Good afternoon everyone. So it's an honor to introduce you to the first presentation on the hepatitis C programming and for the hepatitis C sick. So it's so good to see your faces again. So after almost three years of facing what we face, but it's still a battle, but here we are. So what we're going to do today is we're going to talk about challenges as well. But at this time, it's going to be challenges on hepatitis C. What are they? Still the areas where we have not conquered and we have three experts on the field. So next slide please. And we're going to talk about the remaining challenges and opportunities on hep C and prevention and treatment. Next slide please. Our first speaker is going to be Jennifer Price from University of California, San Francisco. She's going to be talking about challenges and treatment of hep C. Also Julius Wilder after her was from assistant professor from Duke University. He's going to be talking about confronting racial and ethnic disparities and hep C care. And finally, Tatiana Koshner is going to talk about hepatitis C and pregnancy from Mount Sinai. So we have, we're going to have at the end a Q and A session as well. So hold all your questions for the end and here we are. Thank you. Okay. Thank you, Harris, for that introduction. I agree. It's so nice to see so many of you in person. I'll be talking about tackling the remaining challenges and the treatment of hepatitis C. My name is Jennifer Price. I'm associate professor of medicine at UCSF and director of the UCSF Viral Hepatitis Center. And here are my disclosures. So I thought I'd start the talk by describing to you what a typical afternoon in the hepatitis C clinic is like for someone like me, a subspecialist treating hepatitis C in 2022. So this was a regular clinic back in March of 2022. Our one o'clock patient had genotype three cirrhosis. He was decompensated. He had a prior DAA failure. His MELD score was 16 and he had symptoms of decompensation. So we started the liver transplant evaluation, but also started him on sofosbuviravilpativsvir plus ribavirin for a plan 24 week duration. The one 30 patient was a 40 some year old woman who had recently undergone bilateral lung transplant for interstitial lung disease. She was hepatitis C negative prior to transplant, but received a hepatitis C positive organ in order to decrease her waiting list time. She got started on glucapavir perbrentisvir post-op day one with a planned eight week course. And I saw her in clinic again about three weeks after her transplant. The next patient was a new patient, a gentleman who had recently undergone a simultaneous liver kidney transplant for hep C cirrhosis genotype 1A complicated by HCC and end stage renal disease. His hep C was not treated prior to the transplant because of his active HCC. So we got him started on softfel for 12 weeks. Next new patient at 230 was a HIV and hepatitis C co-infected patient with genotype 1 compensated cirrhosis prior DAA experience. Although she wasn't sure how many weeks of treatment she had completed, she knew that she hadn't completed the full course, but nevertheless, because of her prior treatment experience, we treated her with softfel vox for 12 weeks. And then last patient, not the last actual patient, there were a lot of followups in between here, but the last patient was a 65 year old man with genotype 1B non-cirrhotic hep C with end stage renal disease on dialysis, who was not a kidney transplant candidate because of multiple comorbidities. And so we started him on Gleepib for eight weeks. So now fast forward seven months later, following up in clinic, our patient with decompensated cirrhosis had achieved SVR4. He's still awaiting his SVR12 labs. Our lung transplant recipient actually never became viremic after her transplant throughout treatment course or after treatment. And the other three patients all achieved SVR12. So as you can see from these examples, as hepatitis C treatment has rightfully moved out of the subspecialty clinic, people like me who are subspecialists are seeing a lot of the patients who belong to the so-called unique or special populations that traditionally have been challenging to treat and to cure. And a lot of these patients belong to multiple different groups of these populations. So we had someone with a treatment failure who also had decompensated cirrhosis. We have patients with organ transplant, patients with HCC and organ transplant, HIV or hep B co-infection, end stage renal disease. I'm not going to talk about this today, but we also see patients with acute hepatitis C. And then you'll hear later this afternoon about people who are pregnant. But for the remainder of the talk, I'm actually not going to focus on these so-called special populations. So yes, it's true that in some of these key populations, challenges to treatment remain and our decision on the timing of treatment and the specific regimens are nuanced. But generally, if DAAs are started and they're completed, the cure rates are exceedingly high. And I think my examples demonstrate that. So what then are the remaining challenges in hepatitis C treatment? So I would argue that the biggest challenges remaining are really diagnosing hepatitis C viremia and getting treatment started, so initiating treatment. And these are really consistent challenges globally. And I think that was well demonstrated in this figure from a recent Polaris Observatory publication. So they looked at the hep C care cascade from 2015 to 2019, and then again, the annual cascade in 2020. And what you can see here is that the global prevalence of hep C viremia in 2015 was 63.6 million individuals, but only 33% of them were diagnosed. So that's far below our 2030 target of 90%. And then just a fraction of them were treated. And then moving on to 2020, now the global prevalence of hep C viremia was estimated at 56.8 million. So we subtracted 8.7 million cures from 2015 to 2019, as well as, unfortunately, 5.5 million deaths. But we also gained 7.5 million new chronic infections. And you can see here, only a small fraction of them, just 23% were diagnosed in 2020, and just a sliver, 5% were treated. You can't even see that bar. So clearly, across the globe, diagnosing hep C viremia and initiating treatment are major challenges. And the reason for that is really going to vary depending on where you are worldwide, even where you are in the United States. One of the major barriers in the United States is actually self-imposed, where we have these sort of artificial barriers to treatment access. Here in the US in 2022, there's still two states that have fibrosis restrictions to Medicaid access to DAAs in 2022. There's also 12 states that have substance use restrictions, 12 states with prescriber restrictions, meaning that DAAs have to be prescribed either by or in collaboration with the subspecialist. The majority of states still require prior authorizations, which I know many of you in this room realize can be extremely onerous and can take weeks, if not months, to obtain. And then there's numerous other treatment restrictions. I won't read all of these, but most states actually still require genotype documentation. And I'll say, at UCSF, during the height of the COVID-19 pandemic, when our lab was overwhelmed, it could take over three weeks just to get a genotype result back. There's also nine states that still have barriers to replacing lost or stolen medication, even after somebody has started treatment. So this is all very low-hanging fruit that we can address to improve treatment access in the United States. In San Francisco, where I practice, we've actually addressed a lot of this low-hanging fruit already. Some of you may know that in 2016, we became one of the first U.S. cities to launch a hepatitis C elimination initiative, and we call this NTEP-CSF. It's a community-owned, multi-sector, collective impact initiative. And our mission is to support all San Franciscans living with and at risk for hepatitis C. We have several shared values. It's a very diverse group, but we all agree that all people living with hepatitis C deserve access to a cure. We engage populations that have been characterized as quote-unquote difficult to engage, and we address health disparities. And you'll hear more about that topic later this afternoon. So in this environment, we've also adapted our UCSF Viral Hepatitis Clinic. So this is our traditional brick-and-mortar clinic, where we see the patients like the ones that I described. This is actually our brand-new clinic, and I don't know if you can see. If you look really carefully, you can see the Golden Gate Bridge peeking out in the back there, so it's quite nice. But three years ago, we also launched a mobile hep C clinic, which we call the Deliver Care Van. And this actually initially was launched to provide hepatitis C screening and fibrosis staging and linkage to care in impacted communities, but it became clear very quickly that we also needed to provide low-threshold hepatitis C treatment. So about nine months into providing screening, we also just decided to do the whole care cascade on the van. And by having this van, we're able to go directly to communities that need hepatitis C screening and treatment and really literally meet people where they are. So the last patient that I want to present is actually one of the first patients that we treated on the Deliver Care Van. He was a 40-year-old man, and he presented to the van, which was co-located outside of his methadone clinic. So basically, we partnered with this methadone clinic. We parked outside of their clinic every Friday, 6.30 a.m. to 12.30 p.m. They always knew that we were going to be there. The methadone clinic staff encouraged the clients to get tested on our van, so they encouraged this client to get tested. The client had a rapid hep C antibody on the van, which was reactive, and he underwent venipuncture for hepatitis C confirmatory testing. We had to send this out to Quest Lab, so we couldn't give him immediate results, of course, but he came back one week later for his hepatitis C RNA disclosure. He was RNA positive, so his results were disclosed. We actually have a portable fiber scan on the van, so we were able to do his fibrosis staging right there. And then he really wanted to get treated with us on the van, so the staff collected all of his insurance information, and then at the end of the shift, got authorizations for a clinic visit, which happened the following week. So he had a staff-assisted telehealth visit with me. The van staff just set up a laptop on the van and did the Zoom with me. He had his pretreatment labs drawn the same day, and we typically get a CBC, a CMP, HIV, and hepatitis B serologies. Back then, we also had to get genotype because of the insurance restrictions. And then once all those labs came back, we sent the prescription to our pharmacy, and the patient actually signed a consent form to have the deliverer staff pick up the medications on his behalf from the pharmacy. We have a fantastic pharmacy team that really knows how to do these prior authorizations and do them speedy, so they got the prior authorization within the week. The staff brought the DAAs to the patient. He had another video visit, this time with our pharmacist to review the details of treatment, and then he got started on treatment. So four visits in three weeks to get started on the treatment. And then in terms of his treatment, it turns out he was genotype 3. He