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标题: 慢性乙肝肝癌的风险：评估和修改当前的抗病毒治疗 [打印本页]

作者: StephenW 时间: 2015-3-17 07:48 标题: 慢性乙肝肝癌的风险：评估和修改当前的抗病毒治疗

Risk of hepatocellular carcinoma in chronic hepatitis B: Assessment and modification with current antiviral therapy
George V. Papatheodoridis correspondenceemail
,Henry Lik-Yuen Chan,Bettina E. Hansen,Harry L.A. Janssen,Pietro Lampertico
Open Access Article has an altmetric score of 1
DOI: http://dx.doi.org/10.1016/j.jhep.2015.01.002
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Publication History
Published Online: January 13, 2015Accepted: January 4, 2015Received in revised form: December 22, 2014Received: November 3, 2014

Summary

In the treatment of chronic hepatitis B (CHB), the ultimate goal is preventing hepatitis B virus (HBV)-associated liver disease, including hepatocellular carcinoma (HCC). Recently published studies show that in CHB patients treated with the currently recommended first-line nucleos(t)ide analogs (NAs) entecavir or tenofovir, annual HCC incidences range from 0.01% to 1.4% in non-cirrhotic patients, and from 0.9% to 5.4% in those with cirrhosis. In Asian studies including matched untreated controls, current NA therapy consistently resulted in a significantly lower HCC incidence in patients with cirrhosis, amounting to an overall HCC risk reduction of ∼30%; in non-cirrhotic patients, HCC risk reduction was overall ∼80%, but this was only observed in some studies. For patients of Caucasian origin, no appropriate comparative studies are available to date to evaluate the impact of NA treatment on HCC. Achievement of a virologic response under current NA therapy was associated with a lower HCC risk in Asian, but not Caucasian studies. Studies comparing entecavir or tenofovir with older NAs generally found no difference in HCC risk reduction between agents, except for one study which used no rescue therapy in patients developing lamivudine resistance. Overall, these data indicate that with the current, potent NAs, HCC risk can be reduced but not eliminated, probably due to risk factors that are not amenable to change by antiviral therapy, or events that may have taken place before treatment initiation. Validated pre- and on-therapy HCC risk calculators that inform the best practice for HCC surveillance and facilitate patient counseling would be of great practical value.
Abbreviations:
CHB (chronic hepatitis B), HCC (hepatocellular carcinoma), HBV (hepatitis B virus), BCP (basal core promoter), NA (nucleos(t)ide analog), HR (hazard ratio), PS (propensity score), REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B), REVEAL (Risk Evaluation of Viral Load Elevation and Associated Liver Disease), CU-HCC (Chinese University – Hepatocellular Carcinoma score), GAG-HCC (Guide with Age, Gender, HBV DNA, Core promoter mutations and Cirrhosis), ALT (alanine aminotransferase), ADV (adefovir), comb (combination therapy), comp (compensated), ETV (entecavir), LdT (telbivudine), LVD (lamivudine), NA (not assessed), TDF (tenofovir), tx (treatment), cirr (cirrhosis), decomp (decompensated), exp. (experienced), NR (not reported), RR (risk reduction), VR (virologic response), A (Asian), C (Caucasian), yr (year)

作者: StephenW 时间: 2015-3-17 07:49

慢性乙肝肝癌的风险：评估和修改当前的抗病毒治疗
乔治五世Papatheodoridis correspondenceemail
亨利沥，陈源，贝蒂娜汉森，哈利LA扬森，彼得Lampertico
开放获取文章的altmetric比分1
DOI：http://dx.doi.org/10.1016/j.jhep.2015.01.002
hideArticle信息
出版史
网上公布：1月13日，2015Accepted：1月4日，在2015Received修订表格：12月22日，2014Received：2014年11月3日

