HCV: On the road to global elimination

By Lloyd Mudiwa24th June 2016

In one of the greatest success stories of medicine, the elimination of hepatitis C is now firmly in sight, RCSI alumnus and Harvard’s Prof Nezam Afdhal tells Irish Medical Times in an interview with Lloyd Mudiwa

Since his own conferring ceremony at the RCSI (Medicine, Class of 1981),Prof Nezam H. Afdhal, Chief of Hepatology and Director of the Liver Centre at Beth Israel Deaconess Medical Centre, Boston and Professor of Medicine at Harvard Medical School, has become a leading expert on complications of liver disease and has pioneered treatments for hepatitis C virus (HCV) — a virus only discovered in 1989.

“It’s been a 25-year course where we have really gone from not knowing what the disease was to having the ability to cure it globally, and that’s one of the great success stories of medicine, if not the greatest,” Prof Afdhal toldIMTin an exclusive interview. “That, along with HIV, are probably the two biggest success stories in terms of infectious diseases that we’ve had in the past 30 years.”

Back at his alma mater this month some 35 years later as part of the RCSI School of Medicine conferrings, where he was awarded the sixth Honorary Doctorate of the RCSI, the highest academic award of the College, Prof Afdhal took the opportunity to updateIMT on his remarkable contribution to this success story: the discovery, therapy development and possibility for widespread cure of the condition in just over 25 years, which has also been summarised in his recentTEDx Oxford talk).

He Chaired the International Coalition to Conquer C, which produced an agreed global definition of HCV prevalence and burden, led the Georgia Education Program for HCV Elimination — the first large scale programme for Hep C elimination through therapy, and led the global hepatitis C team that developed Harvoni; a new treatment that can cure 97 per cent of all the 200 million patients worldwide.

Prof Afdhal told this publication that massive changes were taking place in the care of hepatitis C, including in Ireland, which was now part of this “whole global awareness and treatment that’s taking place in Hep C”.

Non-A non-B hepatitis
Prior to 1989, the virus was known by its consequences if not its cause, and was called non-A or non-B hepatitis. It was the commonest cause of what experts felt was blood transfusion affiliated hepatitis, he said, citing the case of Irish women who got Hep C from anti-rhesus immunoglobulin as part of that transfusion associated hepatitis.

“At the time that they were infected they got non-A non-B hepatitis and then subsequently, using a very sophisticated molecular genetics approach, the hepatitis C virus was discovered.”

Researchers have worked globally over the past 25 years to understand Hep C and they soon realised that up to 200 million people worldwide were infected with what they first felt was just a rare disease associated with transfusion.

They recognised that Hep C was the most common cause for cirrhosis, liver failure, liver transplant and liver cancer.

“So we began to recognise that it was a very common disease and that it was a disease with a very high burden of morbidity and mortality for liver diseases,” Prof Afdhal said.

In some countries the prevalence was “extremely, extremely high”, such as Egypt, where 10-12 per cent of the population has Hep C mainly related to the schistosoma endemic, also known as bilharzia or snail fever, where physicians successfully eradicated schistosomiasis from the Nile, but gave the country Hep C instead.

This was because in the 1950s and ’60s the schistosomiasis was treated by an injection-based therapy. “They vaccinated and they didn’t change the needles,” Prof Afdhal explained. “Essentially, it was iatrogenic physician associated change. It’s a fascinating story because they did so well with getting rid of schistosomiasis along the Nile Delta, but then they introduced so much Hep C into the country that the burden now is much greater than the burden of schistosomiasis ever was.”

Drug development
For many years the treatment of Hep C was “extremely poor” and people spent a lot of time treating patients with toxic chemotherapeutic-like drugs, Prof Afdhal added. Over the past 25 years, he said the focus had been to try to develop treatments for Hep C. So Prof Afdhal, working with collaborators worldwide, was instrumental in the development of some treatments which turned out to be what are now called new direct acting antivirals (DAAs).

“They are one of the most remarkable drugs in medicine because they cure 97 per cent of people,” Prof Afdhal said. “Not like HIV where you control the disease, but you actually treat people and you cure them and the treatment course is as short as eight weeks.

“We did the research for many years. The drugs were approved in 2013 and already almost 750,000 people in the US alone have been treated and the vast majority of them — 97 per cent — have been cured. One of the amazing things about the drugs is they work just as well in clinical practice as they do in clinical trials. Their effectiveness in real-life is incredible.”

He added: “It was really exciting that the WHO, along with collaboration from academia and the pharmaceutical industry, is creating elimination programmes around the world and these are designed to set up the infrastructure — to identify, diagnose and treat patients on site with these drugs — in countries with high burdens of the disease. We are doing it in Egypt, we are doing it in the Republic of Georgia — where 9 per cent of its population has Hep C — and we are doing it in Mongolia, where 12 per cent has hepatitis C.”

