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BRITISH BROADCASTING CORPORATION
RADIO SCIENCE UNIT
CASE NOTES Programme No. 7 - Liver
RADIO 4
TUESDAY 19TH FEBRUARY 2008
PRESENTER: MARK PORTER
REPORTER: ANNA LACEY
CONTRIBUTORS: NICK SHERON
CHRIS DAY
HUMPHREY HODGSON
RAJIV JALAN
PRODUCER: BETH EASTWOOD
NOT CHECKED AS BROADCAST
PORTER
When was the last time you thought about your liver?
Most of us are familiar with the benefits of looking after our hearts, brains, lungs and even our bones. But we tend to ignore our livers - and by the time yours let's you know that it is trouble, it's probably too late - much of the damage will be irreversible.
The UK is the only major European nation facing an increase in deaths from liver disease. There are a number of reasons why our livers are less healthy than they were just a decade ago - including viral hepatitis - but in this programme we will be concentrating on two - the amount of alcohol we drink, and our expanding waistlines.
And when it comes to alcohol, you don't need to be what most people would regard as a problem drinker to be at risk. So called social drinkers who enjoy their wine are often caught out too.
CLIP
We didn't put ourselves in the heavy drinking bracket really. My husband was drinking more or less the same amounts as me. Of occasions of a weekend we used to joke about the amount of bottles but we never really thought that we were heavy drinkers.
PORTER
In fact you don't need to be a heavy drinker at all - carrying too much fat can cause serious damage too.
CLIP
For years and years when a patient came along with fatty liver and cirrhosis and said they didn't drink and we saw this fat in there but we just assumed they were lying to us and it was obviously a big change to realise no, no you can get this condition without alcohol.
PORTER
I'll be finding out more about the link between weight gain and liver disease a little later, but first could your drinking habits be putting your health at risk? And, other than totting up your weekly consumption, is there a reliable way of picking up the early signs of liver damage?
Dr Nick Sheron is a liver specialist at Southampton General Hospital and one of the founders of Alcohol Health Alliance UK - a coalition of 24 charities and organisations with the common aim of highlighting the growing problem of alcohol related illnesses and devising solutions to tackle them.
SHERON
Most people will be familiar with what normal liver looks like because you can see it in the butchers but as the liver becomes scarred it forms nodules and around each nodule, I call them little marbles, you get a coating of scar tissue. Early on this coating of scar tissue is quite thin, as this proceeds and patients develop what we call cirrhosis each marble becomes surrounded in a really thick coat of scar tissue and that actually prevents the liver from functioning.
PORTER
But the liver is a surprisingly resilient organ and can function almost normally - at least outwardly - even when the damage means it's limited to working at just 20% capacity. So by the time it starts to show signs of failing, the damage can be so extensive that there is no way back. And the only treatment for end stage liver disease is a transplant.
SHERON
There isn't really a first sign of trouble I think, that's the problem. Everybody who drinks above a certain amount of alcohol will get fat within their liver cells but there's no real sign of that happening and it doesn't alter the liver's function at all. The problem is that around about 20-30% of people, if they drink quite a lot over a long period of time, will get scarring in the liver and it's that scarring process that causes the long term problems.
PORTER
And those long term problems are?
SHERON
Well the long term problems are really - are associated with liver failure but chronic liver failure presents really in one of three ways: it either presents with an internal haemorrhage from dilated veins inside the gullet, so the patient vomits blood or suddenly passes a lot of blood or it presents with something we call ascites, which is fluid in the tummy, the tummy swells up and patients look as if they're nine months pregnant but actually the tummy's full of fluid or they present with jaundice. And the problem with all of those three problems is that they occur in end stage liver disease and they have a very, very high mortality.
PORTER
So that might be the first sign of trouble - is literally that they're in end stage liver disease?
SHERON
It usually is the first sign of trouble yes.
JUDITH
I was working in the NHS and had a very stressful job and a lot of my symptoms I put down to stress but we now know were signs of liver failure.
PORTER
Symptoms like?
