Okay, welcome everybody, we're going to get started because we have a busy program today. My name is Jennifer Price, I'm an associate professor at UCSF and I'll be moderating this session along with my co-chair, Harry Torres. And I know that I'm sort of speaking to a well-informed audience about the hepatitis E care cascade. We all recognize that there are many gaps in the cascade from diagnosis to accessing treatment to preventing reinfections as well as new infections. And the purpose of our SIG session today is really to empower all of you as hepatitis E champions and specialists to really develop some practical solutions to overcome these challenges in the hepatitis E care cascade. So we have a series of excellent talks lined up to that end. And the first talk that I'd like to introduce is Dr. Rena Fox. So Dr. Fox is a professor of medicine at UCSF in the Division of General Internal Medicine. She's the director of the UCSF Hepatitis E Cure Initiative and chair of the SF CAN liver cancer task force. She's been a huge champion for hepatitis C at UCSF, particularly educating primary care providers on hepatitis C diagnosis and treatment as well as really spearheading efforts to improve testing as well as treatment. So welcome, Rena. Thank you. Thanks for having me. Good afternoon. Let's see. So the objective today, to learn very practical and specific ways that electronic medical records, EMRs, can be utilized for hepatitis C screening, treatment, and linkage. Okay. Problem here. Healthcare institutions face many barriers to dedicated hepatitis C elimination efforts. The hep C care cascade is complex with many embedded blockages. Systems are not incentivized to invest resources to improve hepatitis C care. Knowledge gaps exist in the leadership. There's inadequate existing infrastructure. And of course, there are competing priorities for systems such as COVID, opiate use, diabetes. As an example, looking at some of the root causes of gaps in hepatitis C care at UCSF. In laboratory tests, patients have had an antibody positive without an RNA prior to a reflex test being developed. In resources, patients are lacking a PCP. Patients are without transportation. In education, non-hepatologists are not confident to treat hepatitis C. In terms of people, PCPs and providers are not necessarily aware of remote results. And in terms of the environment, patients themselves have competing priorities. And then in terms of systems, health systems not incentivized to invest and build systems to improve their hepatitis C outcomes. And specifically in terms of incentives, there is no HEDIS measure for hepatitis C, which is a real problem. HEDIS measures provide benchmarks for performance, tie financial incentives to scores, and promote patient-centered care. We have HEDIS measures to improve mammogram rates for breast cancer screening, to improve colon cancer screening rates, but we don't have a HEDIS measure for hepatitis C. And a HEDIS measure would incentivize healthcare systems to achieve identifying, managing, and treating hepatitis C and screening for HCC. Nonetheless, I would argue that the EMR is still available and can be used to address many of these root causes. There are many potential uses of EMRs for improving hepatitis C care. There are enhancements to the EMR, such as building alerts, building order sets, developing clinical tools. And then there's data sharing, data collection, tracking cases, directing patient outreach, empowering PCPs, developing provider education disseminated through the EMR, and evaluating the impact of clinical services. We're going to be talking about a number of these today. So first, EMR hepatitis C screening alerts. EMR alerts help provide reminders to PCPs, as well as the ER or urgent cares, and they serve as real-time reminders during a patient encounter at the point of care. They're visible in a section of the EMR. It might be called something different at your institution. In our institution, it's called the Healthcare Maintenance Banner, and you can see a list of all of the alerts that a patient may be due for. And implementing these alerts can also help the healthcare system itself, tracking screening rates, identifying specific clinics or even specific providers with low screening rates, designing targeted interventions to address specific gaps, and tracking follow-up care. So in this example, we're looking at a figure from a study done in D.C. implementing two different hepatitis C screening alerts. First was they implemented the birth cohort screening recommendation, and an alert then in the middle of 2018. And then the universal screening alert was implemented in mid-2020. So in the gray line, it's the total of all tested individuals. The blue line is tested individuals who are born in the birth cohort, 45 to 65. And then in the yellow line, patients not born in the birth cohort. So we can see how testing is doing. And then with the implementation of this automatic alert, we see the antibody testing go up in the birth cohort group and in the total group. And then later, when the universal screening is implemented, a really dramatic rise, especially in that non-birth cohort group who hadn't been very well tested previously. And seeing that the absolute number of screens go up 103%, and the screening rate going up 62%. So really demonstrating the effect of these alerts. So in addition to screening alerts, I wanted to also show a few examples of things that you can do to modify your own EMR to kind of prompt and really help PCPs, particularly choosing the appropriate tests. So when we developed an antibody RNA reflex test, we were concerned that PCPs were already in the habit of just ordering a straight antibody, that they wouldn't necessarily know to look for this, and it wouldn't be put to use the way we had hoped. So after creating the reflex test, we then worked with our EMR committee to really push this reflex test to the sort of top of the menu. This means that when a provider puts in even just hep C into the order search, as you can see, the list of choices that they get is anything that contains hep C, but really forced to the top of the list is the reflex test, which has been great. So very small things that can have a truly big impact. So in addition to test preference, we've also developed things like automated calculators. So particularly the FIB4. And building a FIB4 automated calculator is something that we still want more and more PCPs to use, but it's there. So what our calculator does is if a provider types in .FIB4 into their, and this is using Epic, into their Epic note, the program then pulls in the AST, ALT, platelet count, and age with inputs from within 90 days, displays the FIB4 score, and then displays also the last six FIB4 scores and the dates from those scores. It shows you the values that were used in putting into each of those computation. And then we included interpretation because for non-specialists, they wouldn't necessarily know the cutoffs appropriate to interpret the FIB4 score. And so this is just another way that you could think about modifying, making enhancements to your EMR to try to get better results for all of your hepatitis C patients. So so far we've been talking about modifying your EMR, but now we're going to switch to talking about using your EMR for data collection and then implementing change based upon the data that you generate. So EMRs can define and generate patient lists of your hepatitis C population in the healthcare system really at any stage of the hepatitis C care cascade. So you could look for all patients with any evidence of hepatitis C, specifically patients who are fully diagnosed but untreated, patients with spontaneous clearance, patients who are incompletely diagnosed, patients who have been ICD coded for hepatitis C, patients who have achieved SVR, patients prescribed hepatitis C therapy but with an unknown SVR status, and patients who completed therapy but did not achieve an SVR. All of this from a search. And this is an example published in Hepatology in 2021 from the Mount Sinai group. And in this algorithm, their goal was to identify their hepatitis C RNA positive patients. So they used six pretty simple inputs, their base of patients, patients being alive, and then their RNAs, antibody, course of hepatitis C medication prescribed, and a follow-up RNA after the date of the last prescription. And so with just those six inputs, I'll just talk through a couple of the ways that all of this information can be derived. So was an RNA test done? No. Was the patient previously antibody positive? Yes. This patient needs a hepatitis C RNA. If the antibody was negative, they're not on the hepatitis C care cascade past the screening point. What about a patient who did have an RNA test that was done and was positive? Were their medications prescribed? If yes, what was their RNA over three months after the date of the last prescription? If it's negative, then they've achieved SVR. If it's positive, they've remained viremic. And if there are no medication prescribed, but the patient remains viremic, then either this patient, if they're still viremic, they have chronic untreated infection. And if they are not viremic, oops, sorry, then they are presumed spontaneously cleared or perhaps treated somewhere else. So this is a lot of data that you are getting from your EMR with very simple inputs. So what was learned from their algorithm? They started with 2.5 million individual patient records. They found 72,000 with some indication of hepatitis C, 10,000 whose most recent hepatitis C RNA was positive, 6,000 of whom they attempted phone contact. Of those, they learned that about 1,300 were not treatment candidates, 3,000 could not be contacted, but 1,800 did become engaged in hepatitis C care at the time of publication. So they designed an EMR search, established a patient cohort, conducted targeted outreach, and measured their linkage to care. In another algorithm, this algorithm was aiming to identify patients who were antibody positive, whereas the prior one was identifying patients who were RNA positive. And here, with the antibody positive patients, they went directly into callback. And although there are about, I think it's 56 percent of patients did not return in total for their RNA, 15 percent did return for an RNA that was negative, 25 percent were engaged in DAA therapy at the time of publication. So this is going to have a little bit of a lower yield because these patients are only antibody positive to start, but again, depending on what kind of search or what your goals are, there's just a lot that can be generated and done with your EMR. So at UCSF, working with our Office of Population Health, Dr. Price and I designed a search for patients with evidence of hepatitis C. So we looked at patients who were being seen pretty currently. They had to have been seen at least once in the past three years. And then they needed at least one of the following, either a positive antibody, a positive RNA, a prescription for a hepatitis C medication, or an ICD-9 or 10 code for chronic hep C. And we found about 470,000 unique patients were seen in the past three years. 