Everyone, thank you for joining us for the webinar sponsored by ASLD and the Hepatitis C Special Interest Group. Here we wanna show you some of the activities we do have at the LIBER meeting. So feel free to join us. Our plan is to keep you busy during the LIBER meeting so you can see there. So several activities, including meet the experts, the 90 minutes symposium, the business meetings. And the business meeting is extremely important for the SIG. That's where we get all your ideas and input. And everything we have done this year is coming from the ideas you gave us on the last LIBER meeting. And then we have other LIBER meetings, community conversations and other meetings as well. So you can see all these activities on the website, go on the program section of the LIBER meeting and you simply search for Hepatitis C and you will see all this that will take place in five weeks from now, four to five weeks from now. Hope to see you all there. And today we're gonna talk about the priorities and barriers to achieve Hepatitis C elimination in the United States. So we have two outstanding speakers, Dr. Furukawa and Dr. Price. And I'm Dr. Harry Torres and I'm moderating this with my colleague, Dr. Perumal Swami Poni who is also joining us. So I will do the introduction of all the speakers and Poni will do the Q&A session. And let's start with the general information. So it's a webinar designed to review the epidemiology of Hep C in the US and new approaches to increase the diagnosis, discuss strategies, treatment and highlight the challenges we're facing. We are offering CME credits for the live activity and also for the material that will be recorded for one year. You will receive an email in the next few days to complete the evaluation of the program and then you will have access to your credits. We're also offering MOC credit points and the financial disclosure for this program has been reviewed and you may find our list of disclosures on the website and any potential conflicts of interest has been mitigated. So now we're gonna start the program and first is gonna be Dr. Nathan Furukawa who's gonna be talking about hepatitis C elimination, how a new hepatitis C diagnostics will accelerate progress. And Dr. Furukawa is a senior advisor for hepatitis C elimination and the addition of viral hepatitis and works to develop the strategies, programs and partnership necessary to advance the elimination of Hep C. He served up the CDC focal point for the acceleration of the FDA authorization of CFA expert, HCV point of care, HCV RNA test, in collaboration with the NIH Independent Test Assessment Program, ITIP. He's currently guiding development and implementation of a strategy supporting the adoption of point of care testing in the United States. Nate, thank you for joining us and the audience is yours. Thank you. Let me pull up my slides. Where you can see them. All right. So yeah, thanks so much Dr. Torres for the introduction. I have a lot of slides. I'm very excited to present to you all. Maybe a bit off more than I can choose. So I will go through them a little quickly. But first let's just get a brief overview of what the picture of progress towards Hep C elimination looks like nationally. So CDC along with HHS has developed these targets towards eliminating hepatitis C nationally and has specific benchmarks for 2025 and then 2030. And so if we look at these 2025 goals, two of the main ones are the first one on the left there, reducing estimated new hepatitis C virus infections by more than 20% by 2025. And you can see, unfortunately, throughout the 2010s and then early 2020s, we've had a steady march increase of new HCV infections as a consequence of the opiate and substance use disorder epidemic. But in 2022, we did see that decline. We are really far away from our target, which you can see in the dotted line with squares, but perhaps this is some sign of initial progress. On the right, we can see the goal of reducing overall hepatitis C related deaths by 20% by 2025. And here, thanks in part to the amazing DAAs and curing of hepatitis C that we're doing, we're on track and seeing that go down appropriately. And if you just kind of look at the number of people being treated nationally, we know that since DAAs were released in 2014, we've had around 100,000 people or more so treated every year, but we've had a steady decline, probably as those who were easy to treat that were pretty stable and had known chronic infection. Once treatment's available, you start treating those folks. Then it gets to the harder to reach folks that need to be treated. And despite all that progress in treatment that we've made, there's still a significant number of people out there who remain untreated. So this is data from Quest that shows hepatitis C viral clearance cascade. The first bar on the left shows those that had a positive antibody. The second bar that's white shows among those with an antibody, how many of those got RNA testing. And then the middle bar shows of those that got a viral testing, how many had actual RNA positive infection. And then most importantly, as we go from initial infection to cured, cleared, this is showing the number of people that had a subsequent negative HCV RNA, suggesting that they either naturally cleared it or were treated and that's their SPR-12. And our goal here is this to be 80%, but you can see it's actually 34% and it shows a significant gap in the number of people being treated. And if you look at that by different demographics, overall again, that's about one in three getting viral clearance. But if we break that down by people without health insurance, it's only one in four. If it's people under the age of 40, it's still only one in four. And then if we break it down by people under the age of 40 without insurance, that's only one in six people getting viral clearance. And so we're missing a lot of folks. And the people who we do know that are diagnosed, they're not getting treated timely either. So this is a graph showing among Medicaid, Medicare and private insurance recipients, what's the rate of number of people treated within a year of their initial diagnosis. And it's low, 23% for Medicaid is incredibly low. And that's even in a more recent time as we've had the declines and the restrictions and barriers to access, we're still not meeting our mark. And that kind of shows in our prevalence data. So if we look at NHANES, which is our National Health and Nutrition Examination Survey, that goes around the general population and surveys folks and we test them