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Last broadcast last Wednesday, 16:30 on BBC Radio 4 (see all broadcasts).
Synopsis
Experts at Europe's largest liver transplant unit - at King's College Hospital in London - explain how vague symptoms help to keep hepatitis C "hidden" inside the body for years. Dr Mark Porter looks at the latest ways to manage this condition.
Programme Transcript
BRITISH BROADCASTING CORPORATION
RADIO SCIENCE UNIT
CASE NOTES Programme no. 2 - Hepatitis C
RADIO 4
TX DATE: TUESDAY 18TH JANUARY 2011 2100-2130
PRESENTER: MARK PORTER
CONTRIBUTORS: KOSH AGARWAL
MATTHEW BRUCE
KATHRYN OAKES
NIGEL HEATON
PRODUCER: PAULA MCGRATH
NOT CHECKED AS BROADCAST
CRUZ
It was that sort of time; it was just the end of the sort of summer of love and all that sort of thing. I got involved in IVD - drug use - in India and I assume that that's where I must have caught the hepatitis C. Four of us went from here, of which three of us have hepatitis C. The only chap who didn't use hasn't got it.
PORTER
Mervyn de Cruz looking back on a misspent youth, when, while on a tour of India with friends, he probably caught hepatitis C - a viral infection thought to be carried by as many as 150 million people worldwide, half a million of whom live here in the UK. Most of them have no idea that their livers, and their lives, could be under threat.
Mervyn didn't realise he had the virus until things started going wrong decades after his trip to India - an all too common story. The diagnosis came out of the blue for Martin Williams too.
WILLIAMS
I was working with somebody who told me they had something called hepatitis C and I didn't really know whether to believe them, because it's something I'd never ever heard of before - hepatitis A, hepatitis B but no not hepatitis C. As fate would have it within a couple of months I went to the doctor's because I was a social drinker, always at the pub cricket team, football team, I began to have trouble handling alcohol insofar as that I was having terrible hangovers and really finding it hard to sort of get going in the morning. And he run a routine blood test on me and I think my liver function test - the enzymes - were off the scale, so he asked me to abstain from alcohol completely for six weeks. And again the liver function test was off the scale, so he then sent me to King's College Hospital and then I found out yes I too had this unheard of disease called hepatitis C.
PORTER
Where do you think you met the virus in the first place?
WILLIAMS
Well I can't say absolutely for sure. In the mid to late '70s I had dabbled with drugs, with hard drugs, for a brief amount of time and also in the early '80s I'd had an operation that required me to have a blood transfusion.
PORTER
So assuming that the transfusion, which would have been the last chance for you possibly to have caught it, was in the early '80s, this is something that was occurring 20 plus years later?
WILLIAMS
This is true, I mean I've been told, as I'm sure you're aware, that it's a sort of a slow grower. I sort of had no idea how ill I was. I think as you get older you expect yourself perhaps not to have so much energy. I've now had a treatment that was successful and my energy levels are wonderful compared to how they use to be. I power walk 35 miles a week, I gym, I swim but going back all those years yeah I really had no idea at all. Again it's because you don't really have anything to compare it against.
PORTER
You just thought it was middle-age.
WILLIAMS
Just thought it was middle-age yeah.
PORTER
And it's the slow onset of problems, and the vague nature of early symptoms like fatigue, that means the virus often lays hidden for years. Dr Kosh Agarwal is a consultant transplant physician and heads up the Viral Hepatitis Service at the Institute of Liver Studies at Kings College hospital.
AGARWAL
Most people in sort of Westernised societies come across hepatitis C by coming into contact with infected blood. By and large that's most commonly people who've been exposed or have had a period of recreational drug use and certainly IV drug use for some reason is a very efficient means of transmitting hepatitis C from patient to patient.
PORTER
So this is sharing a needle with someone who's already got the virus, you then inject yourself and that's how you catch it?
AGARWAL
Absolutely. However, there are a group of patients that we really can't find a reason why they have been infected by hepatitis C and certainly medical procedures in parts of the world where medical sterility may not be as good as it can be in the UK can be a cause of transmission of hepatitis C. Dental work in places like the Far East, Pakistan, Egypt, Eastern Europe can be a way that people can get exposed to hepatitis C. Clearly before we were screening blood products in 1991 people who'd had blood transfusions.
PORTER
Kosh, when did we first identify the hepatitis C virus?
AGARWAL
Hepatitis C, as a virus, was first identified in 1989, up until then we had had patients who'd presented with what was characterised non A, non B hepatitis with jaundice and end stage liver disease but it was only up until - just up until 1990 really that we started to identify the actual virus to then see that this was the cause of this liver disease.