4,300 met at least one hepatitis C criteria. 628 were currently viremic and had never been treated. About 1,200 had ever been prescribed a medication. 834 had achieved SVR. About 1,000 had incomplete testing. About 1,400 appear to have been spontaneously cleared or perhaps treated elsewhere. And then we had about 200 who appear to be missing SVR labs, at least internally. So keep in mind that these are patients seen pretty recently. So these are not all of the patients ever seen or ever treated. So in addition, we were able to demonstrate real disparities. Here we show that the UCSF hepatitis C population have 60% more black and Latinx patients compared to the UCSF primary care generally population. And that's very important to recognize and see your own real data. And furthermore, we wanted to see whether the hepatitis C patients are engaged in the health care system at all. Are they engaged but they're not being treated? Or are they not really users of the system and maybe they had come in for one ER visit and yet they were still captured in this search? So of the 4,300 patients who had current or prior hep C, we found actually very high engagement in care. You know, patients who had been admitted as an inpatient, patients seen in the ER, about a quarter of the group, having completed at least one office or video visit, almost all, three quarters, having completed another outpatient encounter, whether or not they completed any lab data, imaging data, or had logged on to MyChart, which is the patient portal. So all of this data came from our search and has been able to help us motivate our health care system to develop an outreach program in spite of lacking a HEDIS measure and all the other root causes that we had looked at earlier. So these kinds of EMR data are great for internal use, but they can be used to help more broadly, maybe in your city or your local region, to drive hepatitis C elimination efforts. So both internal data and now collecting that data with others. So the San Francisco Cancer Initiative, SFCAN, is pooling data from San Francisco health systems from the EMRs to help estimate hepatitis C prevalence in the city and even locating specific neighborhoods that need outreach. And there are other micro-elimination efforts that can be driven with these data, such as increasing treatment for people with co-infection, prison-based programs, people who inject drugs, and at community health centers. So furthermore, thinking about population health management, aggregating these data across a system allows your EMRs to be used for population-level health management. VA has been ahead of most systems many years ago, creating the National Hepatitis C Clinical Case Registry, which has been able to track, report, design targeted improvements in hep C testing and treatment. Every veteran in VA care with hepatitis C is followed in the VA registry, and over 100,000 veterans were treated and had achieved SVR by March of 2020. So using your own data, your health system can then establish its own benchmarks, create key performance indicators, metrics, design its own reporting system, and continuously improve your own EMR system and strategies based on feedback, new research, and changing guidelines. And finally, I'd like to just really emphasize the importance of interdisciplinary collaboration, meeting with and really teaming up with people in other fields in your health care system. All of the steps and examples that we discussed today require collaboration, ideally with people who are in primary care as well as other specialists. I would just say that these kinds of relationships will help you, and especially if you can find a champion or more than one champion in your primary care departments, get to know who the governance committee, if that's what it might be termed at your institution, a governance committee of the EMR. You know, the EMR does not belong to any individual or any department, so any time you make a modification to your EMR, it's going to have a ripple effect for others. So that's very important to be sure that any new tool within the EMR is really tested to be sure that it will be consistent for all departments. Does your institution have a population health department or a big QI department? What about the cancer center where they may be driven to try to prevent liver cancer, as well as your local department of public health, and also the emergency department where they may be very interested in joining forces to create better screening, treatment, location, and callback for hepatitis C patients? So to wrap up, my key takeaways are that uses of the EMR for hepatitis C solutions include and are not limited to programming hepatitis C screening alerts, designing clinical tools for PCPs, defining the patients in your institution at each stage of the cascade, and then contributing this data to the city and local hepatitis C elimination efforts, and using this very rich EMR data to motivate health systems to implement outreach to patients. And three kind of extra tips, get to know the procedures and people that you need to request EMR design changes, collaborate, establish relationships and find partners in other departments, and use your EMR data to help motivate the health system to improve its hepatitis C care. Thank you. Thank you. All right. Thank you, Dr. Fox, for that excellent talk. We're going to switch gears now from the health systems approach to the community approach, and our next speaker is Dr. Anthony Martinez, who is an associate professor of medicine at the University of Buffalo, and he's the director of hepatology at La Bodega, which is a really novel co-localized model for managing viral hepatitis as well as addiction disorders. And his talk is titled Meeting Patients Where They Are, What is the Role of the Hepatitis C Specialist in Community-Based Hepatitis C Care? There you go. There you go. Should be coming out. It might just... Yeah, I think... There we go. Do I change from here or from here? Here. How's everybody doing? Thank you all very much for coming out. It's nice to see for the second day in a row that we're filling the room still about this topic. It's still relevant. It still matters. And honestly, right now, it matters more than ever, and we'll talk a little bit about why. So, a lot of you are aware that we have a federal initiative to eliminate Hep C. It's the first time in U.S. history that we've talked about this, and it's a critically essential time right now. Any plan that you have to eradicate a disease has to be built on some key pillars, and I would argue that with... Hepatitis C is probably four. It begins with screening, followed by linkage to care, then treatment initiation, and the fourth pillar is harm reduction. That's something we haven't really talked a lot about in this particular plan. The goal is really to hit 100% in each of the first three, right? You want to get 100% of people screened, 100% linked, 100% started on treatment. You want to keep that fourth pillar as low as you can because harm reduction is synonymous with reinfection prevention, but what we do is going to look different depending on the population whom you're trying to serve. One size is not gonna fit all. And we know what the disenfranchised populations are, so this is really gonna take a mixed and match approach. And really what we're talking about is decentralization of care. We're taking, oops, sorry. We're taking this, I got excited with myself. You see, I'm fired up now. We've made things real easy. The baseline workup's gotten easier, screening's gotten easier, and that enables us to take care out into the community and take it out of the hands of GI, hepatology, ID, the conventional specialists, and introduce new folks who are from different disciplines to carry this work out. And ultimately, what we're trying to do is obviously increase each step in that care cascade. Now, the ultimate goal, I think, is to reach this test and treat model of care. This is the unicorn, right? But to do it, there's a couple key things that we still need. We need a point-of-care test, rapid diagnostic modality, so that we can identify people quickly. Second, we need to eliminate all the restrictions. We still have a few states where these are in place. We have to get rid of the prior authorization process, make things easier to get access to meds. We also ideally would eliminate the nomenclature of acute versus chronic hep C. This holds a lot of things back. While you're waiting six months to figure out if somebody's chronically infected, there's the potential for new infections during that time period. So we really wanna try to move toward viremic being the main nomenclature. And finally, we have to have no limitations on retreatment, something that we've not talked a lot about in this area. But this is kind of a new barrier that's starting