Get Tested For Hepatitis C! – Interview With Abbott’s Gavin Cloherty

Gavin Cloherty is associate director of scientific affairs at the US molecular diagnosis developer Abbott Molecular. Abbott has a long-standing history of developing tests for detecting and monitoring hepatitis, among other areas.

At Abbott Molecular, Cloherty works on commercial organisation of their infectious disease products, including training, establishing clinical trials and developing strategy for new product development.Cloherty previously worked in research and development and commercial leadership roles at Abbott, and holds a degree in Microbiology and Zoology and a Ph.D. in Molecular Biology National both from the University of Ireland in Galway, Ireland.

Gavin Cloherty of Abbott Molecular

The World Health Assembly last week adopted a global resolution for the prevention, diagnosis and treatment of hepatitis C, responsible for 1.4 million deaths per year. The WHO also released recommendation guidelines earlier this year for people with hepatitis C, which recommended testing populations at risk of exposure to the disease, because most people with hepatitis C are not aware of their infection.

With Intellectual Property Watch’s Julia Fraser, Cloherty discussed the burden of hepatitis C, the process of diagnosis and the importance of diagnosis for curbing and treating the disease.

Intellectual Property Watch (IPW): What is the burden of hepatitis C virus (HCV)?

Gavin Cloherty (Cloherty): The hepatitis C virus, or HCV, presents a heavy burden globally. About 150 million people – that’s a conservative estimate – are chronically infected with hepatitis C worldwide. About 20 percent of people infected with the virus will spontaneously clear it through their body’s immune system.

If left untreated, chronic hepatitis C has serious health implications. In many people, the disease can lead to fibrosis – a scarring of the liver – which can lead to cirrhosis if left untreated for a longer period of time, and ultimately hepatocellular carcinoma [liver cancer], which would require a liver transplant.

There are a lot of symptoms and morbidities that occur after infection and while ultimately progressing towards cirrhosis and cancer. Patients can develop ascites, which is fluid build-up in the abdomen, and hepatic encephalopathy, which is a build-up of toxins in the blood, which can result in cognitive impairment. Obviously, signs and symptoms vary by patient.

IPW: What is the distribution globally?

Cloherty: The hepatitis C virus is found all over the world however, the burden is heaviest in Asia followed by Africa. Other regions are affected to a lesser extent with, for example, an estimated 3 million people chronically infected in the United States. The hepatitis C virus is genetically very diverse and is classified into different genotypes based on their genetic makeup. Currently, there are six genotypes (1-6), and now we’re even seeing a seventh. These genotypes vary in their distribution globally. The most common genotype in Europe and the US would be genotype 1. In places like Egypt they are almost exclusively genotype 4. It depends on the origin of the virus and the evolution over time.

Another important factor about genotype is it’s extremely important to understand the viral genotype in order to help a physician make appropriate treatment decisions. Certain genotypes are easier or harder to treat, and certain genotypes respond to some medications and not to others. Doctors should know a patient’s genotype to determine how to appropriately personalize treatment options: how long to treat them, or what drug to put them on.

IPW: What is the process of diagnosis?

Cloherty: Once a person has been infected with the virus the body will have an immune response. The usual way that a patient would get diagnosed would be an antibody test to show if there are antibodies in the body to the virus, to see if the patient has ever been exposed to the virus.

As I mentioned, approximately 20 percent of people will spontaneously cure the virus without any medicine. As a result, it is important to find out whether there is actively replicating virus in that person before you would go through the time and expense of treating them with potentially toxic regimens. Once you’ve established that a patient has been exposed, you would then order a subsequent test such as an HCV RNA or HCV core antigen test to see if they are still actively infected.

An RNA test will give you a baseline viral load (how much RNA per millimetre is present), will tell you if the virus is actively replicating, and can then be used to determine the genotype of the patient. This gives the physician additional information to make treatment decisions.

The physician will also look for markers of liver injury: the aminotransferases ALT and AST. These are enzymes in the liver that are signatures of on-going injury. If these are elevated then they know that damage is being done to the liver which is important. Then they may do a non-invasive fibro scan to assess the level of liver stiffness and how much liver injury has already been done. These are all separate tests. There’s quite a work-up that needs to happen before you start treating a patient.

IPW: The new Gilead drug and some drug combinations work against multiple genotypes – will there be a reduced need for some diagnostic tools?

