Improving Testing and Diagnosis of Hepatitis C with Claudia Hawkins, MD, MPH

Erin Spain, MS: A new rapid Hepatitis C test developed by Northwestern Medicine scientists could change the future of Hepatitis C care by delivering faster diagnosis and treatments for a disease that is estimated to impact 50 million people around the world. The research behind this new test, which was built on the DASH Rapid PCR system developed at Northwestern, was published in the Journal of Infectious Diseases. Dr. Claudia Hawkins was co-author of the study and is an expert in viral Hepatitis as well as Hepatitis and HIV co-infection. She is the Director of the Center for Global Communicable and Emerging Infectious Diseases at the Havey Institute for Global Health at Northwestern, and a Professor of Medicine in the Division of Infectious Diseases at Feinberg. She joins us today to talk about this study and the impact this test could have on the global effort to eliminate Hepatitis C. Welcome to the show, Dr. Hawkins. 

Claudia Hawkins, MD: Thank you very much. It's great to be here. 

Erin Spain, MS: Well, let's talk about Hepatitis in general. There's many different types of hepatitis and it refers to inflammation of the liver. So tell us about Hepatitis C and how that's different from other strains. 

Claudia Hawkins, MD: Yeah. So hepatitis C is caused by the hepatitis C virus, which spreads primarily through contact with infected blood and then infect the liver where over time, and if left on treated can lead to all sorts of liver complications starting with lymph inflammation and then scarring, which results in cirrhosis and then liver failure or liver cancer can develop as a result of that cirrhosis.Unlike other forms of hepatitis, such as hepatitis A or hepatitis E, which are typically spread through contaminated food and water, and usually cause a short term sort of self-limiting illness. Hepatitis C is often when it's acquired, asymptomatic in its early stages. And then importantly about 55 to 85% of people will go on to develop chronic infection with it.And over time, chronic infection leads to progressive liver complications that I mentioned previously. Hepatitis C is similar to another chronic hepatitis virus called Hepatitis B, and those can both cause chronic infection and liver disease. But a key difference between those two viruses is that hepatitis C can now be cured and whereas their hepatitis B antivirals usually just suppress the virus and can reduce risk of liver complications, but don't typically cure that virus. 

Erin Spain, MS: Something interesting about Hepatitis C is that it's often a silent disease. Tell me about that. 

Claudia Hawkins, MD: As I mentioned before about 50, anywhere from 50 to 85% of people who acquire Hepatitis C will go on and develop chronic infections. So i.e. their immune systems don't clear it on their own. But once that chronic infections established those liver complications don't occur for many, many years after that infection. And so that prolonged silent phase is very asymptomatic and contributes to the significantly delayed diagnosis. 'cause people don't have symptoms and so they don't get tested and they don't know about it. And it's really only after the end stage complications like cirrhosis or even liver cancer developers when people first become symptomatic. And when usually we are diagnosing these infections. Here in the US we're getting much better at testing people earlier. Partly because our guidelines now say that at least everyone should get a test at least once in their lifetime. So we are managing to pick up more early infections but still many people we diagnosed are coming in late with liver complications. 

Erin Spain, MS: So you've spent much of your career studying not only Hepatitis, but HIV and viral Hepatitis co-infection. How does Hepatitis C impact patients like those who are living with HIV and why is rapid diagnosis especially important for them? 

Claudia Hawkins, MD: So Hepatitis C has a particularly significant impact on people living with HIV because what co-infection does is accelerate disease progression and worsens clinical outcomes. So people with both HIV and Hepatitis C co-infection experience a faster progression to advance liver disease including the complications I just mentioned, cirrhosis and liver failure. And in fact, liver disease is actually responsible for a lot of the morbidity and mortality among persons with HIV and is one of the most common causes of non AIDS related deaths still in persons with HIV and hepatitis C. And persons with HIV and hepatitis C also have lower rates of hepatitis C clearance after being infected with hepatitis C. And in addition, they're somewhat of an increased risk of acquiring hepatitis C due to the overlapping transmission routes. So including things like injection drug use and high risk sexual exposures particularly among men who have sex with men. 

Erin Spain, MS: So there are vaccines for hepatitis A and B, but not hepatitis C. Why has developing a vaccine for hepatitis C been so challenging? 

