Hepatitis C has a cure, but how do we find those who need it? Patrick Strudwick reports on one attempt to identify some of the estimated 100,000 undiagnosed people in the UK.
A young woman — jeans and boots and wild hair — is sitting in a cubicle in the Accident and Emergency department of the Royal London Hospital as a junior doctor swishes back the curtain.
“I’m just going to take some blood,” says Dr Emma Wallis.
“Just one?” asks the patient, spying the paraphernalia.
“Well, we’ll take a few bottles because you’ve had some palpitations so we need to test your kidneys, thyroid function and blood levels in general. Then this week in A&E, we’re offering everyone the chance of having an HIV, hepatitis B and hepatitis C test. Is that ok?”
The young woman looks confused and mildly irritated.
“I don’t like having blood taken as it is, one is enough, are you going to take loads?”
“No, it’s really easy, just one blood test, then we fill up the bottles and it’s just that much — ” the doctor pinches about an inch ” — extra blood needed. You wouldn’t notice it at all.”
“Yeah I don’t mind, yeah, ok…”
Wallis pulls out a syringe, siphons the blood and, with only that small amount of time and effort, adds one more patient to a landmark project that could change how we respond to the three of the most common life-threatening viral illnesses.
The pilot project involves offering this triple test for a week to all patients already having blood tests in ten A&Es in England and Scotland. It seeks not only to find undiagnosed people, but also to provide a crucial snapshot of how many, and who, might be living with HIV, hepatitis B and hepatitis C. Are the carriers in the populations we expect? Are the existing assumptions about the numbers affected correct? Or is there, as suspected by some, many more people affected, and in unforeseen groups?
This is the front line in the fight against viral disease. And, for one of these viruses, this comes at a critical point in its history.
Hepatitis C — dubbed the slow, silent killer because it can cause chronic liver disease that progresses insidiously, unnoticed for decades — is now within our sights. Just 25 years after the discovery of the virus, we have a cure. In fact, we have several.
With their minimal side-effects and vastly reduced treatment duration, the new drugs offer a dramatic contrast to previous medication, and are what many would call a miracle. Their existence makes hepatitis C the fastest viral disease ever to be identified and cured, and indeed the only chronic viral illness that we can currently rid people of.
Science has succeeded: a disease that affects over 200,000 people in the UK and up to 150 million worldwide could, in principle, now be eradicated.
But this is not a story that ends with scientists punching the air and popping champagne corks. It is also one of doctors’ frustration and desperation to find the infected, to implement this miracle and wipe out a pernicious virus — all while fighting the politics, economics, ignorance and apathy that hold them back.
It is a busy afternoon in the Royal London’s Accident and Emergency department. Cubicles are filling up, trolleys are trundling back and forth, phones are ringing alongside the clatter of clipboards and squeak of whiteboards. This week, 13 — 20 October 2014, there are posters up around the department notifying patients about the triple test being offered. The project is called Going Viral, and is the brainchild of Dr Chloe Orkin, a Consultant and Honorary Reader in HIV Medicine at Barts Health NHS Trust. We perch in the waiting room, on the second day of the project, to discuss her idea.
“Last year I led an HIV testing campaign called Test Me East, testing in the outpatients [departments] and A&Es across six hospitals. And I was standing there, speaking to patients, and saw the liver doctors walking in and out of the clinic. I thought, ‘We’ve missed a trick here, we should really be testing for hepatitis as well.'”
This was not simply a hunch. There is a huge data gap with hepatitis C. “It’s not tested for antenatally,” she says — unlike HIV and hepatitis B — although, in some parts of the UK, women from high-risk groups are screened antenatally. “People like to say that hepatitis C is something only found in people who inject drugs, but actually there are a whole lot of other populations who are at risk.”
Only in recent years have doctors realised that the hepatitis C virus (HCV) can be sexually transmitted. As it is carried in the blood but not, in significant amounts, in semen and other bodily fluids emitted during sex, the risk of transmission during sex was presumed to be negligible. That was until patients who had never injected drugs started testing positive.
Rougher sex, anal sex and the sharing of sex toys, especially among people who are also infected with HIV, make sexual transmission possible. One can also pick up the virus, which is ten times more infectious through blood-to-blood conduct than HIV, by sharing razor blades or even toothbrushes. The virus can exist on surfaces outside the body for a few days, and even weeks within syringes.
It is thought that in the West, hepatitis C is most common in those who have shared needles, or who received blood transfusions or tattoos before the virus was discovered. In low-income countries many transmissions result from unsterile invasive medical treatments. Babies everywhere can inherit it from their mothers.
