World hepatitis day 2014

Hepatitis is a viral infection that causes acute and chronic disease, and sometimes death. World hepatitis day takes place each year on 28 July and the aim of this year’s World Health Organization’s campaign is to raise awareness of viral hepatitis. This is a group of infectious diseases known as Hepatitis A, B, C, D, and E.

Paul Klenerman
Professor Paul Klenerman

NDM spoke to Paul Klenerman, Professor of Immunology in Experimental Medicine, about his research on Hepatitis C and the advances that are being made in treatment approaches.

Q: How big a problem is Hepatitis C infection?

Paul Klenerman: Hepatitis C infection is a real problem in the UK, affecting around a quarter of a million people. It is also a major problem globally, with estimates of around 170 million infected with Hepatitis C. Hepatitis B and Hepatitis C viruses together are thought to infect about half a billion, or 1 in 12, people around the world. Both viruses are leading causes of liver disease; often infection is silent for many years, but ultimately it can progress on to severe scarring of the liver (cirrhosis). This then brings with it the risk of liver failure and liver cancer. One of the problems with assessing the size of the problem is that many people are not diagnosed. These individuals then do not know about the risks of the disease or passing it on to others. One of the main aims of World Hepatitis Day is therefore to simply raise awareness about the problem of hepatitis infection.

Q: Why are some people able to clear the virus but others become chronically infected?

hepatitis virus
Digital illustration of Hepatitis virus

PK: Hepatitis C virus (HCV) is able typically to set up persistent infection - one reason is that it is able to vary its proteins and so continuously escape from immune responses. We often see patients in the clinic who were likely initially infected decades ago, perhaps after a single exposure to the virus. However, although HCV is very good at evading the immune system, some people are able to clear the virus after a brief period - this occurs in about 1 in 4 people overall. We know a few things that contribute to this. Your genetic background is very important. For example there are variations around a gene in the immune system (interferon-lambda) which have a big impact. This gene also affects the response to treatments so overall appears to be very important in clearing virus from the liver. Additionally, and this is what we have been mainly studying in Oxford, you can induce immune responses against HCV which can help clear it. Again, the type of immune responses you make depend on a set of genes (HLA type - the same genes that make up your tissue type used in matching transplants). Although the genetics are important, this doesn't account for everything. Recent studies have shown the strain of virus (or genotype) can have an effect too, and there are likely to be many other factors involved. However, since we know that having a very strong immune response of a particular kind (based on T cells) is linked with being able to clear the virus, the hope is that we can generate such responses using a vaccine. We have helped trial such vaccines at the Oxford University Hospitals and these are now in much bigger studies to see if they work effectively.

Q: Is it possible to tailor treatments to different groups of patients?

PK: Yes. At the moment, there are two main strains (genotypes) of HCV in the UK - type 1 and type 3. We have known for a while that we have to treat these different genotypes differently. It is possible to use the DNA tests described above to help with decision making. We can also see how the virus responds to treatment over time, to see how long it needs to be treated for, which is typically around six months. (However, at the moment, treatments are just changing from the older types, - which are based on interferon injections - to newer types based on tablets, which directly interfere with the virus and are better tolerated. These new drugs can be very quick and effective, curing more than 90% of  people (the current treatments are around 60-70% effective). However, it will be very important to make sure we use these new treatments wisely. For example, depending on the exact drug used, knowing the exact sequence of the virus might be helpful in avoiding resistance. It is still very early days, though and only a few of the very sickest patients who have severe liver failure have been treated so far in the UK. The OUH is an important hub for studies of how best to use these drugs through a national programme called STOP-HCV (led by Dr Ellie Barnes). We are aiming through this programme to design strategies that allow tailored treatments, and help the roll-out of really effective therapy in the coming years. Hopefully we will have cured many patients this way by World Hepatitis Day 2015.