV is not influenced by previous treatment LAM wit ...

这是我的理解:
恩提抗病毒的效果不受早先用拉米的影响（不论是否拉米耐药过）在短期内.

我会尽量找到长期使用的信息

作者: zhujun 时间: 2016-7-4 15:54

本帖最后由 zhujun 于 2016-7-4 15:56 编辑

谢谢！

作者: StephenW 时间: 2016-7-4 16:32

别愁发表于 2016-7-4 13:00
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"The antiviral efficacy of ETV is not influenced by previous treatment LAM wit ...

Discussion

We have demonstrated for the first time, the efficacy of long-term ETV treatment in Chinese NA-experienced CHB patients. Previous treatment of LAM with/without LAM-resistance does not influence the efficacy of ETV treatment. Furthermore, ETV may still be an option in ADV-experienced patients with a partial VR, but is not advised in patients with a primary treatment failure to ADV therapy. LAM and ADV are still wildly used for treatment of CHB in the developing countries. Our current findings on LAM and ADV in relation to ETV treatment may provide guideline in clinical intervention.

ETV has probably superior virologic, biochemical, and histological efficacy compared to other current NAs agents, arguably equal efficacy with tenofovir disoproxil fumarate (TDF)14. The five-year ETV clinical trial (ETV-022) demonstrated that 94% had HBV DNA < 300 copies/mL, 80% had normal ALT levels, and 23% achieved HBeAg seroconversion in NA-naïve CHB patients in Europe15. In addition, >90% ETV treated NA-naïve Chinese CHB patients achieved HBV DNA undetectable after 2 years, VP increased at 12 and 24 weeks, and HBeAg seroconversion achieved 15.4% at year three9. The above findings9,15,16 support our current study, which demonstrated that all NA-naïve patients achieved VR at year five without genotypic ETV-resistance. HBV DNA was reduced substantially accompanied by increased VR at 12 and 24 weeks, in addition to increased rate of ALT normalization. Moreover, our data also showed that the rate of HBeAg seroconversion in the Chinese patients was 17%, 28% or 33% at year two, three or five, respectively, which are similar with the results of previous studies17. The combined data from our study and previous studies demonstrate that ETV is highly effective in NA-naïve patients. It has been reported that ETV has rare occurrence of resistance in NA-naïve patients9, which is consistent with our findings over a five-year period. Thus detecting mutations for pre-existing resistance to ETV in NA-naïve patients is of limited significance from financial and practical point of view.

LAM has been routinely used as a first-line therapy for CHB patients, however has incurred major limitations due to growing resistance over the past decade18. Resistance is usually associated with a rebound in viral load and often associated with exacerbation of hepatitis19. Increasing number of treatment failure to different NA-treatment regimens poses a growing problem in daily clinical practice.

The effect of ETV monotherapy in CHB patients has been categorized into two groups: NA-naïve and NA-experienced in Reijnders’s study12. The presence of LAM-resistant mutations at the start of ETV was significantly associated with a reduced probability of achieving VR compared to LAM-naïve patients. Previous LAM treatment without development of LAM-resistance, or with a prior history of LAM-resistance, did not influence the antiviral response over a one-year period12. This data is consistent with our five-year study, demonstrating antiviral efficacy was not decreased by previous LAM treatment, with or without LAM-resistance. It was reported that ETV resistance developed more frequently in LAM-treated CHB patient over an 18-month period, but no prior history of LAM-resistance did not affect the development of ETV resistance20. Our data showed that among nine developed ETV resistance patients, three did not have LAM-resistance, but four had a prior history of LAM-resistance. Of those four patients, three subjects expressed detectable LAM-resistant mutations at the initiation of ETV monotherapy. Our five-year study suggested that LAM-resistant CHB patients with ETV treatment results in a high probability of progression to ETV-resistance, particularly in the group with previous detectable LAM-resistant mutation at the start of ETV therapy.

ADV, an established medication for the treatment of CHB, has been widely used in China in the past decade. ADV has additionally been associated with a high rate of primary treatment failure, defined as less than a 2-log reduction in viral load after six months of therapy, and a high rate of antiviral resistance2,21,22. The efficacy of ETV in CHB patients previously treated with ADV has been relatively un-studied, particularly in cases with primary treatment failure23,24. It has been also reported that the effects of ETV monotherapy in previous ADV-treated CHB patients demonstrating that partial responders do not display as good effect as ADV-complete responders25,26. Interestingly, previous treatment with ADV and presence of ADV-resistant mutations does not influence the potency of ETV12. Our five-year-period study established that there was almost equal effect with ETV treatment between the CHB patients prior to ADV therapy with a partial virology response and NA-naïve patients. Such discrepancies may be due to a difference in time period (three vs five years) and also in different populations (Caucasians vs Chinese). More importantly, we found that CHB patients with a primary treatment failure history had a reduced probability of achieving VR compared to NA-naïve patients. Therefore, the response to prior treatment is necessary for ADV-experienced patients before starting ETV monotherapy.