was treatment naive. His fiber scan showed F2 fibrosis. He did continue to use methamphetamine and heroin intermittently, but he was highly, highly motivated for hep C treatment. He really, really wanted to get started. And he had been previously unhoused. He was currently staying in a navigation center and had a locker for his medications. So his top priorities were to get started on treatment and he wanted to be done with treatment as soon as possible. So we decided to treat him with Glee-Pib for eight weeks. And the staff went through an individualized treatment plan. I just show an example of a blank example of what that looks like. But they basically work with the patient to decide how many touch points they want, how often they want to come back for their medication pickups. And then each step in the process is also incentivized, which is an important point with a $5 gift card. So for the blood draws, for medication pickups and RNA disclosures. So we got him started. He had weekly follow-up on treatment because he thought that he couldn't hold on to more than one week supply of medication at a time. So he elected to come and check in with us every week, which he did. He got his medication pickups. The staff kind of did adherence check-ins. We could do blood draws as needed. We typically do a four-week blood draw, not because it's required, but we find that our patients like to get the feedback of seeing their viral load drop or even be undetected. And then as I mentioned, he got gift cards and other incentives, hygiene kits and snacks, et cetera. Things were going quite well. His week four lab showed that his hep C RNA was not detected. But then when he came for the week six pickup, he reported that he had been kicked out of his shelter and he lost everything. So all of his items that were important to him were locked in his locker and he was unable to access them. So he lost all of his possessions, including his week five of meds. So his last pill was seven days prior. So the team gave him his next supply of the Glee Pib and he resumed treatment with that one week interruption. And then our fantastic hepatitis C pharmacy team immediately requested and received approval for seven additional days of treatment. So now the end of treatment was postponed one more week. And he went back on, he was doing really well until the week seven pickup and he didn't show up and we couldn't reach him because he had lost his phone. So the methadone clinic staff agreed to hold on to that week supply in a bag and give it to him when he came in to dose his methadone. So we gave them his week supply and kind of crossed our fingers and he picked it up. So that worked. And then post, after his week eight, he was gonna check in to confirm that he had completed treatment. But again, no show and we couldn't reach him. While we were looking for him, we were notified by the San Francisco jail nurse that he actually was in jail. So that's why he didn't show up. But he had brought his medications with him and they allowed him to take it in jail so he was able to complete his treatment while in jail. He was not there for very long. He returned for his SVR visit and labs confirmed that he had achieved SVR. Okay. That's what we all felt also. There were a lot of celebratory text messages. And now it's been two years post his treatment. He does struggle with ongoing substance use and housing instability. But interestingly, unlike when he started treatment, he now is actually regularly engaged with his primary care provider and sees her regularly. She's been checking hepatitis C RNAs regularly because he does have ongoing risk factors for transmission and his hep C RNA remains undetected. So one of the first take home points from the story is that for some of these patients, it really takes a village to achieve a cure. So this was a tremendous achievement from the patient. This is not the actual patient. But this was a lot of work for him. I mean, imagine losing everything that you owned and then still showing up and continuing to take your treatment and then being in jail and bringing your medications with you. So it was a lot of work on his behalf. It was a lot of work from our outreach team. We have a very skilled phlebotomist in our outreach team, which really makes a huge difference. The methadone clinic staff really went above and beyond in supporting the patient and then supporting us supporting the patient. We had multiple clinicians, not just myself, but Lisa Catale, one of our nurse practitioners in the clinic and then our tremendous pharmacy team, including Diana Ong. The jail health team, I didn't have a picture of the jail health nurse and then his primary care team. So I just wanted to take a moment to acknowledge all of the work that it can take to get somebody all the way, not just on treatment, but also through treatment. And then my second take home point was that we really need to make this less difficult. So we have everything streamlined on the van as much as we can. We literally are bringing it out to people and it's still really challenging and a lot of work. And I mentioned in the beginning, we thought this was great that we got somebody screened and started on treatment within three weeks, but there's no reason why this can't all be done in the first visit rather than four visits. It shouldn't take three weeks to get somebody started on treatment. Each of these places are touch points where we could have lost the patient and not seen him again. And I do think it's feasible that we can consolidate or truncate all these visits and do it all in one visit, but it's gonna take a few things. So first of all, we're gonna need molecular point of care testing. We currently do not have any molecular point of care tests that are commercially available in the United States. The Cepheid GeneXpert is available outside of the United States and has been used in multiple settings outside of the US. And I just included one example here. This is from the Combi Clinic, which is also a mobile hepatitis C clinic that operates out of Australia. And they've been very successful at getting people screened and treated. And you can see it doesn't turn up very well because it's in yellow, but on the vans that have the GeneXpert machine where they could do the point of care RNA, they can skip all the way from visit one all the way to visit three in the first visit because they can give people their RNA results the same day. So we definitely need this for a test and treat model. The other thing that we need is to really get people started on treatment right away once they're diagnosed. So even when we know that people have hepatitis C viremia, it takes several steps to get all the authorizations and the labs and the clinician visits. We really should be able to start people as soon as possible. And that's what we did in this study at UCSF that we call the No One Wait Study or No Now Study. It was essentially a point of diagnosis treatment initiation study. So I know there's a lot of information here, but I'll just briefly explain what we did. We screened several hundred people who were at risk for hepatitis C. Most of them were recent injection drug users or were unstably housed. And we did the same thing that we did on the van. We did the rapid antibody finger stick. And if positive, drew blood for RNA confirmatory testing and had them come back the following week. But unlike on the van, when they came back the following week and got their RNA results, if they were RNA positive and they met the criteria for simplified hepatitis C treatment, we offered them treatment on the spot with a two-week starter pack of cefosporavir vilpatisfer, which was provided by the study. And then behind the scenes, we worked to get the remainder of their treatment course approved through their insurance. We also did all their pretreatment lab draws that day. So same day as treatment start. And they had a staff assisted telehealth visit the same day. And we identified 126 individuals who were eligible for hepatitis C treatment, meaning they had active hepatitis C infection. You can see here that 89 returned for the results disclosure. And among those, almost everybody got started when they were offered treatment start. So the rapid treatment start was very successful in getting people started on treatment. But look at all the people that we lost having to have them returned. So that's 29% of people we didn't see again. And so we weren't able to get them started on treatment. So we do have more results. I encourage you to visit our posters on Sunday to see the additional outcomes. And then finally, I've been talking a lot about treatment initiation, and that's obviously a very important goal and endpoint, but we still have to remember that there are a lot of on-treatment barriers that we could remove in order to maximize our patient's chance of cure once they get started on treatment. So certainly we can remove these insurance restrictions that lead people to have to withhold DIAs if a patient is deemed not adherent, or their medication is lost or stolen. These are really decisions that need to be made between patients and their providers, not the insurance companies. I think it's also important to recognize that the MinMon approach showed that dispensing an entire treatment course up front can be extremely effective. So there's no real reason that we have to have people come in for multiple checkpoints and to come in after four weeks to get their refills. If we could just give people their entire course up front, it would greatly streamline the treatment algorithm. For some patients, like the patient that I presented, that would not be sufficient. And for those patients, we really have to assist them with medication security. Directly observed therapy is a great option if appropriate. This can be a really good option for people who dose their methadone on a daily basis because they can get their DIAs at the same time as their methadone. A lot of other programs use storage lockers that they offer to their patients during the course of treatment so that they can safely hold their medications in the storage lockers. We, of course, can't offer that on our mobile van, but what we do is we assist people with what we call personalized medication security devices. So we kind of design these devices to help people keep the medications on their person. And I have just a couple pictures here. This is one patient really liked his two-week medication box, but wanted to actually physically be able to keep it on him rather than put it in his bag, which he was worried would get stolen or swept up in a street sweep. So we fashioned a carabiner on it and he could just loop it to his belt loop and carry it with him at all times. And then this is actually quite popular, this necklace, which has a bag for each day of the week. And we have the pills inside the bag and so the patient can just rip off the bag, take their medication and be done with it. And then when there's no more left, they know that they need to get their refills. So we'll refill on a weekly or biweekly basis. And of course, since there are people that taking a daily medication for eight weeks or 12 weeks can be really challenging, I think for them, a long-acting DAA formulation, preferably an injection, could really be ideal. And there was actually a recent study published where they asked 1500 people who either had hep C or were at risk for hepatitis C