Estimates of prevalence across the globe, therefore, vary wildly — from around 1 per cent in the USA and lower still in Britain to 10 per cent of 15-to-59-year-olds in Egypt. (Egypt has the highest prevalence in the world — a legacy, it’s thought, of a campaign of injected treatments for a disease called schistosomiasis, run between the 1950s and 1980s.)
There are six major variations of HCV, called genotypes. Some 46 per cent of infections globally are of genotype 1 (the most difficult to cure); in many parts of Europe and the Americas, this is even higher.
After infection, an acute stage of disease is followed by a chronic stage for approximately 80 per cent of untreated carriers. The other 20 per cent naturally cure themselves.
Chronic infection can lead, after years or sometimes decades, to problems: inflammation and then scarring (cirrhosis) of the liver in a third of patients, liver disease in a fifth of patients and, in a small minority, liver cancer.
A common symptom before and during liver damage is exhaustion, sometimes coupled with depression, digestive problems, skin conditions, sleep problems and pain, whose causes can often be misattributed. This, together with the fact that many remain asymptomatic for years, has led to its ‘silent killer’ tag. Around 350,000 people die globally each year because of hepatitis-C-related liver diseases.
For those in whom the disease progresses, it is debilitating — leaving many unable to work or look after themselves — before it potentially becomes deadly. Many people are diagnosed late, once there is already organ damage. Treatment can be more difficult in these cases, and a liver transplant may be the only option. The prognosis can be bleak.
It is not surprising, given the profile of the virus, that Dr Orkin included it in her Going Viral test. After just the first day of screening, she is quietly optimistic about the project. “I came in in the morning and the charge nurse said, ‘Eight people had blood tests and eight accepted [the triple test].'”
Orkin expects around 60 per cent of patients across the ten A&Es — five in London and others in Essex, Leicester, Leeds and Glasgow — will consent. This would amount to about 2,000 results, a sufficiently significant figure to provide a telling glimpse into an untold reality. A glimpse, Orkin thinks, that will be particularly useful because it will tell us which kinds of people are affected.
“One in four of us will visit A&E every year,” says Orkin. “And there are people that attend A&E that aren’t covered by GPs — for example migrants who don’t have any healthcare. We know A&Es are disproportionately used by the most disadvantaged 10 per cent. So we can pick up a cohort that isn’t covered by the GPs… and it covers the population in terms of age range very well and in terms of gender and ethnicity.”
About half of the 200,000 people in the UK believed to have chronic hepatitis C are currently undiagnosed, compared to under a quarter of HIV carriers who are undiagnosed. And one of the key problems, says Orkin, is that we don’t know where these people are, and in what populations. She also believes that we are “grossly underestimating” rates of hepatitis C. The snapshot provided by Going Viral could be a wake-up call for policy makers, practitioners and the public.
The number infected, she says, could be between 1 and 4 per cent of those tested. Taking the direst end of this prediction and assuming this cohort is representative of the population, these figures would mean there are not 200,000 but 2.6 million people living in the UK with hepatitis C.
But knowing the true scale of the problem could be daunting. “People are scared of this dataset — if we show that by screening we could diagnose so many hepatitis C patients, are we going to have to treat all these people? The drugs are hugely expensive.” But as Orkin points out, the benefit of screening is not only to find people in order to treat them, but also to give them the chance to make lifestyle changes that will protect them and others at risk of being infected.
People can also change their drinking habits, which massively affect the progress of hepatitis C, Orkin says.
We head back among the patients in A&E. I follow a nurse into a cubicle where a 30-something man has just consented to the triple test. Why did he agree?
“Because you never think about these things,” he says. “But it’s a good opportunity to have this test.” He was a little hesitant at first when asked if he wanted it. “But then I thought about it and said ok because you’d need to go for a GP and be referred for these things.” He has never had a test for any of the viruses before and never been offered any, but, encouragingly, has read about them and knows of some of the symptoms.
We walk round the corner and find a woman, around 40, lying on a bed. She’s just had the test. “I thought I may as well,” she says, as her partner sits listening. “Not that I think for a moment that I need it. I didn’t take offence but I think some people might be a bit stunned by it.”
“If you’ve got a multicultural hospital, you’ve got a lot of immigrants, they might be more at risk, so I think it’s more important that certain regions offer this service,” she says. Indeed, the hospital we’re in, the Royal London in Whitechapel, east London, serves one of the most ethnically diverse populations in Britain.