for hepatitis C and that gives us our national prevalence estimates. And in a period from 2017 to 2020, we're estimating 2.4 million people with prevalent chronic hepatitis C. And that number could be as high as 4 million with some modeling accounting for undersampling of people at higher risk for hepatitis C. And so this just shows that despite all this treatment and these numbers are very similar from the numbers from 2013 to 2016. So despite all that treatment, it's not enough to kind of overcome the new amount of infections we're getting from that opioid crisis. And so that leads us to how are we gonna get the number of people that need to be treated treated? So in some sense, the people who have been treated and it was easy to get, they already show up in care, they're already all engaged. Those people are getting treated. It's the people who are a lot more challenging to get into care and get treated that need to get treated. And so those folks tend to go to high impact settings and not otherwise engage in the regular care system. And so just like thinking about it, there's just so many barriers to actually getting treated. Not even knowing what hepatitis C is, being like having stigma and avoiding healthcare providers. Our older two-step diagnostic process of like an antibody then an RNA may delay care. The high costs of the DAs themselves, the insurance prior authorizations are not even covering the medications that are needed. Having certain restrictions in place based on like meeting certain levels of sobriety. And then having that treatment not in the places where people regularly get care. And then having hepatitis C being disproportionately among populations that are more difficult to reach and don't otherwise engage in care. And so this kind of gets to the point of we need to move to the places where people with hepatitis C are engaging with some part of the healthcare system or public health system. And so that means extending hepatitis C testing and treatment to these high impact settings that may be non-clinical in order to actually reach those elimination targets. So as hepatologists, you yourselves might not be the ones going out and providing that direct care, but you sure are likely to be asked to provide leadership roles, to provide strategy, to understand what bringing hepatitis C care to these settings could look like. So you can help facilitate that implementation. So the places that we've identified that we're really excited about scaling up hepatitis C testing and treatment is insurance service programs, departments of corrections or prisons, large jails, and programs that offer medication for opioid use disorder. That could be like opioid treatment programs, getting methadone, or something like an outpatient MAT clinic offering buprenorphine. So just some justification for why we need to go to these places is, so SSPs, let's start there. These are programs that provide like sterile injection equipment where a lot of people who are actively using drugs go to. So there's an estimated around 3.7 million people who inject drugs nationally. And then half of those people in urban settings report going to a syringe service program in the past year. And then of those syringe service programs, about half say they offer some sort of hepatitis C testing. And then we know from our surveillance that the prevalence among people who inject drugs is really high, ranging from 23%, even closer to like 50%, depending on the population. So this is probably our highest risk population. And there's examples of where this has been done before. This is extract from a study out of New York City where they co-located hepatitis C testing and treatment at an SSP, where they are able to offer all of that care cascade within one co-located setting. And they're able to get a decent amount of people who underwent that pretreatment evaluation, got initially treated, completed treatment, and followed them all the way to SVR. It's not perfect by any means, but it's certainly much better than zero. Let's switch over to thinking about medications for opioid use disorder treatment programs. So there are at least a million people in the US who are on some sort of MOUD. And then methadone is, because of the Controlled Substance Act, only able to be offered by opioid treatment programs that follow certain SAMHSA regulations. Whereas buprenorphine can be provided in a variety of different settings outpatient. And with the removal of the X waiver that required extra training in order to use buprenorphine, this just allows increased access to MOUD outside of the community. And so pairing hepatitis C testing and treatment with MOUD services, again, these are kind of the populations where we need to reach. That's, this is where they're getting care. It can be incredibly powerful. And there's a recent randomized controlled trial from Andrew Tallalin's colleagues that demonstrated if you integrated a hepatitis C telehealth treatment oriented option at opioid treatment programs, you were able to significantly increase the number of people who were able to actually reach SVR. So if you look at this little graph, I think it's worth paying a little bit of attention here, just how impressive it is. So on the gray that represents the telehealth group and the blue represents just your standard of care, like, oh, go out in the community and get hepatitis C treatment. And so they're initially very similar, but that treatment initiation differences is massive. And then that continues to reverberate such that the number of people who were able to have an observed SVR is more than double the number of people compared to those that were in the referred standard of care arm. So then shifting to corrections, specifically DOC. So people who are incarcerated also have a higher prevalence of hepatitis C. So, and just for some definitions here, so prisons are usually federal state or private facilities that hold people who are convicted of a crime and serving longer sentences. Whereas jails are usually run at the local level and they hold people either pre-trial, pre-sentencing or post-sentencing for minor offenses usually less than a year. And there's some older research that suggests as many as one in three people with hepatitis C pass through a jail or prison at some point, at least overnight during one calendar year. So people with hepatitis C have a disproportionate engagement with the criminal justice system. And if we look at hepatitis C within prisons, we see that there are about 1.2 million people who are