what their preferred formulation for a hep C DAA would be. And a sizable minority actually would prefer a long-acting DAA injectable over oral medication. So I think there's definitely a need for a long-acting injection and desire from the patients to have one as well. So in summary, my key takeaways about the remaining challenges in the treatment of hepatitis C are that in our individual clinics, treatment challenges remain for these quote unquote special populations. There's often a nuance of timing or ideal regimen, but the bottom line is that most patients can be cured if they are treated. But diagnosing hepatitis C viremia and starting treatment soon thereafter really remain the biggest challenges to hepatitis C treatment globally. Tackling these barriers is feasible, but it's going to require resources. And perhaps these resources may become available in the future with this National Hepatitis C Elimination Plan. We'll hear a lot more about this plan later on in this conference. So I just want to thank all of the people that I've had the pleasure to work with in San Francisco, including the Deliver Van Care team and volunteers, the Phenomenal Now Study, and the NTEP-CSF community. I want to especially thank Nora Turow who was so supportive in getting this van launched and patiently listened to me talk about van specs and insurance and licensure and risk management and all sorts of things that I had not had prior experience with. And I want to thank all of you for your attention. And now I'll introduce Julius Wilder who is going to be speaking about tackling racial and ethnic disparities in hepatitis C care. Good afternoon, hope you're all doing well. My name is Julius Wilder, happy to be here, appreciate the opportunity to share with you all some thoughts on how we think about addressing racial disparities in Hepatitis C. I think a lot of our conversation will be specific to Hepatitis C, but some of the things we talk about are going to be relevant in other spaces that we can identify disparities. And so what I'd like to do today is to kind of begin, I have a number of disclosures here, none of them are relevant to our talk today. This is the objective, so first we'll talk about equality, equity, and social drivers. Because I think those are things we talk about and hear about all the time, but I want to provide a little perspective on those as we move forward in this space in hepatology and think about addressing health disparities. Then we'll dive into defining some of the disparities that are out there and contextualizing them in the setting of the various social drivers that exist. And then begin to think about how we can challenge ourselves around different ways we can do this research, different approaches to addressing these issues. I always start with this picture here that many of you have seen before, right? That first picture is things being equal, and I'm not really into things being equal. I'm the youngest in my family, I've got two older sisters, they beat me up a lot, there's nothing but equal in my entire life, probably a couple of evil older sisters in the audience right now know exactly what I'm talking about. Equal is not good, right? If you're tall in this picture, equal is great, but you're starting way ahead. And we know what happens when you try to do equity, which is that middle box. And equity is a really interesting thing because we all love talking about equity. In fact, that became a very popular word a couple years ago here in the United States, and around the world quite frankly. And the fact of the matter is that equity is great, and equity in many spaces might be the best we can get to, but you can see what equity is, right? Equity is, yeah, one person in this picture is standing on solid ground, but the other folks are standing on support systems, some more than others, right? What does it mean to be on one box versus two? What does it cost to have two boxes versus one versus none? What happens if you fall off that box? How long do those boxes last, right? So equity is a honorable thing when trying to address disparities, but it is not the answer. And I think if we're going to cost ourselves a lot of medicine and a lot of lives, that's what we think in medicine. And this final picture speaks to where I think we need to get to, which is really addressing the social barriers, creating a system, addressing the issues within our culture that are driving the disparities in the first place. That's how you address the fundamental causes of disease, and that's how you create interventions and changes that are going to be really sustainable, and a win really for everyone across the board. And so we talk about social drivers, and we know what they are. We see them every day. But these things focus really on sort of like the social conditions. They look at single diseases, at single points in time, at single mechanisms. They're not really capturing, right, how complicated these disparities are. They ignore the highly sort of dynamic processes with various social factors contributing to various mechanisms in different ways. And because we don't do that, when we create interventions, they're very specific to a small population, or they're very specific in terms of time period that they're relevant. I don't know if anyone else here is a medical sociologist, but Lincoln Phelan sort of presented an idea, this idea of sort of fundamental causes of disease, which is something that's very prevalent in epidemiology and in the medical sociology literature that speaks to sort of thinking about things in a very different way, understanding that there are a number of factors that can act through multiple intervening mechanisms. They think these things can change over time. You think about what hep C treatment was before versus what it is now, the access issues before versus what you might define as an access issue now, how that's changed. But the disparities have persisted. So unless you begin to think about these mechanisms in this way, I would argue, you're going to continue to create interventions and policies that are not going to make a significant difference, right? I mean, if you said 25 years ago we had a cure you could have in eight weeks, you would think that we'd really address asparagin hepatitis C. And yet, we're still having this conversation today because of silly policies and things like that that are driving it. It's changed over time, and that's why the problem still exists. And let's talk about the problem, right? We know this. The rates are high. And before we get to hep C, let's talk hep B. And they're going on, they're talking about hep B right now. They're talking about disparities in hep B, but it's an issue. The rate of hep B is 12 times higher in our AP populations here, as well as death being nine times higher. And that's before we get to hep C, where, of course, we see a significant higher rates of hepatitis C in our IV drug users, a group that, unfortunately, our policies are created to really hinder what we can really do for those populations, and, of course, what we see with respect to hepatitis C in terms of death in African Americans and our American Indian and Alaskan Native populations. And we'll talk a little bit more about that later on. But, you know, my mom's a history teacher. You may notice that in that slide, I talked about history when talking about fundamental causes of disease. And you can talk about the United States about health disparities, you have to understand the populations you're talking about. And I'm going to talk about the African American population here, because, you know, well, I'm African American. But we know a lot about that population. They have a very interesting history, right? You're talking about a population, right? And I know you guys seem to think you're going to come to history and sociology, but, like, that's a population that's been in the United States through slavery, enslaved, and then for a couple hundred years, and then went through, you know, post-slavery, what was Jim Crow and segregation. And so think about what that means to a population that stayed in that space over that period of time, right? I mean, because you don't, if you look at history, you don't see that very often. So it's very interesting to see how that population, right, why we understand what we see in that population and the policies then and the policies now helping us put into context what we see with respect to African Americans and health across the board, including hepatitis C. And funny enough, when they look back at the study for rheumatic fever back in the, like, these are samples from 1940, 1955, they actually saw evidence of hepatitis C, and they actually saw already evidence that there were disparities with respect to the prevalence of it. And that's stayed over time, not surprisingly, right? That's a fundamental cause of disease. It doesn't matter what we've done, what we've changed with respect to gender, respect to age cohort. We see that over time, this is an enhanced data here, that that disparity has persisted. And interesting enough, it has been exacerbated in different populations in many aspects because of similar mechanisms, and we'll talk about that here in a few minutes. And it's everywhere, you know. The state can vary with respect to its population, but really everywhere in the United States, and particularly in those places where you see more diversity, we see really significant disparities in terms of hepatitis C prevalence and outcomes. In some places, you know, we're seeing, you know, rates three times higher. And again, shocking to see that given what our resources are with respect to treatment. We got people like Jennifer creating these incredible programs that she's created. You know, why have we not leveraged those to make the true difference we want to make? Well, okay. So when we talk about disparities, everyone likes to pretend like, you know, the genetics don't count. And I'm actually a person who I think we need to acknowledge that, you know. When we reflect on the fact that we saw the impact of, you know, we saw hepatitis C was present in the 1940s, right, you know, what does that mean in terms of, you know, hepatitis C being there, us not knowing about it, no one knowing about it, it was probably both in white and black folks. But if you have a genetic proponency to not actually be able to clear the virus, which we know to be the case with African Americans because of the IL-28B, that might explain why over time you saw rates staying higher in certain populations. But the thing about fundamental cause of disease theory says it's not just that, right, because that would be ignorant to think that. You have to think about the context of what these people are living in, right? And so it's not just that you are exposed to a disease because plenty of white folks were exposed to it too, right? But then you do things like segregate the blood supply, which was developed around World War I and continued in World War II, right? And while we're talking about the blood supply and segregation here, remember, it's not just the blood supply, right? They're segregating the hospitals, all of your healthcare, everything, right? And on the left side, you can imagine what that means in a population where we already may have seen, you know, lower likelihood of clearing virus. But come to the right side of this picture and you can see what it means where you live. Again, we