总结

在慢性乙肝治疗（CHB），最终的目标是防止乙肝病毒（HBV）相关的肝脏疾病，包括肝细胞癌（HCC）。最近公布的研究表明，在慢性乙型肝炎患者与目前推荐的一线核苷（酸）类似物（NAS）恩替卡韦或替诺福韦治疗，每年肝癌发病率的范围从0.01％至1.4％，在非肝硬化的患者，以及从0.9％至在那些与肝硬化5.4％。在亚洲的研究，包括匹配的未经处理的控制，目前NA治疗一贯导致显著降低HCC发生率在肝硬化患者，达整体下降约30的HCC％的风险;非肝硬化患者，肝癌的风险降低了整体的约80％，但这只是在一些研究中观察到。对于高加索血统的病人，没有合适的比较研究提供的最新评估NA治疗对肝癌的影响。根据目前的NA治疗的病毒学应答的成就是在亚洲较低的HCC危险性，但不是白种人的研究。比较恩替卡韦或替诺福韦与老港定居人士的研究发现，一般在HCC还原剂之间的风险没有什么区别，除了它没有使用抢救治疗的患者发展拉米夫定耐药的一项研究。总体而言，这些数据表明，与目前的，有力的NAS，肝癌风险可以减少，但不能消除，这可能是由于那些不适合用抗病毒治疗，或者可以在治疗开始前已经发生的事件来改变的危险因素。该通知的最佳实践HCC监视和方便患者咨询验证前和上治疗肝癌的风险计算器将是很大的实用价值。
缩写：
CHB（慢性乙肝），肝癌（肝癌），HBV（乙肝病毒），BCP（基础核心启动子），NA（核苷（酸）类似物IDE），HR（危险比），PS（倾向评分），REACH -B（风险估计肝癌在慢性乙肝），显示（病毒载量提升风险评估和相关的肝脏疾病），CU-HCC（中国大学 - 肝癌的分数），GAG-HCC（指南与年龄，性别， HBV DNA，核心启动子突变和肝硬化），ALT（谷丙转氨酶），ADV（阿德福韦），梳子（联合用药），补偿（补偿），ETV（恩替卡韦），LDT（替比夫定），LVD（拉米夫定），NA（不评估），TDF（替诺福韦），TX（治疗），CIRR（肝硬化），分解（失代偿期），EXP。（经验），NR（未报告），RR（降低风险），VR（病毒学应答），A（亚洲），C（高加索），年（年）

作者: 战天斗hbv 时间: 2015-3-17 09:26

一会有报告说核苷类不能降低hcc发生率、一会又有人说可以、到底哪个对

作者: HBVCURER 时间: 2015-3-17 11:04

本帖最后由 HBVCURER 于 2015-3-17 11:05 编辑

战天斗hbv 发表于 2015-3-17 09:26
一会有报告说核苷类不能降低hcc发生率、一会又有人说可以、到底哪个对

有效的核苷治疗可以显著降低HCC发生率，但是不能彻底消除HCC的风险，这在临床上都是有确切实证的。

作者: 战天斗hbv 时间: 2015-3-17 11:59

回复 HBVCURER 的帖子

上次本版有个文章、言之凿凿说核苷对hcc至少五年内无效、是吧sw？、那文章你还记得不

作者: HBVCURER 时间: 2015-3-17 14:12

战天斗hbv 发表于 2015-3-17 11:59
回复 HBVCURER 的帖子

上次本版有个文章、言之凿凿说核苷对hcc至少五年内无效、是吧sw？、那文章你还记得 ...

“对hcc至少五年内无效”，这个表述有或许可能没有准确反应原文的意思，能发个链接给我吗？对这篇文章我还真没有印象。

HCC本身很大程度就是肌体和HBV经年累月的搏斗所带来的后果，不是一年一日的结果。要观察到抗病毒治疗对HCC风险降低的意义，自然也需要长期的临床观察，这方面首先的突破性研究成果由台湾的研究人员在2011年发表，他们对数千例乙肝携带/患者进行了长达二十多年的持续观察，得出了显著性/置信度很高的结果。随后，他们的结也果得到了世界各地不同人种不同规模的大量临床实验的支持。这方面的文献很多，Google Scholar或者pubmed很容易找的到。

作者: HBVCURER 时间: 2015-3-17 14:16

本帖最后由 HBVCURER 于 2015-3-17 14:42 编辑

http://www.ncbi.nlm.nih.gov/pubmed/24615378

Gut. 2014 Dec;63(12):1943-50. doi: 10.1136/gutjnl-2013-306409. Epub 2014 Mar 10.