incarcerated in any given year. And the prevalence among that population is around 9%. That could be much higher in certain higher burden jurisdictions as high as 15%, maybe even closer to 20% in some of the more disproportionately affected local jails. And then an important message here is that 95% of the people who are incarcerated are going to then go back into the community at some point, emphasizing the point that correctional healthcare is population healthcare. And this has been done before too. Like if we get the right screening policies in place and we make hepatitis C treatment universally acceptable, we can actually move and reach micro-elimination in prison settings. And then a great example of this is California's Department of Correction and Rehabilitation. Starting back in 2018, they launched this large initiative in order to integrate universal opt-out screening of all people entering, receiving hepatitis C virus screening and then everybody who is positive getting treated. And so you can see in this figure on the right demonstrating in the yellow bars and the yellow line, the mid-year prevalence. And you can see that in 2018 being 14% of the population having hepatitis C. And they've been just churning, churning, churning treatments. They've done over 30,000 people treated in a five-year period. And you can see that prevalence within the prison system dropped from 14 down to 4% last year. So they are on their way to micro-elimination. But that's just one part of the carceral system in the United States. And actually most people passing through a carceral system are passing through jails. Those are people coming in after an arrest, maybe staying some time pre-trial before making bail, then being released back. And so there's an order of magnitude more people who interact with jails, about 7.3 million admissions to jails in 2022. And about 2.1 of those admissions were in larger jails where we would expect there's some capacity for hepatitis C testing and treatment. The challenges though, due to like the budgetary landscape, very few jails are actually offering any sort of HCV screening or treatment just because they don't have the budget available for it. One potential evolving emerging opportunity is that there are Medicaid 1115 waivers that would allow continuation of Medicaid coverage during the period of being detained and present within a jail, such that you'd be able to bill Medicaid for testing and treatment of hepatitis C, allowing those sort of services to actually be scaled up within large jail settings. And there's also fewer examples, but still a great example of this is what's happening in New York City. So the New York City system for the longest time has had a jail-based hepatitis C treatment program. And you can see there's a great paper from all like Chan and colleagues demonstrating on the top graph showing the number of overall treatments happening within New York City. And similar to that first earlier slide showing there's an initial peak in treatment around the times of DAAs are released, but then a gradual tapering off. In the jail, by contrast, they were able to continually scale up the number of people being treated just because there's just such a large denominator of people with hepatitis C needing treatment in that setting. And so then I wanted to cover some important advances in decreasing the barriers to hepatitis C testing and treatment. Really, we kind of have this understanding, that was all the setup. So what are we actually gonna be able to do? First off, I just wanted to remind people about the traditional diagnostic approach to hepatitis C virus testing, because that's important how to describe how it's gonna be a little bit different going forward. So traditionally that would be doing hep C antibody screen. And then if that is positive, then doing a HCV RNA tests. And then if that is positive, that indicates current HCV infection. If that is negative, that's indicating no current HCV infection. But there are a lot of challenges with this traditional diagnostic approach. The biggest one being incomplete testing. So if you have two tests within the pathway and they're not done in a way that you can have that happen in one visit, you can have incomplete testing. So if I just draw an antibody test and it's not refluxed to an RNA test of positive, I have to pull that person back and find them again to get them tested for RNA. There's also challenges with loss to follow-up. That's sending a lab test out. Even if it's a HCV antibody to RNA reflux testing, that's still a series of tests that need to get done at a centralized laboratory before that result can then be communicated back. And that delays time to diagnosis. And then lastly, missing early HCV infections, because if we're doing an antibody first approach, within that, especially the kind of two month period between initial HCV infection and testing, the HCV antibody may not be at levels that is detectable. And thus you, for those populations with very high incidence, such as people who inject drugs, you may be missing early HCV infections. So that sort of changes with the fact that now there is a new FDA-authorized point-of-care HCV RNA test. So that is the Cepheid HCV test. And this was something that CDC worked alongside with NIH and the independent test assessment program, the RADx Rapid Diagnostics Program, set up during the COVID pandemic to rapidly bring COVID diagnostics. We jumped on that bandwagon and rode the coattails to be able to utilize that existing infrastructure and program to accelerate very rapidly the availability of this point-of-care HCV RNA test, which unlocks testing in a lot of these high-impact settings I mentioned before, that previously we've had difficulties offering that testing in. So just a little briefly about this new test. So it's the Xpert-HCV, and it runs on the ClioWave GeneXpert Express platform. And that allows us to, with a finger stick, do point-of-care HCV RNA testing that results within a minute, or sorry, within an hour. So it's very simple. It involves getting a finger stick, and then bleeding into a microtainer, and then taking a pipette, sucking from that microtainer and loading it into a cartridge, closing the cartridge, putting it within the Xpert Express itself, and then selecting the test to run. It takes 60 minutes in total to run, but may result earlier if there's a very high viral load and there's an early termination program. So if you reach a certain threshold, which to call it positive, it will just result in as little as 41 