[AASLD]新闻:B型肝炎抗病毒药物减癌症的风险

StephenW

Antiviral Drug Cuts Cancer Risk in Hepatitis B
By Michael Smith, North American Correspondent, MedPage Today
Published: November 12, 2012
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania
Action Points

    This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
    For patients with chronic hepatitis B and cirrhosis, long-term treatment with entecavir significantly reduced the risk of liver cancer.

BOSTON -- For patients with chronic hepatitis B, long-term treatment with entecavir (Baraclude) significantly cut the risk of liver cancer, researchers reported.

In a retrospective cohort of entecavir-treated patients, the cumulative incidence of hepatocellular carcinoma was 3.7% after 5 years of follow-up, according to Tetsuya Hosaka, MD, of Toranomon Hospital in Tokyo.

In an untreated control group, the cumulative incidence was nearly four times as high at 13.7%, Hosaka reported at the annual meeting of the American Association for the Study of Liver Diseases.

The difference was almost entirely driven by patients with cirrhosis, where the cumulative 5-year incidence was 38.9% in the controls and just 7% in the entecavir patients.

Entecavir is a nucleoside analog reverse transcriptase inhibitor.

There was no significant difference between the groups among patients without cirrhosis, Hosaka reported with a cumulative incidence of 2.5% for entecavir and 3.5% for the controls.

In essence, he said, entecavir "rescues" cirrhotic patients, restoring their cancer risk to levels similar to those among patients who had not developed cirrhosis.

Older drugs in the same class, notably lamivudine (3TC), have also been shown to reduce the incidence of hepatocellular carcinoma among chronic HBV patients, Hosaka said.

But resistance to lamivudine develops rapidly, making long-term treatment difficult, he said. In contrast, resistance mutations to entecavir appeared in just 0.8% of patients, he reported, and in none of those who developed cancer.

From 2004 through 2010, Hosaka and colleagues at Toranomon Hospital recruited consecutive patients who were being treated with entecavir and compared them with a historical control group treated between 1973 and 1999, before the approval of nucleoside analogs.

Using propensity matching, they created demographically similar treatment and control groups of 316 patients each.

In a multivariate Cox proportional hazard regression, Hosaka and colleagues found that factors affecting the incidence of cancer at 5 years included:

    Entecavir treatment: hazard ratio 0.37, 95% CI 0.15 to 0.91 (P=0.03)
    Age: HR per year 1.06, 95% CI 1.03 to 1.09 (P<0.001)
    Preexisting cirrhosis: HR 4.28, 95% CI 1.88 to 9.73 (P=0.013)
    Presence of the HBV e antigen: HR 2.26, 95% CI 1.88 to 4.34 (P=0.014)
    Platelet count below 1.5 x 105 per cubic millimeter: HR 5.64, 95% CI 2.13 to 15 (P=0.001)

The findings are not surprising, but they do add to the growing clinical conviction that treating hepatitis B prevents cancer, according to Robert Perrillo, of Baylor University School of Medicine in Dallas, who was not involved in the study.

Perrillo told MedPage Today that earlier research with other drugs in the class -- such as the REVEAL-HBV study of lamivudine -- have shown that treatment reduces clinical progression, complications, and cancer.

There are two main reasons why treatment might help prevent cancer, he said.

In the first place, therapy reduces the level of HBV DNA. Since the virus integrates its own DNA into cells, high levels of virus mean that "sooner or later it's going to knock out an oncogene" and reducing the level can help prevent that.

Secondly, he said, there's evidence that treatment reverses cirrhosis, which has a strong element of regeneration. Cirrhotic regeneration -- involving large numbers of cell divisions -- increases the chance of cell mutations that can lead to cancer.

The researchers did not report external support for the study.

Hosaka reported no conflicts.

Perillo reported financial links with Bristol Myers Squibb, Merck, and Gilead.

Primary source: American Association for the Study of Liver Diseases
Source reference:
Hosaka T, et al "Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with chronic hepatitis B" AASLD 2012.

