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Liver disease, Hepatitis C

Duration:
28 minutes
First broadcast:
Tuesday 31 July 2012

If you believe recent headlines the growing increase in deaths from liver disease is entirely down to excessive alcohol consumption, but it's estimated that two thirds of liver related deaths are caused by other conditions. Dr Mark Porter investigates two liver conditions that do not hit the headlines but could be silently creeping up on millions of people in the UK.

  • Programme Transcript - Inside Health

    THE ATTACHED TRANSCRIPT WAS TYPED FROM A RECORDING AND NOT COPIED FROM AN ORIGINAL SCRIPT. BECAUSE OF THE RISK OF MISHEARING AND THE DIFFICULTY IN SOME CASES OF IDENTIFYING INDIVIDUAL SPEAKERS, THE BBC CANNOT VOUCH FOR ITS COMPLETE ACCURACY.

    INSIDE HEALTH

    TX: 31.07.12 2100-2130

    PRESENTER: MARK PORTER

    PRODUCER: ERIKA WRIGHT


    Porter
    Hello. In today's programme we take a closer look at the growing burden of liver disease. The latest figures show that liver related deaths have soared over the last decade - and, if you believe the headlines, it's all down to alcohol.

    Alcohol headlines
    Binge drinking leads to 25% rise in liver disease.

    Alcohol linked to 25% increase in deaths.

    Alcohol abuse contributes to big rise in deaths from liver disease.

    Porter
    But alcohol isn't the only major threat to our livers. Two other, much lower profile types of liver disease could, between them, be silently creeping up on millions of people in the UK.

    Professor Julia Verne is National Clinical Lead for the End of Life Care Intelligence Network.

    Verne
    One of the problems is because we publish statistics showing that a high proportion of people die from alcoholic related liver disease is that people tend to think everybody's who's got liver disease drinks too much. About a third of people who are dying are dying of alcohol related liver disease but that means that two-thirds are dying from other causes. Even more striking is the young age at which people are dying - 90% are under the age of 70.

    Gray
    My name's Yvonne Gray, I'm a 57 year old woman, I've recently retired from a job which I loved dearly which was being a primary school head teacher, I've had to retire early because of ill health. One of the ill health conditions being my liver disease. We've heard a lot about the increase of liver disease, now certainly I'm not an alcoholic, I don't drink alcohol, alcohol's never been important to me in life. I have had a glass of wine with a meal, the odd gin and tonic when it came to a holiday period but I'm certainly not the stereotypical person that people would think of with liver disease.

    Porter
    Yvonne has non-alcoholic fatty liver disease - a condition thought to affect millions of people in the UK, and which is often indistinguishable from the sort of liver damage caused by heavy drinking. No one knows exactly how many people are affected but best estimates suggest one in five adults has too much fat in their liver, one in 20 of whom will go to develop inflammation that could eventually lead to scarring and cirrhosis.

    Dr Gideon Hirschfield is Consultant Hepatologist at Queen Elizabeth Hospital in Birmingham.

    Hirschfield
    One of the most important and rising causes of liver disease both in the United Kingdom and in the developed world is fatty liver which is really a feature of what we would call metabolic syndrome - it's our lifestyle, it's the fact that with time our waist circumferences are getting bigger. And when that happens the liver is put under strain and that's actually going to become one of the most important causes of liver disease in the developed world.

    Porter
    What is it about somebody's diet or their lifestyle that causes problems for the liver and why is it associated with fatty deposits?

    Hirschfield
    The liver's a very central organ to our metabolism and it's a very important organ because it sits there taking the blood from your bowel and then detoxifying them and making many, many thousands of different proteins and then passing the blood back to the heart. So of course it's fed everything that you're eating. And there's a difference between just simple fat and simple fat with inflammation. Simple fat really is just a marker of what you know already - you may be overweight - it just tells you that you're at risk of metabolic syndrome, which is fatty liver, diabetes, high blood pressure. What we don't understand is why a smaller proportion of our patients go from simple fat to simple fat plus inflammation because it's that inflammation - it's that response to the fat in their liver cells - that then leads to liver scarring. It builds up over many, many years and decades and that scarring may in a few patients become quite significant and then threaten the function of the liver.