PORTER
And what about sexual transmission, is that a factor?
AGARWAL
The very nature of hepatitis C means that it's very difficult to be absolutely clear about this. More recent data looking at monogamous couples and the risk of transmission's actually very, very low. Remember this is a chronic disease, people aren't feeling unwell, often this is picked up incidentally. There is, I'm afraid, still a lot of misperception and stigma associated with a diagnosis of hepatitis C, patients come to me, they're very worried and absolutely they want to find out how they might have been exposed to this and what the risk is of transmission to other members of their family. We recommend patients don't share razors or toothbrushes, we suggest that they tell their dentist but in essence day to day contact means a very low risk of transmission with hepatitis C.
PORTER
The term hepatitis means inflammation of the liver, what's the virus actually doing to the liver?
AGARWAL
So hepatitis C is a virus that sits in the liver, it could be termed a sneaky virus because it doesn't give you a lot of symptoms, it doesn't make you yellow by and large and hepatitis C tends to be a chronic virus that sits in the liver cells and over a long period of time - and that can be between 15-30 years - it can cause damage to the liver cells, scarring of the liver and can lead to what we call cirrhosis, which is end stage damage to the liver. And it is now one of the most common causes for liver transplantation and is a significant cause of liver morbidity and also liver death.
PORTER
And in terms of outlook for everybody that catches the virus are there some people that get rid of it completely?
AGARWAL
A small proportion of patients, probably about 10-15% of patients will get exposed to hepatitis C and then will get rid of it spontaneously. It changes itself as it replicates. So the immune system isn't very good at controlling the virus, understanding the virus and getting rid of it, so by and large hepatitis C becomes a chronic virus that sits in the liver and in some patients it can go on to cause significant liver damage.
PORTER
Is there something about the patient that determines whether they're going to be one of these lucky group who can get rid of the virus or go on to develop nastier complications like cirrhosis and cancer?
AGARWAL
There is certainly good evidence to show that if you drink heavily, if you are older, if you're a man and that your liver disease may be more progressive - that's the scarring that we see in the liver - but also now we're finding out that there are other more immunological based issues that may promote more aggressive scarring and more aggressive damage.
PORTER
How is the condition diagnosed, if this is a slow burner that doesn't cause obvious symptoms how's it being picked up?
AGARWAL
Most often patients have been screened because they have mildly abnormal liver tests and there are numerous causes of people having abnormal liver tests - one of the tests that should be done is looking for blood borne viruses - such as hepatitis B and hepatitis C. And if people have had a distant risk factor for experimentation with drugs or other risk factors for acquisition my recommendation is people should be screened for hepatitis C and unfortunately only about one in eight of patients in the UK who has hepatitis C is currently even diagnosed, let alone referred to specialist services.
PORTER
Well to find out more about how people are diagnosed with hepatitis C I've come down to the hepatitis testing section to meet clinical scientist Matthew Bruce.
Right Matthew this is where the samples come in to be tested, can you show us what happens?
BRUCE
Yes. Right well basically the samples will be dropped off to us in the lab, then the sample will be spun down on a centrifuge to separate out the red blood cells and white blood cells and we'll be left with the liquid section, which is called serum, where we can find the virus and the antibodies to the virus.
PORTER
So that's the bit that you're interested in - the serum.
BRUCE
That's the bit we're interested in.
PORTER
And what are you actually looking for to be sure that it's hepatitis C?
BRUCE
Well to be sure it's hepatitis C we'll be looking for viral RNA, which is the genome for hepatitis C.
PORTER
And how many samples can you do at a time here?
BRUCE
This has quite a large capacity, I think we could do probably a hundred, couple of hundred.
PORTER
When you're looking for the hepatitis C virus are you looking for one virus or does it come in different guises?
BRUCE
It comes in different guises - hepatitis C is the overall term but basically within hepatitis C you have sub-populations of genotypes, they're called, which just means that there's a genetic variation between those different viruses which make up the population that is called hep C.
PORTER
Do they behave differently - are some more aggressive or problem causing than others?
BRUCE
In terms of treatment certainly we've found that the hepatitis C genotype 1 has been more difficult to treat and requires a more aggressive approach, and genotypes 2 and 3 tend to respond more favourably to …
PORTER
So that's the sort of information that you can hand back to the clinicians, the doctors, and say look this is a genotype that looks like it might respond well to the treatment, so might help them in the decision about when to start?