to emerge as more people, particularly people who inject drugs, come into care. Okay, how are we gonna do this? It's really a mix-and-match approach. And we know, we've been asking for 20 years, where are the patients? We asked this forever with hep C. How do we find the patients? We know where the patients are. You've robbed banks because that's where the money is. We know where these patients access care. There's a number of different settings. And we've seen over the years, there's a lot of models. We've seen mobile units, treatment and addiction, treatment in homeless encampments, prison, jail. We've seen all kinds of different models. But each of these settings has different resources. And we have to really assess what they have, and maybe more importantly, what they lack. Because you can't tell somebody just get a reflex test if they can't draw blood, for example, right? You have a number of different providers now doing this work. Most of the hep C care being delivered in the United States right now is carried out by APPs. So we have to engage that community. We have to engage pharmacists. So really, this is gonna take a joint effort, but it's really gonna take a mix-and-match approach. When we think about treatment models, it's kind of three big groups. So there's conventional referral, and that's fine. That works, it can work, and I'll show you my own model in a minute. But the system is kind of hard to navigate. It's hard for patients to navigate. It's hard for providers sometimes to navigate. Transportation is always an issue there. You can make it work easier with community health workers, peer navigators, case managers. Telemedicine, great, easy, convenient, easy for patients to utilize, easy for providers. You can access patients wherever they might be. I'll show you our experience with that in a second and some of the limitations. And then finally, co-localization. This is one-stop shopping. Everything happens under one roof, one team, wraparound services for all your patients' needs. And that streamlines care and kind of makes things real easy for everybody. So this is our shop in Buffalo, New York. This is called La Bodega. We get asked a lot, is it conventional hepatology? Is it addiction? What exactly is it? And the answer is it's whatever the patients need it to be. So some folks come in and just need hepatology care. They just need management of cirrhosis, or they just need hep C treatment. Some just come in, they need addiction treatment. They need medically-assisted therapy. Most, though, there's an overlap with liver disease and addiction, whether it's alcohol, hep B, hep C. So that's what the clinic looks like. When people get cured, we let them graffiti the wall. Ring a bell, a cow bell. I can tell you, if any of you want to steal this idea, don't let them write directly on the wall because it pisses your hospital off. So they ask us, can you have them write on a canvas or something? But the clinic is covered in these names. And it's a motivator, not only for your patients, but also for your crew. If you're getting down on things in the world, you can sit in that space and look at the wall, and it's a very tangible reminder. When you see a couple thousand names of people who turn the page on this thing. So how does it work? It's kind of a series of micro models of elimination, micro elimination models under a larger macro. And it's a bit of a hybrid program, but it's basically a rapid start test and treat model of care. So like I said, we know where the patients are. So we've gone and partnered with all these different sites, whether it's jail, prison, high risk OB, foster care, addiction clinics. And we've given each of them a dedicated screening protocol based on what they have, and again, what they lack. So they've each are screening in a different way. And we have one number, one positive test. All they have to do is call us, give us the demographics, and then our guys take over from there. So again, it's important to meet the patients where they are, but it's important to meet the providers where they are. If you want primary care and some of these other settings to do this kind of work, you have to make it really easy for them to get patients through the system to you. So we facilitate the transportation, we schedule patients, we try to do it within a couple days. Once the patients come in, we then take a co-localized approach. So when they come on site, we have everything available for them, prep services, HIV services, and partly a disclaimer, this model works because we're in New York State, we're a green light state, there's no restrictions, no prior auths. Medicaid expansion state, patients are covered, we're able to keep the medications on site. So when patients come in, most of them have had labs somewhere, we're able to rapidly start them, I mean, it literally takes 20 minutes, they can leave with their medications for medically assisted therapy and their hep C meds. We use this triage system, red light, yellow light, green light, I came up with this, I'm not that smart, which is why it's kind of analog, but a green light patient is somebody who I know if I gave you all the meds, I could see you back in five or six months and I know you're gonna be fine, you'll take them, you're gonna get cured. Yellow light patient, I know if you have the meds, you'll take them, but you're not gonna answer the phone from the pharmacy, you're not gonna call for your refill necessarily, you need a little bit more support. A red light patient, I probably just gave you Narcan in the clinic to wake you up to talk to me, we're still gonna treat you and nothing changes, we just need to give you a little bit more, even more support, maybe we need to hold those meds for you, for example. And we take a minimal monitoring approach, we don't check any additional labs or anything like that, and the model works. So this is some of our data through 2021, we've treated about 1131 patients who met criteria for active drug use. And I can assure you, this is not a Mickey Mouse drug using community, this is heavy fentanyl users in general, in the old days it was a little bit of heroin. And what jumps out at you from the start is the adherence rates among people who are actively using, it's around 91%. The same clinic with the same model, we've treated about 2500 other people who don't have a history of substance use, and their adherence rate is 81%. So people who use drugs actually did better in terms of adherence, overall cure rate 95%. We do about 8,000 visits a year with an 80% show rate, there are no incentives to come, there's no reason to come and see us besides we treat you properly. And there's a 85% retention and care, those individuals who are not already on OAT, there's 100% uptake. So COVID was like gas on a fire, we saw the rates of substance use go through the roof, opiate related overdose deaths went through the roof, we added about 600 people to this cohort during that period of time, really no impact on the SVR, that hasn't changed, and we've got about 400 people that are somewhere in the cascade, either on treatment or in that SVR assessment phase, and we've got a solid handful that have been lost to follow up. But that's where we're at right now, we're trying to break down some of the additional data on regiments. So why does the model work? How does it work? I think the key thing, I'll start three bars in there, we navigate the system, we're navigating it for the people, the patients and the providers, arranging that transportation, facilitating the linkage. Facilitating linkage, one thing that doesn't get talked a lot about is the schedule. So in a lot of clinics, they have a schedule, and if you're five minutes late or 10 minutes late, they don't see you. If you miss three appointments, that's it, there's no chance to be seen. We have a schedule, it's a rough suggestion. My theory is if everybody's 10 minutes late, then they're all sort of on time. It just seems to work out. I follow that rule in my own life. But it's very low threshold, it's flexible and forgiving. And the way we look at this is that, these patients, a lot of them are using public transportation they maybe show up three hours late, three days late, but they showed up. And just the fact that they got there means that we owe it to them to do what needs doing. So the schedule is a key thing. Everybody gets our cell phone number. Getting your cell phone number is the difference between an overdose on Saturday morning and getting a buprenorphine refill on a Friday night. They don't abuse it, it's odd that they don't abuse it. I have one guy that calls me every Easter, I don't know why Easter, and he wishes me happy Easter. So give him your phone number, maybe you'll get a call too. And you can see, look, this is a million body city. And you can see that this is a mixed and match approach even within a smaller community. And we recognize that one size doesn't fit all. And I'll talk about the harm reduction measures in, oh, I'll talk about them in a sec. Telemedicine, we rolled this out during COVID. We ended up doing about 750 visits by video, most of them by video by the end of the second week. 51 patients came in for initial hep C eval with this. We started 49 of them, they all got treated. They hated it. The patients did not like telemedicine. They live with their stressors. They felt like they could not speak freely about a lot of what was going on. They wanted to come in the clinic, they wanted to be in the room with us, you know, to talk and speak freely. We still utilize it. The other main limitation was that it really slows the cascade down. What I can do literally in 20 minutes was taken 90 days. You have to mail the lab slip, they have to receive that in the mail, go to some quest or lab core, and it just slowed everything down dramatically. Every room in the clinic has a red box on the wall. These are the harm reduction supplies that we provide. There's availability of Narcan, fentanyl test strips, zalazine test