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发表于 2017-6-30 21:56 |只看该作者 |倒序浏览 |打印
Review
Current clinical evidence for nucleos(t)ide analogues in patients with HBV-related hepatocellular carcinoma
Yiqi Yu, Jingwen Ai & Wenhong Zhang
Pages 1-13 | Received 01 Mar 2017, Accepted 14 Jun 2017, Published online: 29 Jun 2017

    Download citation http://dx.doi.org/10.1080/17474124.2017.1343665



ABSTRACT

Introduction: Hepatocellular carcinoma (HCC) is a leading cause of death globally and is frequently seen following Hepatitis B virus (HBV) or Hepatitis C virus infection. Areas with high HBV infection rates, such as Asia and sub-Saharan Africa, are therefore also high-risk areas for HCC.

Areas covered: This review identifies and discusses the current evidence from robust clinical trials which have investigated the benefits of Nucleos(t)ide analogue (NA) antiviral therapy in HBV-related HCC patients, including HCC patients that underwent liver transplantation and HCC patients with or without curative treatment. In addition, we assess how this evidence has influenced current clinical practice, with a particular focus on those areas of high HBV infection rates.

Expert commentary: A number of studies have assessed whether NA antiviral treatment can improve the prognosis of HBV-related HCC patients. In this review we evaluate the current evidence, including that from trials in Asia, for antiviral NA treatments in HBV-related HCC patients. We also focus on those NAs with a high genetic barrier to resistance (i.e. ETV or TDF), on different therapeutic approaches, and on the future evidence that is required in this field.
KEYWORDS: Hepatocellular carcinoma, Hepatitis B virus, antiviral, nucleos(t)ide analogue, clinical practice, Asia

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发表于 2017-6-30 21:56 |只看该作者
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目前HBV相关性肝细胞癌患者核型(t)ide类似物的临床证据
余奕琦,景文爱文文张
第1-13页收到2017年3月01日,接受日期:2017年06月14日,在线发布:2017年06月29日

    下载引用http://dx.doi.org/10.1080/17474124.2017.1343665



抽象

介绍:肝细胞癌(HCC)是全球死亡的主要原因,常见于乙型肝炎病毒(HBV)或丙型肝炎病毒感染。因此,亚洲和撒哈拉以南非洲地区HBV感染率较高的地区也是HCC的高风险地区。

覆盖的领域:本次审查确定并讨论了强化临床试验的现有证据,研究了HBV相关HCC患者,包括接受肝移植的HCC患者和HCC患者的肝细胞癌(N)抗病毒治疗的益处或无治疗。此外,我们评估这一证据如何影响当前的临床实践,特别关注那些高HBV感染率的领域。

专家评论:一些研究评估了NA抗病毒治疗是否可以改善HBV相关HCC患者的预后。在本次审查中,我们评估了目前的证据,包括来自亚洲试验的HBV相关HCC患者抗病毒药物治疗的证据。我们还将重点放在具有高抗遗传基因阻力(即ETV或TDF)的不同治疗方法的NAs以及该领域所需的未来证据上。
关键词:肝细胞癌,乙型肝炎病毒,抗病毒药物,核苷类似物,临床实践,亚洲

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发表于 2017-6-30 21:59 |只看该作者
3. Conclusion
The goal of antiviral therapy for HBV-related HCC is to suppress viral replication, reduce the recurrence rate of HCC,
and increase patient overall survival. To date, the use of
antiviral therapy in HBV-related HCC has been recommended by several global organizations. Both pre- and
post-operative antiviral therapy could reduce the recurrence
rate of HCC in patients, but little data are currently available
comparing the efficacy of different NAs. Studies have recommended ETV and TDF as first-line antiviral agents for treatment-naïve patients with decompensated cirrhosis both pre-
and post-transplantation, and using NAs with a low genetic
barrier to drug resistance should be avoided. The use of
antiviral agents should be combined with HBIg to further
reduce HBV recurrence rates, while monotherapy of potent
NAs with a high genetic barrier can be an alternative to
combination  therapy  for  post-transplant  patients.  For
patients receiving chemotherapy treatment, LAM can reduce
the risk and the severity of HBV reactivation but poses a
drug resistance threat. Potent NAs with lower resistance
rates than LAM, such as TVF and ETV, showed effectiveness
in  preventing  HBV  reactivation  in  patients  receiving
chemotherapy.
In future, large, multicenter randomized trials comparing
the efficacy of different antiviral therapies in HBV-related HCC
patients should be conducted.