    Newsome
    My name is Philip Newsome, I'm a Senior Lecturer in Hepatology at the university and a Consultant Hepatologist at the Queen Elizabeth Hospital in Birmingham.

    Porter
    Phil, we're sitting here in a brand new clinic, four doctors, it's called The Fatty Liver Clinic, now I can remember when I was working in a hospital there was no such clinic and I'm not that old.

    Newsome
    Sure, I think that reflects really the changes that have occurred in society, I think we look at levels of obesity over the last 15-20 years and they've risen really quite dramatically. And there have also been changes in people's patterns of exercise as lifestyles get busier. So as a consequence we're seeing a lot more disease that's induced by people being overweight and having diabetes and that's really reflected in this clinic here.

    Porter
    Now the people in the clinic here are people that have been picked up, I'm presuming most of them have been picked incidentally have they, they've been having tests for other things?

    Newsome
    That's right, I mean the majority of cases are often picked up for investigation of other symptoms - abdominal pain, often they're on drugs such as statins which lower cholesterols and they notice that their liver function test, their liver blood tests, are abnormal and that then results in a further test, often an ultrasound scan which shows a bit of fat in the liver and then they get referred up.

    Hirschfield
    The typical patient is a patient who goes to their GP with high blood pressure or goes to their GP with slightly high cholesterol, that's what the GP identifies, they're in their 40s, they're in their 50s, male or female, they're not necessarily morbidly obese, they're just a little bit overweight, I mean - there's the whole spectrum, and you listen to their story - mother's got diabetes which is late onset, grandfather had a stroke, etc., - and you've got this risk factor for metabolic changes. And they come to see you in clinic, they feel well, they have no symptoms and they may just be on a tablet for blood pressure or cholesterol - and that's your typical patient, so that's your normal person that you walk past in the street every day.

    Porter
    So a fatty liver is a marker of increased risk of cardiovascular disease which kills one in three or nearly half of us in some cases, so that's what makes it important as well.

    Hirschfield
    Yeah, remember why when you go for life insurance do they measure your liver enzymes? They do that because the French data that showed that if you had an elevated Gamma-GT.ALT you had an increased risk of death. Up to a 30% of North Americans have got fat on their liver so anything that involves 30% of people that's not rare. Fifteen per cent of American teenagers have got abnormal liver enzymes, almost certainly all due to metabolic liver disease, fatty liver.

    Porter
    And how do those figures compare to the UK - you think we're following suit do you?

    Hirschfield
    I think we will follow suit in years to come and I think if you look at the literature from surveys of general practice fatty liver's the commonest reason to have abnormal liver enzymes by far and it's a similar sort of picture, we're fortunately 10 years behind North America so we can still make a difference.

    Porter
    And the statistics on obesity confirmed that where America leads, Britain often follows, as Inside Health's Dr Kamran Abbasi has been discovering.

    Abbasi
    From the '70s we begin to measure obesity levels on an international scale, in terms of England we had an obesity prevalence of somewhere around 5%, 5-6% which at that time was around 10% behind the levels in the US. And the interesting phenomenon is that the obesity levels in the US have increased at the fastest rate of any nation but we have tracked that increase closer than any other country in the world pretty much, so their obesity levels are now around 35% and we're at 25% of our adult population.

    Porter
    And that's a fivefold increase in - since the '70s, I mean that's pretty significant.

    Abbasi
    Yeah that is a big increase and the projections are - and these are rather alarming - that by 2050 the proportion of men in the UK who are obese will be 60% and 50% of women and 25% of children - these are alarming statistics.

    Porter
    Some people may be familiar with those sorts of long term predictions and they're based on extrapolating the line that we've been following since the '70s is what you're saying.

    Abbasi
    Yeah it's a very consistent increase but I think that's again another alarming aspect of this.

    Porter
    And is there any evidence from the data that the rise in the States is slowing down, given that they're 10 years ahead of us, is there a top to this curve?

    Abbasi
    Yes I'm looking at the curve right now and it seems to be accelerating if anything.

    Porter
    So if anything the problem could get worse?

    Abbasi
    I think that's the message yes.

