核苷（酸）类似物耐药的检测—Keeffe教授对话张欣欣教授

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Emmet Keeffe  美国斯坦福大学医学院

张欣欣  上海交通大学医学院附属瑞金医院

Hepatology Digest: With nucleoside/nucleotide analogues treatment, what are the clinical criteria for diagnosis of antiviral resistance and how can we detect the antiviral resistant mutations, Professor Keeffe?

《国际肝病》：核苷(酸)类抗病毒药物产生耐药的诊断标准是什么？我们如何检测耐药的相关变异呢？Keeffe教授？

Prof. Keeffe: Well I think the traditional approach has been to have a baseline serum HBV DNA level and then you have to monitor the patient at some regular interval, probably initially every three months with repeated serum HBV DNA levels. They will typically fall with all of the oral antiviral agents and then will either become undetectable or will reach some low nadir level. As the patient is then monitored every three or six months, resistance is defined by so-called “breakthrough” when serum HBV DNA level will increase by more than one log. Now today in some countries although not everywhere around the world, we have access to actually measure for the resistant viral species through resistance testing. So that is often performed as a confirmatory test to see if there is a specific mutation to whichever agent is being utilized. There’s always a differential diagnosis when the serum HBV DNA level rises which is the fact that the patient may not be taking their medication, so in fact there is not a resistance virus they’ve simply become non-compliant for economic or personal reasons and are no longer taking their medication.

Keeffe教授：传统方法是首先确定一个血清学HBV DNA水平基线，再对患者进行定期监测，开始时可能每隔3个月就要监测一次血清HBV DNA水平。口服抗病毒药物后，病毒水平会有明显的下降，随后或是检测不到或是达到一个最低水平。然后如前所述，每隔3~6个月再对患者进行检测，耐药的定义是所谓的病毒学“突破”——此时血清中HBV DNA水平会升高超过1 log。现在，在一些国家——并不是世界上所有的地方，我们可以通过耐药检测测量实际耐药的病毒株。因此，这种检测通常用作确证试验，用以探查是否有特异变异及这种变异针对何种药物。当血清HBV DNA水平升高的时候，需要进行鉴别诊断，因为有些时候患者并没有服用药物，因而此时实际上并没有产生病毒耐药，只是因为患者的个人原因或经济原因而未依从治疗。

Hepatology Digest: Professor Zhang, Professor Keeffe mentioned access to tests. Can you talk about the situation in China and testing and access in general. Can you speak about that?

《国际肝病》：张欣欣教授，Keeffe教授提到了现在已经可以进行的这种检测，您能不能大体介绍一下这种检测方法在中国的应用？

Prof. Zhang: Yes, in China we also have the detection of HBV DNA done regularly about two or three months during the antiviral treatment especially in the big cities. But in some small cities or small hospitals, DNA commercial detection kits may not be available. Moreover, detection of genotypic mutation is not very popular in China because of the reagent. It is too expensive and not very popular but DNA detection it is quite popular. So we based it on the breakthrough of DNA to monitor the antiviral therapy and monitor the appearance of mutation.

张欣欣教授：是的，在中国，特别是在一些大城市，我们也有检测HBV DNA水平的方法，一般是在抗病毒治疗过程中，每隔2~3个月检测一次。但在一些小城市或小医院，还没有这种商业化的DNA水平检测设备。而且由于试剂的原因，基因变异的检测在中国也不很广泛。由于试剂太昂贵，所以应用不广泛。但DNA检测在中国应用还是比较广泛的。因此，我们通过HBV DNA水平突破来监测抗病毒治疗效果和是否有变异的出现。

Prof. Keeffe: And I think it’s perfectly adequate to do it that way. There’s a sequence of events that occurs when resistance develops and that is first of all the development of a resistant species that becomes the dominant virus within the patient. That’s followed by a raise in the serum HBV levels and then later a raise in the ALT level and potential clinical deterioration. So if one intervenes at the time there’s a rise in the HBV DNA level there is plenty of time to map out a new strategy on how to best manage the patient.  Would you agree? I think it is perfectly adequate.

Keeffe教授：我认为这样做......

以上资料为独家一手资料，来自国际肝病网站APASL2009会议专题，可以登录国际肝病网站阅读中英文对照和采访视频