minutes and provide a qualitative positive or negative result. So one of the important things that we quickly pivoted, realizing that our existing traditional approach didn't really accommodate the possibility that there's this new point-of-care device. So we looked back at our old 2013 guidance and algorithm, and noted that there was actually two footnotes that indicated that for folks who were exposed to HCV within the past six months, that there's an indication for our direct RNA testing. And so based on that, we came out with a recommendation clarifying that HCV RNA testing is recommended for diagnosis of HCV infection among people who might have been exposed to the virus HCV within the past six months. And that's regardless of antibody testing or antibody result. And I think we would encourage some flexibility with the might have been exposed. There is some limitation in specifically asking for risk within like a clinical setting, and so risk could be assumed based on the population. So now it opens up this exciting new reality where we have a potential two-step and a single-step antibody approach. And that could be laboratory based or point-of-care based. We know all about the two-step laboratory bases I described before, but this opens up this opportunity to this new two-step point-of-care HCV antibody, point-of-care HCV RNA, to allow everything to happen with finger stick testing at the point of care. The challenge here is that still misses early HCV infections, and then there's some complexities with the expert HCV test itself. And it may be a little bit more expensive than the laboratory version. There's still this option of a single-step HCV RNA approach by lab, but that is technically off-label, and so you may run into some issues with labs not offering it. And then there's the single-step point-of-care HCV RNA approach, which again consolidates all that benefit of it being all within a finger stick and then all at the point of care. But a challenge here is that that might be more expensive, and then their capacity for high volume testing might be limited to how fast the machine can run samples. And so what we'd love to see is like incorporation of point-of-care testing with easy access to treatment. So that can be through having co-located treatment, bringing treatment to the place where people need to be treated. But that might be challenging, especially if there's not a viable path for reimbursement. So having telehealth options available for treatment can be helpful and can include reimbursement. Or using funds to set up a mobile unit, allowing consolidation of testing and treatment resources within a unit that can move around and bring testing and treatment to different places. And then lastly, short of that is if you don't have an option to readily pair testing and treatment to have a robust way to ensure people are navigated and linked to care. And so putting kind of all that together, what we'd love to see in these sort of high-impact settings is in syringe service programs. Here you have very high prevalence. You have a decent client volume of people coming in. A lot of folks might be coming and going, but a lot of them are also regular clients. But here there's absolutely no access to phlebotomy or large laboratory systems. So here that single-step point-of-care HCBRNA test might be really helpful. Similar for opioid treatment programs. In outpatient medication-assisted treatment clinics here, you may have the ability to have phlebotomy and lab access. So it might not make sense to have a point-of-care option to get that earlier test result, but it's still an option if you want to pair it with early hepatitis C treatment. And these are all potential strategies. Again, nothing is one-size-fits-all. These all have to be customized to whatever the situation is. Then for carceral settings here, for large jails, since it might be a brief encounter before they're released, you might want to do a point-of-care single-step option, but two-step might be okay too. And then prisons, because they're going to be around for a while, with and have access to phlebotomy and large laboratory systems, doing a single-step or two-step laboratory approach based on prevalence might be helpful. So this all kind of moves us towards what I think Dr. Price will cover in a little bit about how do we get towards that same-day test and treat approach. We've got really close with the simplified guidance, but there's still some things that are missing. So we've got an antibody test, now we have an RNA test, but we don't have a hepatitis B surface antigen test to rule out HPV co-infection. But we do have an HIV point-of-care test and a pregnancy test. The good news is that the FDA has signaled they want to down classify HPV diagnostics, which will open up that as an opportunity for new tests to come through. And the ASLD-IDSA group is working on some even further simplified guidance, and I'm able to share that the CDC is supporting a new RADx ITAP project to actually bring to market such a point-of-care hepatitis B surface antigen test with the link below. And I notice I'm running a little short on time, so I'm going to speed up for the last few slides. That doesn't remove all the barriers. Certainly there's still a lot of prior authorizations that exist here. I'm going to skip over this slide. This just shows that a prior analysis showing that not expanding Medicaid, having fibrosis restrictions, and then having periods of sobriety required reduce the number of people who are actually able to get treated. But there is some really exciting opportunities in that there has been proposed a national hepatitis C elimination initiative, which would include components of accelerating diagnostics, having a Netflix-like model drug procurement program to increase access and provide drugs to those who are in a carceral system, uninsured, or with Medicaid, or receiving care at an IHS clinic. And then that's paired with a comprehensive public health implementation plan that includes awareness campaigns, provider training, funds to integrate services in different high-impact settings, and then expanding prevention activities. And this is something under consideration in Congress currently, and the Congressional Budget Office is scoring whether this is ultimately cost savings, and if so, we're hoping that we'll have bipartisan support of such a hepatitis C elimination initiative. So with that, I think that's the extent of my time, and I would like to turn it over to Dr. Torres again. Thank you, Dr. Furukawa. Excellent