    Porter
    Actually it's no laughing matter - and even if we do manage to buck the trend and get control of our waistlines, you don't have to be seriously overweight to develop fatty changes in your liver. Yvonne Gray.

    Gray
    People think they've got this picture in their mind of someone who is very, very large, drinks a lot, eats a lot, eats a lot of fast foods perhaps and I can tell you that that is not the case. I take a size 10 trousers, I take a size 12 top. I am however diabetic, I'm a Type 2 diabetic and throughout my life because of my diabetes I've had to be very careful in terms of my diet and actually have been.

    Porter
    Type 2 diabetes, like Yvonne's, and obesity, are major risk factors, but many people with fatty liver disease have neither - although they do tend to have other associated problems such as high blood pressure and raised cholesterol levels. Whatever the cause, one thing does tend to be common to most cases - there are rarely any symptoms - at least not until serious liver damage has been done.

    Hirschfield
    For the vast majority of time when you've got liver disease you feel well and that's because the liver takes a hit, gets some inflammation, but it tries to heal itself, so you don't feel anything. As liver disease progresses the symptoms are often very non-specific, so you may not get anything other than tiredness and tiredness is really a feature of living really, so people don't really notice it.

    Gray
    The strange thing was about it that I actually wasn't presenting any symptoms, I didn't have any liver pain, I had no symptoms that you would possibly people might think might be linked to liver disease. I was being tested for other things - for my diabetes - I was picked up in a blood test, regular routine blood test, where a liver function test was picked up.

    Hirschfield
    When you've got very advanced liver disease then it's different, you may go yellow, your wife or your husband might look at your eyes one day and say you've got jaundice, you've got yellowness of the eyes but that's a very late presentation of liver disease. You may itch, but again that's something that we tend to see as the disease has progressed. So actually what we now see quite commonly in our practice and our referrals is that a patient goes to the general practitioner for one problem, the general practitioner is shrewd and takes the opportunity to do some sort of general health kind of assessment at the same time, measures their liver enzymes which you wouldn't - you don't have any symptoms from having high liver enzymes - and says you've got high liver enzymes, I don't know why and that triggers the investigation of liver disease. And lots of our patient, in fact the majority of our patients, hopefully come to us without symptoms and more importantly we hope at a point where we might be able to make a difference.

    Porter
    Can you tell when these people present - the typical 40 year old man or woman with fatty change - whether they're going to be someone who's going to have fatty change all their life and it's not really going to cause them any trouble or whether they're going to be that small but significant number, the sub-group, who go on to get serious liver disease as a result?

    Hirschfield
    Great question, we don't know. The answer is not reliably enough. Some of our colleagues, and me included, will select a group of patients who have got the risk factors, they've got abnormal liver enzymes, and we'll do a liver biopsy. Old fashioned test but fantastically useful - we actually look at where the problem is.

    Gray
    From the blood tests the doctors decided that I would need a liver biopsy which involves going into hospital and the liver biopsy's done and then the doctor reports the findings from the liver biopsy because it's only really from the liver biopsy that the doctors can determine how much damage has been done. If non-alcoholic fatty liver disease is a disease in four stages, the fourth stage being cirrhosis, then I'm at stage three.

    Hirschfield
    When your doctor diagnoses you with a fatty liver what they actually diagnose you with non-alcoholic fatty liver disease because they listen to your history because the pathologist can't tell the difference between alcohol causing fat and your lifestyle causing fat. If you look at a liver, a severe liver, with severe fatty liver it's greasy and that's what the pathologist sees, they see fat deposits, they can actually see them, we actually ask our pathologists - how much of this is fat, how much is inflammation and is there scarring, is there already signs of damage - and if there is then of course we're very worried about that group and that's the group we want to really focus in on.

    Hubscher
    Please come in Mark, take a seat. I'm currently looking at a liver biopsy slide under the microscope which I can discuss with you.

    This injury is an important...

    Porter
    Stefan Hubscher is Professor of Hepatic Pathology at the University of Birmingham.

    Hubscher
    I'm looking down the microscope now at a piece of tissue that's been obtained from a middle aged woman who is overweight. She was found to have abnormal liver blood tests and a sample of tissue has been removed to see what structural changes are occurring in her liver.