Claudia Hawkins, MD: You're right, yeah, there is no current hepatitis C vaccine. And that's really largely because of the virus's extreme genetic variability. So hepatitis C exists as at least eight major genotypes with numerous subtypes, and it mutates very rapidly. And that constant mutation, generates extensive viral diversity and allows the virus to evade immune recognition and therefore making it really difficult to design a single vaccine that sort of provides a durable protection across those genotypes and subtypes. 

Erin Spain, MS: The good news is there are effective therapies for Hepatitis C. Tell me about that. How is Hepatitis C treated today? 

Claudia Hawkins, MD: Yeah, so we now have very effective therapies for hepatitis C, which are curative in over 95% of people with hepatitis C. And this sort of high cure rates came about with the introduction of these direct acting antivirals or so-called DAAs which were introduced in 2011 and really revolutionized the Hepatitis C landscape. So before that we had treatments that were what we call interferon-based treatments, which were injectable therapies. And they had to be taken over a long period of time. They were associated with a lot of side effects. And were very well tolerated, but also not very effective at clearing the virus. So after 2011, when we had discovered these new direct acting antivirals which specifically inhibit key viral proteins in hepatitis C we've started to see some significant responses in terms of cure rates. The first DAAs that were introduced in 2011, actually still included these protease inhibitors called boceprevir and telaprevir and we're still using them in combination with interferon based therapy, but we started to see very good response rates with them. And then shortly thereafter the major breakthrough came in 2013 with the approval of Sofosbuvir, which really paved the way for a fully oral interferon free treatment regimen. And these now exist in many different fixed dose combinations that we use regularly and are associated with these high cure rates over 95% in most patient populations that we see today. 

And another great thing about them is that these oral therapies are very short in duration as little as 8 to 12 weeks can completely cure the virus. 

Erin Spain, MS: But the problem remains that it is hard to get this diagnosis. Right now it's a two step process, and people have to come to a clinic and come back again. Tell me about the process right now to be diagnosed with hepatitis C. 

Claudia Hawkins, MD: So you are absolutely right. It's not a simple test. So currently hepatitis C is diagnosed typically through a two step process. So the first test we have to do is an antibody test which detects whether a person has been exposed to hepatitis C, but that positive antibody test doesn't confirm current infection; 'cause antibodies can remain detectable even in people who've cleared the virus before. So we still have to do a second step, which is the Hepatitis C PCR test, which detects the viral rNA in the blood, and if present confirms active infection in a person. At Northwestern, our hepatitis C PCR testing is automatically performed in the lab when we send down their tests for an antibody. And it's automatically done if that person tests antibodies positive. However, in many other centers and other countries PCR tests have to be performed separately. So requiring the patient to have their antibody test first, and they may then have to return later on for another blood draw to get the confirmatory PCR testing done. This delay in getting the patient back for another test or the delay in getting that result back, which is especially a problem in resource poor settings where those tests can't be done in any reasonable amount of time. During that time, patients are lost to follow up and then never receive treatment. And this is a big gap in being able to diagnose hepatitis C effectively in many populations. 

Erin Spain, MS: So enter this technology developed at Northwestern, the DASH Rapid PCR system. This was developed at Northwestern during COVID-19. Tell me about DASH and why you all decided to apply this technology to hepatitis C. 

Claudia Hawkins, MD: So the DASH PCR platform, DASH stands for diagnostic analyzer for specific hybridization was developed as an innovative point of care molecular diagnostic system designed to combine lab grade PCR accuracy with a rapid, simple, near patient testing capabilities that the traditional PCR techniques and instruments can't provide 'cause they're lab based and they're huge in size and they're complex. So this DASH platform originated from research at Northwestern's University's Center for Innovation in Global Health Technologies otherwise known as CIGHT which is headed up by my colleague, Dr. Sally McFall and her team, and was initially, as you'd mentioned, developed and deployed as a rapid PCR test for SARS-CoV-2 during the COVID pandemic. It received approval from the US FDA in 2022 demonstrating really high sensitivity PCR testing can be performed really with similar turnaround times and much more at the point of care compared to rapid antigen tests.So after this initial success with COVID Dr. McFall and her team began adapting the dashboard platform to detect additional pathogens. The really great and novel thing about DASH compared to some many other sort of point-of-care molecular tests, was that it was developed to be able to process very different specimen types, including respiratory swabs, vaginal swabs, plasma or blood for other bloodborne pathogens. And previously Sally and I had collaborated on other hepatitis C diagnostic projects, including antigen based tests that really ultimately lacked sufficient sensitivity and we didn't take any further. But then we started to discuss adapting the DASH for Hepatitis C PCR and potentially doing some validation work in Nigeria where I was working and also happened to be identifying a lot of hepatitis C there. 