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在B型肝炎抗病毒药物减癌症的风险
迈克尔·史密斯，北美的记者，MedPage今天
发布日期：十一月12，2012
Zalman的S.阿古斯，MD;佩雷尔曼在美国宾夕法尼亚大学医学院的名誉教授，
行动要点

    这项研究结果发表作为一个抽象的，在一次会议上。这些数据和结论应被视为是初步的，直到在同行评审期刊发表。
    长期恩替卡韦治疗慢性乙型肝炎和肝硬化患者，显着降低肝癌的风险。

波士顿 - 对于慢性乙型肝炎患者，长期治疗用恩替卡韦（博路定）的患者显着减少肝癌的风险，研究人员报告。

恩替卡韦治疗的患者在一项回顾性队列研究，肝癌的累积发生率分别为3.7％，5年后的后续行动，根据哲也保坂，医学博士，在东京虎之门医院。

在未经处理的对照组，累计发病近4倍高13.7％，保坂的美国肝病研究协会年会上报告的。

几乎完全是不同的肝硬化患者，其中5年累计发生率分别为38.9％，在对照组和恩替卡韦的病人仅7％的患者。

恩替卡韦是核苷类似物逆转录酶抑制剂。

有没有显着差异，各组之间无肝硬化的患者中，保坂，累计发病率恩替卡韦组为2.5％和3.5％的控制。

在本质上，他说，恩替卡韦“抢救”肝硬化患者，恢复他们的癌症风险没有肝硬化的患者相似的水平。

老药在同一个班级，尤其是拉米夫定（3TC），也被证实可以降低肝癌的发病率在慢性乙肝患者中，保坂说。

但对拉米夫定的耐药发展迅速，使得长期治疗带来困难，“他说。相比之下，只有0.8％的患者出现恩替卡韦的耐药性突变，他的报道，并没有患上癌症的人。

从2004年到2010年，保坂和他的同事在虎之门医院招募例正在接受恩替卡韦和他们相比，与历史对照组在1973年和1999年之间，之前批准的核苷类似物。

使用倾向匹配，他们创造了人口统计学类似的治疗组和对照组各316例。

在多变量Cox比例风险回归，保坂和他的同事们发现，癌症的发病率在5年的影响因素包括：

    恩替卡韦治疗：风险比0.37，95％CI 0.15〜0.91（P = 0.03）
    年龄：HR每年1.06，95％CI 1.03〜1.09（P <0.001）
    先前存在的肝硬化：HR 4.28，95％CI 1.88〜9.73（P = 0.013）
    乙肝病毒e抗原的存在：HR 2.26，95％CI 1.88〜4.34（P = 0.014）
    血小板计数低于1.5×105每立方毫米：HR 5.64，95％CI为2.13至15（P = 0.001）

调查结果并不令人惊讶，但他们的越来越多的临床信念，治疗B型肝炎预防癌症，根据罗伯特Perrillo，贝勒大学医学院的达拉斯，谁没有参与这项研究。

Perrillo告诉MedPage今天，在课堂上与其他药物 - 如拉米夫定REVEAL-HBV研究 - 早期的研究表明，降低临床治疗的进展，并发症和癌症。

，为什么治疗可能有助于预防癌症主要有两个原因，他说。

首先，治疗的HBV DNA水平降低。由于该病毒将自己的DNA进入细胞内，高浓度的病毒的意思是说：“迟早是要淘汰的基因”，减少的水平可以帮助防止这种情况。

其次，他说，有证据表明，治疗逆转肝硬化，具有强烈的元素的再生。肝硬化再生 - 涉及大量的细胞分裂 - 增加细胞突变，可导致癌症的机会。

研究人员并没有外部支持的研究报告。

保坂没有冲突。

佩里洛的财务报告与Bristol Myers Squibb公司，默克公司和Gilead。

主要来源：美国肝病研究协会
来源参考：
保坂T，等“长期恩替卡韦治疗肝癌的发病率降低患者的慢性乙型肝炎”AASLD 2012。

疯一点好