结论
HBV相关HCC的抗病毒治疗目标是抑制病毒复制,降低HCC复发率,
并增加患者的总体生存。到目前为止,使用
HBV相关HCC的抗病毒治疗已被几个全球性组织推荐使用。前和后
术后抗病毒治疗可以减少复发
患者HCC发生率,但目前尚无数据
比较不同NAs的疗效。研究已经推荐ETV和TDF作为一线抗病毒剂,用于治疗无效的失代偿期肝硬化患者,
和移植后,并使用具有低遗传的NAs
应避免阻碍耐药性。指某东西的用途
抗病毒药物应与HBIg联合使用
降低HBV复发率,而单药治疗有效
具有高遗传屏障的NAs可以替代
移植后患者的联合疗法。对于
接受化疗治疗的患者,LAM可减少
HBV再激活的风险和严重程度,但构成a
耐药性威胁。具有较低阻力的强力NAs
价格比LAM(如TVF和ETV)显示有效
预防患者接受HBV再次激活
化疗。
未来,大,多中心随机试验比较
不同抗病毒疗法在HBV相关HCC中的疗效
患者应进行。

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发表于 2017-6-30 22:02 |只看该作者

4. Expert commentary
HCC is a leading cause of cancer-related death, with an estimated 750,000 new cases of HCC worldwide every year. It is
further estimated that up to 80% of these cases are as a result
of HBV or HCV infection, with evidence showing that HCC
mortality and incidence is correlated with prevalence of HBV.
Surgical resection, lT, chemotherapy, and local tumor ablation
are currently the main treatment options available, however in
cases related to HBV infection there should also be an antiviral
component of treatment to prevent recurrence. Considering
the continued high rates of Hepatitis B in sub-Saharan Africa
and East Asia, there remains a high need for clear and effective
antiviral treatment pathways in these regions for HBV patients
that subsequently develop HCC. This need exists in three
distinct but related patient populations, namely:
(1) HBV-related HCC patients who have undergone lT. In
these patients, a combination of HBIg and NAs with a
high genetic barrier to resistance (i.e. ETV or TDF) prove
to effectively prevent HBV recurrence posttransplant. It
is still unclear whether HBIg discontinuation after prior
combination therapy or NA monotherapy could provide
equivalent long-term benefits, and this should be investigated in the future from both an efficacy and cost-effectiveness perspective.
(2) HBV-related HCC patients with curative treatment.
Accumulating evidence shows that NA antiviral treatment could reduce HCC recurrence and improve overall
survival rate. This supports the use of NA antiviral therapy in the tertiary prevention of HCC.
(3) HBV-related HCC patients without curative treatment.
NAs have been shown to be effective in preventing HBV
reactivation  in  patients  receiving  chemotherapy.
However,  future  considerations  should  evaluate
whether NAs should be administered in all or only a
subset of late-stage HCC patients. This question should
be considered from both a disease status perspective
and an expected lifespan status.
An important next step would therefore be to conduct a series of
clinical trials. Of particular interest would be the initiation of large
multicenter trials with longer treatment duration from across
Asia. This would enable specific sub-analyses and meta-analyses
of the data to confirm the safety and efficacy of existing treatments in these high-risk populations, and would be of benefit in
the generation of robust local guidelines. By understanding this
issue more thoroughly, it will not only be possible to assess the
best treatment option for each patient but will also provide data
on the total healthcare cost associated with the long-term outcomes of the patients. This in turn will allow for more thorough
total cost assessments, and potentially lead to an improved
economic strategy for treatment of HBV-related HCC.
Although treatments are available for HBV-related HCC,
future focus should also be on the prevention of HBV, thus
avoiding HBV-related HCC. Safe and effective vaccines for HBV
are available which have enabled infection rates to drop to
less than 1% in Western Europe and North America. With
improved prevention and clearer guidance for treatment of
HBV-related HCC, we hope that the healthcare burden of this
disease can be reduced across the region.