presentation, really outstanding. Thank you for sharing with us, and we're going to move to the next presentation. Just a reminder, well, first, thanks everyone who have joined us. So we have over 100 people registered, and they are joining us with questions. So we're going to address as many questions as we can at the end. If not, we will try to put our answers in the chat as well. But thank you all for joining us, and thank you ASLD for making this possible. So thank you, Sally, thank you, Julie Hoffman, and Aquender Dot for also putting this together. And then we're going to move to the next speaker, Dr. Jennifer Price is a past chair of the Hepatitis C Special Interest Group, and Dr. Price is an associate professor in the Department of Medicine in the Division of Vascular Enterology, Hepatology, and the University of California, UCSF, and the director of the UCSF Vital Hepatitis Center. So her research examines the contribution of novel and traditional factors associated with liver disease and fibrosis progression in large observational HIV cohorts with or without HIV. Dr. Price is a principal investigator of the San Francisco Bay Area site of the multicenter AIDS cohort study, and which integrates two of the largest and longest running NIH-funded prospective cohorts of men and women with at risk for HIV. She also serves as the co-chair of the MWCCS liver group working group and the past chair of the ASLD Special Interest Group. She's a member of the N Hepatitis C San Francisco Coordinating Committee and leads the UCSF ECHO program, and she's a founding director of the liver care van and mobile unit aimed at improving access to HIV screening and high-quality liver-related health care. And I'm sure Jenny's going to talk to us about that fantastic initiative. Jenny, the audience is all yours, and thank you for joining us. Great. Thank you so much for that introduction, and I want to thank Dr. Furukawa for really teeing me up for this talk. I'll be presenting on an update on hepatitis C management and treatment simplification. So here are my disclosures. The grant support was to my institution. I do want to disclose that I'm one of the co-chairs of the ASLD IDSA hepatitis C guidance. So in terms of the outline for this talk, I want to review the current hepatitis C treatment regimens that are recommended through the ASLD IDSA hepatitis C guidance, and I'll spend a little bit of time talking about the current simplified algorithms, and then we'll move on to sort of thinking about a framework for moving into this hepatitis C test and treat approach. So before talking about our current recommended treatment regimens, I just wanted to take a moment to remind everyone of how much hepatitis C therapy has really evolved in the past 10 years, and in particular, how there was this period between 2014 and around 2018 when things were evolving very, very rapidly. And so I actually went back to an old talk that I gave on current hepatitis C recommendations for hepatitis C treatment. This was back in 2018, and I'm not going to go through all the details here, but you can see that while there were several excellent options for hepatitis C treatment by 2018, it was still rather complicated. You know, different treatment durations depending on whether or not someone had cirrhosis, different nuances depending on the genotype, more need for resistance-associated substitution or RAS testing. So still not particularly simple, as you can see from this slide. But now if you fast forward to 2024, we still have several excellent options, but you can see here that it's much simpler in terms of just the regimens themselves, particularly with the pan-genotypic regimens. So really the treatment duration is similar regardless of genotype and even regardless of having compensated cirrhosis. And I just want to note that these regimens are also extremely effective. This is a summary of the clinical trials of cefosporavirabel-patasvir for 12 weeks across genotypes. And really the bottom line here is that the SVR12 rates are very, very high, over 95%. And we see similarly excellent SVR12 rates with glacapaviraprebentosvir for eight weeks. So really highly, highly effective medications. So now while the Hepatitis C guidance still includes a lot of details about the nuances of treatment, particularly in certain special populations, we now have what we call our simplified treatment algorithms to really try to make this a lot simpler for providers. And essentially anybody who has chronic Hepatitis C and has not previously received Hepatitis C treatment is potentially eligible for the simplified treatment. There's two different algorithms. They're both available as a downloadable PDF on our guidance website. One is for individuals without cirrhosis and the other is for individuals with compensated cirrhosis. I'm going to walk you through some of the details of the algorithm for those without cirrhosis, but it's very similar for those with compensated cirrhosis. So I told you who is potentially eligible. Who is not eligible are individuals with decompensated cirrhosis, people who are Hepatitis B surface antigen positive or currently pregnant, and people with a known or suspected HCC or prior transplant. But I'd say most of our patients who we're seeing now with Hepatitis C viremia really fall in the other bucket of being eligible for simplified treatment. So if someone is eligible for simplified treatment, the next step is to do the pretreatment assessment. I know this is a little bit busy. I'm not going to go through all the details on the slide, but on the right here you can see that this includes pretreatment laboratory testing, which includes getting a CBC hepatic function panel and a renal function, ideally within six months of initiating treatment, and then at any time HIV and Hepatitis B surface antigen screening. This pretreatment laboratory testing is actually sufficient to use for assessing fibrosis stage. So you can use the ALT, the AST, the platelet count, and the age to calculate FIB4. And FIB4 alone is actually sufficient for fibrosis staging. If someone's FIB4 is over 3.25, we would presume them to have cirrhosis. There are other ways that you can assess for fibrosis, which are listed here, but these aren't required if you have a FIB4. Other things that you would want to do before initiating treatment is to perform a good medication reconciliation and then use that information to assess for drug-drug interactions, which can be done using the resources we have in our guidance or other excellent