Erin Spain, MS: Just a little bit more about DASH. Can you describe what the device itself looks like? It's not very big. 

Claudia Hawkins, MD: Yeah, so the DASH is sort of a small portable machine. It's about the size of a cereal box, although a little heavier and can operate obviously outside of a lab. And it's a whole sort of idea behind a point of care device. It can be operated off an external battery with an eight hour life without relying on a continuous power source. And that's obviously crucial in low middle income country settings where we have the highest burden of hepatitis C and really need this particular device. And obviously where power cuts are not infrequent. The test itself meets all the sort of key metrics from optimal point of care assay as defined by the foundation for innovative new diagnostics.  

Erin Spain, MS: So you move forward with this study and you found that the DASH test delivered results for hepatitis C in just 15 minutes, and that's up to 75% faster than other rapid HCV tests. Tell me about this result. Why is this speed so important and what was your reaction to this result? 

Claudia Hawkins, MD:  We just don't have anything that enables hepatitis C to be diagnosed in an effective, fast way that allows the patients to get the treatment they deserve. So this test really addresses a key diagnostic gap, including time to result of less than 15 minutes. Analytics sensitivity, which we just recently established of less than 200, which would pick up over 95% of hepatitis C cases. Specificity of 99% in use of capillary whole blood for determination of the virus and some integrated sample preparation that requires no precise timing or volume control. As I mentioned before, with the complexity of the testing that we have so far. There is a two step process requiring that sort of second PCR test to confirm active infection and often that is not done in real time, especially in low middle income country settings where they may not have access to a lab that can do this test or those are less accessible. More importantly, another reason why people don't get those PCR tests is just purely because of cost. I mean, right now PCR tests in Nigeria, for instance, cost about 60 per test. And you can imagine that's unaffordable for most people. So by removing the need for returning for a visit for that PCR, getting that result on the same day would enable, same-day treatment decisions much more simplify the workload and reduce much of the cost and complexity of testing and get people linked to care much faster. This will be particularly critical in low or middle-income countries, of course, where it's not just about the sort of slowness of getting that PCR testing, but it's truly the access. This will be a much cheaper way of doing it as well. 

Erin Spain, MS: You did use an independent group at Johns Hopkins to evaluate 97 clinical specimens, and then it confirmed the tests. 100% agreement when compared to the commercial platforms, that kind of independent validation, how important is that when doing these studies and introducing a new diagnostic platform? 

Claudia Hawkins, MD: Yeah, the validation work's really crucial to confirm the accuracy of the DASH test including its sensitivity and specificity and to demonstrate, when we get to the clinical studies, its performance in real world settings. But it also is necessary to support the path to regulatory approval, the WHO prequalification, and then of course its routine use and patient care. 

Erin Spain, MS: The World Health Organization has really set ambitious goals for hepatitis C elimination. How could this test help them progress towards eliminating this disease? 

Claudia Hawkins, MD: In 2016 the WHO called for the elimination of hepatitis of the public health threat by 2030 and under its Global Health Sector Strategy right back in 2016, and then updated again in 2022 they set really ambitious targets for hepatitis C, including a 90% reduction in new chronic infections and a 65% reduction in mortality. And to get to achieving those targets requires diagnosing almost everyone with hepatitis C, so diagnosing 90% of people living with hepatitis C and treating 80% of those eligible individuals. The real gap meeting those targets is currently getting people diagnosed and that's how our DASH device is gonna help hopefully close that gap. Even despite these benchmarks and targets that were set many years ago progress is still really well short of what's needed. And, despite the call for 90% of people to get diagnosed and many more on treatment, still only about 36% of people living with chronic Hepatitis C are aware of their infection status and even fewer have received the direct acting antivirals that are available now. It's not all complete doom and gloom. We've got many more people in therapy now as a result of those revolutionary treatments I was talking about earlier. But it's the diagnosis and getting people diagnosed is really the major bottleneck to these elimination efforts and meeting those targets. So this sort of decentralized, the rapid user-friendly molecular platform that DASH is as really the potential to directly address these constraints/ 

Erin Spain, MS: You've talked about cost. What would this test on the DASH platform cost in a real world setting, both in the US and globally? 