JUDITH
Well my liver actually failed in the July, so it was building up to a warm period, so I had swollen ankles but again I put that down to it being warm and on my feet all day. I was vomiting sort of yellow thick bile, not wanting to eat, very, very tired. And it was only one morning when I went into work and I did work for a doctor and he pointed out I'd got yellow eyes that that was the first sign that we knew there was something wrong with my liver.
PORTER
How much were you drinking and when did you start?
JUDITH
I mean I've always been a social drinker, so my husband and I - a bottle of wine in an evening was the norm for us...
PORTER
Between the two of you or each?
JUDITH
No between the two of us and perhaps a little bit more at weekends. But towards the end of 2003 when I was coming under the particular stress at work I did increase my alcohol at home whereby I was coming in from work and my husband was greeting me with a glass of wine to sort of calm me down, it began to increase to about a bottle, a bottle and a half a night.
PORTER
And did you have any idea that you were putting your health at risk because that's quite a lot of units of alcohol?
JUDITH
Probably deep down I probably did but it was a way of really masking the problems that I'd got at work and I just wanted to come home, have a drink, relax and forget about what was going on.
PORTER
So you saw yourself as a heavy social drinker, not a problem drinker?
JUDITH
No not a problem drinker at all, no.
PORTER
And in terms of your health now, what have the implications been?
JUDITH
My liver's okay, I still have ultrasounds regularly, I don't think it'll ever be fully functioning, like it was before, because it has been damaged.
PORTER
But you haven't touched any alcohol since the diagnosis was made?
JUDITH
No, I wouldn't want to go through what I went through again.
PORTER
Judith is one of the lucky ones. At least one in five of the people who present with outward signs of liver damage die within a few months of their first consultation with a liver specialist. Which is why Nick Sheron is working on a screening programme that can pick up damage long before it would otherwise become evident.
SHERON
What we're trying to do is we're trying to pick up people who are developing the significant form of liver disease, so they're on the way to developing scarring and cirrhosis. And we're going to be looking in six general practices, in and around Southampton, we're going to be screening those people within those practices to see if they are drinking at a dangerous level, first of all, and we'll be using a standard questionnaire. So we e-mail out a questionnaire to 10,000 people. We expect about 10% of those individuals to be drinking at a hazardous or harmful level and all of those people will be invited into the surgery for a further interview and a blood test. The blood test will tell us with a 95% accuracy whether they've got severe scarring or cirrhosis and with about a 70% accuracy whether they've got the early forms of scarring or fibrosis. If they do look as though they're developing significant liver damage then they'll be referred along to a liver clinic and they'll be treated in much the normal way.
PORTER
So the screening has two advantages that I can see: one, is that you're a. picking up people who otherwise wouldn't know that they had a problem but b. possibly that by actually showing them what they're doing to themselves early on that that will have some impact on their drinking habits. Do we have evidence to suggest that that sort of intervention is more effective than simply counselling them on their consumption?
SHERON
We know that if you have a sensible conversation with people about their alcohol intake and you reflect the sort of damage that they could be doing to themselves and that's called a brief intervention, then it is pretty successful, it works in half of people and they cut their intake by half. If you're able to tell somebody that there's something very specific happening to them and not just might happen to them, as one of a group of people, then our experience as liver doctors is that that's effective in a roundabout 70 or 80% of people. And you have to remember that the majority of these people are not alcohol dependent, they're not alcoholics as such, they're heavy social drinkers, they've got jobs, families, it's perfectly possible for them to modify their lifestyles but they just need to have a good reason to do it.
PORTER
So what tests should we be using in a general practice environment to pick out drinkers who are at particular risk?
SHERON
I don't think the tests are widely available but there are two tests that we've been using. One of them is called Collagen P3 Peptide and the other one is called Hyaluronic Acid. Now these tests have been widely used on the continent for many, many years and as you know there's a certain inertia in medicine to the development of new ideas and this is an idea that's in the process of developing, I'm absolutely certain in five or 10 years time these tests will be used everywhere.
PORTER
Nick Sheron talking to me earlier from our studio in Southampton. My guest today is Professor Humphrey Hodgson, he's Director of the Centre for Hepatology at the Royal Free and University College Medical School.