Cloherty: A very interesting topic for discussion and debate right now is with the ever-improving potency of the therapeutics where will diagnostics play a role. If you look at the most recent European Association for the Study of the Liver guidelines, they reinforced the importance of diagnostics as monitoring and measuring these markers as still quite important. As it stands, diagnostic tests are extremely important and central to the treatment of patients for hepatitis C.

IPW: How do monitoring tools work?

Cloherty: Monitoring tools measure drug effectiveness through direct quantitation of the virus in blood (viral kinetics). When you put the person on a therapy, the therapy stops replication of the virus so you want to see a dramatic decrease of the virus that’s detectable in the blood. And also a decrease over time of the markers of liver injury: ALT and AST. The endpoint of therapy is for the virus to be undetectable in the blood and a “cure” known as a Sustained Virologic Response (SVR) is considered undetectable virus 12 or 24 weeks after the completion of therapy.

Also an interesting area to explore with these new therapies is to see if looking at very early viral kinetics might segment or differentiate patients into who could be eligible for a shortened duration of therapy, or indicate which therapy might be working slightly better. This is particularly important since while these new therapies are highly effective, they can also be expensive. Diagnostics might have a role in managing these patients appropriately.

IPW: The WHO has raised some issues concerning the complexity and suitability of some of these diagnostic tools for use in low-resource settings. Is there research going into simplifying and adapting tests?

Cloherty: We are aware of the testing needs and where the majority of the patients are. We have an access programme here at Abbott Molecular to work with agencies and funders to make sure that diagnostics are not an impediment to people getting on treatment. In a similar way to HIV, where dried blood spots are being used to scale-up therapy in sub-Saharan Africa, the same approach is being discussed in groups like the WHO as to whether this approach might be appropriate for HCV as well. It is definitely an on-going discussion on what’s the best way to get access to therapeutics and diagnostics. It’s also done at a very local level because the needs of countries will vary.

IPW: What work is going on at the local level?

Cloherty: Disease state awareness and education is critical at the local level. From a technical perspective there’s a whole process very similar to the work on what’s been done with HIV. First you make sure that the technology is available and compatible with local infrastructure, and then you’ve got to field-test it. The tests are relatively simple; it’s more for the application of the technology in these resource limited settings which needs to be developed. It’s clearly been demonstrated that these technologies are adaptable to resource limited settings – you just need to look at HIV as an example.

IPW: What about the high costs of some of the tests?

Cloherty: Costs per test are worked out at the local level or with funders. There are a lot of parameters that go into costs – it’s not a one size fits all. Overall, testing is a small cost to pay and plays a critical role in determining proper treatment and management of patients chronically infected with hepatitis C. Diagnostic tests can lessen the amount of trial and error related to treatment options and ultimately get a patient on the right treatment path earlier.

IPW: What is the role of prevention such as through vaccines and awareness campaigns?

Cloherty: Campaigns to raise awareness are extremely important. In the US, there is a push to have the baby boomers tested. A lot of the challenge with this disease is that you can have it for 10-20 years and never know until you reach a tipping point and start showing clinical signs of liver disease. What drives these epidemics is a lot of people don’t know they’re infected and then they’re engaging in at risk behaviours that are driving further infections.

It’s proving to be quite challenging to develop a vaccine for hepatitis C because it’s so genetically diverse. The good news I think from a perspective of eradicating the virus is aggressively treating. As the treatment regimens become more potent and simpler, the key will be to find patients and treat them. It used to be that when you had hepatitis C you had to get on interferon-based therapies which would last up to a year. Additionally, a patient might feel like they have the flu for a year, so it was challenging to get people to sign up for that, especially when cure rates were 20-40 percent. Now you’ve got 95-98 percent cure rate of 12-weeks with interferon-free therapy, so I think it will get much easier to get people to sign-up for treatment.

Overall awareness of the disease and the need to be tested is important as the drugs get more accessible, and simpler. Overall improvements in healthcare globally will also reduce the incidence, as medical practices also get better and safer.

IPW: Thank you.

(Note: Below are key points of an Abbott campaign against HCV):

• HCV is a chronic infection and you may not know you are infected for decades.
• It is important to know your status (are you actively infected with HCV or not, what is your genotype?).
• Treatment for HCV has gotten much better – simpler, shorter, well-tolerated and with very high cure rates.
• Get tested – Get treated – Get cured!

Julia Fraser is an intern at Intellectual Property Watch. She is currently training to be a solicitor and will start work at an international law firm in London in 2015. She has a BSc Honours in Biology from Edinburgh University where she developed an interest in public health related intellectual property issues.