It is the case, as Orkin points out, that 96 per cent of known hepatitis B cases are in people “who were infected outside of this country”. But question marks exist over who else might be undiagnosed. And with the huge amounts of missing data for hepatitis C, it is impossible to know which groups are at risk — which is partly the trigger for the project in the first place.
Not all the patients we observe give their consent. One young pregnant woman, rushed in with severe sickness, feels too queasy to spend even a few seconds more having blood taken, but she thinks that the screening is a great idea nonetheless and would also like to see the triple test available in antenatal clinics.
But how manageable it is for health practitioners in a busy A&E to offer this extra service with all the many more pressing priorities? “It’s really simple,” says Jamil Khodabaccus, an Emergency Department Assistant, who does a lot of the blood testing in the unit.
“All you need to do is get approval from the patient, which is easy. It’s just one question and one more vial.” Indeed, having previously worked on Test Me East, where only the HIV test was offered, Khodabaccus finds it easier to offer patients a three-in-one. “It’s the way of presenting it that causes less anxiety to patients. The first one we did people were scared when they heard the word HIV.”
Awareness and fear, he says, are markedly different between HIV and the hepatitis viruses. Patients will sometimes request an HIV test in A&E but people never ask about hepatitis B or C, he says. “It’s a question of education — all these years we’ve heard about HIV.”
All the patients screened during Going Viral will be phoned two weeks later if any of their results are positive, before being invited back in and connected to the relevant clinic for treatment.
One other person I meet in A&E is the former Radio 1 DJ Tim Westwood, 57. As a patron of the Hepatitis C Trust, he’s visiting to witness the Going Viral project first hand.
“My mother had polio and now polio is extinct in the Western world, and if we could do the same with hepatitis B and C… I’ve known a lot of people with that disease. It’s so important we try and wipe this disease out,” he says. “It’s achievable if the will is there and people get themselves tested. We need to seize the moment.”
But when I ask if he’s ever had a hepatitis C test he looks rather sheepish and admits he hasn’t. Maybe it’s time you get one? I suggest. With that he agrees, walks into a cubicle and holds out his arm.
Downstairs in the HIV/genito-urinary medicine unit I meet Peter Martin, one of Orkin’s patients. This summer he joined a trial for MK-5172 and MK-8742, one of the new wonder drug combinations for hepatitis C (produced by Merck). He’s 49 and an artist and photographer. Smartly dressed in a shirt and tie, and softly spoken, he seems in good health. It is a dramatic, sudden change from just a few months ago before the treatment, he explains.
“I was diagnosed over 20 years ago,” he says. “I didn’t feel very well, I was living in Spain, went to a GP who sent a blood test for me and it came back positive for hepatitis C. I was very tired, lethargic and that was it. They didn’t have anything to look after me so we came back to London — me and my wife.” His wife, Laura, also tested positive for the virus.
“My wife got very ill and was treated several times [on interferon and ribavirin, the older drug combination] and she couldn’t cope with the medication so I was immersed in looking after her.” Over ten years, Peter looked after Laura during three bouts of treatment. So involved was her care and so frail was her health that Peter felt unable to seek treatment for his own infections, as he needed to be well enough to nurse her. It also meant he could see exactly what effect the drugs can have.
“It frightened the life out of me: massive depression, no will to live, loss of weight, nausea, pain, like a person who’s about to pass away. It was prolonged.” And then five years ago, after the agony of treatment, it finally failed, and her liver broke down. Laura died.
“By the time she passed away Dr Orkin was apprehensive about giving me the old treatment because I’d had hepatitis C for a long time. More than anything we were afraid of the depression. I’d just made a huge effort to come back from my girl passing away and I was still…” Peter stops and gathers himself, before looking up again.
“We were teenage sweethearts, we’d never been apart, it tears half of you, just like that. We did some scans of the liver, there was damage there already, and this new treatment was hanging on the door, so she thought we might just wait to get me on this trial.”
By July 2014, when the trial began, Peter was in a terrible state. “I was very depressed and already suffering the effects of hepatitis C on the body. It’s very gradual, you don’t realise you’re losing all your energy.
“The last year I was in bed, no will to get up, pain around this area,” he gestures to his side near the liver. “Very debilitating. I had people coming over from abroad to be with me, people staying with me constantly, meals being prepared for me. It robs you of everything.”
He began taking the daily pill.
“The only effects I could feel were a very drastic improvement within two weeks. The inflammation went down, it’s absolutely amazing. My energy began to come back.”