Humphrey, we'll come back to those blood tests a little later along with other methods for picking up liver damage. But first what sort of weekly alcohol consumption does pose a serious hazard? We heard Nick there talking about harmful levels because many people do regard the official guidelines as being somewhat conservative.
HODGSON
Okay, well we've got the official guidelines and those are safe limits and that's 14 units for women, 21 units for men.
PORTER
A week.
HODGSON
A week. Now in terms of hazardous drinking I think it's probably 30, 30+ for men and 21 units for women. Which then puts you into a group into which we know you're beginning to have an increased mortality from alcohol associated liver disease.
PORTER
And the interesting thing about units of course is that you know we're drinking quite strong drinks these days - a bottle of wine we think of as having maybe having six units but actually it's probably got more like 10 in them, modern wine.
HODGSON
Yes and if it's really strong Australian it's probably got 11.
PORTER
So half a bottle of wine, that could be - in the evening - is 6 units, could be or five and a half.
HODGSON
Five to six units yes.
PORTER
It doesn't take many of those to tot up to your hazardous level of 30 plus units then.
HODGSON
No.
PORTER
Are you seeing a change in the type of present that's presenting to units like yours, as a result of the change in our drinking habits?
HODGSON
Well firstly we're seeing more, many more women, certain ethnic groups - Asians, Asian women we see who drink, Afro Caribbean people who drink.
PORTER
Is there a change in age profile?
HODGSON
Yes much significantly younger.
PORTER
And that's a direct result of drinking at an earlier stage presumably?
HODGSON
The risks are directly proportional to how much you drink - that's one for any one individual and it's also for the population as a whole.
PORTER
One of the difficult things that I often see when I'm dealing with my patients is they say well I drink no more than the rest of the guys in the pub or the rest of the people in my social group, why have I been the one that's been affected by it because some people do seem to more prone to the problem?
HODGSON
Sure, there's a lot we don't understand, some of that is genetic susceptibility. Some of it is of course is that that's what's happening to them this year and it may happen to their drinking companion next year or the year after.
PORTER
So some people may be more genetically susceptible to alcohol, the problem is of course we can't predict who those people are going to be so we have to assume everybody is.
HODGSON
There are quite interesting genetic traits, for example in the Far East there are some people who have a genetic enzyme deficiency - when they take alcohol they feel really sick, as a result of which they never get into the group in which they'd drink hazardously. But yes there are undefined genetic differences.
PORTER
Assuming a listener is now worried, they're drinking more than 30 units a week and they think well maybe I should go along and have a test, we've talked about these screening tests that are in the pipeline, we'll talk a little bit more about them later on, but at the moment what sort of tests are available? We got sent this liver check test in the post this morning and it's basically a do-it-yourself test, it cost £150 privately, but I mean that doesn't offer anything I can't offer as a GP does it?
HODGSON
No I think it'll cost the NHS about £1.20 to do those tests in the laboratory.
PORTER
And the patients free presumably. So if I go along - I mean say if someone comes along and asks me for what we would call a liver function test, a bog standard liver function test, how good is that at picking up signs of damage?
HODGSON
They are helpful but they - there are two areas in which they fail. Firstly, that they may not identify somebody who in a few months time is actually drinking enough to cause themselves damage and you can therefore get a sense of false security, so that if somebody is drinking heavily they are putting themselves in a hazardous category and actually the mere fact that the blood test is normal doesn't let themselves off the hook. And at the other extreme, these very minor changes that you'll pick up in your surgery in the enzyme levels etc., may not turn out to be of any significant importance but it is appropriate then that the patient gets checked out and then there's a lot of reassurance and other things that may be found.
PORTER
So Humphrey how do the tests that Nick was talking about, these tests that pick up signs of scarring, how do they differ from the liver function test, are they a more accurate predictor of trouble ahead?
HODGSON
I think we don't know as yet and that's why he's got to do the research. But in fact they're looking at a different factor. The tests that the GP routinely does look - can change very rapidly, people stop drinking they can go back quickly to normal. What Nick is looking for is something which means has damage and scarring taken place. And that's a thing which may be permanent but certainly shows that people have progressed from transient damage that can get better into a group in which it is likely to be getting worse. And as he said it's really to identify the people who are moving towards the serious end and therefore are heading towards those aspects of liver failure, jaundice, ascites and possibility of bleeding from the gut that he was talking about.