    Porter
    I mean the obvious thing to me is it's like a pink strip, maybe a quarter or a third of the area's taken up by what look like poached eggs actually.

    Hubscher
    Yes that's right. So in fact what's happened here is that this person has got fatty liver disease and in this particular condition you can see that more or less the whole liver cell here is occupied by the simple accumulation of fat.

    Porter
    Now is this fat inside the liver cell then or in between them?

    Hubscher
    No it's inside the liver cell itself.

    Porter
    I'm looking at this liver, there's quite a lot of fatty change to my mind, can you tell what's caused that?

    Hubscher
    No, for the majority of cases we can't. It's interesting that the full spectrum of fatty liver disease is remarkably similar, both in people who drink excessively and in people overweight.

    Porter
    So what you're saying Stefan is if I was to give you a slide of a liver that showed fatty change but not give the story behind it, in this case we know this woman is 40 and is overweight, you wouldn't actually know whether this was caused by dietary or lifestyle measures or whether it was caused by alcohol?

    Hubscher
    That's right, yes. What I could tell you in that hypothetical scenario is that this person has got fatty liver disease and I could give you information about its severity and how advanced it was but in the majority of cases I would not be able to tell you which of the two main risk factors had caused the damage.

    Porter
    And that's because essentially the liver is responding to these insults in the same way.

    Hubscher
    Yes certainly in terms of the structural changes that occur within the liver, the two diseases are remarkably similar.

    Hirschfield
    So the liver is really clever but it's also really stupid. You can kick it in the teeth in many different ways but it expresses that injury in the same way. And so inflammation is inflammation and so when it comes to alcohol and non-alcoholic fatty liver what you see is fat deposits and you can't tell where those fat deposits were triggered. We don't really understand why only one in six people who drink to excess get alcoholic liver disease but the pathway that they follow is very similar to fatty liver - fat deposits, fat plus inflammation - and it's this business that there are lots of common pathways into liver injury but there are only very few exit strategies for the liver and that's one of our challenges is that lots of things will cause liver inflammation but they all go down this pathway of fibrosis - scarring - scarring eventually can become cirrhosis, cirrhosis eventually is the soil for liver cancer and for liver failure.

    Porter
    Back in the fatty liver clinic, Dr Phil Newsome has looked at what happens when GPs turn up an abnormal liver function test - often in an otherwise healthy individual.

    Newsome
    One of the things I've gathered from speaking to general practitioners is that they often check a liver function test in these patients, they come back abnormal and then the default is to re-check them and this results in a spiral of re-checking and the reality is that in many cases they stay abnormal. So the notion of repeating of blood tests is often not particularly helpful because you're likely to find the same thing.

    Porter
    So what you're saying is doctors get a result, it's abnormal, and say oh we'll just check it's abnormal again in three months or whatever?

    Newsome
    And that's human nature but I think if we're going to believe research then I think that would suggest that that's not the right thing to do.

    Porter
    Rather than repeating the blood tests in the hope they will return to normal, we should be taking a closer look at the results to see if they fit established patterns suggesting a more serious problem. It is these patterns, rather than absolute levels of individual markers, that matter most.

    Hirschfield
    Your liver sits under your ribcage but there's lots of metabolic processes going on all the time and some of those enzymes leak out and if the liver's inflamed more of those enzymes leak out. And what your GP can do and what your local lab can do is measure those enzymes and the pattern of those changes in those enzymes is like a roadmap for a liver doctor - if certain enzymes are high they think the liver cells are inflamed, if other enzymes are high they think the bile ducts are inflamed. And they put those together to work out how to identify what kind of disease process you've got. Usually you've got no symptoms but you've got slightly elevated liver enzymes but the really important thing for patients who really worry about the number is that there isn't really a numerical relationship, it's more - it's the opening of the door so that you can work out what's going on, it's pointing your doctor in the direction of the right tests. It's not saying just because your one enzyme is 200 that it's 200 times worse than if someone else's was one, it doesn't mean that, it's a flag. So patients should try not to worry too much about the number but see it as their opportunity to work out the problem.