BRUCE
Yeah it will do, yeah.
PORTER
What about the genotype of the patient themselves, is there anything about the patient that's helpful in terms of treatment?
BRUCE
Yeah well there's been some interesting new developments which has highlighted a - what's called a SNIP, which is a single nuclear type polymorphism. All that means is a single DNA base change a specific location and that change can give an indication as to whether patients with genotype 1 will respond better or worse to the treatments that we offer.
PORTER
Could we talk about that being a mutation, that you might be able to identify?
BRUCE
We could do.
PORTER
Which might have an effect on the clinical decision that the doctor might make as to when to start treatment with what?
BRUCE
Yeah, yeah based on the research that's come out it's shown that the host genotype CC responds better to treatment than genotype 1.
PORTER
And that might be the first of others do you think?
BRUCE
It could well be, there's others that are speculated and we're currently developing a test that will pick up the SNIP that has been shown to affect treatment response.
PORTER
So all of this hopefully is leading to the individualisation of therapy - we can choose specific treatments for specific patients?
BRUCE
Absolutely yeah, if we can identify the viral genotype, the host genotype, then we can tailor the treatment to that patient's specific needs and hopefully a cure.
AGARWAL
The therapies we have are based around pegylated interferon once a week as an injection and a tablet called ribavirin twice daily and currently we can cure - and it's very important to re-emphasise that we can cure patients of their hepatitis C about 50% of the people who walk through the door in the UK. The treatment, it has to be said, is measured in months, as opposed to weeks and if you have the harder to treat type of hepatitis C, which is called genotype 1, and that occurs in about six out of 10 patients in the UK, then you have to undergo 12 months of antiviral therapy, with interferon and ribavirin and there can be a side effect profile associated with these medications. We see patients through their cause of therapy, we support them but it is not a simple cause of medication to take.
PORTER
What sort of side effects do the patients on pegylated interferon and ribavirin complain about?
AGARWAL
The first thing to say is that a lot of patients have fairly minimal side effects and patients are - that I've seen - certainly whether they are professionals, whether they're just coming forward for treatment, by and large with the right education, with the right support at King's probably about 80% of the patients who start treatment get to the end of treatment and get good outcomes. The side effects that we see from interferon and ribavirin can be sort of wide ranging, from sort of non-specific flu like symptoms around the time injection to significant fatigue because there are interactions with the blood count and people's haemoglobin may drop and therefore they may be more symptomatic and tired.
PORTER
Become anaemic.
AGARWAL
They become anaemic, exactly. So part of our job of monitoring patients is to support them psychologically, to support them physically and to try and help them through in any way that they can so that they can tolerate the best dose for them and certainly our plan is to individualise patient's treatment to get them through the treatment and give them the best result.
SABATINI
I was carrying hepatitis probably for 50 years, as far as I know, it could have been an infected needle from a dentist, we don't really know. The good thing is if I carried hepatitis for such a long time well my future doesn't look so bleak.
PORTER
Max Sabatini is another patient at King's who, typically for many people with hepatitis C, has been unwittingly carrying the virus for years - and all the time it has been quietly damaging his liver.
And it's this damage - often picked up on routine testing for other problems - that may be the first clue to the diagnosis. In Max's case he went his GP about a problem with his prostate, only for blood tests to reveal a problem with his liver which was later confirmed to be hepatitis C.
SABATINI
They told me I had genotype A which is not a very good one for hepatitis C. Eventually I was given a fibre scan; my liver was probably into the moderate to serious state. They did say that there were options, if I wanted medication, so we discussed the possibility with a special nurse here at the hospital who went to lengths to explain the side effects.
OAKES
My name's Kathryn Oakes I'm the senior nurse for viral hepatitis at King's College Hospital. We see patients who are being considered for treatment and we do a full assessment with them and then we go through the side effects of treatment with them as well, to make sure they understand.
PORTER
So these are patients that have been told that they've got hepatitis C, somebody's - the consultant or the doctor - has run through the basics of the treatment, said now what you need to do is come along and speak to the nurses about whether you're going to go for it.
OAKES
Yes, usually by the time they've got to the nurse led clinic they've got a pretty good idea about it but we just tend to emphasise more of what the outcome might be if they don't have treatment.
PORTER
And by outcome you mean?
OAKES
That they may develop cirrhosis, which obviously there can be life threatening complications.
PORTER
So once you've explained the benefits of treatment, then the next question is but what about the downside - it has quite a reputation - the treatment for hepatitis C.