PORTER
Dr Rajiv Jalan is a liver specialist at University College Hospital and offers a private screening service using a new type of ultrasound scanner - the Fibroscan - that can detect early signs of scarring in the liver. I went along to his rooms in Harley Street to put the technology to the test.
Okay Rajiv you've got one of the machines here and I suppose I ought to volunteer myself to find out whether my drinking habits have been doing my liver any harm.
JALAN
Yes so just come up to the bed here, this is the machine, it's called the Fibroscan and I'm just turning it on full. Have a little lie down. And if you put your right arm over your head. So here is the machine, this basically reflects the stiffness of the liver and as you might imagine as the liver gets injured it heals by scarring and as a liver scars with greater the scarring the more stiff this liver would be and that's what it measures.
PORTER
Because I suppose people would have handled at the butcher's maybe a raw healthy animal liver and that's what our livers are like, they're sort of soft and resilient and elastic and spongy really but what you're saying is it gets a little bit more like cooked liver as more and more damage ...
JALAN
I think that's a great analogy, it really is. So what I'm going to do is to have a little feel of your liver, if I may, and I'll use one of the windows through the rib cage to look at the liver and collect some information from that.
PORTER
Because you would expect a normal liver to be mainly concealed behind the rib cage, so I hope you can't feel mine below.
JALAN
No you can't. What I'm doing is just percussing to see where the upper end of the liver might be. We'll try and use that there. There's a little bit of jelly here.
PORTER
So it's like an ultrasound that you'd have during pregnancy.
JALAN
Absolutely. So this is the probe that creates the wave and we collect the information through here as well. It can take a couple of minutes to try and find a good window.
PORTER
And it was at this stage that we ran into trouble - Rajiv couldn't find that window. It seems my ribs are too close together for the Fibroscan to work properly. So the state of my liver remains unknown. But had Rajiv been able to get a good view, how accurate would the result have been?
JALAN
It can be fair to say that we have got the first generation technology, it's not perfect but up to 95% of people that are abnormal we'll pick up with the technology that we have in place today.
PORTER
At the moment there aren't many of these machines in the UK, what 10 or 15 or something, they're not available on the NHS, do you see a day when you might be using this sort of technology in your NHS practice?
JALAN
Oh almost certainly, there are more and more NHS hospitals that are buying machines like this but I think the concept of liver health has lagged behind the cardiovascular health, the cholesterol checking, colon cancer screening and so on and so on and so on. Not to know that one has got liver disease can have devastating consequences and that is what we are seeing in my clinical practice in the hospital today.
PORTER
Dr Rajiv Jalan.
You are listening to Case Notes, I am Dr Mark Porter and I'm discussing liver disease with my guest Professor Humphrey Hodgson.
Humphrey, do you use that technology?
HODGSON
We use it at the Royal Free, not as a general screening test though.
PORTER
And do you think we'll ever have a general screening test - I thinking we've heard about blood tests that can pick up screening, we've heard about the Fibroscan which may be able to pick up early signs of scarring as well - could we combine those two and have some sort of useful screening programme?
HODGSON
Oh I think the movement is that way, yes, and that by - it may well need a combination of both this sort of function imaging, taking a picture and seeing what the state of both inflammation and fibrosis in the liver on the basis of blood tests, if you put all of them together you would get more information.
PORTER
Because one of the things about a screening test is I mean a. it has to be accurate and that's yet to be determined but also you've got to have good evidence that intervention makes a difference, there's no point in highlighting a problem unless we can do something about it. But actually you know I suppose we could use that to get people to stop drinking, or cut back.
HODGSON
Yes I mean that is the nub of the problem, we can put a lot of resources into the technological and medical aspect but on the other hand if the only people who are going to turn up are people who are feeling guilty because they are drinking too much the answer is almost certainly they are drinking too much and the sociological educational approach might be much more productive.
PORTER
In the meantime then we wouldn't need a screening programme if we didn't have such an alcohol problem in the UK. What would you like to be seeing done as a liver specialist, what tactics do you think might work?