can talk about your healthcare resources, your neighborhood. We can talk about how your exposures, right, can increase significantly in the setting of where you live and who you are and how policies created this. And so when we try to understand health disparities in this country, and we can talk about any health, any health issue, you know, understanding the people and their history is really important. And it really, and I love Hep C for a number of reasons, but the history of it's very interesting when I think we try to contextualize the disparities that we currently see. Now, one other thing about that idea of residential segregation is that when you look at populations over time, hypersegregation, this idea that you place people in places that are resource poor and you create policies and starve them of high quality resources and important resources like health, that often leads to adverse health consequences. And one of the mechanisms that occurs is behaviors. You see upticks with respect to alcohol, you see upticks with respect to violence, and you see upticks in many cases with respect to IV drug use. And so when we think about this idea of what we're seeing right now in the United States, it's not, I would argue, it's not that different from what we know to have been a contributing factor to some of our early understandings of disparities in the African American population. You know, this idea of segregation contributing to higher IV drug use in the black population then, and in many respects, explaining what we're seeing right now in the United States, you know, as we reflect on who are we seeing IV, or who we're seeing hepatitis C in, and what are the populations right now we're seeing big rises with respect to hepatitis C. And you know, it's interesting, as we talk about this stuff, and as I was kind of going through this, there are interesting places to think about sort of blind spots when we do this research and think about this stuff. And you know, Native Americans is a blind spot. You know, that is a population that we have not really dived into and really began to address that we need to. And looking at these numbers, it's really scary. And I will say, there's actually some more data from 2020 that just came out that looks a little bit better, but still ridiculously high. But nonetheless, I believe strongly that when you think about the isolation and deprived resources within the American Indian and Alaskan Native populations as well, in many rural white populations where we've seen hepatitis C go up, similar mechanisms, different people, that's going to explain a lot in terms of understanding the mechanisms driving hepatitis C disparities in these populations. And then it gets really interesting. And you guys are really going to love this piece, right, because when you think about this idea of who you are and where you live, right, and because I don't want to talk about I don't want to show pictures of SVI, right? What is the SVI? What does that even mean? People love talking about social vulnerability, but let's talk about what it means to live in a place, right? And so if you're living in a place where you're over-policed, right, I mean, you know, I live in a very nice neighborhood. We've got very nice houses, we've got, you know, an acre, we've got woods, you know, but if the police came to my neighborhood and started policing us the way they police other neighborhoods, I promise you, many of my colleagues and friends and whatnot would have a lot more issues with the police. So when you put a population of people in a situation like that and you police them and they go to jail and their sentences are longer and they're in a place, prison, which is known to be a major vector for hepatitis C, then you're creating a horrible, vicious cycle, right, particularly with recidivism where you can have people exposed coming out and when you compound that by not having programs in prisons, right, to address this idea of hepatitis C. And we have data that speaks to the importance of what it would mean to address these issues. But nonetheless, our policies are in a space where they're increasing, again, the exposures that people are seeing, particularly in certain populations, in this case, the African American population. And Jennifer touched on some of this, but it gets more complicated, right, because you think about the idea of like a Medicaid population, right, and a population that we know is at greater risk, again, of hepatitis C for a number of issues and social drivers that contribute to that. You create policies that becomes an impediment to those groups being treated. Then it becomes clear why you can see, obviously, worse outcomes down the road in these populations. Here you're looking at, based off your insurance, what happens with respect to your access. This is actually recent CDC data in terms of your access to being treated. And then that changes, and this is actually by race as well, and looking at age cohorts where depending upon your insurance, you're seeing much lower rates of hepatitis C treatment initiation. And so, again, these policies that exist have a number of consequences in communities, and with respect to hepatitis C, the mechanisms can be directly related to them. Now we're all excited about the idea of hep C elimination, but if we're going to do that, we need to think about health disparities and what that's going to mean, right? We have not done great to this point. Prior to COVID, we were suffering in terms of hitting a lot of our numbers, and so we were already beginning to sort of back off with respect to where we thought we were going to go, what we thought we were going to achieve in terms of timing with hepatitis C elimination. COVID messed that up even more. And so a lot of the dates have been pushed back, and some of those are still even tentative in terms of our ability to achieve what we want to. But as we think about hep C elimination, it's important that a part of that conversation is the populations involved. What does it mean? What does that look like? And COVID was really, really a problem, but it may be a blessing in disguise in some respects. When COVID hit, it obviously, and many of you all can probably speak to this as providers, it impacted your access to your patients, right? You have many patients, some of whom had access, for instance, to internet access, and some didn't. Some who were able to make it to clinic, get their vaccinations, some who didn't. Some who even understood the process of this and how to navigate those issues. And certainly, if we think about the populations that we're most concerned about right now, we understand the importance of things like your community-based organizations, right? Well, they also really, really suffered, right? They had tremendous drops in their funding. That resulted in their inability to continue the screening the way they wanted to do, which of course had an impact with respect to testing. And these same populations that had issues around access to their providers, that then had lost resources with respect to community-based organizations that may have been important for them, important resources for them, those same populations, again, had another loss with respect to health departments. A lot of these patients, a key factor for them is being able to get access to care when they need it through our health departments. And those also suffered in terms of what they were able to do in this space. And this is just speaking to viral hepatitis, but of course, we could be speaking about almost anything in terms of healthcare in these populations. And so, you know, we are all sitting here, most of us not wearing masks. I took the plunge a couple of weeks ago, I'm still alive, thankfully. But that having been said, as we move forward, you know, COVID is not really over yet. And we're going to need to think about how we can navigate some of these issues moving forward in the setting of COVID, particularly thinking about hepatitis C elimination. I will say, one of the things going backwards now is that now health departments have connections to patients and providers in a way, including health systems that they didn't before, because they had to because of COVID. Now, some of these community-based organizations have that connection to health departments and academic organizations in ways they didn't because of COVID. Now, many health systems, as well as patients, have some access to things like broadband internet. And there's the new policy, the name's escaping me right now, that was just passed by the Biden administration around access to internet, including creation of little hubs where people can, if you don't have it in your house, you can go to this sort of place in your neighborhood to get access to internet. And so there may be some things down the line that, despite the damage COVID did with respect to our ability to move forward and hepatitis C elimination, maybe we can leverage some of the infrastructure and things as a result of COVID to move things forward in a positive direction. And it works. If we treat people with DAAs, it matters. It works. And even in those populations, again, we're talking about fundamental causes of disease. Things change over time in a dynamic climate. There were issues in these populations before that are not issues now with these medications and they work very well and we need to take advantage of that, but we actually need to treat them to do that. And so as we reflect on how we move forward, what are the things we can do in this sort of next step, particularly as we think about this idea of hep C eradication, it's not going to just be like a one intervention thing that we do and you drop in some community and say, run with it. We need to spend some time to really understand and explore all the mechanisms at play that we've been talking about so far to understand what's really driving what we're seeing in these populations, particularly some of these understudied populations, as I was, when I was referring to before, because we may think we know, but we really may not know. And I think as we do that, we need to study things differently. This idea of us, you know, getting a data set and running some statistics and then saying, ha, look what I have. That's not really credible. And that's why those interventions fall off and don't matter and don't last very long. And so I would argue that we need to think more about some of these sort of mixed methods where we combine that quantitative work with the qualitative work. I think it's going to be an important step for us to think about really creating policy that's going to have a significant impact longterm around disparities in many spaces, including hepatitis C. I think being novel about how we study it. You know, as we mentioned, you know, social drivers is a very linear way of thinking, but we've already talked about how this is not a very linear thing. And so our statistics shouldn't be totally linear either. And so things like social network analysis, where we look at the nodes of who you are and where you meet and where you live and how they all come together and which node going which direction is important in terms of driving your decision making and access. Those kinds of sort of ways of beginning to quantify and understand, model what's happening to our patients with hepatitis C will really help us think about really creative and ways to address the