Patients with chronic hepatitis B treated with oral antiviral therapy retain a higher risk for HCC compared with patients with inactive stage disease.

Abstract
BACKGROUND: It is generally stated that oral antiviral therapy in patients with chronic hepatitis B (CHB) decreases the risk of developing hepatocellular carcinoma (HCC). Although oral nucleos(t)ide analogues (NUCs) may induce a state similar to inactive stage CHB, the long-term risk for HCC in patients treated with NUCs compared with inactive CHB is unclear.
METHODS: A total of 1378 patients who were treatment naïve and started NUC therapy and 1014 patients with inactive stage CHB who were HBeAg-negative and continuously had hepatitis B DNA <2000 IU/mL during follow-up were enrolled. The NUC group was divided into two groups by continuous viral suppression: NUC complete responder (CR) group and NUC incomplete responder (IR) group. Cumulative HCC incidence rates were compared between the groups.
RESULTS: The risk of developing HCC was significantly higher in the NUC CR group compared with the inactive CHB group, regardless of the presence of baseline liver cirrhosis (p<0.001). Risk factors associated with the development of HCC were treatment groups (p<0.001), age (p<0.001), sex (p<0.001) and the presence of liver cirrhosis at baseline (p=0.005). Of the NUC group, the cumulative incidence of HCC in the NUC IR group was significantly higher compared with the NUC CR group (p=0.028).
CONCLUSIONS: The use of potent oral antiviral therapy can effectively suppress HBV replication in patients with CHB. However, the risk of HCC development in patients treated with oral antiviral agent is still significantly higher than patients with inactive stage CHB.

尽管抗病毒治疗能够有效降低HCC的风险，但是仍然高于不活跃的HBV携带者。因此免疫控制对于降低HCC风险有很重要的意义。

http://www.ncbi.nlm.nih.gov/pubmed/24691291

作者: 战天斗hbv 时间: 2015-3-17 18:48

http://hbvhbv.info/forum/thread-1385627-1-4.html
似乎应该不是这个帖子，但是这是我能找到最接近我看到的那个了，现贴出来，我继续找找，另，召唤sw

作者: 战天斗hbv 时间: 2015-3-17 18:56

http://hbvhbv.info/forum/thread-1386812-1-1.html
还有这个

作者: 战天斗hbv 时间: 2015-3-17 19:02

http://hbvhbv.info/forum/thread-1385741-1-3.html
就这个
最初5年TDF有效治疗对HCC发生率并无影响，但5年后两组的差异有统计学意义 (图2)。

作者: StephenW 时间: 2015-3-17 19:11

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"言之凿凿说核苷对hcc至少五年内无效" - 这是你自己的理解

In conclusion, our large nationwide study indicates that the HCC risk remains increased in entecavir-treated HBeAg-negative CHB patients with cirrhosis, particularly of older age, at least for the first 5 years. The HCC risk does not seem to be significantly reduced with entecavir compared with antiviral therapy starting with lamivudine.
总之，我们的大型全国性研究表明，肝癌的风险仍然在恩替卡韦治疗HBeAg阴性慢性乙型肝炎肝硬化患者增多，尤其是年龄较大，至少在第一个5年。肝癌的风险似乎不恩替卡韦被显著降低与抗病毒治疗开始拉米夫定比较

"remains increased" 仍然保持较高的风险.

Overall, these data indicate that with the current, potent NAs, HCC risk can be reduced but not eliminated, probably due to risk factors that are not amenable to change by antiviral therapy, or events that may have taken place before treatment initiation.

作者: 战天斗hbv 时间: 2015-3-17 21:16

回复 StephenW 的帖子

哦，原来是和拉米比

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