专家评论
HCC是癌症相关死亡的主要原因,每年在全球范围内估计有75万例HCC。它是
进一步估计,这些案件中高达80%是结果
的HBV或HCV感染,有证据表明HCC
死亡率和发病率与HBV流行率相关。
手术切除,lT,化疗和局部肿瘤消融
目前是可用的主要治疗方案,但是
与HBV感染相关的病例也应该是抗病毒药物
组成部分治疗以预防复发。考虑到
撒哈拉以南非洲地区乙型肝炎持续高发
而东亚地区仍然需要清晰有效
这些区域的HBV病人的抗病毒治疗途径
随后发展HCC。这个需求存在于三个
不同但相关的患者群体,即:
(1)经历了lT的HBV相关HCC患者。在
这些患者,HBIg和NAs的组合与a
高抗遗传屏障(即ETV或TDF)证明
有效预防移植后HBV复发。它
HBIg以前是否停药仍不清楚
联合治疗或NA单药治疗可提供
等效的长期利益,今后应从效能和成本效益的角度进行调查。
(2)治疗性HBV相关性肝癌患者。
积累的证据表明,NA抗病毒治疗可以减少HCC复发并改善整体
存活率。这支持在三联预防肝癌中使用NA抗病毒治疗。
(3)HBV相关HCC患者无治疗。
NAs已被证明能有效预防HBV
接受化疗的患者重新激活。
然而,未来的考虑应该是评估的
是否应该全部或只管理一个
晚期HCC患者的子集。这个问题应该
从疾病状态角度考虑
和预期的使用寿命状态。
因此,重要的下一步是进行一系列的工作
临床试验。特别感兴趣的是启动大型
多中心试验,治疗持续时间较长
亚洲。这将有助于进行具体的次级分析和荟萃分析
的数据,以确认现有治疗在这些高危人群中的安全性和有效性,并将受益
生成强大的本地指南。通过了解这一点
问题更彻底,不仅可以评估
每个病人的最佳治疗方案,但也将提供数据
关于与患者长期结局相关的总医疗费用。这反过来又会让更彻底的
总成本评估,并可能导致改进
治疗HBV相关HCC的经济策略。
虽然治疗可用于HBV相关HCC,
未来重点还应该是预防HBV,因此
避免与HBV相关的HCC。安全有效的HBV疫苗
可以使感染率下降到
不到1%在西欧和北美。同
改善预防和更明确的治疗指导
HBV相关HCC,我们希望这个的医疗负担
整个地区的疾病可以减少。

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5
发表于 2017-6-30 22:03 |只看该作者

Key issues

A high prevalence of HBV infection is associated with an
increased incidence of HCC

Antiviral Nucleos(t)ide analogues (NA) treatment improves
HBV-related HCC prognosis

Drug resistance can be an issue with some currently available NAs. NAs with a high genetic barrier to resistance are
recommended by international guidelines.

More data are required that directly compare the safety and
efficacy of current NAs

关键的问题

HBV感染的高发率与a相关
肝癌发病率增加

抗病毒核(t)ide类似物(NA)治疗改善
HBV相关HCC预后

耐药性可能是一些目前可用的NAs的问题。 具有高遗传阻力的NAs
由国际准则推荐。

需要更多的数据直接比较安全性和
目前NAs的疗效
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