issues. In fact, Jennifer spoke to it with her patient, right? Everything's going hunky-dory. It's all going good. And then he's like in jail. He was in prison, right? For the local jail. Yeah. I mean, I mean, I guess it happens, right? But I mean, the fact of the matter is, is that, you know, Jennifer had to leverage his network, right? To do that. Thankfully, you had a connection in that network already. But understanding those networks, right? And what does that network mean, depending upon who your patients are, where you are, who you're taking care of, what community you're in is going to be important. If you want to, you know, address hepatitis C, eradicate it, especially in those kinds of communities with those kinds of patients. And so doing those analyses in the front end to understand, you know, how those networks look like and how you can leverage those is going to be really important. And then, as I alluded to already, this idea of sort of, you know, community engagement. You know, we as academic, I'm at Duke, but we as, you know, large academic medical centers really need to begin to leverage our community partners and collaborators so that we can, again, create authentic relationships. Really begin to contextualize and understand what they're going through and then work with them. You know, this should not be a hep C eradication plan where, you know, those of us who are really smart at the top say, hey, do A, B, and C and drop it in the community. That's not going to work. So we need to be an active, engaged partner in the creation of any plan around addressing disparities and hep C eradication as we move forward so that we can be successful, again, in creating something that's going to work in the various diverse communities we have across this country. And I think, you know, a lot of issues around disparities, particularly in hepatitis C, could be, would benefit significantly from this idea of engaging communities better in that space. And so, you know, there are a number of potential ways we can address it. I touched on some of these. I think Medicaid expansion, removing those restrictions is going to be important. Thinking about how we can treat hepatitis C in the prison system. And I think a big hurdle for us is going to be not just federal, but private. You know, that's a big business now. Right? A lot of that over-policing was happening for a reason. People made a lot of money off it. And then, you know, this idea of how we can sort of study things differently in a way to be more effective in what we create and how we implement it, and then community engagement. And I think, you know, I talk a lot about African Americans today because we have data, but we need to think about how we can grow data in other populations, particularly populations where we're seeing even greater rising rates of acute hepatitis C, including American, Indian, Alaskan Native, and populations like that. I will stop there. I appreciate your time and look forward to hearing your questions later on. Excellent presentation, Julius. And now, the last talk in the afternoon is going to be related to hepatitis C and pregnancy. And Tatiana Kirshner is going to talk about that. All right, good afternoon, everyone, and thank you to the organizers for the opportunity to speak today about one of my favorite topics, which is really the challenges and opportunities in addressing hepatitis C in the pregnant population. So I'm an associate professor in the Division of Liver Diseases at Mount Sinai, and I've had a research interest in hepatitis C in pregnant people. I'm also a recent member of the HCV Guidance Committee, as well as an advisor to the recently developed TIP-HEP-C registry. This is a registry developed by the CDC to collect information about DAA exposure in pregnancy that I'll mention again later. These are my disclosures. So I think that, you know, we've been thinking about this idea of hepatitis C in pregnant people for some time, but I have been very happy to see that recently I think it's coming more to the forefront in terms of thinking about populations in which it's really important to address hepatitis C. And that's because elimination means everyone, so we need to target hepatitis C in infants and pregnant people. Previously, these populations were largely excluded from elimination efforts and elimination programs, but right now is the time to really think of strategies to include them as we work towards elimination. There are articles suggesting that we need to have responsible inclusion of pregnant individuals in eradicating hepatitis C, and that includes considering the role of treatment during pregnancy and the postpartum period. And some think of hepatitis C treatment in the pregnancy population as the last treatment frontier. We basically have developed guidelines and protocols for treating virtually every other patient population, and yet we don't have really specific recommendations about what to do with the pregnant person in front of you. And finally, a call to action really to defer no more in order to diagnose and treat hepatitis C in treatment, in children, and as I'll demonstrate, we're really not doing an excellent job in screening children as well. So why is it important to address hepatitis C in pregnant people? Well, we've seen a changing epidemiology of hepatitis C in general. As I'll show, we're seeing more hepatitis C in young people, which of course includes women of childbearing age. We're also learning that having hepatitis C in pregnancy has significant implications on pregnancy outcomes. So eradicating hepatitis C prior to or during pregnancy is important to optimize pregnancy outcomes. There's also a risk of mother-to-child transmission. And so when we think about hepatitis C elimination, this is a really important time period because we're considering two lives at the same time, the mother and the infant who potentially can be infected as well. And this really leads to several important opportunities where we can screen for hepatitis C in pregnancy and in children, and opportunities for DA treatment in pregnancy, postpartum, and in children. So I'll address each of these key points throughout the presentation. So this is some data that has demonstrated specifically that there has been an increase in hepatitis C in women of childbearing age. This is a study that was published in 2017 that has showed that specifically among women, hepatitis C in women of childbearing age, age 15 to 44, has surpassed that in women who were in the baby boomer age group, demonstrating that we're seeing more hepatitis C in women of childbearing age, which of course translates to hepatitis C in pregnancy. There's also data showing that women who inject drugs, which of course is the major risk factor in the US for hepatitis C, are at higher risk of acquiring hepatitis C than men. This is an international meta-analysis that showed that overall, women who inject drugs are 36% more likely to be anti-hepatitis C positive than men. Why might this be the case? Well, several reasons. Women tend to engage higher risk injection behaviors. In addition, they may face more stigma and may be less likely to pursue harm reduction services. Again, pointing to the importance of hepatitis C in women specifically. This has now translated to data that clearly shows that we're seeing more hepatitis C in pregnant people. There have been now several studies and reports that have shown really a significant increase in hepatitis C diagnosed in pregnant people. This is a study published last year that looked at all births in the United States from 2009 to 2019 and saw a significant increased rate of hepatitis C diagnosed in pregnant people. And it was associated with factors including being on Medicaid, having less than a four-year degree, living in rural settings, and being in settings with lower density of care providers and obstetricians. So we're seeing more hepatitis C in pregnant people. And these kind of statistics have also led to the question of what should we do about screening for hepatitis C in pregnancy? So this is one recent study, but there have been other studies looking at this as well. So previously, the recommendation was for risk-based screening in pregnant people, meaning if a pregnant patient shares her risk factors, then you would screen if you believe that they're at risk. And previously, the approach was to do risk-based screening. And in this study, they compared a risk-based screening approach compared to implementation of universal screening at one health center and found that among the people undergoing universal screening, only 69% would have had known risk factors. And so universal hepatitis C screening in pregnancy would identify an additional 31% of hepatitis C positive people that wouldn't be diagnosed otherwise. I think the study also was very important because it demonstrated that it's not just about screening and diagnosing in pregnancy. Pregnancy is a time period which also is very challenging in terms of linkage to care and follow-up. And that's particularly true in the postpartum period. So a lot of times, patients may lose health insurance coverage postpartum. In addition, they may not show up to appointments. And this is not just for hepatitis C. This is many chronic conditions that there's really significant loss to follow-up after delivery of the baby. So when we think about implementing screening during pregnancy, we also need to think about programs that we should have in place in order to optimize linkage and follow-up. So based on studies such as the one that I showed, as well as several cost-effectiveness analysis that compared universal and risk-based screening, there really now has been a movement by all societies to go from a recommendation for risk-based screening to universal screening in pregnancy. So the ASLD-IDSA Guidance Committee initially recommended this back in 2018. And then subsequently in 2020, the USPSTF and the CDC has recommended screening in all pregnant people. And finally, last year, ACOG, the American College of Obstetricians and Gynecologists, and SMFM, which are the two guideline committees that obstetricians who are doing the screening follow most closely, have also recommended universal screening in pregnancy, which is an excellent advancement in terms of our ability to, again, work towards elimination and incorporate this population in our elimination efforts. However, how are we doing with that? So the recommendations have been made. And this study from Quest looked at the uptake of recommendations for screening in pregnancy. And you see that in around 2020 and 2021, there is an increase in the amount of people who had hepatitis C as part of their prenatal lab panel. But it's not adequate because it only goes up to 40%. So still in 2021, only 40% of people were being screened for hepatitis C in pregnancy. And furthermore, on the right, you see that people with commercial insurance were more likely to have screening than Medicaid insurance. So pointing again to provider and patient disparities and access to screening that we need to work on. And so I mentioned, it's not just about diagnosing, it's also about counseling the patients and about the hepatitis C associated risk in pregnancy and afterwards. And we're learning that having hepatitis C in pregnancy is associated with adverse pregnancy outcomes. So there have been several studies that have compared people with hepatitis C compared to people