    The next test that I like to do that brings things together is I like an ultrasound of the liver and that's really, really simple, easy but very helpful - I want to know what the liver looks like, does it look smooth, does it look rough, does it look scarred? And in addition to that when I look at the ultrasound I'm not just looking at the liver, I'm looking at the spleen because everything's plumbed together - if the liver is inflamed and scarred, the blood can't get through the liver correctly back to the heart, there may be scarring in the liver, the blood's got to get back to the heart someway, so it basically goes backwards, if it starts to go backwards the spleen gets bigger and that to me is a sign that maybe they've got liver disease that's significant.

    Porter
    When you look at the liver on a scan can you tell what sort of insult it's had?

    Hirschfield
    Not specifically but you can get an idea of the severity of the insult. So there are different kinds of scans nowadays, so obviously there's the classic radiology scan - so that's an ultrasound, a CT, an MRI scan - and that tells us how big the liver is, is it large, is it greasy, is it fat, is it very knobbly and small and scarred and at those spectrums it's quite good. We sometimes now, wherever possible, do other sort of tests of liver scarring, something called a fibroscan where we actually see how stiff the liver is, because that's another way of seeing whether there's any liver scarring. And you'll increasingly find that our colleagues certainly in our unit and many, many colleagues around the country have fibroscans in their clinic and will do a fibroscan in clinic and tell you immediately whether or not there's the potential that you've got liver scarring. And there's even the concept that maybe one day that could be done in the general practitioner's sort of office as well.

    Actuality - Maria
    I'm Maria and I'm just going to do a quick scan on you. Okay? So pop your arm above your head for me, I'm just going to quickly examine you. So a bit of cold jelly, like you're having a baby scan.

    Porter
    Better not be pregnant. It's just like someone flicking you...

    Maria
    It is, it is, yeah.

    Porter
    The Fibroscan looks at how the liver responds to a series of shockwaves and the results are averaged out to give a single score - the stiffer the liver the higher that resulting score.

    Are you taking 10 from different parts of the liver or the same?

    Maria
    The same.

    Porter
    The same - and take the average of the score.

    Maria
    Yes.

    Porter
    Phil's scratching his head at the back there. What does it look like?

    Newsome
    So around a score of seven to eight would be normal, so 6.9 is fine. And there are other aspects of the test which we look for and they're all fine as well, suggesting it's a good reading, which is very reassuring.

    Porter
    And in terms of the high score - how high can it get?

    Newsome
    We've seen scores of up to 60 and 70, that's in patients that have got quite advanced cirrhosis.

    Porter
    But at 50 my liver's normal at the moment?

    Newsome
    Correct.

    Porter
    Hurray.

    Dr Phil Newsome and the team at QEH in Birmingham. And just to be clear - that is my age, not my Fibroscan score!

    And talking of age - if I lived in America I may soon be having a test for another threat to the liver that can also lie hidden for years. The Centres for Disease Control and Prevention (CDC) wants to offer everyone born between 1945 and 1965 - the baby boomer generation - a one off test to see if they are carrying hepatitis C. A blood borne virus that typically causes a slow burning infection that can lead to cirrhosis, liver failure or cancer, 25 years or more after you catch it.

    Bryce David Smith is Lead Health Scientist at the CDC.

    Smith
    In the United States baby boomers are at particular risk for hepatitis C, our evidence shows that about one in 30 of them have been infected over their lives but the vast majority of them don't know it. So that means that more than two million US baby boomers are living with chronic hepatitis C, baby boomers are five times more likely than other adults Americans to be infected but problematically most are unaware that they're affected. We estimate that anywhere from 50-75% persons who are infected are unaware of their status. They've been infected for as many as 20-40 years or longer which means that the disease that they've had has existed silently in their body, doing damage to their liver over an extended period of time.

    Porter
    Bryce, how would baby boomers have caught the hepatitis - what puts them at particular risk?

    Smith
    Well there are probably a couple of primary things that really put them at risk. One is that during the '60s and '70s injection drug use was a somewhat more common activity and something that persons may have tried even just once and even if you were to have injected drugs just on one occasion it's still quite possible that someone was exposed to hepatitis C. It's also through blood transfusions in the US prior to the implementation of universal precautions July of 1992, it's possible that persons were exposed to hepatitis C, people may actually be unaware that they even received a transfusion, so often times persons believe that they've had no exposure yet there are still infected.