HODGSON
I think it has to be education primarily. We probably have between six and nine million people in this country who are drinking heavily, hazardously. People don't realise that the incidence of death from alcoholic cirrhosis is progressively rising in men and women at a progressively younger age group. And they don't have in many cases a link between just how much alcohol they are taking and the hazard, exactly like the lady we heard the interview of earlier on. So I think education is the first thing. And the second is cost, if you look in broad economic and historical terms the incidents of alcohol liver disease has always gone up when the cost of alcohol's gone down and it's always gone up when the consumption of alcohol has gone up and we are facing both those things in the country at the moment.
PORTER
At the moment alcohol is comparatively cheap.
HODGSON
It is comparatively cheap, very much cheaper than it was 20-30 years ago, consumption is going up and the consequence of that is progressively rising alcoholic liver disease.
PORTER
I want to move on to another threat to the liver now. While most people will be familiar with the potential risks faced by people who drink too much, few will know that being overweight can seriously damage your liver too. A comparatively recently recognised condition known as Non Alcoholic Fatty Liver Disease.
We sent our reporter Anna Lacey to meet Chris Day - professor of liver medicine at Newcastle University - to find out more. He started by showing her some slices of fatty liver under the microscope.
DAY
On the left here is just the stage of fatty liver, so as you can see these are large single liver cells with a nucleus, there's the dark dot, distended by one single swollen fat droplet and if anyone's ever had pate foie gras that's what it looks like, it looks like a yellow fatty liver rather than a nice pink sort of tongue coloured liver.
LACEY
Away from the biopsy samples, Professor Day explained why a fatty liver is such a problem.
DAY
Normally we store fat in our adipose tissue on our arms and our legs and round our tummy for use when we're starving, if you like, so that in between meals fat gets released from these stores, goes to the liver where it's made into sugar, to then be released round the body. If you are very overweight or even a bit overweight then fat continually gets released from this adipose tissue, it's almost like when your adipose tissue gets too large it becomes leaky and fat just pours out of it all the time, even when we don't need it. The liver, therefore, doesn't really know what to do with this, so it does what it thinks it should do which is to just the store the fatty acids as fat droplets in the liver. The problem is that these fatty acids, as it sounds from their name, they're acids, they're toxin and so if you have enough fatty acids coming into the liver you essentially overwhelm the ability of the liver to mop them up and they're the things that cause the trouble.
LACEY
So it's almost as though the fatty acids are literally burning away part of the liver?
DAY
Yeah that's exactly right, there are lots of very complicated mechanisms but essentially these fatty acids are burning the liver themselves.
ACTUALITY
Hello Mark. How's it going?
Alright.
So I since I last saw you have you had any new symptoms at all to report?
No, I think I've lost some weight ...
LACEY
Mark Ashwell is 23 and has fatty liver disease. Although he's classed as overweight his body size is fairly average, showing that it's not just the morbidly obese who are at risk.
ASHWELL
I went originally to the doctor's just for a random blood test and it came up in me blood test that me liver function was abnormal, which I think it's due - because I was quite overweight, I put a lot of weight quickly and obviously that's resulted in me getting the fatty liver.
LACEY
And had you noticed any symptoms at all, had you felt strange or felt any discomfort?
ASHWELL
No it wasn't discomfort, I just felt like lazy and slow and that's when I decided to go to me GP to see what was up.
LACEY
And when you got the results back, how bad was the fatty liver disease in your case?
ASHWELL
It was quite bad, it scarred my liver, so that's when we decided that we needed to take some action and start losing some weight.
LACEY
Even though Mark's liver was being damaged, it took a liver blood test to show that anything was wrong. And in fact most people only find out they have the disease when they visit their GP for something completely different. But Professor Day says that until a fatty liver is diagnosed, people are at risk of the disease progressing to severe scarring and even a liver transplant.