resources, like the University of Liverpool Drug Interaction Checker, and then, of course, patient education. Our first-line recommended regimens are the two first-line pangenotypic regimens. I already showed you Glicapivir-Prebrentisvir for eight weeks or Cefospivir-Velpatisvir for 12 weeks. And I think what's important to highlight here is that on-treatment monitoring is actually quite minimal. In fact, no laboratory monitoring is required, and even clinician visits are not required. They can be done if needed for patient support, but they're not necessary for simplified treatment. And this minimal on-treatment monitoring approach is really supported by the MINMON study, which was published in 2022. In this study, they enrolled individuals with chronic hepatitis C and treated them with Cefospivir-Velpatisvir for 12 weeks. They did not do any pretreatment genotyping. They actually provided all 12 weeks of treatment up front at entry, so all 84 tablets. They did not have any scheduled on-treatment clinic visits or laboratory testing, and they just had remote contact with participants at week 4 and then before the SVR12 lab draw. And they determined cirrhosis based purely on the FIB4 score. And overall, the bottom line, what they found was that the SVR12 rate was excellent at 95%, and this was despite giving all the pills up front, and again, with that very minimal monitoring. So that really supports our recommendations in the simplified algorithm to really minimally monitor people once they've been started on treatment. Now, having said that, I will say, as we heard earlier, while this simplified algorithm has been, you know, a welcome addition, I would say, to the guidance. And it's certainly, I think, has simplified treatment from a clinician standpoint and allowed treatment to be a bit more accessible to non-hepatitis C specialists to sort of move treatment outside of, you know, the infectious disease clinics or the hepatology clinics. It's not particularly streamlined, especially from the patient perspective. So if you're looking from the current path from testing to treatment, there's still a lot of steps along the way. So you've got the initial hep C screening visit. Somebody needs to come back to get their results disclosure. They need to get their pre-treatment labs done. They need a clinician visit to do all of that counseling that we talked about and to prescribe the DAAs. This might be one visit. It might be two visits. And then finally, you know, the patient starts their DAAs. So lots of steps between screening and treatment, which really makes things more complicated for the patients. And it also provides opportunities for us to lose people along the way across all of these steps. So I think what I want to talk about for the remainder of my time is really thinking about how we could streamline this process and simplify it further. And this is a question that we actually asked in San Francisco a few years ago. We wondered whether we could use an adapted, simplified treatment algorithm, but shorten the steps from testing to treatment by starting treatment on the same day as a diagnosis disclosure. So this led to what we call the No One Wait Study or Now Study. We conducted this study actually in a community-based site. It was not a clinical site. It was the Quaker Meeting House, which is located near the Civic Center in San Francisco, which I circled on the little cartoon map here of San Francisco. For those of you who are not familiar with San Francisco, the site is in an area close to where people who use drugs and people who are experiencing homelessness congregate. And then it also happens to be close to public transportation. So it's a convenient location to kind of meet people where they are for screening and for treatment. And what we did was we initially conducted hep C screening with the two-step approach versus the point-of-care antibody and a positive venipuncture for hep C RNA. And then when the participant came back for their RNA result disclosure, they were offered same-day treatment with a two-week starter pack of cefosporavir velpatasvir with the plan for the study team to attempt to obtain insurance authorization for the remainder of the 12-week treatment course. And then we did have several touch points throughout treatment, primarily because of the demographics of our population and the need to help assist with safe medication storage as well as other navigation services. So I just want to walk through a few details about the procedures. The first step of the consent and the first phase was really that antibody testing. We did do the rapid finger stick hep C antibody and we did the HIV rapid point-of-care test at the same time. And then, like I mentioned, if the antibody was positive, then moved on to venipuncture for the hep C RNA for confirmation. We did at the same time as drawing the hep C RNA, we did send a sample for hepatitis B surface antigen because we wanted to know the participant's surface antigen status before determining eligibility, you know, the following week for same-day hep C treatment. When people came back for their results disclosure, we assessed whether or not they were eligible for same-day treatment. People who were DAA experienced, had untreated HIV, had hepatitis B surface antigen positivity, or had decompensated cirrhosis based on history or clinical symptoms were not eligible. But those who were eligible and were RNA positive, then were offered enrollment into the study. And if they enrolled, that we performed the pretreatment tests at that time, including a CBC, a CMP, and an INR, did all of that counseling that I already discussed, and then provided that two-week starter pack of cefosbovir, velpatasvir. And then people came back, you know, for the remainder of their course and the follow-up visits. So from July of 2020 to October of 2021, so just a little bit over a year, we screened 492 people for hepatitis C and 246 had reactive hep C antibody. I want to point out here that 18 of them were unable to get confirmatory hep C RNA testing because we were unable to successfully draw blood. So this is, you know, a group of people that could really benefit from that gene expert device that we heard about that requires just a finger stick and not a venipuncture. Among those who were able to get hep C RNA testing, we had 126 who were RNA positive, and the majority of them, 88%, were potentially eligible for this modified simplified hepatitis C treatment. There were a handful of people who were DAA experienced, so they were ineligible