Results of research must reach people who are in need. But when we speak about HCV we see only the top of the iceberg – “in Europe we probably have identified less than 50% of those patients infected”- floating in a sea of possible new choices represented by many new coming drugs: this is the problem we are facing now, according to Mark Thursz, professor of hepatology at Imperial College, London and currently vice-secretary of the European Association for Study of the Liver (EASL). In this role he has special responsibility for EU policy and advocacy in Brussels. I met professor Thursz during last EASL meeting in Berlin, last April.
The feeling is that now we living the first days of the new era for the therapy of hepatitis thanks to protease inhibitors. Before the use of these new drugs, what are the unmet needs with the current therapies?
Obviously the problem we have with the current therapies is the side effect profile, the success rates of treatment, particularly in the difficult-to-treat genotypes, genotype 1 and genotype 4, and we also can’t use interferon and ribavirin in patients who have got advanced liver disease, so this is something that we need to be thinking about in the future.
Going slightly broader, though, one of the major issues that we have is actually finding the patients: that may seem a silly concept but, actually, if you want to reduce the burden of liver disease that is caused by hepatitis C you have to identify the patients with the infection and then they can be put through treatment protocols, but at the moment in Europe we probably have identified less than 50% of those patients infected and, because it’s a asymptomatic infection, they don’t feel as though they are ill, then patients don’t necessarily come forward, so we need the public health authorities around Europe to do something about that.
The first two new drugs approved are protease inhibitors. In HIV field, protease inhibitors made possible HAART, a real revolution. Now HIV infection is a chronic condition, thanks to the HAART. Do you think that new anti HCV drugs will do the same?
These are the first class of drugs to get into our clinical practice and protease is important in hepatitis C particularly because the protease has effects on the immune response to the virus, so by inhibiting this particular viral enzyme actually you can let some, or theoretically at least, you let some of the natural immune responses help you to clear the viral infection.
The first two drugs are boceprevir and telaprevir: what are the main advantages?
The both of them have excellent sustained viral response rates and obviously in hepatitis C, unlike HIV, a sustained viral response means a cure and they increase the rate substantially, both in treatment-naive individuals but, in particular, as we have heard this week, in patients who have previously had treatment with pegylated interferon and ribavirin and then failed treatment and that’s a group of patients that every Liver Unit or every Infectious Diseases Unit around Europe they have a large cohort of those patients and they are desperately in need of something to stop their liver sliding down to cirrhosis.
These drugs must be used in combination with current therapies…
Yes, that is true, so at the moment we are adding in direct antivirals to our standard-of-care, so the standard-of-care of pegylated interferon and ribavirin, and one thing I should say is actually in many patients the addition of a direct antiviral allows us to shorten the duration of treatment, which is good for patients, so we have been treating genotype- 1 infection for 48 weeks, now that comes down to about 24 weeks in many patients, so a big improvement.
Maybe we are going to face a new issue in HCV, that is viral resistance: how to deal with this?
This is true, so any direct antiviral will generate resistance. We already know it happens in the protease inhibitors and the polymerase inhibitors, we anticipate it in most classes of drugs and is well documented in the HIV field. I think the problem will need to be addressed by using multiple classes of drugs in due course, what we might, once we have got a handle on this problem, what we might be able to anticipate is using probably three different classes of drugs in a potentially interferon-free regime in the future.
Is the interferon-free therapy the future goal?
Here in Berlin at the International Liver Congress we have one abstract been presented which is a tiny, tiny little study but is really the light at the end of the tunnel for those people who are not going to tolerate pegylated interferon and ribavirin, so this is a study in which a small group of patients were given a protease inhibitor and a NS5A inhibitor and some of them cleared the virus during treatment. So, it’s early days, but it suggests that interferon-free regimes will be viable in the future, which is what many of us have been looking forward to.
This Conference occurs in an historical phase of financial crisis, we are speaking about new drugs and maybe we are afraid about prices of these drugs.
So, this is always a problem, new drugs mean better quality of healthcare but more expensive healthcare, but in this situation we have to pay attention to the fact that actually the cost of treating somebody who develops end-stage liver disease, liver cancer and then requires transplantation, as well as the socioeconomic cost of somebody being that unwell, are extremely high, so you have to invest now in clearing their infection in order to reduce the future cost and the future health burden because a patient is terminally ill or requires transplantation and if they have a transplant then they permanently need treatment.
At the beginning of this conversation, you said that there is a large amount of hepatitis cases or infections that are not recognized, at the same time we have new tools in order to reduce the viral burden, what is, in terms of public health, the potential impact of these new drugs in fighting against hepatitis?
It is crucial to identify a patient who has got chronic viral hepatitis, but if you were to identify them and then tell them there was no successful treatment, then you wouldn’t really be helping that individual, but what we can offer those people now is actually a sensible chance of clearing the infection, so you can then, you can go to screen a population, identify people who have got the infection and offer them a treatment that is 80% successful, even if they have got a hard-to-treat genotype. So, the impact is partly on the attitude of the patients because many patients say “Well, if you give me a treatment that is only 50/50, then I am not going to take it, thank you very much”, now more patients are going to accept treatment, that means we can make an impact on the overall disease burden.
Articolo presente in – HAART and correlated pathologies n. 13 –