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?
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.
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?
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.
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.