for that reason. We actually had three people who had untreated HIV. Interestingly, we had three people who we were able to get enough blood for the hep C RNA, but not enough for the hep B surface antigen. So we put it in rollout, hepatitis B, and that's why they were ineligible. And then one person who actually tested positive for hepatitis B. Among those 111 that would have been eligible to enroll in same day treatment, 22 actually did not return for the RNA results. That was 20%. So again, another area, another group that could be better served with a point of care viral test. We don't know, of course, if they had known their status on the same day, if that would have affected their ability to get treatment or desire to get treatment on same day, but at least they would have known what their status was. Among those who did return for their RNA disclosure, the majority, 98% actually elected to enroll in same day treatment. And the two people that declined enrollment, they just didn't want to be treated in the setting of a clinical trial, but they had their hep C treated elsewhere. So just really briefly about our study population, 71% were male, 44% were non-white. The majority were what we would consider to be unstably housed with almost two thirds having slept outside or in a vehicle in the past 12 months. And 80% had reported having used injection drugs in the past three months. So a relatively recent injection drug use. And then I think it's important to highlight in the context of this talk, you know, 94% were insured at the time of enrollment in the study. So that really speaks to our safety net system in San Francisco, that the vast majority of people actually had health insurance when they enrolled. If they didn't, we assisted them in trying to get health insurance. And then finally, I won't go through all of this in the interest of time, but our per protocol SPR-12 was 84%. The median time from antibody screening to treatment initiation was seven days. And I think what's important to highlight here is that we actually didn't have to make any alterations in the treatment course based on those pretreatment labs that were drawn the same day that the DAAs were started. So we got all of the pretreatment labs that, you know, we planned to with the simplified algorithm, but we actually didn't have the results back until after people had started their starter packs. And we didn't have to make any alterations when the results of the, you know, CMP and the CBC came back. So, you know, what can this tell us about how we could approach a same day test and treatment with the gene expert device that we now heard about? I'm going to sort of walk you through a potential hepatitis C test and treat same day approach. I just want to be clear that this is not the official hepatitis C guidance. This is something that we've been discussing on the guidance panel. The updates are still being worked out, but this is sort of my approach to a same day test and treat and how to think about how we can do this. So first we would start with the point of care test, as we already heard about. Next, we would determine, you know, eligibility, people who would be ineligible, those people that we kind of already have discussed. After determining that somebody would be eligible for same day treatment, then we would do laboratory tests. I think the bare minimum of a laboratory test that we would want would be a AST, ALT, and platelet count, which would allow you to calculate a Fib4 and a hepatitis B surface antigen. And then, and excuse me, so the hepatitis B surface antigen is going to be very important in terms of the counseling to try to determine your plan for what you're going to do when those surface antigen results come back. So in addition to all these labs, you still want to do all the medication reconciliation, all of the other counseling that I already talked about, but also discuss the potential risks of treating hepatitis C in somebody who might also have hepatitis B, who's not on antiviral therapy, and then come up with a plan for what to do and how to reach the patient when the surface antigen results come back. Treatment course would be the same, Glee-Pib for eight weeks or Soft-Bell for 12 weeks. And then with that surface antigen follow-up, we would, if it's positive, I would recommend starting hepatitis B treatment at that time, so concomitant with the hep C treatment, and then referring to a specialist for long-term hepatitis B management. So potential obstacles to this approach. So one is that this still requires phlebotomy, which I already told you is a barrier, and that's for the surface antigen testing as well as the fibrosis staging labs. The need for a clinician to be able to prescribe the meds and do all this counseling, you know, same day and on-site, and then also to be able to provide, to give the medications the same day. So I'm just going to briefly kind of walk through these obstacles. I'm going to go in the sort of reverse order, but in terms of the same day medication, in the NOW study, as I mentioned, we provided these two-week starter packs. So that was all provided, you know, by the study to the participants. And then we transitioned to insurance-provided treatment. And, you know, we were able to transition to insurance-provider treatment, and the majority of our participants, and actually 70%, we were able to do that. We were able to get to insurance-covered treatment within two weeks, so once that starter pack was done. But there were some important barriers and reasons for delay in this transition, and the most notable one was actually the pharmacy consent process. So our managed Medi-Cal plans often required us to use specific specialty pharmacies, and then some of these specialty pharmacies required a telephone consent process that, of course, was complicated by the fact that many of our patients did not have reliable cell phone access. So that ended up leading to a lot of delays. So this is something that, you know, ideally, if we had a national procurement plan, it would really help, you know, overcome these barriers and these delays. But until we have that, things that we need to kind of think about when we're thinking about how to get from that diagnosis to, you know, actually giving somebody the DAAs. What about access to a clinician for same-day treatment start? I want to remind everybody that it doesn't necessarily require that the clinician be on-site. We already heard about the study that Dr. Talal and colleagues, including Dr. Prumal Swamy, conducted within