OAKES
Absolutely, one of the main concerns are the side effects of treatment. And so we'll spend a little bit of time going through the main side effects that we see because obviously there's about 70 listed for each product - both the pegylated interferon and the ribavirin. So we'll talk to them about the main side effects that we see for each but we do stress that everybody is different, everybody has a different treatment journey, they may get some side effects at the beginning of treatment and then sort of settle into the treatment regime or they may sort of gradually develop anaemia or fatigue or insomnia.
SABATINI
Some days are not very good, they normally coincide with the injection, which I take every Friday - pains and nausea and very difficulties with sleep and itching on the skin. But after a few weeks you learn what they are so they come - when they come so you don't worry about it anymore, I mean you just have to live with it.
OAKES
Most people get a severe flu like reaction following their first dose of pegylated interferon and so we're always very clear to emphasise to them you may feel unwell for the first couple of days of treatment. After that the onset tends to be fairly gradual and there are different side effects at different times of the treatment, which is why we see them regularly to talk about their side effects.
PORTER
And are they coming in to meet you face to face?
OAKES
Absolutely. Initially they come weekly throughout the first month of treatment, then they would come monthly. Obviously if someone's struggling and they phone up or e-mail us to let us know there's a problem then we'll get them in sooner or if their blood tests are unstable or they're starting to feel depressed then we'll invite them in, so we can actually see them and have a good chat with them and spend a bit of time with them.
PORTER
Do you have any evidence to show that your intervention and your support and being at the end of the phone or the end of the e-mail and people being able to come to you actually makes a difference to how many patients stick with the therapy?
OAKES
Oh absolutely, the fact that people tend to remain on treatment and tolerate treatment with support, we have very few patients who discontinue their treatment early because of the side effects because of the levels of support they get. We are able to intervene, for example, if they're suffering from depression, then we're able to pick it up quite early and refer them to our liaison psychiatrist. So actually the support does make a huge amount of difference.
PORTER
What about the patients supporting themselves - do you encourage them to meet and talk to each other?
OAKES
We do, we've set up a support group called the Hepatitis United Group, which has been running for a year now and that is predominantly led by patients. And so there's a meeting every month for patients and they will discuss treatment with patients who are perhaps thinking of going on to treatment but are a little bit nervous and patients who are on treatment but struggling with some of the side effects.
PORTER
For many patients the outcome of treatment will be very good but for some it won't be and they're going to be living with their hepatitis C thereafter and a chance that they're going to go on to develop problems, do you offer on-going support to that group?
OAKES
They're very welcome to come to hug and also discuss with other patients but also there are now lots of clinical trials available and so they will have the support of the trials team if they're referred on.
SABATINI
I was on a trial for four weeks, it was successful for me and my - they call it viral load - how much hepatitis you have in your blood, it zero out after the clinical trial. So they were so pleased and immediately they put me on the 48 week standard of care, which I'm on now and now I'm on just about week 30.
PORTER
For the minority who do not respond to antiviral therapy, or for those whose hepatitis C is picked up comparatively late, the future is less certain. Left to its own devices for many years the virus can cause irreversible scarring, liver cancer and organ failure. In cases like these replacing the diseased liver is the only hope of a cure.
Surgeon Nigel Heaton is Professor in Transplant Surgery at King's.
HEATON
For liver transplantation hepatitis C will probably account for between 25-30% of our work. If I took you back 10 years liver transplantation for liver cancer from various causes that accounted for about 10% of our work, today it's about 20%. And if I look forwards 10 years to my successors I suspect it'll account for perhaps even half of the work load.
CRUZ
I was quite shocked when they rang and said oh is that Mervyn, I said yes, they said oh it's King's, we'd like you to come in. It was 12 o'clock on a Sunday night the 14th March, we'd like you - we've got a liver we'd like you to come in. About a quarter of the way through I said hang on, hang on I think you've got the wrong person; I said I've only just been listed not even a month now. And they went no, no we'll be sending an ambulance and that was it.
PORTER
Obviously transplanting someone's liver is a significant challenge; does the fact that the patient has hepatitis C make any specific difference to you the surgeon?
HEATON
For the patient who's currently being transplanted the virus remains active and in all patients the virus recurs in the new liver. The course of liver disease and the rapidity of its progression varies from patient to patient.
PORTER
Is a patient with hepatitis C who's had a liver transplant is the disease likely to progress more rapidly because presumably you're having to put them on drugs that are suppressing their immune system as well?
