Summit dialogue Prof. Lai Wei VS Prof. Foster

Hepatology Digest: The treatment guidelines don’t differentiate between the two, now with these new studies, like in your presentation you mentioned IDEAL and some other studies do you think now that we have these more head-to-head comparisons, do you see that that might influence the guidelines, Prof. Foster?

Prof. Foster: No, I don’t think they should. I think that the best opportunity for patients is to have a choice of treatment. I think the best opportunity for clinicians is to have a choice of drugs because there are undoubtedly circumstances where you may want to use one or the other interferon depending on circumstances. My own view is that it is to the best advantage to the patient that clinicians have access to both interferons and they can make their own personal choices based on the data they have seen in their own patient population. So I would be very opposed to a restriction of the prescribing of pegylated interferons. They are my personal views. Other clinicians have slightly different personal opinions and I think it is important that doctors are allowed to choose and the patient should have a choice. Do you agree?

Prof. Wei: Yes, I agree.

Hepatology Digest: So how about in the case again for Hepatitis C treatment with interferon and Ribaviron, perhaps some older patients can’t tolerate the therapy so what would be your approach for treating older patients and should we detect or test their HCV antigen more frequently perhaps than younger patients?

Prof. Foster: I think the patients have to be individualised. I don’t think there is a correct answer for every patient. If you have an elderly patient, you have firstly to look at the extent of their liver damage and you then have to look at their general health. If you have someone who is elderly with heart problems, with lung problems, then perhaps their liver is not the priority for treatment. On the other hand, if you treat a fit healthy 80 year old with hepatitis C because they have got bad fibrosis in their liver, so I think you have to personalise the therapy. You can’t go on the actual age of the patient, you’ve got to go on how the patient behaves. If you have an 80 year old patient who is behaving like a 60 year old, he’s got bad liver fibrosis, may well get cancer and die from their Hepatitis C then I think you are justified in treating them quite aggressively. But if you have got a 60 year old patient who has got a bad heart, who has bad chest problems, not a lot of scarring on their liver biopsy then I personally don’t think those patients should be treated.

Prof. Wei: Actually for some of the older patients, older than 60 years old, it seems the efficacy is in a lower order and I think sometimes it depends on the stage of the disease and in some of the old patients they were often infected very young.  Then they have time to get to the end stage of liver disease.  Then it is difficult to predict.  So for these patients, I think we should stage a bit earlier.  If we can do some biopsy on someone old then you can know what time and what stage the patient location is.  Then you can give the patient more appropriate treatment.  And otherwise if the patient has very slow developments then you do not worry about it.  You can do something and give the patient some detectors.  As for the HCV antigens, sometimes, actually commonly we just use the HCV-RNA detector because HCV-antigen detecting is not approved at all in China.  And so maybe sometime you can change and switch the HCV-RNA detecting to the HCV-antigen detectors because if you use the antigen detecting it may be easier.  But right now because of sensitivity of the HCV-antigen, detecting is quite low.  And so for some low viral load patients, we cannot detect anything using the antigen assay so we don’t administer it at all.  So in answering this question, I think because there is no data that indicates the relationship between HCV and viral load or the thesis directly, therefore I think we cannot use HCV-RNA to be sure to locate the patients status.  What we need to do is a biopsy. 

Hepatology Digest: Do you agree, Prof. Foster?

Prof. Foster: I agree entirely that it’s the right approach for the personalised case.

Hepatology Digest: How about in the case of the treatment of relapse of Hepatitis C Professor, how is the efficacy and would you treat with peg. Interferon alpha-2a and Ribaviron and what maybe special things would you consider in that case?

Prof. Wei :  Actually, sometimes for the relapse for the breakthrough and for maybe all the different basis that use interferon.  In China we still use some conventional interferon so the relapse prediction is higher for these patients.  For these patients we can switch them to the pegylated interferons and also for the pegylated interferon if the patient has a breakthrough or relapse maybe what you can do is to identify which factor that has affected the HCV species.  And some patients have a relapsed after the treatment so we switch to other interferons such as for genotype 3 type we show that if we use the pegylated interferon alpha-2b maybe we can have a little bit higher efficacy for this patients.  Also to my knowledge and to my experience, if most of the patient is relapsed you can also switch to pegylated interferon alpha-2a then you also can have a little higher efficacy for these patients but I have to say the efficacy for these patients – I mean the VSR for these patients is the lower than that of the other patients. 

Prof. Foster: I would agree. I think you are absolutely right. The sustained response rate is much lower in this patient population and you have got to personalise treatment: you have to look at the first course of treatment; decide how they responded first time round; look at the extent of fibrosis in their liver biopsy and then make a decision with the patient as to whether the benefits of the treatment are worth the very considerable inconvenience and the very considerable expense.