strips, cookers, cottons, whatever they need to safely use. These are available. We fill them about three times a day. One thing we've seen is that patients will come back in and they'll tell us, the Narcan I took out of the box last week, we use three times out in the community. Can we get more? So this stuff works. It's really important to prevent reinfection. Okay, I just want to leave you with a couple of practical steps that you can maybe utilize if some of you are here practicing in your own clinics. How do we increase screening? One, eliminate the ability to order a standalone antibody test. Rena did a great presentation about the EMR. We implemented this in our own place. You cannot order an antibody test, period. It is only a reflex test. That changed a lot. Really heightened the cascade. Those EMR prompts are key. If you're in settings where maybe you can't draw blood, if you're working in addiction settings, maybe lab field trips work well. So we talk a lot about, you know, people maybe phlebotomy coming on site. You can also take patients to the lab. Use your mobile van, bring them into the Quest and LabCorp. Also, a lot of places don't realize what point-of-care tests are available in their area. This is true even in New York. We didn't realize that New York State supports the utilization of dried blood spot tests. Not a true point-of-care test, but available, free. They'll come and they'll train your staff, but it's not widely publicized. So look into your states. If you have hep C elimination plans or your public health department, you might find some things that you weren't aware of. How do we facilitate linkage to care? Utilization of peer navigators is essential. The heartbeat of my clinic are peers, case managers, social workers. These are the folks that make everything work. It's really that simple. Telemedicine, and I don't wanna put it out there that I'm not an advocate of telemedicine. It is a very useful, Andy Talal has an oral presentation about exactly this. It's very effective. Our particular population, it's a little bit different, but this is, I think, a key modality going forward. Co-localization of services, I can't overemphasize that enough. I really think that that's one of the key things. And that schedule, I think, is an important thing. We lose a lot of people when clinics are dogmatically adherent to that schedule. We know that a lot of our folks with hep C who have been diagnosed, it may take six touches before they make it into the clinic. So six no-shows before they ultimately make it in. But the point is like a kindling effect. Keep trying because eventually they will get there. Treatment and adherence. One of the things that really helps is collecting social media handles and putting them in your EMR. So we hear a lot like, you know, patients, they don't have the same phone number, we can't get in touch with them. The way things kind of work out there in the world right now in the narcotics trade, it's via social media. So even if the cricket minutes run out on their phone, they all manage their Telegram, Snapchat, Instagram, their handles. They find a way to log on. So you can relink patients utilizing the social media handles and you can do it in a HIPAA compliant way where you're not revealing any PHI, you have a blank account for your own clinic. Hey, you got to connect with us. That can be an effective strategy. Partner with the pharmacy. Like I said, we put the pharmacies in our clinic right now. It's literally attached. The pharmacists are right there. This is huge. They really overcome a lot of the gaps. That triage system for med management, you know, I showed you the data, whether it was an eight-week regimen, a 12-week regimen, didn't matter what the regimen was, the adherence was 91%, I think in part because we use that system. We have a tendency in medicine to want to turn everything into the algorithm, but there's still a little bit of art to it. So when you're sitting in the room with a patient, you have 10 minutes to figure out what they need from you in that moment. And you can, you know, that's where that system really comes into play. And we ask patients, where do you feel like you fall in this spectrum of colors? Because somebody who I think is a green light patient will say to me, no, I want you to hold the meds. I don't want to handle it. So there's this shared decision-making that's really, really critically important. Also, a lot of times we get hung up on the fact that they don't have labs, we have to get the labs. Most of these folks have had blood work at some point in their life that will enable you to rapidly initiate them. It takes a little legwork to do the forensics, but both Quest and LabCorp, you can get an account for your institution, you can access that, you can look people up. A lot of times you can find this data that's already in there. So even if you don't have those labs readily available or they don't have good venous access, a lot of times you can find this information that you need. Okay, quick thing here. We don't talk a lot about this in the Hep C space. Sustainability, it sounds counterintuitive. We're trying to eliminate Hep C, so why do we need to sustain? You need to keep your doors open. This is important. So from just the office visits alone, if you follow down your clinic's downstream worth and what it actually earns your institution on lab work, the baseline labs, if they need it, follow-up labs if it's relevant, radiology, fiber scans, ultrasounds, CAT scans, your cirrhotic patients, every six months you're getting imaging, the pharmacy, 340B meds, whether it's Hep C meds, PrEP, MAT medications, vaccines, hepatitis B. This is a new guideline essential that we immunize everybody, screen everybody. These are all ways to generate revenue for your clinic, but if you track that downstream revenue, it can really be a game changer when you're trying to convince your institution to hire you a peer navigator or a case manager. These folks reduce the no-show rate, which increases your show rate, which increases all of this downstream benefit to the institution. So something to keep in mind when you're building out your programs. I'm gonna leave you with this. People ask why any of this works, and it's all about the people. The best programs that are out there, because there's a million programs, why do some work and some don't? The best ones are born of the community for the community. It's all about the people. This is my crew right here. You need the right people in front of the right person at the right time with the right tools. It's all about the folks who are doing the work. Thank you all for sticking with me. Hello, everyone. So the next speaker is Dr. Arthur Kim. Arthur is a past chair of the ASLD IDSA HCV Guidance, and he's an associate professor and the vital hepatitis director of the Mass General. So he's going to be talking to us about life after hep C cure. So we're curing almost everyone, so but what's happened after that? Arthur, join us. All right, what a hard act to follow. Can I just say, preach it, brother? So these are my disclosures. And let's see, it goes straight to my slides, I hope. There we go. And so in 15 minutes that I was assigned, we are going to talk about life after hepatitis C cure. Out of the four talks, we chose ours to reduce to 15 minutes, and there will be a couple sacrifices made as a caveat. This is my bio, another disclosure side. And the idea is that at the end of this 15 minutes, you'll understand key elements of the care of patients after hepatitis C cure. But we will be focusing on risk factors for reinfection. I believe there was feedback from last year's meeting to talk about reinfection more, and so hence an ID guy comes to talk about reinfection, and to counsel and provide preventive messages, and to kind of provide a framework for how we think about as a frontline provider dealing with reinfection, the emotions that come with it, and the logistics that happen. So there will be a few slides, since it is a post-SVR talk, on the management of cirrhosis post-SVR, just a few, before we delve into the meat of the topic. Just to summarize, a large number of studies that are now out there, posters at this meeting. Numerous studies, if you look pre and post-DAAs, and particularly HCV cure, you do see relaxation of liver stiffness, and you see non-invasive markers improve. But at this time, to my knowledge, it is unknown which of those subgroups, if you already have advanced fibrosis or cirrhosis, are no longer at risk for HCC. And so the recommendation exists to continue screening persons indefinitely. For now, the epigenetic changes that have occurred in the liver, the things that are pro-carcinogenic, may still be there, and thus the recommendation that still exists in the guidance. For those who have lower levels of fibrosis, you kind of, you know, we can provide some general tips on liver health, but the recommended follow-up is really the same as if they were never infected with hepatitis C, and so this is where simplification, and you allow patients to kind of leave your practice very readily. But the, and then other guidance for F3, F4 that we talked about, including surveillance for varices. And of course, the workup that occurs when the ALT does not normalize after HCV cure, to be sure there's not another cause of liver disease, such as a particularly fatty liver. And so we heard a lot about harm reduction, and so just very briefly, I like to think about harm reduction in my clinic. And so as an ID person learning from you all about liver disease, sort of what is deleterious, and what is kind of neutral. You get asked a lot about, hey, how does my marijuana work with my hepatitis C care, and I think the studies, at least from HIV cohorts that look at marijuana use versus not, do not really show an accelerated effect, unlike some previous studies in our literature. Ask about supplements, and then the potential coffee. What I find in a visit, it's kind of nice to not