In our current study, all ADV-experienced and NA-naïve patients were treated with 0.5 mg ETV; whereas all LAM-experienced patients were treated with 1 mg ETV monotherapy, while NA-naïve patients were treated with 0.5 mg ETV. This data suggests that 1 mg of ETV provides no more obvious anti-viral benefit in LAM-experienced patients compared to that of NA-naïve patients with 0.5 mg ETV treatment. During the follow up, there was no significantly different follow-up time between LAM-experienced and naïve groups, however a significant difference was detected between ADV-experienced and naïve groups. As those non-VR patients had already experienced viral breakthrough within three years, the extended follow-up period may not contribute to the major cause of reduced VR among NA-experienced patients. In this study, no significant difference was observed between cirrhotic and chronic hepatitis patients, however this is more likely due to a relatively small number of patients. A large cohort study is currently being investigated.

Limitations of our study include the heterogeneous group and relative small sample size. Cox regression has been applied to correct for confounders as treatment duration, HBV DNA, HBeAg status. Nevertheless, the Out-patient Department of Infectious Diseases in Shanghai Ruijin Hospital with consultation number is 12000 per month, one of the biggest in the China, and covers large areas of patients. Thus, the patients still represent of clinical practice and make it possible to compare different groups of NA-experienced patients. We appreciate the small scale of the study, despite spanning a five-year period. A large scale study with an expanded population size, and extended period of time is currently in the process of being investigated.

Despite the influence of previous IFN exposure on the efficacy of ETV, only 17 (19%) of patients had prior experience of IFN treatment within our current study. The impact of IFN to long-term ETV therapy is currently lacking in understanding, and still requires further exploration.

In conclusion, ETV proved to be efficacious in NA-naïve patients. ETV may still be an option in ADV-experienced patients with a partial virology response, however it is not recommended in patients with a primary treatment failure to ADV therapy.

作者: StephenW 时间: 2016-7-4 16:33

我们已经证明用于第一次，长期ETV治疗在中国NA-经历慢性乙型肝炎患者的疗效。与/ LAM的以前治疗没有LAM-电阻不影响ETV治疗的功效。此外，ETV仍可能在ADV经验的患者与部分VR一种选择，但患者不建议用初级治疗失败ADV治疗。 LAM和ADV仍广泛用于对发展中国家治疗慢性乙型肝炎的。关于ETV对治疗LAM和ADV我们目前的研究结果可能在临床干预提供指导。

ETV有可能优于病毒学，生物化学和组织学功效相比其他当前NAS剂，可以说是同等功效与富马酸替诺福韦酯（TDF）14。五年ETV的临床试验（ETV-022）显示，94％的患者HBV DNA <300拷贝/毫升，80％的ALT水平正常，23％实现HBeAg血清转换在NA初治慢性乙肝患者在Europe15。此外，> 90％，ETV治疗NA初治中国慢性乙型肝炎患者达到HBV DNA 2年后检测不到，增加了副总裁在12和24周，HBeAg血清转换在今年three9达到15.4％。以上findings9,15,16支持我们目前的研究，这表明，所有NA初治患者在第五年实现无VR ETV基因型耐药性。 HBV DNA的混合物在12和24周显着减少伴随增加的VR，除了增加的ALT正常化的速率。此外，我们的数据还显示，血清转换的在中国的患者的比率为17％，28％，或在一年分别两个，三个或五个，33％，这是与以前的studies17的结果相似。从我们的研究和以前的研究合并数据表明，ETV是NA初治患者非常有效。据报道，ETV在NA-天真patients9，这与我们在5年的研究结果一致抵抗罕见。因此，检测突变为ETV到预先存在的阻力NA初治患者是从财务和实际点意义有限。

林已被常规用作一线治疗慢性乙型肝炎的患者，但是已经招致重大的局限性，由于在过去decade18生长阻力。电阻通常与病毒载量的反弹相关联，并且经常与hepatitis19的恶化有关。增加治疗失败的数目不同的NA-治疗方案提出在日常临床实践的问题日益严重。