Hepatology Digest: Obviously with genotype 1 patients, it is very difficult in that, I believe the numbers are 40 to 50 percent that can achieve SVR. I am sure there is not a simple answer to this Prof. Foster, but what is your personal approach in treating these genotype 1 patients and your advice?

Prof. Foster: Well I think the evidence at the moment is that if you treat these patients early you have much better response rates, so I am a great advocate for catching patients at an early stage of disease and getting them on treatment. For genotype 1, we do however know that we have some new drugs in development. There are a lot of small molecules being tested at the moment, and I think we have every chance that one or two of those will start to come through over the next three or four years. So my view at the moment is to discuss the choice with the patient, talk about the benefits of early treatment, talk about the potential benefits of delaying treatment while the new drugs become available, and that’s not a risk-free procedure as of course if the new drugs don’t pan out then we may find we’ve missed an opportunity to treat. So I think you have to personalise the treatment, talk to the patient about the choices and then try to pick what’s right for them.

Prof. Wei :  Except in HCV drugs maybe some patients you can extend the treatment.  You can use the long term treatment for these patients except for some patients they have the either older viral response or slow response for these patients and you can’t extend the treatment, say two weeks treatment.  Then you have higher SVR with these patients.  And also in China you have some patients – very difficult patients, the viral load is in fact reduced very very slowly.  For the patients who have been waiting for two years or three years for treatment then they become candidates for early treatment.

Hepatology Digest: Just now Professor Foster mentioned some of the new agents being developed, how about from your experience and what’s your view, perhaps for the future and how soon we may see some new agents and such?

Prof. Wei: Yeah after all the new data has showed us that the combined surface interferon and new agents improved SVR in some difficult to treat patients such as genotype 1 or patients with high viral load and patients who relapse and so on.  All these treatments were needed for treatment resistant patients.  So in the future we have to find the new drugs and also patient uses it and the HCV resistant drugs could be given to the patient.  And therefore a necessary step, is maybe combining drugs and bypass difficult treatment.

Prof. Foster: I agree with that. I think we still don’t know enough about these new drugs to be able to predict which patients are going to need them. I think we are all hopeful that by 2011 we are going to start to see the first licensing of these new agents. How expensive they will be, which patients they will work with, we still don’t know. So there is a lot of interesting data to come but I think it is a little early to start predicting who is going to benefit and who isn’t.

Hepatology Digest: With these new agents will there again still be a combination approach?

Prof. Foster: I’m sure the first few years will be a combination of pegylated interferon, ribaviron, and the new small molecule. Then as we get more small molecules then maybe we will start to change. It is going to be a combination to begin with.

Prof. Wei: I agree.

Hepatology Digest:  Finally, obviously there are differences between your experience in the West and the East, how about some special local conditions that you might encounter in China that perhaps some of your western colleagues don’t see? Are there any special problems that you see in China that perhaps you would like to talk about?

Prof. Wei: Firstly in China, in some provinces, medical insurance system covers the pegylated interferon and in some provinces it does not cover the pegylated interferon.  Therefore for in these provinces they have to use the conventional interferon.  So this is the first challenge.  And so we had to present the new medical data and action statements to the government and medical insurance office so they can know and understand the data and maybe change the policy so more and more people can use the standard treatment.  The second issue is we should have some older age patients, old age patients infected in the 1980s or earlier than the 1990s.  Therefore because these patient have now history of more than eight years, so most of these patients are in the end stage of liver disease.  So for these patients sometimes there are a lot of side effects with the pegylated interferon.  So we have to find from the drugs, maybe do some trials of using low dose interferon to see if we can obtain some stall, prevent, or even delay the disease progression.  That is the second reason.  The third is if we have increase instances of cirrhosis in China, then we also have some patients who is core instance is the C and the cirrhosis.  So for these patients we have to combine the treatment for the cirrhosis and the HCV infection so therefore we really need some balance in the drugs and some decisions for the important actions.

Prof. Foster: I think you make a very interesting point about the costs of treatment, and I think as the western world’s markets go into decline, we are going to have to learn some lessons here to help economise on our drugs budget. So I think it will be a very challenging time for all of us.

Hepatology Digest:  Thank you both for joining me here today at APASL.

Prof. Wei: Excuse me.  For China, I want to add one more thing.  In China we also use the domestic reagents.  This just means that IRP is made in China.  So the sensitivity is sometimes not as good as TaqMan.  Therefore it seems that what time you can identify the IVR and the EVR actually we would identify the IVR and the EVR that means we need to use the sensitive reagents.  Actually in China, TaqMan is not approved at all though maybe in the near future it will be approved.  But before that, it is difficult for dcotors to use IVR because we don’t have the exact IVR in China.  Therefore we have to keep them one year of treatment for these patients.