say, don't do this, don't do that, don't gain weight, here's something that might be good for you, and so drink up your coffee. But I would point out also in the care of patients with cirrhosis, and I see primarily patients in cohort A, which is, this is a clinic in Italy, you may be in the room, that divided their cured patients by their CPT scores, A, B, and C, or A, with prior non-HCC-related events, and so recompensated, so to speak. And what you're seeing here over a five-year period are the liver-related events, as well as non-liver-related events. And so you can see, as expected, based on their ABC, you know, higher levels of liver-related events. But you're also seeing a very high rate of non-liver-related events. And what are those? They are defined in this study as cerebral events, or strokes, or MIs, or cancer, non-HCC cancer, and or end-stage renal disease. And so if you zoom in on the upper right, liver-related death for CPTA was 0.5%, whereas non-liver-related death was 4.5%. And I think in a clinic, you know, when after you release someone after their SVR, you know, it'd be nice if they didn't have an MI shortly thereafter. And so, you know, I do find that it's important to integrate these elements of other care, promoting what their primary care or their other providers are telling them about smoking cessation, statins. Oftentimes, the moment of SVR cure, that cure talk that you're having, is a great opportunity to also reemphasize, well, now maybe you could work on your smoking. So all along, hepatitis C care has not only been about treatment, it's not only about DAAs. And so this sort of package of counseling, an initial visit you might provide, running the full circle from promoting liver health, preventing comorbidity that we just talked about, and also assessing other aspects that could affect the readiness for care, prevention of reinfection also begins at that point. And you're going to start talking about it early, because adult learning, especially if you're providing all of this information in your initial visit, do you really think your patient in that 20 minutes is absorbing it all? So in adult learning, it's important to reinforce. And so to continually reinforce these messages would be important as well. And we'll get into some of the prevention of co-infections in a little bit. And so a patient that you might see, perhaps an older patient, the risk factors are really far in the past. You would focus on promoting liver health and preventing comorbidity, so that pie graph looks a little different than the counseling messages you might give to a younger patient with SVR, with ongoing or recently resolved risk factors for reinfection. And so to move into the reinfection, it's clear that cure of hep C does not restore protective immunity. There's exhausted T cells. The viruses that come in are different and likely escape previous responses. Let's acknowledge this is a disappointing result for both the patient and the provider. I'll go into a little bit more in a moment. But ultimately, the goal is that if you're trying to eliminate and do your part as an individual provider to eliminate, is to reduce community transmission in high-risk groups. And so those of us who thought about it kind of state this. If you're not seeing reinfection in your clinic, you're not actually in the population that would be reducing community transmission. And so briefly, I know for this room, this is very straightforward, but why are we trying to identify a new infection? Well, you know, you want to reduce further transmission, provide that benefit, and reduce hep C's complications. And how do we do it? Well, quite simply, the baseline is to check an HCV RNA, perhaps yearly, after documentation of SVR and or seeing a different genotype or subtype. And what this means in terms of the advancement of simplification strategies is that for the patients that I see who have recently resolved or recently active risk factors, that I do check the genotype. I still think that it can be useful, especially for acquiring retreatment protocols should they become reinfected later. So I still do include it in certain patients. And then you can also offer it per ASLD and IDSA guidelines to people with activities, exposures, or conditions, or circumstances associated with an increased risk of exposure. Now we're also meeting many individuals who are having exposures almost every day. And so how do you, you don't screen them every day, you don't retest every day. So how do you think about that? Well, you can do it as sort of, you can think about ALT as one element. You can't check an HCV RNA every day. But perhaps more often than the year would be, you don't want to leave them by remit for a year and potentially able to then reinfect others. And so you'll hear a lot more about point of care testing, which would really transform this area in terms of offering it more frequently. The HERO study was presented at this meeting a few years back, Alan Littman may be in the room. It's a U.S.-based multi-center, eight-city site, pragmatic treatment trial, really addressing this population. And rather than previous trials that looked at six months since their last active drug use, they really looked at, we really looked at 90 days. So very active, kind of the patients, I think, that Dr. Martina sees. And just, this isn't been reported at the ACLD meeting, but the reinfection rate that we saw was 11.4 per 100 person years. So I don't know how that strikes you. It's associated with younger age and methamphetamine detection, but there was wide variation by site. And this raises sort of your social context. So there are sites where there is harm reduction around these individuals. Patient have, if they're not in the study, the ones around them had access to treatment, whereas the one site where that wasn't the case, you know, if they reused, they would encounter someone with hepatitis C. And so thinking about that sort of herd level of infection that is, drives reinfection. And qualitative interviews as part of the study demonstrate that most experience immense shame and stigma at the time of reinfection. And so I'll just read one of the quotes from the paper. This isn't even the most poignant quote, but it is related to the provider. So, and then I was like, I found out I was reinfected and I like felt so ashamed because I was doing so good up until that point. And then to see the people that were curing me, and you know, it was kind of like, it was definitely embarrassing at the time. So and there are more poignant quotes from this qualitative work. And so if you think about that, if you're informing a patient about reinfection and sort of the impact on them, believe me, it's impacting them more than it's impacting you. But that immense amounts of caring, shame and stigma that they might walk in. And so trying to counteract that as a provider has been kind of an art that I think needs to be developed. And I'm still exercising it. I'm still learning about this as a provider who sees such patients. The younger age and, you know, the types of substances and the density of injection, you know, not surprisingly help drive reinfection. And so this is a meta-analysis that spans studies from both the interferon and the DAA era. And, you know, overall with recent injecting drug use in particular, a 6.6 percentage per 100 person years. But you can see that protective effect in the left graft of opioid agonist therapy. And so harm reduction, referral, allying with someone, co-localizing as Dr. Martinez does the care, really can help prevent reinfection. And you can also see the age effect in the first part of the right-hand graph. And there's also a signal here about problematic alcohol use, another factor. And so this slide was begun by Sean Folati-Nwilla at Hopkins, and I updated it. But there are a variety of different studies. And I apologize if you're in the room and your study is not at the bottom there. But there's a theme. I mean, it's active drug use. It's reporting specific equipment sharing, younger age. If you had recent acute infection, almost by definition, you probably should be surveilled more after your hep C cure. And then particular substances, if you compare fentanyl to heroin, you know, fentanyl being more frequently injected, methamphetamine use, mixed use. We'll get back to injection partners in a later slide. And then housing instability. Homelessness is a major risk factor, incarceration, all the driving forces that interrupt life and can result in risk for reinfection. If you ask patients a simple question, how confident are you that you would avoid reinfection? Many patients kind of know. So you can ask them and kind of tailor a package to them based on what their answer is. Ultimately, when you look across these studies, there is good news. There are places where there are low rates of reinfection, 2% per 100 person years, 3%. And these tend to be the places you might imagine with high levels of harm reduction. And we'll go over a great example at the end. So one concept that helps me as a clinician who also like integrates a little bit of public health thinking is the R0. And fortunately, this is easier to explain since COVID and the pandemic. The basic reproductive number, this number, this defined as the average number of cases that one infectious person transmits to another person who's susceptible. And a highly contagious disease like measles, if that were in the room and we're all not susceptible, guess what? A bunch of us would come down with measles. And we don't want to think too much about COVID in this setting at the moment since I don't see anyone masked. But let's divide the basic reproductive number even further. So how do people think about this who are infectious disease type modelers? The probability of transmission per contact with infectious person, then C, the number of contacts per unit of time, and then D, the duration that the patient is infectious to others. Now, a single needle stick exposure is felt