without a history of hepatitis C in pregnancy, and have demonstrated an increased risk of adverse pregnancy outcomes. But the challenge of those studies is that there are confounding factors such as injection drug use and other associated factors that may also increase the risk of adverse pregnancy outcomes. So we tried to do a population-based study using a large cohort from Ontario, using the ICES database. And we looked at over 2000 pregnancies who were hep C antibody positive. And we compared outcomes in people who actually were viremic in pregnancy compared to those with a history of hepatitis C who were not viremic in pregnancy to try to tease out the actual effect of having the virus on pregnancy outcomes. And what we found is that there was a significant increase in adverse pregnancy outcomes. There was significant increase in intra-hepatoclostasis of pregnancy, which in turn is associated with adverse fetal outcomes and even fetal death. There's an increased risk of postpartum hemorrhage, and increased risk of preterm delivery in people who have active hepatitis C in pregnancy. So I think this is one of the reasons, one of several reasons to think about treatment of hepatitis C. Of course, ideally before pregnancy, but if not, then potentially during pregnancy in order to optimize the maternal health and pregnancy outcomes. We also know that there's a risk of vertical transmission or mother-to-child transmission. So in this large systematic review published back in 2014, the estimated risk of mother-to-child transmission is around 6%, but for women who are HIV-co-infected, it's significantly increased, about 11%. And so, of course, another potential reason to consider treatment, either prior or during pregnancy, is to reduce that risk of vertical transmission. We also are beginning to understand that similar to hepatitis B, there may be a viral load cutoff at which mother-to-child transmission is increased, which is not surprising. So in that same cohort from Ontario, we looked at different viral loads to see when mother-to-child transmission was more likely to occur, and there were no cases of transmission at viral loads less than 3.5 logs, and having HCV RNA over six logs was almost four times more likely to lead to mother-to-child transmission. So I think that in the future, as we learn more, potentially, when we think about who we should be treating during pregnancy, then we may categorize patients into the higher-risk patients for mother-to-child transmission, similar to what we do for hepatitis B, based on their hep C viral load. And so if we are speaking about vertical transmission, what is the recommended strategy for testing of infants to determine if mother-to-child transmission has occurred? So this is the ASLD guidelines, which recommends that all children born to hepatitis C-infected women be tested for hepatitis C at 18 months of age with hepatitis C antibody testing. And potentially, you can test with HCV RNA earlier, as young as at two months of age, but repetitive HCV RNA testing is not recommended. So really, the recommendation is testing at 18 months with hep C antibody. So that leads to the next question of, is this actually being done? And I think this is a significant gap in this care cascade. This is one of several studies that looked at a large cohort of hep C-exposed infants. This was done at University of Pittsburgh. And in over 1,000 hep C-exposed infants, 30% actually were engaged in care. They were receiving well-child services in the healthcare system. And even among those who were actually engaged in care and followed up in the health system, only 30% were actually screened for hepatitis C. So I think we really need to do better in terms of delineating ways to actually make sure that infants born to mothers with hepatitis C are being tested and treated before they have more advanced liver disease. And so the question is whether there are other strategies that may be beneficial for testing of infants. So in this retrospective study at Nationwide Children's Hospital, earlier HCV RNA testing was done at two to six months of age. And what they did is they looked at whether earlier HCV RNA positivity at two to six months of age was sensitive and specific to their case definition of positive hepatitis C in the infants. And what they found is actually that earlier HCV RNA testing was 100% sensitive and specific for that later testing time point. And so in this study, they recommend a pediatric screening strategy where the maternal infants who were exposed to hepatitis C are tested early at two to four months of age, and then they are linked to care after being tested at that time point with pediatric infectious disease so that again, they're not lost to follow up before that 18 month time point. And then they are of course tested later to confirm. And others have also suggested that perhaps we should have a more universal approach to testing children. So now all of the guidelines recommend testing of all adults age 18 to 79. But in this editorial, they say, which is true, that risky behavior does not start at age 18 in many children, many adolescents. And so we need to think about whether there should be an earlier time point for universal testing, such as part of school physicals, where children can be universally tested and promptly referred for hepatitis C treatment. And when can we treat children with hepatitis C? So the recommendations is that we can treat children as young as at age three, which is excellent news. But again, the challenge similar to what was said before with Jennifer, we can treat a lot of these populations, but the challenge is testing them and linking them to the treatment. And finally, I'll end the discussion with the question about the role for antiviral therapy, DAA treatment in pregnant people. So when we think about treatment of pregnant people, I think it's still an active area of discussion and perhaps debate, but there are potential benefits and potential reservations about treatment in pregnant people. I think the potential benefit is that we can, of course, cure the mom while she's engaged in pregnancy care. Pregnant people have to come to the hospital. They have to deliver their baby in a hospital. So they're there in front of you and you can cure them. In addition, there's a potential that treatment in pregnancy can improve their pregnancy outcomes and decrease the risk of vertical transmission. However, I think the reservations come from the issue of really the use of medications in pregnancy, hepatitis C medication or others. We really need safety data for providers and patients alike to feel comfortable about the idea of taking medication during pregnancy and during breastfeeding as well. And some would say that we have established guidelines for treatment of children at age three. So even if vertical transmission occurs, then you can just treat the child later. I think that we also now have expert recommendations, but the expert recommendations are also not entirely clear about when or in whom we should be using DAA treatment in pregnancy. So you see the ASLD-IDSA guidance says, kind of vaguely, that despite the lack of a recommendation, treatment can be considered during pregnancy on an individual basis after a patient-physician discussion. So this really puts the ball completely in the court of the provider and the patient. It really doesn't provide specific guidance about who potentially we should be treating, but it does say that you can consider treatment on a case-by-case basis. On the other side, you see the Society for Maternal-Fetal Medicine, and they have also a very interesting recommendation. They say that we recommend that DAA regimens only be initiated in the setting of a clinical trial during pregnancy. So that suggests that perhaps they think that in a more controlled setting with informed consent, this would be a more acceptable approach. What data do we have? So we do have a published phase one pharmacokinetic study of the use of Lidipospir, Ciposavir in pregnant women. This was published in 2020, and this was a study conducted by Catherine Chappell in Pittsburgh, and in this study, they used a 12-week course of Lidipospir, Ciposavir in second and third trimester of pregnancy. They recruited nine pregnant people, and they all, not surprisingly, achieved SVR, and there really were no signals towards significant adverse events in the mother or the baby. We also are now having some real-world data. So because of the ASLD recommendation that treatment can be considered on a case-by-case basis, we have done this in our clinical practice. So we have a co-located women's liver clinic. It's a liver clinic in our obstetrics department, and we had 23 pregnant women who were referred to us with active hepatitis C in pregnancy, and we did end up treating seven of these women during pregnancy and eight postpartum. But I think the big learning point here, again, was this significant drop-off in people in terms of completion of their medication treatment, as well as even adherence to the SVR-12 visit, again, pointing to the challenges in maintaining engagement, particularly in the postpartum period. So we also have exciting ongoing efforts to improve and expand our knowledge on safety and efficacy of DAA treatment in pregnancy. We have launched the STORC clinical trial. It has a great name, which we really love. It's a trial of cephalospiravapatosphere treatment for chronic hepatitis C during pregnancy. This is a phase four study where we're offering treatment to pregnant people in second and third trimester of pregnancy with SoftVal, and there are six sites who are participating in this study, including sites in Pittsburgh, Cincinnati, Denver, us in New York, Toronto, and Utah, and recruitment is underway. So if you do have patients who are potentially eligible and interested, please reach out. In addition, there's the recently launched Treatment in Pregnancy for Hepatitis C TIP Hep C Registry. This was established by the CDC and the Coalition for Global Hepatitis C Elimination and was publicly launched this past summer, and it's collecting clinical information and case reports about DAA use in pregnancy, whether intentionally started or whether people became pregnant while on DAA treatment. And so again, if you have cases of patients who had DAA exposure in pregnancy, please contribute to this registry. And the hope is with this STORC clinical trial, as well as this real world data from the registry, we'll accumulate enough safety data and efficacy data to make this a part of potential care protocols. So what are the key takeaways for hepatitis C in pregnant people? So I think that there are significant challenges in these patient population, but also amazing opportunities for hepatitis C in pregnant women. So what are the challenges? The challenges is, well, we have screening recommendations to screen all pregnant people during pregnancy, but the uptake is only 40%. So we need to provide education and increase uptake of these recommendations so that we actually are screening all pregnant women. With hepatitis C, there's often coexistent maternal substance use. And so when we address hepatitis C, we need to also address that and make sure that we are offering services to these individuals, harm reduction services and substance use treatment programs as well. And when we think about use of any medication in pregnancy, we really need to have enough safety and efficacy