ETV单药治疗慢性乙型肝炎患者的影响已经被分为两类：NA初治和Reijnders的study12 NA-经历。 LAM耐药突变在ETV开始存在下用实现VR相比林初治患者的降低的概率显著相关联。上一页LAM治疗LAM无耐药性的发展，或者与LAM耐药的病史，不影响超过一年period12的抗病毒反应。这个数据与我们的五年研究是一致的，这表明抗病毒效力不是由前面的LAM治疗降低，有或没有LAM-阻力。据报道，恩替卡韦耐药性LAM治疗的慢性乙肝患者在18个月内开发出更加频繁，但没有事先林阻力历史并没有影响ETV电阻20的发展。我们的数据显示，在9个发达ETV耐药患者，三没有LAM-抵抗，但四人曾经LAM耐药性病史。这四个病人中，三科表达了ETV单药治疗开始检测LAM耐药突变。我们的五年研究表明，LAM耐药CHB患者具有高概率进展为ETV性，特别是在与ETV治疗开始之前的检测的LAM耐药突变的组ETV治疗效果。

ADV，慢性乙型肝炎的治疗既定的药物，在过去十年中已广泛应用于中国。 ADV已经另外地被以高速率主要治疗失败的，定义为少于六个月的治疗后病毒载量的2 log减少，和抗病毒resistance2,21,22率高有关。 ETV在CHB患者以前用ADV治疗的疗效已经相对取消了研究，特别是在主要治疗failure23,24案件。它一直还报告说，展示ETV单一疗法的先前ADV治疗慢性乙型肝炎患者的效果，部分应答不显示作为ADV-完整responders25,26为良好的效果。有趣的是，与ADV和ADV耐药突变的存在以前的治疗不影响ETV12的效力。我们的五年期研究，建立，有有和NA初治患者ADV治疗前CHB患者之间ETV治疗与部分病毒学应答几乎相等的效果。这种差异可能是由于在时间段（三级VS五年）的差，并在不同的人群（白种人VS中国）。更重要的是，我们发现，慢性乙型肝炎患者与伯治疗失败历史不得不实现VR相比NA初治患者的降低的概率。因此，先前治疗的反应是必要的ADV-经验的患者开始ETV单一疗法之前。

在我们目前的研究中，所有ADV-经验和NA初治患者用0.5毫克ETV治疗;而所有LAM经验的患者用1毫克ETV单药治疗，而NA初治患者用0.5毫克的ETV治疗。该数据表明，1毫克ETV的提供在LAM经验的患者没有更明显的抗病毒好处相比，NA初治患者用0.5mg ETV治疗。在跟进，出现了LAM-经验丰富，天真组之间没有显著不同的随访时间，但被ADV-经验丰富，天真群体之间检测到显著差异。由于这些非VR患者已经三年内经历病毒突破，扩展的随访期间可能不会有助于减少VR的NA经验的患者中的主要原因。在这项研究中，肝硬化，慢性肝炎患者之间没有观察到显著差异，然而，这是更可能是由于相对小的数目的患者。一个大型的队列研究，目前正在调查。

我们研究的限制包括异构组和相对较小的样本大小。 Cox回归已应用于以校正干扰因素如治疗持续时间，HBV-DNA，HBeAg状态。然而，传染病门诊系上海瑞金医院与咨询号码是12000元不等，在中国最大的一个，占地面积患者的广大地区。因此，患者仍然代表临床实践的，并有可能以比较NA-经验的患者的不同的组。我们赞赏这项研究的规模小，尽管跨越五年。具有扩展的人口尺寸，在延长的时间期间A大规模研究是目前在被调查的过程。

尽管此前IFN暴露对ETV的疗效的影响，只有17（19％）的患者有我们目前的研究中干扰素治疗的经验。 IFN的长期治疗ETV的影响，目前缺乏理解，还需要进一步探索。

总之，ETV被证明是有效的NA初治患者。 ETV仍可能在ADV经验的患者具有部分病毒学应答的选项，但它是不建议患者与伯治疗失败ADV治疗。
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作者: StephenW 时间: 2016-7-4 16:47

