Hepatitis C in the Clinic

06 December 2009

Interview with 

Dr Graeme Alexander, Addenbrookes Hospital


Kat -   What does Hepatitis Cactually do to the body, and how can we treat it?  It's now time to find out from Dr. Graeme Alexander, he's a Clinical Hepatologist at Addenbrooke's Hospital.  So, hello Graeme.  Welcome to the show.

Graeme -   Hello.

Kat -   Now, just before we start, we've had a quick question from SecondLife, from Dali Waverider.  He wants to know how many classes of hepatitis virus are there and how are they different?

Graeme -   Well a lot of viruses can affect the liver, but there's five that we recognize as important in the liver and they're Hepatitis A, B, C, D, and E - rather imaginative aren't we?

Kat -   Fair enough.

Human LiverGraeme -   The most important thing about hepatitis C is that it, by and large causes an infection that lasts for a lifetime while the other viruses don't (usually).  So that differentiates it quite easily.  And it's an RNA virus whereas hepatitis B is a DNA virus infection.  But that's a semantic difference.  The important thing about hepatitis C is that it causes lifelong infection in many people.

Kat -   So let's look at this kind of infection.  So we've discovered that it goes in to the cells in the liver  and it sort of turns them into little virus factories.  What effect does that actually have on the liver?

Graeme -   Well I think the most important thing to stress straight away is that for most people, you don't know you've got hepatitis.  It doesn't cause liver damage in the majority of people.  But about 5%, perhaps as high as 20%, of people in some populations get into a situation where they develop liver damage.  And you might not know you've got liver damage evolving until maybe 50 or 20 years after you've been infected with the virus.  In a way, the virus wears the liver down over a period of years, causing scarring within the liver and once the scarring is present, then the patient is at risk of liver failure and the complications thereof.

Histopatholgical image of hepatocellular carcinoma Kat -   So presumably, there must be something to do with the differences between people, as to why some people are susceptible to having liver damage from hepatitis infection and why some people aren't.  Do we know anything about those kind of genetic factors?

Graeme -   Well, we do.  We know quite a lot about those genetic factors and we know that for example, men do much worse than women.  We know that it matters how old you are when you catch the virus.  Men who are over 40 when they catch the hepatitis C do very much worse than say, a young girl of 20 who catches the virus.  We know that people who are overweight do very much worse than the patients who are thin, and we know that people who drink heavily increase their risk of liver damage from hepatitis C very, very much so.

Kat -   And this, we bring in a little question here from Meera Maquana who says, "Why does chronic liver disease, and things like chronic drinking, lead to cirrhosis and what's the process of this scarring that's going on?"

Graeme -   The liver cells are part of a complicated organ - the liver - where there's lots of different types of cells.  There's another cell sitting next to the liver cell called a stellate cell and there are signals sent out by an injured liver cell to those stellate cells which scar the liver.  So the liver ends up being scarred in exactly the same way as someone who's had an operation and there's a scar on their skin, but this scar is spread finely and diffusely throughout the whole liver.

Kat -   Now, something I do know from my work at Cancer Research UK is that rates of liver cancer are going up and we know also that liver cancer is linked to hepatitis infection.  How does that work?  What's the link there?

Graeme -   Well it's all through liver disease.  All forms of liver disease predispose Secondary tumor deposits in the liver from a primary cancer of the pancreaspatients to liver cancer in the longer term and it's one of the things that we take great care for is to look for liver cancer at an early state to try and pick it up.  Hepatitis C is one of the major causes of liver disease in this country.  So it's now one of the major causes of liver cancer.  And if you have advanced liver disease, you've got a one in four risk of getting on to get liver cancer subsequently.  It's also a significant problem.

Kat -   So, it strikes me.  Is that it's fairly important to try and treat, and probably even prevent hepatitis infection.  Where are we currently with treatments?  And we've heard already about some current ideas, you know, this microRNA drug for future treatments, but where are we currently with treating hepatitis?

Graeme -   Well, there's been enormous progress in the last four or five years.  We've been known about interferon which is what you and I produce when we get an infection, flu for example.  We've known about that for quite a time and on its own, it didn't really work very well.  And then another drug called 'ribavirin' was introduced, but that on its own didn't do very well either.  But when we combined these two drugs, we got striking improvements in response rates which was unexpected, but very gratifying.  So now, we think that we can treat something towards about a half of the patients that come to see us.  But the most important point to stress here is that the earlier we treat the patients, the better, so younger patients did much better with treatment than older patients.  So it's quite important that we do see people at an early stage and we can consider treatment as early as possible in the course of the disease.

Kat -   And do we already have vaccines against hepatitis C? What hope is there for preventing the transmission of it?

Graeme -   Well, hope is all we have at the present.  There are a lot of people working on this area and you've heard from Joe Grove earlier about the virus evading the immune responses and the number of tricks that it has to do this.  The problem we face at the present is we don't recognize the population who are immune to hepatitis C in the long term.  They don't develop neutralizing immunity and if you can't develop neutralizing immunity, it's very hard to see how you would target a vaccine response.  So sadly, I think, vaccine responses are some distance away and we're really looking at prevention for now rather than a vaccine.


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