Claudia Hawkins, MD:  So we're hoping it will be significantly less than certainly the standard molecular testing depending on which country you're in. We're hoping to get it well below $10 per test. 

Erin Spain, MS: This work is truly interdisciplinary here at Northwestern with experts in engineering and clinical care and global health all coming together. How critical are these types of interdisciplinary partnerships, especially when advancing global health. 

Claudia Hawkins, MD: They're really critical. I'll take an example of our collaboration with Sally over in the McCormick School of Engineering. So, you know, interdisciplinary collaboration between engineering and clinical medicine is really essential, I think,being able to translate that sort of scientific innovation of a new device or testing, diagnostic into the real world patient impact. And, we can design and come up with all the devices and diagnostics that we like, but they have to be really effective in clinical environments. And so you kind of really have to have an engineer and a clinician collaborating on these types of new diagnostics as well as implementation partners to ensure that these technologies are not just technically sound, but they're also practical in a day-to-day healthcare setting. 

Erin Spain, MS:  So what's next for this technology? What are some of the biggest hurdles ahead to get this into widespread clinical practice? 

Claudia Hawkins, MD: What's next is really doing as much of this work in terms of validating the device as we can in different settings with different populations. You know, Nigeria is just one place I've mentioned where we're doing some of this validation work, but we'd like to do it here domestically as well with various partners and within our own institution , which we're embarking on some projects related to that. Right now we can only use DASH for research purposes, but the whole idea is to do these studies to demonstrate the advantages of this point of care as well as obviously its feasibility. And then, you know, our partners who have the licensed DASH technology hopefully will really work on bringing the test to market with more evidence of its worth. 

Erin Spain, MS: As a clinician, this must be really exciting to see this path forward where this was a problem, you have these treatments that are available, they're just not getting to the people that need them necessarily all the time. What excites you about this as a clinician treating these patients? 

Claudia Hawkins, MD: We are actually working currently on adapting this device for Hepatitis B where it will hopefully be embarking on similar validation type work as we are with the Hepatitis C platform in the not too distant future. I'm excited about that as Hepatitis B is a particular area of interest to me, both on the research and the clinical side. In my role as a clinician and a researcher working in the hepatitis field, I obviously see a lot of different types of populations with hepatitis C and work closely with them. You know, here I might see persons with hepatitis C who have relatively easy access to a test and treatment, whereas in Nigeria or Tanzania, I see people who can't afford even the initial test or that initial test is not available. And so I think, you know, working in the field of diagnostics, which is really the biggest hurdle we have to get over to hepatitis C and, hep B elimination is a really exciting field to be in. I work all over in research and treatment trials as well as observational studies of outcomes. So I do a lot of different types of research, but I would say that working in diagnostics is the most rewarding. And I really do think it's going to be the one thing, especially this DASH test, if it really is, as successful as we are starting to see it is now will be a big step forward in terms of achieving those WHO targets and elimination goals. 

Erin Spain, MS: Dr. Claudia Hawkins, thank you so much for coming on and describing the progress with this DASH platform and the impact it could have on hepatitis C and possibly other hepatitis infections in the future. Thank you so much for your time today. 

Claudia Hawkins, MD: You're welcome and thanks for having me. 

Erin Spain, MS: Thanks for listening. Please click the bell to receive notifications about our latest episodes and follow us on social media @NUFeinbergMed to stay up to date with our latest research findings. 

Physicians who listen to this podcast may claim continuing medical education credit after listening to an episode of this program.

Target Audience

Academic/Research, Multiple specialties

Learning Objectives

At the conclusion of this activity, participants will be able to:

1. Identify the research interests and initiatives of Feinberg faculty.
2. Discuss new updates in clinical and translational research.

Accreditation Statement

The Northwestern University Feinberg School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit Designation Statement

The Northwestern University Feinberg School of Medicine designates this Enduring Material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

American Board of Surgery Continuous Certification Program

Successful completion of this CME activity enables the learner to earn credit toward the CME requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.

Disclosure Statement

Claudia Hawkins, MD, MPH, has nothing to disclose. Course director, Robert Rosa, MD, has nothing to disclose. Planning committee member, Erin Spain, has nothing to disclose. FSM’s CME Leadership, Review Committee, and Staff have no relevant financial relationships with ineligible companies to disclose.

All the relevant financial relationships for these individuals have been mitigated.