to be, what, 1% risk, something on that order. So it's really about the density, the regular use, the regular exposures. So the probability isn't what's driving it. It's the number of contacts per time, but in particular, the duration. So if you leave someone out there who's infectious, that's really going to potentially infect all the others around them who are susceptible. And so when you think about DA treatment and SVR, DA treatment reduces that duration for that individual. And then if you do it on a population level, even better. And then harm reduction, you can concentrate on each of those other aspects, whether it's the individual details of how one is injecting. And even ID people, we're constantly trying to work on this ourselves in terms of reducing risk of bacterial infections, fungal infections, and whatnot. And getting into some of the nitty-gritty details would be important. And then number of contacts per time. And so all of that comes with harm reduction. And so social networks is another key element that you could potentially integrate into practice. I mean, this doesn't seem, when you just look at it, like you're integrating anything. What you're seeing here are the self-reported injecting networks in Melbourne. And what you're seeing is, as revealed by phylogenetic analysis, the Wisconsin networks based on the virus. And so what it's showing you is that oftentimes there are these sort of complex networks and hubs and people who seem to be at the center of injection groups. But in clinical practice, a lot of people are dyads. And then one person may cheat on their other user and use outside of the network and bring it into the network. But nonetheless, it really does provide a rationale that treating within social networks, and particularly that strong injecting partner, may reduce risk. So this idea of bringing your friends to clinic. I really love this paper by Greg Doerr from the Kirby Institute in Australia, who's the leader in this field, who thinks about hep C reinfection as really a positive thing. If you're seeing reinfection, I mean, not if it's 100%, but if you're seeing reinfection, you're actually in the population that you're trying to treat towards elimination and reducing that R0. So we actually have a shrinking number of people who are infecting each other. And so these are great strategies. Acknowledge that fact that reinfections will occur. That may help with that sort of idea of disappointment. Assess reinfection risk, again, at multiple points during your patient contacts. And then, because also their risks may change over time. Explore injecting partner relationships we just talked about, optimizing the harm reduction, overdose prevention, monitoring for reinfection with at least a hep C RNA assessment, and then retreatment. So critical, as Dr. Martinez said, without stigma and discrimination. I do have a couple minutes left, so syndemics. So the other than R0, I think about syndemics. So hep C is occurring in the context of overlapping epidemics. In particular, we saw the rise of the opioid epidemic in the last couple of decades. And that is a synergy. That is something that amplifies the hep C. And so when you begin to think about in your communities, whether it's opioids, whether it's homelessness, and how your community is addressing homelessness, all of this helps drive reinfection as well. And so apart from your individual patient interactions, there are roles that we can play in terms of addressing these in a broader context. Now in the 15 minutes I was assigned, I had to give short shrift not only to cirrhosis, but also to MSM, people that we see in our HIV clinics. But to point out that this is a syndemic as well. This overlap between sex, drugs, and not rock and roll, sex, drugs, and perhaps HIV, where it really does result in many transmissions. In fact, reinfection rates in general in the literature tend to be quite high in this population. Perhaps surprising to some, higher than people who inject drugs. And this is defined by chem sex or sex under the influence of drugs. Crystal meth and related compounds are particularly, they facilitate and disinhibit, et cetera. Sexual partners, group sex, traumatic practices, and concomitant STIs. And sexual health clinics was mentioned as one of the allies to the hep C elimination effort. And so if you have one near you, this is another place that could refer to you, hep C patients, but also be a place that you're referring back to provide sexual health preventive approaches. And by the way, just so you know, the people in Europe are designing great preventive approach packages, you know, try to address this and behavioral modification and sort of other cognitive behavioral approach based therapies, I'm sorry, packages to try to reduce these risks. And that is also true within people who inject drugs. Preventing other infections, provision of clean injection equipment and practices. Many hospitals can't do this because of their license. But at least if you know where they can go in your neighborhood, keep a list, I think that can be helpful. So this kind of defines you as an ally to who they are as well, and meeting them where they're at, even if you're in a hospital-based clinic. Vaccination, of course, and a reminder about the new MPOX vaccine for those with certain risk factors. And then maybe not familiar to this room, but HIV PrEP, actually many of you are familiar with this, but HIV PrEP has been seen to be effective in people who inject drugs, a 50% reduction with use of just tenofovir alone. But notably, a bunch of surveys done recently, even though people have those overlapping risk factors, I mean, people who inject drugs also engage in risky sex, et cetera, there's a high rate of risk factors and yet a very low awareness of PrEP. And so in the last minute, I just wanted to point out the Iceland achievement, the TRAPPEP-C, which has been presented at this meeting, I believe, on a couple of occasions. This really innovative, very inclusive treatment strategy, and you can see the elements here, I won't read them through, but I actually include a lot of what was just described. And reinfection rate was reported to 7.7%. I mean, how does that sound to you? But in the end, what they're doing by treating so often is that eventually you will be less likely in Iceland, if you're a person who injects drugs, to encounter someone else with hep C. And so that, they are hopefully going to approach the low levels that they see in Amsterdam, in Belgium, and other places, and work towards elimination. And so just a few takeaways, this is just on the left, kind of describing that differential package of counseling messages. But the key takeaways, hep C care does not really end with cure. You can provide ongoing prevention and treatment for other conditions. You can tailor your post-SVR counseling. You can become familiar, at least, even if you are not yourself, someone who is engaged in harm reduction, but ally with people. I have a bunch of hepatology friends who don't provide PrEP, and they just send the ones they think need it to me. And so connecting that interdisciplinary, such a theme of today, address the social factors and advocate within your communities for broader change, and play your part towards elimination. Thank you for your attention. Thank you. Arthur, that was a fantastic presentation, and you did it so well in 50 minutes. So now the last speaker is Dr. Dave Thomas. He doesn't need introduction, so he's really a celebrity in the world of infectious diseases and hepatitis C. So he's a professor of medicine at Johns Hopkins University School of Medicine and Epidemiology at Bloomberg School of Public Health. He's a previous director of the Division of I.D. at Johns Hopkins, and he's going to be with us, telling us what is new in terms of innovation to eliminate hepatitis C. Dr. Thomas. Thank you, Harry. It's delightful to present in this session, and to have learned so much from the preceding outstanding three talks. So yeah, I'm delighted to speak with you today about some new tools for elimination of hepatitis C, and these are my disclosures. So I think everyone's pretty comfortable with the existing tools, right? We have these blood screening, safe injections, harm reduction, to all those clustered around this goal of preventing new 90% reduction in new chronic hepatitis. That's elimination goal number one. And then testing and treatment, which is principally the way we're meant to eliminate the mortality, to achieve a 65% reduction in mortality. So those are the elimination targets, and the elimination goals, and the interventions and the targets to reach them. So that's kind of the paradigm I'm entering into, but we know that these goals are, these interventions are working. These tools are working in some places. You just heard about Iceland, the elimination, the metrics have already been achieved there. So that's spectacular, but we know in other places that they're not, and so the question is why. I'll just give a couple examples of the problem. Here's the incidence goal in the United States. We're supposed to reduce hep C incidence by 80% as a way of reducing chronic hepatitis by 90%, but instead of reducing, the incidence of new infections, of course, has doubled. So the problem is we're not even close to eliminating, we're going in the wrong direction. One reason we need new tools. And then likewise, on the goal of reducing mortality, we're also, whereas in some places we're on target for doing that, and some have already, but remember, I think there's more people on Anthony's wall than there are people with hep C in Iceland. So that's actually true, because he said 2,000, they have 1,000. So there is different context in which these tools don't work as well in some contexts as in others, and there's multiple reasons for that. And so my challenge is to say, okay, so given that, given that there's some places where they're working, some places where there aren't, one way to think about that is, well, let's