the opioid treatment programs, in which they showed that facilitated telemedicine was actually highly effective and, in fact, more successful than regular off-site referral to achieve hepatitis C cure. This model included a hepatitis C clinician who was off-site, but an on-site case manager who facilitated the telemedicine encounter. So this is something, as you heard, that we could incorporate into these sort of test and treat models. And, in fact, we similarly used staff-assisted telemedicine in the NOW study. And then, finally, I want to touch on the risk of hepatitis B reactivation because this is important. This is a result from a meta-analysis that looked at 35 articles looking at the risk of reactivation in people treated with DAAs who were surface antigen positive. And the bottom line is that the pooled reactivation risk for hepatitis B was 12%. The 95% confidence interval was 6% to 19%. This is for people who are surface antigen positive. People who are surface antigen negative, but core antibody positive, the risk was actually quite low. So it's really, this is the concern just for the surface antigen positive individuals. If you're wondering how many people this is, the estimated hepatitis B prevalence in the United States among people living with hepatitis C is up to 6% and among people who inject drugs is 12%. So, you know, these are a minority of patients, so 12% reactivation risk is low, but it's not insignificant. And similarly, hep B prevalence is not high, but it still, you know, could be as high as 6% to 12%, which is not insignificant. And so there is a black box warning on the DAAs that say that we need to test for hepatitis B surface antigen before initiating treatment. And this is why that's important. And then very quickly, I just would be remiss if I didn't mention that there are gaps in hepatitis B vaccination among people living with hepatitis C. And I'm not going to go into the details here in the interest of time, but we've done a couple of studies in San Francisco, which showed that people living with hepatitis C, many are still susceptible to hepatitis B infection and could use vaccination. And so I think it's important to remember that while we focus on hep C elimination, we should think about co-localizing hepatitis B vaccination with these test and treat models. So take-home points, hep C treatment is much less complex than it was 10 years ago. Same day test and treat is feasible with a point of care hep C RNA, but it does still require venipuncture. And we do still have to think about fibrosis staging. And then finally, you know, additional resources are going to be needed to really implement the test and treat, even with the point of care RNA, including medication access and then infrastructure to support staffing and clinician visits and navigation. So thank you for your attention. I look forward to the Q and A. I'd like to thank Drs. Price and Furukawa for their amazing, really outstanding presentations to get us kind of caught up to speed with respect to hepatitis C barriers and elimination efforts. We're going to quickly move to questions since we only have two minutes left. Dr. Furukawa, I think you can maybe address one question that's come up twice. I know you answered it in the chat already, but it came up again in the Q and A. So the question was, can you speak directly to the potential lack of other testing around HIV pregnancy hepatitis B prior to treatment? Yeah. So, you know, as, as Dr. Price mentioned, you know, it's particularly the hepatitis B is an important component because of that risk of reactivation and progression to clinical hepatitis. And at the moment there is no, in the United States available point of care hepatitis B surface antigen. And so the challenge there is like still having to do phlebotomy and follow that lab up. But we, as mentioned, are trying to get, bring that to market because they exist outside the U.S. There's this couple options. So we're hoping to get at least one of those tests in a very rapid fashion in a similar way that we did with expert, the expert HCV test. HIV point of care tests have existed for a long time, several dozen of them. Pregnancy tests are abundant as well. You can pick that up at your local drug store. And so those are like probably the biggest point of care pieces. So we've got everything except for the point of care B surface antigen. The expert express version itself doesn't have that option. The Cepheid products typically do nucleic acid testing and here we're looking for like antibody antigen tests. Thank you so much. Really quickly, briefly, Dr. Price, I'm going to combine two of the chat questions. Can you give some talking points around monitoring coagulation and glucose was listed on one of your slides. And then what do you do when fib four reads cirrhosis, but elastography rules out cirrhosis? Yeah. So there were two points about monitoring somebody who's on diabetes medication should, you know, monitor their glucose because there could be a decrease in need for the diabetes medicine while the, when the hepatitis C is cleared. So, you know, those individuals should be monitoring their blood glucose anyway, but additional counseling to make sure that they know to just be mindful and check their blood glucose. And similarly with warfarin, there could be a decrease in the INR as, as someone's treated with hepatitis C if their liver function improves. So that's really the motivation behind those monitoring. Again, those are individuals that are getting regular monitoring anyway, when someone's on warfarin, they are getting regular INR checks. And then the second question was, I think, related to discordance between elastography and fib four. And now I can't remember which one was higher, but if the fib, if the, if the elastography does suggest cirrhosis, I would go with that. Even if the fib four is just under the 3.25. Great. I think with that, we're actually at time. I'd like to again, thank our wonderful speakers for presenting today to all of the ASLD staff, that Dr. Torres also thanked at the beginning and all of the attendees. So I believe the webinar will get posted along with some CME questions. Dr. Torres, did you have anything else to end and close us out on? No, thank you everyone for joining us. I think it was a very well attended session. Thanks to all of you and to the speakers as well. Thanks guys.

Hepatitis C

elimination

ASLD

LIBER meeting

diagnostic approaches

point-of-care test

treatment accessibility

healthcare barriers

HCV RNA test

test-and-treat