Now, he has completely cleared the virus and feels 90 per cent better. “I haven’t felt like this in ten, maybe 15, years. It’s such a strange thing to go from being depressed to how I feel now, in such a brief period of time. Like I’ve just woken up.”
Although he is recovered, Peter is left with a horrible sense of loss — and not only because his wife died. “I’ve lost at least ten years. I need to face that.”
Richard (who prefers not to be identified) is 31, a highly active, educated man who runs his own business. He is HIV-positive and caught hepatitis C in February 2014 from a rougher-than-normal sexual encounter. He was diagnosed in April, during the virus’s six-month acute stage.
When we meet he is 18 weeks into a 24-week course of interferon and ribavirin, which involves twice-daily pills and weekly self-administered injections.
“[Side-effects] only really kicked in after a month and then it was a fairly slippery slope — it went down and down. It was tough. The doctor said about 5 per cent aren’t affected, 5 per cent are severe — suicidal — and in the middle is this massive grey area, a spectrum. I had moments where I would be sitting watching telly — nothing emotional — and just uncontrollably break down into tears. The toughest was always the Saturday as I would do the injections on the Friday night to avoid it impacting work.”
He’s never had depression before. He stopped drinking alcohol altogether, and started going to the gym, to try and boost his mood, but it was the loss of energy that was the hardest to deal with. “Being self-employed I didn’t have the option of slowing down. I would get to Wednesday afternoon at 3pm and would just have to go to bed.”
Richard also suffered from insomnia — another common side-effect — and would wake up two or three times a night, further exacerbating his low energy and mood. Three months into treatment he started having breathing problems, caused by a drop in haemoglobin, the protein that carries oxygen in the blood.
With the end of treatment in sight and the side-effects stabilising, Richard is coping. But the scale of the challenge comes sharply into focus when he compares treatment for hepatitis C with drugs he takes for HIV. “I’ve gone through having HIV, a pill once a day, no side-effects, and now experiencing the toughest lesson of my life.”
Richard has private healthcare and asked his provider if he could have access to one of the new treatments. He was advised that it would be possible if his doctor could make the medical case for this. But there were two issues, he was told: first, for those in the initial six months of infection, the success rate of the old treatment is 95 per cent.
The second was caused by another data gap. “The doctor said, ‘There are no studies for your stage of disease development to justify the use of this very expensive drug. The only medical cases I can refer to is people who have chronic-stage disease.'”
And so we arrive at the other two frontiers in the fight against hepatitis C: money and politics.
On 10 October 2014, three days before Going Viral started, the US Food and Drug Administration gave approval to Harvoni (ledipasvir and sofosbuvir), the first single-pill treatment for the common genotype 1 form of hepatitis C, produced by Gilead. Harvoni currently costs $US94,500 for a typical 12-week course — $US1,125 per pill.
In England, the National Institute for Health and Care Excellence has approved the use of Sovaldi (sofosbuvir alone, also made by Gilead) for hepatitis C. Even though England is getting the drug at a discounted price — £35,000 (about $US54,000) for a 12-week course rather than the $US84,000 wholesale price — the cost is causing delays.
NICE is allowing NHS England to postpone implementation for 180 days rather than the standard 90, which means that the drug is unlikely to be available widely until the end of July 2015.
Such prices for treatment are likely locking out patients with hepatitis C around the world — for the time being at least.
The economic barrier was one unforeseen by the virologist who co-discovered hepatitis C in 1988, Professor Mike Houghton. “It’s very frustrating,” he says, on the phone from the University of Alberta. “It’s very frustrating for all of us in the field to have come up with a cure after 40 or 50 years of research, a great achievement, and now we can’t get it to all the carriers because it’s too expensive.
“It’s no longer a research challenge, it’s a political/economic challenge.”
However, Houghton does not blame Gilead, as the price is not what it seems. “They have produced a very potent pill and many patients are going to be cured within two months — some three months.” This new treatment is actually cheaper.
He points out that although the price for interferon and ribavirin was around $US50,000, it was less effective — “a cure rate of 50 per cent” — so it works out as “$US100,000 per cure”. If patients are cured in 12 weeks on Harvoni, it would work out at about $US94,500 (and just $US63,000 if achieved in 8 weeks). “And it cures virtually everybody.”
The price is already falling as other drugs are soon to come on to the market — including Merck’s combination. But still many governments could not afford to treat all their citizens infected with hepatitis C. It would cost trillions, globally, to wipe out hepatitis C using the new medications, says Houghton. So, he has another idea.