data for people to really feel comfortable with this. And the question is, what will be enough to really inform practice? And finally, with hepatitis C, as I mentioned a few times, a very challenging aspect is the postpartum period and the linkage to care. And the fragmented healthcare system leads to difficulty and continuity from the maternal care to pediatric care and pediatric testing and subsequent treatment. However, there are significant opportunities in this population. One is we can address hepatitis C in both the mother and the child. This is two hepatitis C cures we can have at the, you know, really in the same care period. So this is an opportunity to really work towards elimination by addressing hepatitis C in two people at once. There's a potential for co-located care and the potential to address hepatitis C in people that are already seeking healthcare. So easier potentially than what Jennifer is doing with the van. These people are already in the hospital. They're already being seen in clinic. There's an opportunity to engage hepatitis C patients while they're otherwise seeking medical care. And treatment in pregnancy can improve pregnancy and infant outcomes. So we can improve their overall health by addressing treatment in pregnancy. And programs to identify hepatitis C early, such as in infants born to mothers with hepatitis C, can really improve disease outcomes. If we screen and diagnose these children early, hopefully they won't have disease progression in advanced liver disease. And finally, clinical trials in pregnant people. So we can put our hepatology community on the map as working in terms of bringing medications to pregnant people, as opposed to excluding pregnant people from investigation of potentially beneficial medications. And we can include the obstetric providers in hepatitis C elimination efforts. So the more the better in terms of working towards elimination, and the obstetric providers can be part of this. I'll end there. Thank you so much. Excellent presentation, Diana. So now we have time for a Q&A session. And before doing that, I want to present what else is at the liver meeting this year in terms of hepatitis C. So we do have a session. So today at 5 PM, we have the poster hall reception. So you can see the posters related to the hepatitis C. So on Sunday, we have the plenary session as well. So some studies on hepatitis C hopefully will be discussed. Then at noon on Sunday, we have the hepatitis C therapy session as well. And on Monday, we are going to be busy. So we have the late-breaking session, the hep C epidemiology at 9 AM. Then we have at 11 AM the vital hepatitis elimination session with multiple presentations at that time. Then at 2 PM, we have the late-breaking oral session where some studies on hep C will be discussed. And then at 345, so we have the special session with Dr. Francis Colling about the national strategy about hep C elimination. And we're all here because we really care about hepatitis C. And when we see this about hepatitis C elimination, and my background is infectious diseases, I just want to remind you that we have been able to only eradicate one infection in humans, which is a smallpox. We have not been able to do the same with any other infection. So we can do it with hep C. So working together is where we have now seemed to have the interest of the federal government on doing this. So let's work together. Certainly, we will have to work at our level on micro-elimination, do a better job in our centers screening those patients. So let's join us. Let's embrace that concept that we can eliminate this infection. And now we're open for the Q&A session. So we have the first question. And if you don't mind, you can identify yourself. Sam So from the Asian Liver Center at Stanford. My question is to Dr. Kushner. Is there a viral load threshold above which increases the risk of perinatal transmission, just like in hepatitis B? Do we have any data on that? Yeah, so we did look at that in that large cohort from Ontario where we had linked data between mother and baby. And we looked at different maternal viral loads during pregnancy and risk of transmission. And we found that viral loads over 10 to the 6 logs were definitely almost four times more likely to have mother-child transmission. And we saw no transmission under 3.5 logs. There are also other studies as well. But it's not surprising that similar to hepatitis B at higher viral loads that there's a higher risk of transmission. So would that be incorporated in the future guidelines as based on viral load rather than treating all pregnant women? I agree and I disagree. I think, yes, potentially it can be incorporated in future guidelines. But I also think that there are other reasons to treat hepatitis C in pregnant people other than just for the prevention of mother-to-child transmission. For example, if we find that treating hepatitis C in pregnancy can decrease the risk of cholestasis of pregnancy, that's a reason to treat. In addition, similar to all the efforts that people like Jennifer have, we need to treat the patient in front of us. We know that we see them in pregnancy. And most times after, we never see them again until maybe they become pregnant again. So I think that is a reason also to treat, to provide maternal cure while they're in front of you, obviously considering safety. One last question. Is the recommendation if they decide to treat, is in the last trimester? Yes. So as part of the STORC clinical trial and in our clinical care efforts, we only treat in second and third trimesters. So the idea is that we don't want to expose during first trimester because there is increased risk of teratogenesis, just with any medication. And because it's a finite treatment, why not just treat as safely as possible in second and third trimester? Thank you. And no ribavirin, correct? No ribavirin, correct? Ribavirin. Oh, yeah, no ribavirin. Definitely no ribavirin. And no interferon. Next question. Hi. Brian Conway from Vancouver to Dr. Price. This is heroic work. So two things. One is, in your program, do you have the opportunity to look at other outcomes in SVR-12 in terms of improvement of the health of this population? So engagement in addiction care, decreased overdose, decreased overdose death, increased quality of life. Because this is really what these programs have the opportunity to do. And my second question is about scalability. What you have described is great. It needs to be done tens of thousands of times. This isn't subtle. It's tens of thousands of repetitions of what you do to do this at the level of population. So thoughts about scalability, even across your city or your state? Because that really is the challenge. Combi Clinic that you quoted in Australia is fantastic. I know them well. They treat dozens of patients a year, which is fantastic for that dozen. But it's scalability that is the issue. Yeah, excellent question. So to your first question, we have not been systematically following people to see their long-term outcomes. It's really sort of a clinical service. And actually, the model that we have that's been working for us is we'll partner with another organization. Excuse me, we'll sort of pull up. We'll be there for a finite period of time. And it's usually very busy in the beginning when we're screening a bunch of people, and then very busy when we're starting people on treatment. And then it sort of peters out towards the end. And we can look people up in the medical record. But we don't have the long-term continuity with the patients. But I think that's extremely important. That's something that Megan Morris, my colleague, and I are really interested in doing in our now study, where we do actually have a formal study that we can look at these people that got a point of diagnosis hep C treatment and see if there was an impact on these other outcomes. And then to scalability, I agree. I don't. It's challenging. We can't necessarily have just vans everywhere. Although I think that the model is scalable. Maybe not the mobile van model, but the concept of meeting people where they are, having them screened there, doing their labs there, doing a telehealth-assisted clinician visit, all of these things that I described, I'm not on the van. I could be at my home. I could be in the clinic. I could be anywhere when I'm doing the telehealth visit. So that certainly is reproducible. And if you can get a skilled phlebotomist on site, if it's at a harm reduction center or an SRO, the lab draws are reproducible, too. So I think that's where the scalability could come into play. But it does require a lot of coordination with these other organizations. You really need to have someone, really good community partners, and then at least one champion at the community partner organization. And we have found sometimes we haven't had the champion identified. We just say, we'll take care of everything. We'll be right outside. You guys don't have to do anything. And then after six months of us there, someone emerges as a champion. And that's what happened with the case that I presented. That methadone clinic, the staff was super engaged when they didn't think they had the bandwidth even to screen at the very beginning of our time there. And thank you for the question. I think this is a time also to be creative. So on Sunday at 3.30, so the hepatitis C group, H-Z group is going to meet and bring your ideas. So if you have any recommendations that we can take as ISLD to this national elimination plan, please bring your ideas. Next question. Thank you very much for the opportunity to ask this question. And my question goes to Dr. Price. When you did present, you talked about your rapid treatment program. And you mentioned the fact that you give a two-week starter pack. Did you collect any data on the people that you were not able to get coverage for? And what did they look like? And what was the plan for the people that you couldn't get coverage for to follow up after the two weeks? Yeah, so the backup, if we couldn't get insurance authorized approval within two weeks was not to just leave them hanging. We did have backup study provided medication. So we would just keep giving them two-week starter packs. But over 90% of our participants actually got insurance authorized DAAs to finish the course, and about 3 quarters within that two weeks. So that two weeks was sufficient. Since we started the study, there have been removal of a lot more of the payer restrictions in San Francisco. So I would imagine that actually we would be more successful with the rapid turnaround. I'm wondering what it would be like in other states other than California. What's that? I'm wondering what the numbers would be like in another state other than California. The south and other parts of the US may have more higher numbers. And it also required a tremendous amount of effort, like a tremendous amount of effort. Next question. Hey, thanks everyone. I'm Ben. I'm coming from Mount Sinai. I'm an internal medicine intern. And so we did some research here in the DMV area on hep C screening. And one of the findings was that Medicaid patients were not being screened at all proportionately to privately insured patients. And that was kind of alluded to in everyone's talk in one way or another. And the question is, these are patients who are already engaged in care. They're coming to clinic, but then still not getting the kind of screening that they