HEATON
Yes that is clearly the case, that the liver disease from hepatitis C appears to run a more rapid course after transplantation and we think almost certainly that that's because of the immunosuppressant drugs. But there may be some other factors such as the journey the donor liver has that may make it more susceptible to this type of injury.
PORTER
Obviously the patients are going to be talking to you are going to want to know what the long term prospects are, what sort of figures can you give them, I mean if I said to you right I'll go for it but what are my chances in the longer term?
HEATON
It's always difficult giving people percentages because these are all individuals. If you look at liver transplantation overall we'd expect something like 80-85% of our adult patients to be alive at five years with good liver function. And by and large patients with hepatitis C follow that early course. But if I say at 10 years your chances of being alive, for the adult patient, it'll probably be about 70%, that's liver disease of all causes. But now hepatitis C is starting to have an impact in terms of losing the liver and from probably eight or nine years on patients with hepatitis C are losing their liver and facing re-transplantation or dying.
PORTER
So in view of the fact you've still got the virus are you going to be taking some more therapy?
CRUZ
Yes as I understand it Dr Agarwal saw me at my six months, said that once they've seen how the liver's settling in and how fast the virus is loading again - the hepatitis C - they will have a look and see about treating the hepatitis C.
PORTER
But you're going to give it a go are you?
CRUZ
I'm going to give it a go, yeah.
HEATON
What we're hoping is this next generation of drugs which are currently in trial around the world and which we're running clinical trials with are going to transform the response rates and transplant patients are probably the most difficult group to treat the virus effectively and to keep them free of the virus in the longer term.
PORTER
One would imagine they're also quite a motivated group, is there anything that they can do themselves in terms of lifestyle to help maintain a healthier liver in the longer term?
HEATON
Well there's some pretty critical things that they're asked to do both in the lead up to transplantation and after transplant. It's absolutely mandatory that they take no alcohol, that clearly is a co-factor and will make any susceptibility to liver disease worse. And things like smoking may also play a role both in the longevity of the graft and the patient and is clearly a risk factor. So we're asking them to abide by what I would describe as sort of healthy lifestyle choices - they need to take real care of themselves.
CRUZ
I've always smoked since I was about 14, I'm 58 now and I've drunk since I was a young man in my teens and also taken drugs since I was a young person. So it was a sort of a wakeup call - here's an opportunity to change your life before it's too late.
PORTER
Start looking after yourself.
CRUZ
Looking after myself, yeah, you know and I've had 40 years of drinking, abusing my body and so on, so a little break won't do it no harm.
PORTER
Mervyn de Cruz who is enjoying a new lease of life thanks to his transplanted liver and some major improvements in his lifestyle.
And newer treatments in the pipeline will hopefully improve the outcome for others too. Kosh Agarwal.
AGARWAL
There are a whole array of newer therapies that are I think going to really change the landscape for treatment for hepatitis C and will deliver us much, much better cure rates. And this is a very exciting time and potentially provides a lot of opportunities for our patients.
PORTER
And are these new treatments better tolerated as well?
AGARWAL
Absolutely. We've now got to an understanding - and it has taken a bit of time - as to more of the cellular processes around hepatitis C and how it replicates and as a part of that we're now able to target various steps to look at directly acting antiviral agents that decrease the rate of replication and seem to be very potent. They will come with much less in the way of side effects than we currently have. They may have some side effects but in reality they will deliver a much, much better chance of success and cure for our patients with a shorter course of treatment, which I think will be much better tolerated.
PORTER
And whereabouts are we on the pipeline, are these drugs available now?
AGARWAL
At King's, as a large unit and as an academic health science centre, we have access to these newer agents as part of the work we do with clinical trials. So at present these aren't available but we are able to offer them to selected patients through clinical trials. And obviously being in a clinical trial means patients need to be much more focused, that we need to put more work in and that safety is really our paramount option. It is likely that the first two new agents are going to be licensed globally over the next six to eight months. It's unclear as to how available they'll be in the NHS, given the changes that we're seeing in the environment, but at the moment this is a very big focus for us at King's, from a research perspective because we're really interested in translating these new developments straight into patient care to offer the best care for our patients.
PORTER
Kosh Agarwal.
If you'd like more information on the diagnosis and treatment of hepatitis C, including a list of the new therapies in development, then do visit our website at bbc.co.uk/radio4 just click on C for Case Notes and you'll find the useful links.
Next week's programme comes from Moorfields Hospital in London, where I'll be finding out about the latest developments in treating the commonest single cause of blindness in the UK - glaucoma - including a new test that doctors hope will help identify the problem earlier. Join me next week to find out more.
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