make the tools work better in the context where they're not working. And of course we should. But another way to think about it is instead of fixing the context, then let's come up with new tools. I've been asked to speak on three. The first is the idea of vaccination. So vaccination as a way of preventing new chronic hepatitis C, as a way of combating the rising incidence that we have in the U.S. and in other places where there's an opioid epidemic. We know in principle that we should be able to vaccinate to protect against chronic hepatitis C. And these data really came back from studies that we did back in the 90s. We started to notice that persons who inject drugs who had spontaneous clearance, if you kept looking in their blood over time, even though they were in some instances using daily and shooting galleries and row houses in very, very high-risk situations, the prevalence of viremia in persons who had once cleared remained very, very low. And when they did get a viremia, it almost always cleared quickly and had low ALT and had low peak viremia. So we had this sense that not only could you spontaneously clear, but also that that spontaneous clearance had protective immunity, giving us an idea that, hey, why not? Why not make a vaccine to protect against persistent hepatitis C? So we have some animal studies that were done by Michael Houghton chiefly, showing in principle that some level of protective immunity could be achieved. And then this pivotal study done at Hopkins in San Francisco, Kathleen Page and Andrea Cox leading the study, taking a chimp adeno prime boost with MVA and then giving this or placebo to persons who are at high risk of hepatitis C because they injected drugs. And then giving them observation after the vaccination to see whether there'd be incident hepatitis C. And then the main thing, would those incident cases persist less in the group with the vaccine? There were some promising early results showing that the peak viremias were indeed lower in the vaccinated group in comparison to the group that had placebo shown in the dark line there. So that's high peak. Maybe this works. Yeah. High peak viremia in that group and low in the group that got the vaccine. So that was promising and there's ELI spot data and other more complex immunology showing that viremia, that there was some level of immunity achieved. But unfortunately, the same exact number of chronic hepatitis C cases in the vaccine group as in the placebo group. Absolutely zero evidence of protection. So in that, the first study that was done to use a vaccination to prevent chronic hepatitis C has failed and took about seven years and raised the question of whether alternative strategies should be considered because we're still needing a tool, right? We still have an opioid epidemic. We still have incident infections. And to my knowledge, nobody has a really strong idea of how to solve that problem without a vaccine. So the other new tool, new way of using a new tool would be this controlled human infection model. It's been used for malaria and dengue and influenza and Shigella, lots of other infectious diseases where individuals' candidate vaccines are rapidly screened by enrolling volunteers who are willing to receive an inoculation after vaccination to characterize the efficacy of a vaccine quickly and then set the stage for pivotal phase three trials. There's a whole session on this later on in the meeting and a supplement in CID that you can refer to if you're really interested in this model. So model, my new tool number one that I was asked to address is vaccination. There's good preliminary data to support that we should be able to produce immunity. We've seriously tried only once and it was with a vaccine that didn't produce humoral immunity. It only produced T cell responses and we have failed. And then this is a new way of trying to develop that new tool for the future. Tool number one. Tool number two, I'm going to, oh, and I'm sorry, I should have mentioned to be complete that in addition to this of course we should be thinking of new ways to achieve harm reduction. I don't mean to imply that the only thing we should do is this vaccine, it goes without saying that innovation in this space would be especially welcome, innovation in ways of interdicting the complications of drug use and making it safer. But there's a lot of big challenges in that and as our CDC has shown in the United States where many of the new infections occur far from where there'd be traditional harm reduction services could be provided. Okay. So just to be clear on that. That's tool number one. Tool number two would be better diagnostics, innovations in diagnostics for hepatitis C. You've heard already about the rapid testing. Anthony's talked about that. Other people have integrated point of care testing for screening for hepatitis C. There's also a literature that I'm about to show on using methods for confirmatory testing at the point of care. And that's the missing tool. That's the one that we all kind of hope for. The use of either the circulating core antigen or perhaps more likely hep C RNA and being able to detect that at the point of care rapidly so that not just so that you could make that diagnosis but so that you could implement and deliver care immediately without the delays. And it goes without saying that for that goal to be achieved, for it to be, for point of care hep C confirmation to be useful then it also has to involve screening for hepatitis B surface antigen because you have to eliminate persons with chronic hepatitis B so that you can safely administer hep C DAAs or at least be aware of their status. So there's been some research led chiefly by Jason Grebely in Australia taking the gene expert which has really revolutionized diagnostics in tuberculosis around the world and taking this and basically using finger prick a small roughly 100 microliters of blood, of whole blood loading into the gene expert cartridges and detecting hepatitis C RNA. These tests and a series of studies that he's published have very high sensitivity and specificity for detection of the RNA. Unfortunately the time that it took to get a, especially to be confident on a negative was in the first instance 108 minutes and I know a lot of people working in harm reduction settings don't feel like most people want to hang around for a couple of hours waiting for a point of care confirmatory assay. With further research Jason's been able to adapt the assay and shown that most of the time you can get a positive down to about a half an hour. I think a lot of people are thinking it should be somewhere in the 10 to 15 minute range for it to be really useful and sort of balance the other issues that someone's dealing with coming in for a substance abuse visit. So that's where things stand right now. These tests are used in some settings I think in England and Australia and I think there's even a poster on a homeless outreach in England where it's been deployed. But in the United States the pivotal studies are now just being conducted and being conducted under fortunately the President's initiative for hepatitis elimination. There's also just as I mentioned with vaccination other ways to do harm reduction. There's of course other ways to innovate in the area of diagnostics to help achieve elimination. Lots of other tools, lots of other approaches. Not just for example the chemistry being different for detection of core antigen compared to RNA but also different paradigms for testing. And I thought this one was especially interesting in Pakistan self-testing, sending out kits, allowing people to do their own diagnostics showed improvements in ascertainment of new cases and engagement and care. I know some of my colleagues at Hopkins have been doing that with STIs for decades. Sending out STI testing kits and allowing people to take their own health into their own hands. In some instances that's very helpful. Okay, that was tool number two was on the diagnostics. The third tool I was asked to address gets to this problem here because we talked about confirmatory care, point of care diagnostics and that really is critical. But in some contexts such as in the United States a lot of people already know they have hepatitis C and are not treated. Okay, so the CDC has been publishing on this and drawing attention to this paradox. In the U.S. even highly insured, even settings with private insurance, Medicare, private insurance, the rate of viremic persons receiving care can be as low as 50% and in settings with Medicaid and other and no insurance it's much lower. So what about how are we going to deal with the fact that people that know they have hep C RNA and are already known to be positive aren't getting treated? And here the new tool that I'm going to suggest is the idea of a single injection cure. So this would be coupled with point of care diagnostics and the idea here is to deliver care, to deliver cure at the same time as making the diagnosis ideally with this point of care test. We have a lot of the features with hep C that would make you excited about a possible long acting treatment that could achieve a single injection cure. For example, we have pan genotypic medications. They don't have hypersensitivity issues and wouldn't require oral lead in. There's no serious problems that I'm aware of with resistance. And no tail issues like we had with HIV that were made us fret a bit in the early days. We can cure with GP with eight weeks with very, very high confidence, high real world efficacy even when the adherence is much, much lower than in clinical trials. And there's already evidence of patient, high patient interest in this form of, in this new tool. And as is shown by Dr. Gupta at this meeting, provider interest and support for this approach. There's, so then the question is down to can you do it? Can, is the chemistry right? Can you, can you actually make these molecules long acting? And I think the question, that question hasn't been answered