Resistance

During a median follow-up of 63 (12–75) months, 10 of 89 (11%) patients experienced a virologic breakthrough, and 9 of 10 (90%) experienced ETV-resistance. Among 56 NA-experienced patients 50 patients achieved VR during the follow-up. In these 6 non VR patients, the serum HBV DNA levels increased more than 1 log10 IU/ml compared to the nadir (lowest value) HBV DNA level on therapy at least two occasions. Thus, the 6 non VR patients were classified as virological breakthrough, based on the guideline of EASL. Additionally, four out of 50 VR patients experienced a virological breakthrough at diffierent times, resulting in a total patient count of 10/56 with virological breakthrough. Four out of nine ETV-resistance patients switched to ETV plus ADV regimen, while other five patients remained ETV monotherapy, due to financial difficulty. Three of these ten virologic breakthrough patients had a prior history of developed LAM-resistance. Among these three patients, two had LAM-resistant mutation (rtL180M) at the start of ETV monotherapy, and further developed ETV-resistant mutations (rtT184A, rtM204V) during the follow-up. One patient with mutation (rtM204I) related to both LAM-resistance and ETV-resistance at baseline, achieved virologic response at 36 weeks and experienced a virologic breakthrough at 96 weeks. Unfortunately, this patient changed to ETV plus ADV regimen at very late stage (204 weeks) due to financial difficulty and developed HCC at 216 weeks. Only 5/9 ETV resistant patients achieved VR. None of NA-naïve patients experienced a virologic breakthrough during follow-up compared with NA-experienced patients.

抵抗性

在63（12-75）个月，中位随访89（11％）患者10经历了病毒学突破，和9 10（90％）出现ETV耐药。在56 NA-经验的患者50例随访期间取得VR。在这6个非VR患者中，血清HBV DNA水平上升超过1 log10的IU / ML相比最低点（最低值）对治疗至少有两次HBV DNA水平。因此，6个非VR患者分为病毒学突破的基础上，EASL的方针。此外，四明50 VR的患者经历了病毒学突破在diffierent次，造成五十六分之十与病毒学突破总病人数。四明九ETV耐药患者改用ETV加ADV方案，而其他五名患者保持ETV单药治疗，由于财政困难。这十病毒学突破的患者有三林发展阻力的病史。这三例患者中，2例在ETV单药治疗开始LAM耐药突变（rtL180M），并进一步发展ETV耐药性突变的随访期间（rtT184A，rtM204V）。与突变（rtM204I）与两个LAM-性和ETV耐药基线一名患者，在第36周达到病毒学应答，并在96周经历了病毒学突破。不幸的是，这名患者改为ETV加ADV方案在很后期（204周），由于财政困难，在216周的时间开发肝癌。只有5/9 ETV耐药的患者取得了VR。与NA-经验的患者相比，在随访期间NA初治患者中没有经历过病毒学突破。

作者: zhujun 时间: 2016-7-5 09:09

想了解：拉米耐药，1毫克恩替的耐药数据是多少？

作者: smilingcloud 时间: 2016-7-5 10:20

本帖最后由 smilingcloud 于 2016-7-5 10:21 编辑

论文原文，共8页。表1 参加研究的病例基础情况
表2 采用恩替治疗后病例状况
图1 初始恩替治疗的累积疗效与时间关系
图2 初始拉米切换恩替后，累积疗效与时间关系
图3 初始阿德切换恩替后，累积疗效与时间关系

作者: smilingcloud 时间: 2016-7-5 10:50

这篇报告采用89例病例，来源于上海瑞金医院（传染病门诊量12000/月）的2007年3月和2013年5月间调查研究。
调查研究受到国家自然科学基金以及上海市政府的。。。等支持。

-----
但是论文写的，看着有点累。有几处数字瑕疵。外行也能发现。[attach]500329[/attach]

该报告中的结论，与之前其他研究结论有一些分歧。
1，无论拉米是否发生耐药，切换恩替后累积疗效没有区别。（其他研究表示有区别）
2，阿德疗效不好病例，切换恩替后积累疗效有受影响有下降。（其他研究表示阿德不影响后续恩替疗效）

该报告中既往抗病毒治疗56病例中，39例疗效不良，17例停药中位数9个月（1-74个月）。
56例既往抗病毒病例中，8例肝硬化，37例慢性乙肝，11例缺乏纤维化数据。
56例既往病例切换恩替后，没有发现肝硬化病例和慢性乙肝病例的疗效区别。

既往病例治疗中，9例恩替耐药病例中5例，因为经济原因没有加阿德，而继续恩替。

1例拉米既往耐药病例，采用恩替后32周疗效良好（HBV-DNA<100IU/ml），但96周病毒反弹。
病人没有立刻加阿德，而是继续单药恩替用到204周才加阿德。不幸的是216周发现肝癌了。

作者: smilingcloud 时间: 2016-7-5 10:52

老王卖麻花发表于 2016-7-4 13:19
感谢分享。

这是一份迟来的小样本的报告。

老王大夫一到正经问题的时候就不出现，别指望他了。

作者: smilingcloud 时间: 2016-7-5 10:58

zhujun 发表于 2016-7-5 09:09
想了解：拉米耐药，1毫克恩替的耐药数据是多少？

文中介绍情况是10既往拉米耐药病例，切换恩替后6年有4个出现恩替耐药。出现时间如下图，第二年共2名恩替耐药，第三年共3名恩替耐药，第五年共4名恩替耐药。
文章中评述认为1mg恩替对于拉米既往病例来说，没有什么特殊作用。