deserve. So I just kind of want to hear your thoughts about where is that disconnect, and how do we bridge that gap? Thanks. Yeah, I mean, so what you're speaking to is physician bias in many respects, right? I mean, because we can talk about hepatitis C in that setting, hepatitis C screening. But there are other examples of where that particular population and populations like it, underinsured individuals, uninsured individuals, even when those resources are available, are not appropriately receiving screening. Quite frankly, we're not even screening really anyone the way we should, the rate we should, to the point that you're making. So there's an opportunity there for an intervention to address that and take advantage of those opportunities and to try and make us as providers more aware of those issues. But I will say that that probably needs to be something done in parallel as well with patient education too. I think that, unfortunately, we can't rely on us to do the right thing all the time. So we need to think about how we can build infrastructures, means of communicating important health information to our patient populations, particularly those who are at greater risk for anything like hepatitis C. And how can we make them aware of what they need to talk to their provider with? Because the other important thing you're saying is that it's not just that they're seeing that they have insurance and they have a provider, but they're actually coming to the hospital being seen by someone. You're talking about people who were seen someplace by a physician and still not screened. Because a lot of times, we like to blame the victim and say, oh, but they don't come in. Well, these people are coming in. And so we should take advantage of their engagement in that setting and provide them with the tools so that they are aware of what their opportunities and resources are as well. And so I think that working in those two spaces in parallel is a way to address that. I think the cause of it, though, is physician bias and our general inability to address screening across the board in medicine. Next question. Hi, I have a question for Jenny and for Tatiana. And I'm Jennifer Slepin, a nurse and a patient advocate for Hep C from Raleigh, North Carolina. So for Tatiana, I want to know, is there a particular trimester in which you think it's best to treat, or does it matter? So really, second or third trimester, not first trimester. Even to the point where I would say, if someone is on DAA treatment and becomes pregnant, I would have the discussion with them about stopping treatment during first trimester, just because during first trimester, they're most susceptible to potential impact, adverse outcome in the infant. So really, second and third trimester, and that's how the STORC trial is designed, and that's what we've been doing in clinical practice. And for Jenny, you talked way back at the beginning of your talk about the guy who came in who achieved SVR. But in terms of folks coming back with reinfection, I'm just curious if you're seeing that, and if, I know you said you can't really follow people, but are you seeing change in behaviors in terms of harm reduction in protection of their cure? Yeah, so we have not seen any cases of reinfection. I mean, we've treated over 100 people. We haven't seen it yet. Maybe it's out there, and we just haven't seen it because they haven't been retested or they're not seeing us. But the studies show that reinfection risk is actually relatively low. So it's still important for people to get screened, but that hasn't been an issue for us yet. And I forgot, oh, your second question was changing in health behavior. We have not been systematically following that, but I would say yes. We've had actually a handful of patients with HIV and hepatitis C co-infection who had untreated HIV who, after getting their hepatitis C cured, engaged in HIV care. Just anecdotally, do you hear people say, I'm never gonna get infected again, or? Yeah, we do talk a lot about prevention of reinfection, and people are very, I mean, to be honest, people are so excited to get treated, they really don't wanna get infected again. And we actually are now, to your other question, we are trying to capture what they want next. We're asking people, what do you want next now that you've been cured? Because we can't necessarily offer that ourselves in the van, we're just staffed by a liver team. But we wanna know how we can help people with the next stage. Next question. My name is Jackie Chen. I'm a patient support group. We just have a patient that was referred by the doctor, the treating physician, to us, asked us to help that patient. That patient has been treated with GP, failed, actually succeeded, and reinfected again, and then he got treated again with IBCUSA, and then was successful, and then reinfected again. So the doctor run out of option and referred the patient to us. Now, I wonder, do you have any suggestion how we can help that patient to complete another round of treatment and not getting reinfected? This is something that we are still learning how to support those patients. Yeah, I think, in our, I'm still learning how to support patients like that as well. I will say, I mean, it's a little bit off topic, but during the pandemic, when we started treating again, we actually had three overdose deaths. So we had more of our patients die, or our van patients die from overdose than liver disease. So we're trying to figure out how we can partner with other groups to really assist people, because there's lots of programs in San Francisco to help with addiction, but everything's very siloed, and like Tatiana said, you have a patient in front of you, and they've got these issues, like we should be able to try to address them. So I know that doesn't answer your question, but it's something that we're kind of struggling with as well. I would actually add what Jennifer said. I think that, why is that patient becoming reinfected? You know, like, there's clearly some other issues, and it may be drug use or whatever, but the question is like, you know, what is the underlying factor driving that? You know, why are they seeking that? You know, have they been, you know, resourced to a place that can help them with that addiction? Do we understand their mental health issues that might be driving that addiction? So that means, so, while we spend a lot of money treating hepatitis C, you know, thinking about that person as a whole individual, and understanding all the variables contributing to their risk for hepatitis C, and helping, while we treat their hep C, addressing those fundamental things, those as well are probably helpful in that scenario. Okay, we have two more questions. Please go ahead. Hi, my name is Lauren Liu. I'm an epidemiologist at Gilead Sciences. Just want to say thank you so much for your great presentations and really inspiring work. My question's for Dr. Wilder. You mentioned about mixed methods research, combining qualitative and quantitative. I was just wondering if you'd like to share more thoughts on what that would look like, or if you have any current projects in that area? Thanks. Yeah, actually, it's funny. We have a project right now in liver transplantation where we did that. You know, we wanted to understand barriers with respect to listing. And so there's the very clear things you can measure quantitatively, you know, the normal sort of sociodemographic things. We looked at other variables, sociological variables, like, you know, social support, depression. We looked at things around financial sort of issues in terms of paying your bills and whatnot. But then we actually had conversations with them to understand, you know, what was that experience like going through the evaluation process? What were your barriers to the evaluation process? And what you can do is you can begin to sort of really contextualize it, understanding who are these people, where are they coming from, and how, although they may have similar origins, how they're sort of the mechanism might play out differently. And obviously you can't speak to an answer or one thing that answers everyone's problem, but what you can do in that setting is maybe find something that's fairly central, or maybe a node that has tremendous benefit or significance in that space, and that's the intervention that you do at your transplant center, or in this case, at your treatment center, to understand how you can address these issues. And so there've been projects like that that we're doing right now in transportation, looking at that data, but they've done work like this around cancer screening as well as cancer treatment. You know, some of this is how they came up with the idea of like transportation, some of the sort of care coordinators and so forth. I mean, a lot of it was sort of born out of this kind of research to really understand those mechanisms in that respect. That's great. I think it's really important to elevate that research as it fills some real important evidence gaps for hepatitis C, so thank you for your work. Next question. Hello. Sometimes in Latin America, we have the problem that patient that start treatment, for example, a patient that will start for 12 weeks, and then between the six and the eight week, or less, four and six weeks, they stop the treatment sometimes because of administrative procedure. They didn't give the second bottle or something like that. So, and especially the pee-weeds, for example, they do not came to the, again, to the visit and the clinic. So what do you do with this kind of patients that at least they have six weeks of treatment and they stop for some reason? So there's actually some formal guidance now in the ASLD IDSA guidelines for this exact scenario. So there's a whole algorithm that you can follow there. The first thing that I do is I'll check the viral load if it's been a long period that they haven't been on meds. If it was just like a one week interruption, like the patient that I presented, I'll continue the treatment. But we've had people get cured with just six weeks of treatment. So it's certainly possible that that would be sufficient to be cured. We had someone recently who had to stop treatment because he got very ill and was in the hospital, and he had only four weeks of treatment and was cured. Okay, and just if, for example, if it's a positive, you will start again other three, 12 weeks, or? Yeah, so we'll talk about what the issues were that first time, if they were positive and we wanna get started again, then you're in the tricky scenarios. Do you treat as a DAA failure, or do you treat as a de novo, treatment naive patient? And it's sort of nuanced. In my opinion, it depends on how long they've been on treatment, how much you think they were really on treatment. Maybe RAS testing may be helpful, but usually it's just sort of a gestalt. So usually people, I'm pretty confident, it's only been about four weeks. I'll just re-treat them with a primary treatment and not a salvage regimen. Thank you. Okay, so obviously we haven't seen each other for more than two years. We wanna stay here for longer, but it's 5 p.m., so we finish the session for today, and thank you everyone for coming today. Thank you.

video transcript

hepatitis C

diagnosing

treating

barriers

treatment access

point-of-care testing

racial disparities

ethnic disparities

social factors

underserved communities

improved access

systemic factors