Cost factor
These drugs are “phenomenally expensive” and this has ignited a lot of debate about the high cost of drugs. Prof Afdhal elaborated: “If you think about it 750,000 people treated at $100,000 (€88,458) a course is a lot of money. What’s happened is the Hep C treatments have caused this huge debate in the US among the healthcare systems, payers and governments. There’s been Senate hearings about this, so it’s become a very topical issue of what is the correct cost of these drugs. And the funny thing is that of all the drugs that are out there, everybody has come to the conclusion that this one is worth it because it actually cures everybody and prevents them all from developing liver cancer and needing transplantation etc.”

Harvoni, which is one of the main treatments, is €1,000 (€884.428) a day for each pill, he said, and the treatment of up to 12 weeks can cost up to €84,000 (€74,292). According to Prof Afdhal, the “real key” now is to work on strategies to make these treatments available and affordable for healthcare systems and countries in which they want to eliminate the condition.

These treatments are being given in the high prevalence developing countries by the pharmaceutical industry at an incredibly reduced price at about 1 per cent of the price in the US. In Egypt, the new price is $900 while they are free in Georgia.

Elimination programmes
“I ran a programme in Georgia, where we have just finished year one, which is a collaboration between the government of Georgia, who are incredibly motivated for this programme — 9 per cent of their population wants to be involved — along with the WHO, US Center for Disease Control and pharmaceutical company Gilead. We are building the infrastructure, we have educated the physicians using eco-based (distance learning) training to educate physicians to start treatment.

“We have created five treatment hubs in Tbilisi and this year — I’m going there next week to launch 25 treatment hubs. And the goal is to treat 50,000 patients a year for the next 10 years and eradicate Hep C from Georgia. This is the pilot programme that is looking at how best to set up these elimination programmes.

“There is only one infectious disease that’s ever been successfully eliminated with medications and that’s onchocerciasis, or river blindness, which takes just one pill and you can eradicate it. Former US President Jimmy Carter’s Foundation has so far eradicated river blindness from South American countries like Brazil, Bolivia, and they have massive programmes in Africa.

“What we are trying to do with a little bit more of a complicated regimen, but an equally effective treatment is to try to see if it can be done for another complex disease,” Prof Afdhal said.

Screening
Screening has taken off because treatment has improved, submits Prof Afdhal. “The reason why people want to screen today now is because they now have a very safe and effective treatment, whereas years ago if you were diagnosed with Hep C you had to go on a year of interferon-based therapy which was a very tough treatment that almost half of all the patients couldn’t tolerate. In some ways it was a ‘mini-chemotherapy’ and the success rate was only 40 per cent, so you can understand that there was hardly any excitement to screen when you have that. But now it’s a completely different situation.”

Hep C, which has a significant disease burden, and is seen in patients who receive blood transfusions, is “very common” in injecting drug users and there is sexual transmission of it in Ireland.

Citing Ireland’s significant hidden burden, approximately 8,000 access tertiary care in Ireland although it is estimated that somewhere between 20,000 and 50,000 people are chronically infected with the virus, Prof Afdhal said there were two ways of doing screening for Hep C.

One way involves risk-factor/disease-based screening, which is to ask people specific questions such as ‘Did you ever receive blood transfusion or have a surgery before 1990, have you ever used a form of intravenous or recreational drugs?’

A second way involved population-based screening. Prof Afdhal said in the US 75 per cent of people with Hep C were baby boomers (born between 1945 and 1965).

Thus in the US they have mandated ‘baby boomer’ screening for the virus and the screening test is a $5 antibody test — an ELISA. “It costs very little money. You only ever have to do it once,” he explained.

“Because we know our epidemiology very well in the US and we know where the disease is, that’s the rationale for ‘baby boomer’ screening in the US, which takes place at the primary care visit.”

He added: “In fact, there is a huge push to make treatment more cost-effective that actually treatment could be done in primary care. It’s not a complicated treatment: it’s one tablet once a day for eight to 12 weeks. So that’s not bad.”

In countries like Ireland where the epidemiology of Hep C was less well known, disease-based screening was preferred as it was more cost-effective, he suggested.

Finger stick test
Finger stick tests and salivary tests were being developed for the diagnosis of Hep C by identifying antibodies in either saliva or the serum and the ability to do that enabled the concept of ‘diagnose and treat’. The ability to rapidly diagnose somebody and then treat them was practical in countries where there was limited access to healthcare, Prof Afdhal said.

“The prevalence in Ireland is probably less than 1 per cent, so 50,000 people. It becomes very difficult at that level to suggest population-based screening. It’s just not cost-effective. Whereas in the countries with the high prevalence rates, you know at the 10 per cent rates, there a national screening programme is extremely cost-effective, especially if you have treatment attached to it,” he said, stressing the need to link screening to education, referral and care, otherwise it was “totally pointless”.