Hello, I'm Dr. Mary Thompson, I'm a hepatologist at the University of Minnesota, and I'm very excited to welcome everyone to the ASLD's webinar on hepatitis C treatment in unique patient populations. This webinar was created by the ASLD Public Health and Hepatitis C Special Interest Group, and we're going to hear from experts in the field on hepatitis C treatment in people who are pregnant and those who are incarcerated. First we'll be hearing from Dr. Gia Landry, discussing her work eradicating hepatitis C in the Louisiana Correctional System, and this will be followed by Dr. Tatiana Kushner, who will be discussing hepatitis C treatment in pregnancy. So without further ado, I'm going to get started introducing Dr. Gia Landry. So she is an assistant professor of medicine at Louisiana State University Health Science. She's a practicing transplant hepatologist and the director and founder of the Liver Center at Ochsner Baton Rouge. This center has brought advanced liver and transplant related care to the region and beyond, servicing patients throughout the state of Louisiana. She is a native of New Orleans. She attended college at Howard University, went to medical school at Harvard, and then went to Johns Hopkins for residency, and then to Baylor in Houston for her gastroenterology fellowship, and then Tulane, back to Tulane for transplant hepatology. While in fellowship, she earned her master's in public health degree in epidemiology from the University of Texas School of Public Health. And she utilizes her clinical background and her MPH as a clinical network specialist for the Louisiana Department of Health's initiative to initiate hepatitis C. This program is the first of its kind in the United States, and we're really excited to hear more about it. So I'll let you get started, Dr. Landry. All right. Thank you very much. I appreciate that introduction. I'm excited, really, to be with you today to talk about screening and treatment of hepatitis C virus in the incarcerated population. I'm really proud of the work that we've been doing with the Louisiana Department of Health's elimination plan, and I want to share that with you, especially because it's not often looked at in the Department of Corrections. So next slide. In terms of the disclosures, I'm on the Speaker's Bureaus for Gilead Sciences, as well as Fujifilm, as well as Magical. And so I want you to just make sure you're aware of that. Next slide. One second, please. And then a little housekeeping while we're getting the slides started. So we're going to start with Dr. Landry's talk, then Dr. Kushner's talk, and at the end, we'll have time for questions for both of our panelists. Okay. Wonderful. If anyone has any questions, also put them in the chat. Thank you. So this is going to be our agenda for today. We're going to go through the kind of global hepatitis C elimination goals, as well as talk about hepatitis C epidemiology, the Louisiana Department of Health elimination plan specifically, and then we'll also talk about the Department of Corrections elimination plan, talk about hepatitis C screening and treatment in the Department of Health, as well as the public health implications and challenges. And as was mentioned, we'll do questions, but we will save questions till the very end. So as most of you know, hepatitis C virus is an infection that can be cured, and because it can be cured, that means that it can be eliminated. So you can go to the next slide, and you'll see here that we have the World Health Organization has set the objective of eliminating hepatitis C as a public health threat by 2030. And the goal of that elimination is to get 90% of people diagnosed and 80% of those individuals who are diagnosed actually treated. And the thought is that if we can reach these targets, that will minimize new chronic hepatitis C infections and decrease hepatitis C related mortality. So it's certainly a lofty goal, but if we're going to achieve that goal, we certainly have to do it in the state of Louisiana, not to mention the United States and the continent. Obviously, globally, so that mandate has been put forth. What about hepatitis C epidemiology in the United States? So the National Health and Nutrition Examination Survey, or NHANES, had estimated that there are around 2.5 million people with hepatitis C in 2020. Now we always worried that NHANES was actually an underestimate of the burden of hepatitis C in the United States, and that's because it often excluded people who injected drugs, those who were incarcerated or the unhoused. And so there's actually been some data and studies to look at when you really account adequately for those who are people who inject drugs or PWIDs, the estimate is really thought to be closer to around 4 million, if not perhaps 5.6 million individuals in the United States with hepatitis C. So that's a pretty big discrepancy. So we already had a heavy lift with hepatitis C elimination in the United States, and that was heavy at 2.5 million. Well, if that's an underestimate closer to 4 million, or if not 5.6 million, we certainly have a lot of work that needs to be done. Next slide. I'm sorry, this was the next slide. Go ahead to the next slide. You can go. This is the information that I was just kind of presenting to you about that data as it relates to NHANES having a 2.5 million, but we really think that estimate is somewhere between 4 and 5.6 million, especially when you account for those people who inject drugs. Next slide. So what about hepatitis C in the incarcerated population? So it's thought that the prevalence of hepatitis C in the incarcerated is going to be higher than the general population. In the general population, we think it's around 1 to 3%. Well, in those who are incarcerated, it's around 11 to 16%. So a significantly higher prevalence of hep C in that population. Well, look at those who are PWIDs, people who inject drugs who are also incarcerated. We think the prevalence is around 40%. So this is pretty staggering. I mean, this lets us know that if we really want to achieve hepatitis C elimination, we can't do it if we're not going into correctional facilities and making sure that we're treating people who are incarcerated. So it's estimated that around 1.34 million persons who are incarcerated have hepatitis C, and that only around 36% of those diagnosed with only 4% being cured. So again, this is another point to the fact that we have to address this population because they have a higher prevalence, yet unfortunately, they're not diagnosed and then certainly undertreated in the correctional system. You can continue going. So with this challenges, we see that there are different challenges to kind of treating incarcerated populations. And two of those are really affordability. You know, how do we pay for treating these individuals in the correctional facilities? And then how do we move forward with implementing treatment in the Department of Corrections? Next slide. So Louisiana Department of Health put forth an elimination plan. And our