    Porter
    So how big a problem is hepatitis C here in the UK? Dr Kosh Agarwal is Consultant Hepatologist at King's College Hospital in London.

    Agarwal
    I'm not sure we really know or we have accurate data. The data we do have from the Health Protection Agency suggests that there are between 200-250,000 infected with hepatitis C and that would equate to between point five of a per cent of the population in the UK. My personal feeling is that you could probably double that number, the reasons I would say this is that we have more accurate data from Scotland, who've been much more organised in looking at the public perspective of hepatitis C and they have about a one per cent prevalence rate of hepatitis C in those patients that they diagnose. I think the other issue is is that with all of this data that's produced there are invisible populations and those are the populations where I think it's likely that we'll see more disease. We're talking about patients who aren't going to their GP, who may not have a GP, who sit underneath the radar with regard to healthcare as being a primary issue and therefore aren't ever being seen in a healthcare environment. And the last thing I'd say to this question would be is that even those patients who we think have hepatitis C who are out there we're probably diagnosing no more than 30% of them. So we're not identifying those patients, the messages aren't there for public health providers and GPs, the services aren't there and most importantly we're still not very good at getting the population and potential patients access and diagnosis before we even think about curative treatments. So the issue is is that there's an under-recognition of hepatitis C generally in the UK and in sort of Northern Europe.

    Porter
    Do you think we should follow the Americans and offer a similar testing programme here in the UK?

    Agarwal
    I'm not sure, I think that in the UK we see patients who are of a younger age, who have a more recent history of exposure to hepatitis C, predominantly related to IV drug use, who are not being identified and diagnosed.

    Porter
    Do you consider baby boomers per se as a cohort to be at particular risk from hepatitis C?

    Agarwal
    That's a good question. I think that there's a balance risk - I think they do have a risk but I think that I would focus on those more vulnerable populations and those particularly I think for the UK it's a younger population who have a more recent history of IV drug exposure or recreational drug use who are coming through into drug and alcohol and other service settings - those groups of patients should be targeted for screening in my personal opinion.

    Smith
    What we estimate is that this testing could identify over 800,000 additional baby boomers with hepatitis C who are currently unaware of their infection and avert up to 121,000 deaths. What we're hoping is that it would become a routine, one time setting, within primary care, routine family practice type settings, very similar to just other sorts of screenings that are a standard part of medical care for all baby boomers in the US like colonoscopies and mammograms, so it's just something that would happen almost automatically. The difference is that hepatitis C testing - once someone's been found to be negative, if they don't have any other exposure risks and it's very unlikely that they do, they probably don't need to be tested again, so it's really just a onetime test. Treatment also has become dramatically more effective just in the past year, is that there are new medications that are available, that I refer to as direct acting antivirals, that have increased the effectiveness of treatment overall and so many more persons now are able to benefit from treatment. Once treatment has been effective we find that the risk for liver disease, things like liver cancer, drop dramatically.

    Agarwal
    Right now we're sitting at a stage of our development of treatments for hepatitis C where we can now think about treating patients and curing them with much more effective and useful treatments that are NICE endorsed with response rates in the more difficult to treat populations of over 70%. The issue is not that we don't have good treatments for hepatitis C now, we have those treatments, the issue is about patients' awareness, education and referral to specialist centres so they can have a cure of their hepatitis C to stop them developing the complications of liver disease and the burden on our healthcare resources that operations such as liver transplants bring.

    Porter
    And presumably the earlier people like me test for hepatitis C, pick it up and refer the patients on to you the better in terms of outlook?

    Agarwal
    Absolutely, no issue.

    Porter
    Dr Kosh Agarwal. And if you would like to know more about who is likely to be most at risk of hepatitis C, and how it can be picked up and treated - there is a useful link on our website. As well as more information on fatty liver discussed earlier in the programme. Go to bbc.co.uk/radio4 and follow the links to Inside Health.

    Normal service resumes for next week's programme when we will be looking at how the internet is being harnessed to improve emergency stroke treatment - and I visit a hand clinic to find out about the latest treatments for Dupuytren's contracture. Something that 1 in 10 of us develops at some stage during our lives - a gift from our Viking ancestors. Join me next time to find out more.

    ENDS

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