but with their permission I'm showing the results of the group from Liverpool that have taken Glicapivir and Preventivir have created a long acting formulation and injected it into rats. And you can see on the PK and the human C-troph, the idea being that all's we have to do is stay above C-troph and we should be okay. And then look out there to the, to an eight week time point. And they're already able to achieve in rats in this rat model with a single injection, semens, or concentrations that are above the human C-troph. And super importantly, given that there's a parenteral injections, these levels are also comparably high in liver tissue to that, that's been achieved with oral ingestion. So that's, I mean, as I see Ray Shannazi in the back, I mean, the people that do drug development know, okay, that they've got a long way to go. You don't, you know, write a prescription tomorrow for these. So there's a long, long, long way to go. But at least there's some, certainly enthusiasm, certainly public health need, and perhaps even some early preclinical work to suggest that that's possible. So three tools that I've talked about, three new tools in HCV vaccine. Point of care confirmation, and then these long-acting cures. I think those are the three main new tools that I was asked to talk about, and which in some contexts will be super important to augment, and could be important to augment the existing ones. I'm going to add a couple that I wasn't asked to speak on because I've got Arthur's five minutes that he gave generously to me. So I'm just going to go ahead and use them. And mention briefly that, of course, surveillance, we need to do much, much better with surveillance than we do now. You have to find out where the EMR, you know, ideas were terrific. But there's so many ways we have to know where the people are. In Maryland, the hep C's are portable, and the positives come back, and they go to the health departments where they go in a drawer. Because there's no case, there's no case management. So they literally go into a drawer. We have to, I mean, so much as a clinician, I didn't really appreciate how much is, how much of the space requires downstream and important movement with patents and licensing and pricing. There has to be a financial upside for companies. There's just no other reason that they would bother to develop these. That's their job. And so there's a lot of complicated things that have to happen in order to bring about new tools, whether they're diagnostic or therapeutic, or a vaccine. And which aren't as evident as one might hope right now to help us achieve elimination. And likewise, some situations like the downgrading of the FDA requirements for diagnostics and some preapprovals that WHO have can be very, very helpful in this space. There's probably, in my view, nothing more important than politics to actually bring this about. I say that because in places like Egypt where there's an amazing elimination program, there's very, very strong high-level political support. And now it's exciting because in the United States, we now appear finally to have that sort of, we've always had John Ward, and we've always had CDC. We've always had support, but now we have support that may have some money attached to it. And that's terribly, terribly exciting and important. And if you didn't get a chance, listen to the webinar from yesterday on that. And then don't forget the other new tool. It's not new. We've been doing this all along. But I have a growing appreciation for the importance of engaging civil society, engaging persons with hepatitis C or at risk or who know somebody with hepatitis C to find these solutions. I think there's a lot of different solutions for a lot of different contexts, and it's important to learn from them what the best paths forward are. So I've got my three practical tips I was asked to give to, and mine are quite simple, adapt and innovate. Adapt the tools that we already have and try to make them fit as well as possible in your context, as you heard with the EMR and with all the exciting innovations that the first three speakers discussed. But also involve persons living with hepatitis C to try to figure out the solutions in contexts where they're not working very well, such as in the United States. You'll get some interesting ideas. And different ideas. No two people even say the same thing in my experience. And then prioritize trying to come up with new ones like the vaccine. We need funding for these kinds of tools, and we need funding for the companies so that they can make some money if they make the tools. And those things will then incentivize movement in this space. And those are my three practical tips. I've learned a lot from a lot of different people on this topic, and I'm showing their pictures here. And thank you very much for your attention. Okay, so we have five minutes for questions. After this session, so we are starting the hepatitis C sick business meeting. If you are in the business of eliminating hepatitis C, you can stay. If you are not a member of the sick, you can join the sick. Okay, but we need your input. Okay, we have time for a couple of questions. Short questions, please. And you will receive short answers as well. Hi, Jessie Torgerson, University of Pennsylvania. I'm really excited to see the EMR initiatives be incorporated into improving hepatitis C screening. We at Penn have been able to integrate a default admission order to implement hepatitis C screening on everybody admitted to the hospital with great success. And that allows us to identify people quite early on in their hospital stay, link them to care, and even offer expedited treatment. That would not be possible without a dedicated team to link and offer that care navigation. And so I wonder, with these EHR tools, how have you been able to leverage the needed resources to ensure that linkage and care navigation is coupled with that screening and diagnosis? Thank you. That is a great question. How to leverage resources to support the linking and navigation? Short answer, to be creative. It's definitely the hardest part. I think, you know, showing your institution your own data is motivating, showing them that there's a White House elimination plan, showing them that there are global needs for this. I think really emphasizing some of the existing disparities, the use of the system by hepatitis C patients has been persuasive. And resources may or may not, you know, be really available, but I think we're finding some success with those approaches. One more question. Hi. Kirsten Ramers from San Diego. Specifically for David and Arthur, you know, during COVID, the Abbott ID Now test was developed. That was an isothermal PCR with, like, a molecular result within 10 to 15 minutes. And as far as I know, the gene expert is a thermal cycler. That's why it still takes a longer time. And I have patients like Tony's, that they're not going to stick around for 15 minutes. They're going to go out and want to inject again. So is there some technical reason why HCV RNA cannot be amplified the way SARS-CoV-RNA can in 15 minutes? Dave, do you want to take that one? Yeah, I think the technical reason is that there's not a strong perception that there would be money for doing that. Like, there wouldn't be the company. If a company did it, they won't make money. And there was for SARS-CoV-2. And there was an easier regulatory path. I think it's that simple. I don't think the chemistry is that hard. I'm not a chemist. Somebody maybe smarter than me could say, but it's an RNA virus of 9KB, and I don't really... I think it's... In both cases, I think it's down to the... Jean-Michel, is there, like, a chemical reason why that couldn't work? I mean, you're the diagnostics guy. Is there any reason why you shouldn't be able to do an isothermal RNA detection, or is it just because there's no money and so no one's working on it? Thanks for reviving me. Um... Yeah, you look tired. Jet lag. No, but you gave the right answer. I mean, I think there is a prototype for HIV RNA of the ID now, but there is a technical reason for this not to work. But it's just the money that doesn't come behind it, and there is no reason to invest in this. But I think the American situation with the opioid epidemic is something that can really help you convince companies to jump into this. But as always, you have to be quite pushy. Yeah, thank you. Sorry to disrupt you. Okay, Dave, I have one question. On the long-acting formulation, so do we know for the HIV world that we use long-acting HIV drugs on patients who are stable on previous antiretroviral therapies? So we don't use this, I say, for naive patients. So knowing the differences between HIV and hep C, are you concerned with, you know, using this drug for patients with very high viral load that they may have resistant associative substitutions as a baseline? Are you concerned with that, using this long-acting? I would love to have that problem. You know, I think that, I am not terribly concerned. First of all, asking 1,200 persons with hepatitis C what they think, they're 91% were very willing, and about 40% preferred taking pills. The idea of an injection. Just be done with it. Don't have to bother with carrying the pills around. So I think there's plenty of interest. And I don't really think there's, we haven't had as many problems with resistance, have we? You know, it's just been interesting. And so, obviously, if there was some imbalance and there was some exposure to the NS5 acting, the more susceptible drug, maybe. But that would be on the tail, and that's on the end, and that's when there's not much virus left. So no, I'm not that worried about it. Any other questions? Then thank you, everyone, for coming, and to our speakers. Thank you.

Hepatitis C

care cascade

diagnosis

treatment

prevention

electronic medical records

interdisciplinary collaboration

post-cure care

harm reduction strategies

vaccine

point-of-care testing

single-injection cure

civil society