作者: smilingcloud 时间: 2016-7-5 11:01

23楼提到的其他研究是
http://www.ncbi.nlm.nih.gov/pubm ... act&holding=npg
J Hepatol. 2010 Apr;52(4):493-500. doi: 10.1016/j.jhep.2010.01.012. Epub 2010 Feb 4.
Antiviral effect of entecavir in chronic hepatitis B: influence of prior exposure to nucleos(t)ide analogues.
Reijnders JG1, Deterding K, Petersen J, Zoulim F, Santantonio T, Buti M, van Bömmel F, Hansen BE, Wedemeyer H, Janssen HL; VIRGIL Surveillance Study Group.
Author information
Abstract
BACKGROUND & AIMS:
Entecavir is a potent inhibitor of viral replication in nucleos(t)ide analogue (NA)-naïve chronic hepatitis B patients, but data on the efficacy in NA-experienced subjects are limited.
METHODS:
In a multi-center cohort study we investigated 161 chronic hepatitis B patients (34% NA-experienced) treated with entecavir monotherapy.
RESULTS:
During a median follow-up of 11 (3-23)months, 82 (79%) of 104 NA-naïve patients achieved virologic response (VR), defined as HBV DNA <80IU/ml, and none of the patients (0%) developed genotypic entecavir-resistance. VR was demonstrated in 31 (54%) of 57 NA-experienced patients during a median follow-up of 12 (3-31)months. Patients with lamivudine-resistant mutations at the start of entecavir monotherapy had a reduced probability of achieving VR compared to lamivudine-naïve patients (HR 0.14; 95% CI 0.04-0.58; p=0.007). Antiviral efficacy was not decreased by prior treatment with lamivudine when lamivudine-resistance had never developed (HR 0.81; 95% CI 0.43-1.52; p=0.52). Prior adefovir therapy without development of adefovir-resistance (HR 0.84; 95% CI 0.43-1.64; p=0.61) and presence of adefovir-resistance (HR 0.86; 95% CI 0.27-2.71; p=0.80) did not influence antiviral response to entecavir. Switching to a tenofovir-containing treatment regimen resulted in viral load decline in patients with entecavir-resistance associated mutations.
CONCLUSIONS:
Entecavir proved to be efficacious in NA-naïve patients. The antiviral efficacy of entecavir was not influenced by prior treatment with adefovir or presence of adefovir-resistance. Entecavir should not be used in patients with previous lamivudine-resistance, yet it may still be an option in lamivudine-experienced patients in case lamivudine-resistance never developed.

作者: zhujun 时间: 2016-7-5 11:52

回复 smilingcloud 的帖子

谢谢您的指点，现在懂了，意思是：只要你用过拉米，不管耐药与否，换恩替，最终恩替的耐药的结果差异不大。除非你初次使用恩替。

作者: zhujun 时间: 2016-7-5 11:56

本帖最后由 zhujun 于 2016-7-5 12:02 编辑

也就是说，乘拉米没有耐药换恩替意义不大。

作者: smilingcloud 时间: 2016-7-5 12:08

zhujun 发表于 2016-7-5 11:52
回复 smilingcloud 的帖子

谢谢您的指点，现在懂了，意思是：只要你用过拉米，不管耐药与否，换恩替，最终 ...

不客气，我就是搬运原文内容而已。

日本治疗指南中介绍对于拉米耐药病例治疗。
http://hbvhbv.info/forum/thread-1395364-1-1.html

上面链接中帖子7楼，日本的研究数据，病毒阴性的拉米耐药病例，恩替耐药并不是特别增加。

作者: smilingcloud 时间: 2016-7-5 12:14

本帖最后由 smilingcloud 于 2016-7-5 12:15 编辑

zhujun 发表于 2016-7-5 11:56
也就是说，乘拉米没有耐药换恩替意义不大。

国外治疗指南建议拉米没耐药要换恩替。
http://hbvhbv.info/forum/thread-1395372-1-1.html

上海瑞金医院这个报告有些太晚了，不及时。------2013年结束调查，2016年文章才发表。
而且样本小，病例用药也不规范。
期待后续的大样本报告---不知道又要等几年才公开发表。

作者: 老王卖麻花 时间: 2016-7-6 10:30

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