DAY
If you took a hundred overweight people off the street around 80-90% would have some excess fat in their liver, so almost everybody who's overweight has some fat in their liver. The majority of those people will remain with too much fat in their liver for the rest of their lives but they will die of their heart attacks or their strokes at some point in the future and never have known it was there. Probably around 20% of those people, one in five, will start to cause some liver damage - inflammation, healing by scarring - if that scarring and damage goes on unabated then eventually there will be enough scarring to call the cirrhotic liver and probably two or three of them might end up eventually with a cirrhosis stage and need the transplants and everything else.
LACEY
So what should people do, people might not even be able to tell that they even have a problem or have fat in their liver?
DAY
In terms of the population themselves it's just yet another reason to try and keep trim, you know by the usual eating healthy, regular exercising. Exercise to a fatty liver seems to be particularly important, so it seems that the liver is the last place you dump fat when you're overweight and therefore it seems to be the first place that clears out when you lose even five or six pounds and certainly a stone or so, you'd be expecting your liver to be much improved.
LACEY
But treating anything with a better diet and more exercise can be difficult. Mark's weight loss was helped along with a drug that reduces the amount of fat absorbed by the body.
ASHWELL
I was put on some tablets called xenical which if you eat too much fat makes you go to the toilet. So obviously you know if you've eaten something too fatty then you know there's going to be side effects.
LACEY
And about how much weight have you lost would you say?
ASHWELL
I'm I think it was about half a stone. It was hard at first because I was used to eating whatever I wanted but I gradually got to used to eating the right food and doing regular exercise.
LACEY
And how is your liver now?
ASHWELL
I had my biopsy at first and it was scarred, then I had my biopsy a year later and the scarring's gone now, so I've had me last appointment today, so I don't think I'll need to return anymore.
PORTER
A new, slimmer Mark Ashwell talking to Anna Lacey.
Humphrey, Mark says his liver seems to have recovered thanks to his weight loss - does that mean scarring is reversible if it's picked up in time?
HODGSON
Yes it's one of the things that actually we've learnt in the last decade. Really severe scarring - cirrhosis - we don't think gets better but those intermediate, early, stages yes remove the cause and it can go back to normal.
PORTER
And would that apply to alcohol as well?
HODGSON
Yes.
PORTER
So that's another reason for the benefits of early intervention.
HODGSON
It's a really good reason for early intervention.
PORTER
And interesting thing that comes out of this that pub law would have it that the fatter you are the more alcohol you can handle but Anna's report there suggests that the reality may be exactly the opposite - if you've got a liver that's struggling because it's full of fat and then you overload it by drinking too much?
HODGSON
I'm afraid that's a double whammy yes, it does get worse - the obese alcoholic male is at a very high risk of progressive liver disease and cirrhosis.
PORTER
And of course society as a whole, not only are we drinking more but we're getting fatter too. Is that going to accelerate the number of cases coming to clinics like yours?
HODGSON
I think it is. And I think that the other point that Chris Day made about many people who've got fatty liver are going to go on and actually die of heart attacks and strokes, I think we should emphasise that actually if you are obese and do have a fatty liver your chances of going on to have a heart attack, a stroke, developing diabetes are significantly greater than the person who's slim, who takes a lot of exercise. And so that a lot of people's general health outlook gets improved by recognising the fact that they've got fatty liver which identifies the fact that they are at risk from a heart attack and strokes.
PORTER
Right so what you're saying is that there's a problem there but also actually there's major general health implications.
HODGSON
Yes.
PORTER
And I was interested by the concept that you don't actually have to be super fat, you don't have to be grossly obese, to have a problem with your liver. I mean can you see people with problems with fatty liver who are a stone or two overweight or is it something that tends to be on the heavier end?
HODGSON
It's about 20% of the general population can be identified as having more than "normal" amounts of fat in their liver. But the more obese the greater the risk that that's going to be problematic.
PORTER
The more likely your liver is to be like fois gras.
We must leave it there. Professor Humphrey Hodgson, thank you very much.
Just time to tell you all about next week's programme - the last in the current series - which is about fainting. I'll be visiting a clinic in Manchester that specialises in investigating and treating people who are prone to passing out. So, if you have ever wondered why people faint, how doctors differentiate faints from other causes of loss of consciousness such as fits, or what to do if you happen to be with someone who does faint, then do join me next week to find out.
ENDS
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