Development and research of vaccines to prevent liver cancer

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Published: 24 Jul 2013
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Dr Pierre Hainaut – International Prevention research Institute, Lyon, France

Dr Pierre Hainaut talks to ecancer at the 2013 National Cancer Institute Directors Meeting (NCID 2013) in Lyon about the main risk factors, such as hepatitis, alcohol consumption and metabolic diseases, for liver cancer.

Even with a vaccine for hepatitis B, and a developing vaccine for hepatitis C, there is a large question as to whether or not this will provide long-term prevention results.

Dr Hainaut stresses that the main research that needs to be completed is on how to implement prevention methods and quickly collect results while monitoring progress.

 

Filming supported by the International Prevention Research Institute

 

There are about 700,000 people dying from liver cancer every year, 80% of them in developing countries. The main risk factors are hepatitis viruses and this is very much changing; hepatitis B we have a vaccine, will it be efficient to prevent cancer in the long term we still do not really know. Hepatitis C is developing, we have no vaccine for that one. Typical other traditional risk factors are alcohol, and alcohol consumption is changing everywhere in the world, metabolic syndromes, physical inactivity, obesity and this is increasing everywhere in the world. So it’s one of these cancers where things are moving a lot.

But with the viral etiology there is something you can do and HepB vaccination is a big factor, isn’t it?

Yes, that’s the two main handles we have now: we can intervene by vaccinating against HepB which is probably the key risk factor in about 50% of the cases. And we can treat for chronic liver disease, have a better treatment for people who are chronically infected.

And you can eliminate, hopefully, things like aflatoxin.

And we can eradicate aflatoxin. None of these things can be done 100%; viruses adapt to this, people develop chronic liver disease even despite being vaccinated in some cases and aflatoxin there’s no way you can bring it to but at least you can implement serious changes with reduction. We have evidence that all these things work, the problem is to implement them in a concerted way and to have the markers, the indicators, that would allow us to know whether this intervention works without having to wait for two generations to come to death.

Yes, and indeed you’re a molecular biologist so what sort of markers are giving you ways of making progress against this disease?

I’m a molecular biologist, yes. We have plenty of biomarkers, we can monitor the progress of liver disease, hepatitis, hepatitis virus related liver disease in populations, that’s fairly simple and straightforward to do. And we have also very good complex markers that predict the evolution of hepatitis disease so that’s something we can monitor. It doesn’t mean we do it but it’s feasible. Second, we have markers from exposure to things like aflatoxin. This is done on a very little scale, this must be expanded, but this is also something which is feasible. We can monitor individual or collective contamination via aflatoxin. What we are missing is sufficiently good markers of the very early steps of development of carcinogenesis and that’s a very big area for research using proteomics, metabolomics to identify better markers that would allow to go from someone with a chronically infected person exposed to various risk factors in the context of low resource countries, to predict the risk of this individual to develop liver cancer. And there we need better markers.

What, then, can you do and have you been able to do? Because you’ve described a very dynamic situation, some parts of the world with obvious targets like hepatitis B, other parts of the world where things are increasing. What do you recommend? Let’s start first of all with the low resource setting. If you’ve got a lot of hepatitis B is your first priority vaccination or what?

I think the first priority is clearly to continue with vaccination but also monitoring the impact of vaccination, this we do not know.

So your biomarkers help there?

Yes, vaccination has been started about 25 years ago for the earliest cases or more recently over the last ten years. We need to know what’s going to happen to these vaccinated kids in ten years, in twenty years, in thirty years, will vaccinating a newborn be sufficient to have an effect on the adult when they are 40 years old and so on. So we need to evaluate efficacy, the protection against and the protection against liver disease and liver cancer. That takes two generations so very long work and it is not sufficiently done.

And you need vigilance in high resource settings because this disease can creep up, can’t it?

Yes, and in high resource settings we have several things: we have the expansion of HCV, we have the interaction, probably background interaction, with HBV which is still there at a low level and we have the development of metabolic disease linked to obesity, linked to inactivity, linked to changes in food consumption patterns and so on.

So the metabolic syndrome is associated with liver cancer.

Very much, very much. It’s one of the manifestations, fatty liver disease there are manifestations and then one of the outcomes is the development of liver cancer. Liver cancer has been increasing by about 20-25% in West European countries over the past ten years and it’s the same in the US.

OK, there’s a lot to distil but, in a few words, if you were to summarise what the big messages are for doctors all over the world, how would you make that summary?

Vaccinate whenever it’s possible against HBV. Monitor and treat people with chronic liver disease. Prevent metabolic syndrome by implementing and disseminating the message about better food and above all about physical activity. And develop a worldwide effort to reduce aflatoxin exposures. I think that’s the key four things. Probably by blending these things together we could, I would say, do the best model we have, we can maybe prevent half of the deaths from liver cancer in the next three or four decades by combining these things.