“Many of us think this whole debate about hepatitis C drugs is initiating a new concept and that is: rely on the private sector to come in with the first waves of drugs — like Harvoni — but then it’s economical for the governments around the world to develop a novel set of drugs themselves.”
The reduction in cost could be immense. Otherwise, in the UK alone, it would take billions to treat everyone who has hepatitis C. “Why doesn’t the EU get together and make its own drugs? £500 million can treat all their carriers in seven or eight years, at cost.”
There are many barriers to governments or the EU doing this: notably, lack of political will and lack of public pressure, two sides of one coin — one that was spun to great effect during the AIDS crisis.
“HIV advocacy groups were blocking the Bay Bridge and the Golden Gate Bridge,” says Houghton. But no such equivalent patient force exists around hepatitis C — in part he says, because of the demographics of the disease.
The result of a failure to create a new model to pay for treatment is, says Houghton, not simply that people like Richard continue to suffer toxic, traumatic side-effects for months on end. “If you just reserve those [new] drugs for the most ill patients that’s not the most effective way to eradicate the disease — the longer you wait the greater the risk of the patient developing liver cancer or end-stage liver disease. And you leave them infectious.”
Like Orkin, Houghton is convinced screening, which costs around £7 per test for hepatitis C, is vital. “It’s crystal clear: with HCV you have to identify the carriers first of all — good community screening is essential.” But, he thinks, even in the UK, with its comparatively small infected population, eradication will probably take many, many decades.
In the meantime there is another hope: a vaccine. A phase II efficacy trial is underway in Italy, and Houghton is also working on a separate vaccine in Canada.
The urgency of the need for both vaccine and cures is increasing, as fears grow around hepatitis C blooming as a sexually transmitted infection.
“For many years I saw the data and concluded it was not sexually transmissible but now the new data says that [for] men who have sex with men, some of them are at risk from the sexual transmission of HCV. Especially if they are co-infected with HIV.
“I get the feeling HIV is on the rise again because people are feeling, ‘Well, I’m not going to die from it because there’s therapies,’ so I think there’s a relaxation going on in the community. [But] everyone needs to be vigilant.”
Two weeks after Going Viral finishes, the data is back. Orkin agrees to release to me two days’ data, from the A&E department I visited; she will present the complete findings later this year in medical journals and conferences to trigger follow-up studies.
On those two days, 57 and 59 patients who were having bloods taken at the Royal London A&E consented to the extra triple test — a take-up of about two-thirds. On the first day, one patient tested positive for hepatitis B, unaware they had it. One patient tested positive for hepatitis C and one for HIV, but both already knew their statuses. On the second day, one patient was diagnosed with both HIV and hepatitis C, unaware they were carrying either.
These results are, of course, a snapshot of a snapshot, but if we take the figures for hepatitis C and scale them up, it would look like this. Two patients out of 116 is 1.7 per cent with hepatitis C, within Orkin’s prediction of between 1 and 4 per cent. And if we assume — for the sake of scale if not accuracy — this was a representative sample of the UK population, this would mean 1.1m people with hepatitis C — about five times the current estimate. Orkin, who has analysed the complete data, will tell me only that the overall results are “significant”.
I consider again the patients I met and the clinicians doing the research. All are unified by one belief: the need to test. If we cannot yet work out how to pay for treatment, if we suspect more transmissions are occurring from sex, if we know that screening can help prevent further transmissions and further liver damage, what then is it going to take for governments to try and find out who has the virus? A sudden outbreak like HIV or Ebola? An orchestrated campaign by people with hepatitis C? Publicity from celebrities who are infected? (Pamela Anderson and Marianne Faithfull are the best-known of very few who have ‘come out’ about their illness.)
The stigma is certainly not helping — Richard felt more stigmatised by hepatitis C than HIV — but it is apathy that seems to be the biggest constraint on action.
As accusations mount over the neglectfully slow reaction to Ebola, the death toll of which is dwarfed by that of hepatitis C, we are turning a corner for that virus. The press and public have been galvanised, forcing the hand of at least a clutch of governments, all terrified of the killer virus spreading.
But HCV is a slow killer; it creeps, quietly. In a media age, in a world that reacts to the dramatic, the instant, hepatitis C will, if we let it, shame us. If we do not take Orkin’s radical testing ideas into wider arenas and search out affordable drugs, HCV will paint us as the proverbial frogs in hot water, sitting unaware as the temperature gradually rises and, with it, the death toll.
This article first appeared on Mosaic and is republished here under Creative Commons licence.