elimination plan, which I'm really proud of, said that we have to focus not just kind of on our Medicaid population, but also Department of Correction populations, both of which have a higher prevalence of hepatitis C, and that if we're going to eliminate hepatitis C in our state, this is where we have to start and put our focus. So we estimated that there were around 39,000 persons with hepatitis C who are on Medicaid and in the Department of Corrections. We had a five-year plan that started in 2019 going to 2024 for the elimination of hepatitis C. And we had a goal of treating around 10,000 persons per year starting in 2020. Obviously, that was a difficult year to be starting anything with COVID. And so that, of course, has influenced the plan, but that was how it was set out initially. And then we were going to use a subscription model to provide unlimited access to authorize generic EPCLUSA so that we could keep costs basically fixed while treating anyone in the program. And then the ultimate goal was to expand the hep C provider network. We used the same definitions of elimination as the World Health Organization in terms of getting 90% of individuals in Louisiana diagnosed with hepatitis C and then get 80% of those treated. Next slide. So what did that plan actually look like? And you can build out this slide and they'll show you the different components of the hepatitis C elimination plan that we had. Of course, we knew that we had to figure out the cost situation. So we established the modified hepatitis C medication subscription model for Medicaid and corrections so that costs would be fixed and that we could get everyone treated. We knew we had to have a public education component as well and really educate the public on the availability of cure and mobilize priority populations for screening, as well as expand the screening and linkage to care network. So we do have linkage to care coordinators who they have a list and they know who's diagnosed with hepatitis C and they are linking those individuals to treatment. We had to strengthen our hepatitis C surveillance system. I found that this seems to be a fairly novel aspect of what we've done in the state because there are a number of states that really don't collect adequate initial data on those who are infected. And one thing that changed with the start of our elimination plan is not only did we capture positive data, but we also captured negative data, which really allowed us to better capture who really was being screened. So both positive and negative data as it relates to hepatitis C screening. And then of course, expanding the provider network, which is a big part of my role, treating a lot of primary providers. We have done that. We have over 900 first-time prescribers of DAAs, directly acting antivirals, in the state of Louisiana. And then as I mentioned, because the prevalence of hep C is so much higher in people who inject drugs, we couldn't leave out harm reduction. And so through our initiative, we actually started two Project ECHO series. One Project ECHO focusing on treating hepatitis C amongst primary care providers. And then a second one that was really focused on harm reduction. And then even though we started with Medicaid and Department of Corrections, the overall goal was obviously to extend elimination to all populations within the state. Next slide. So when we look at Department of Corrections and the hepatitis C elimination plan, we see that we had to start by really eliminating the restrictions related to substance use, fibrosis staging, and specialty of provider. A lot of states have since made that change. And that's because we know that if we're going to treat these individuals, we can't wait six months for them to be off of drugs and alcohol. From a public health perspective, we need to get them treated now, regardless of level of fibrosis, and then allow anyone to treat, even primary providers. We then started with universal screening for hepatitis C, HIV, hep B, and hep A, as well as syphilis and corrections. That wasn't happening before. Obviously all of these tend to be higher in the persons who are incarcerated. So you would think maybe that was standard, but it was not. So that is now something that has changed. And certainly, as I'll share with you, we've screened the entire Department of Corrections, at least at the DOC facilities, we've screened those individuals for hepatitis C. And then we had to train providers at each of our eight DOC facilities to do onsite treatment. And then, of course, telemedicine is very important when we want to treat and corrections because you have persons who are incarcerated, you know, at different facilities. And when I talk about the parish jails, that's a number of locations. And so you have to utilize telemedicine to really effectively and efficiently get people treated. Well, what about the funding? Because people often ask us about the funding models. And to be honest, I don't know all the details of this. You can go to the next slide. But these are the ones that I do want to share with you in terms of a broad perspective of how the funding works. So in Louisiana Department of Health, as it relates to getting treatment available for Medicaid population, we have a contract with Assebo Pharmaceuticals, which is a subsidiary of Gilead. So therefore, we have access to all of the authorized generic Epfluza for all the Medicaid patients really without a need for prior authorization, and it's at a fixed cost. So some people have called this the innovative payment model or the subscription model, or I like the most, you know, the Netflix model, this idea that we have, you know, one cost, one payment that we make, yet we have access to all the medications that we could need. And so clearly that was key to keep costs contained if we wanted to do a full elimination strategy. Well, initially, and a lot of people think this, that we have the same method for Medicaid as the Department of Corrections, but that's actually not the case. So the Department of Corrections is actually a different pricing model. So the Department of Corrections actually had to be certified by the Office of Public Health STD grant. Once that happened, then the DOC was established as a 340B entity. And the medication is actually supplied based off of 340B pricing. And so because of that, access really has to be limited to the Department of Corrections. This becomes relevant as I start to share more with you about the parish jails, because we are treating in the parish jails, but we can only treat those who are DOC incarcerated in the parish jails because of the 340B pricing. And so then our Office of Public Health dispenses the authorized generic Epfluza to the correctional facilities. Next slide. So here you can see just some of the demographics in the Department of Corrections or actually in our correctional facilities. There's around a total of 445,000, excuse me, of persons who are incarcerated, 27,000 of those are in specifically the Department of Corrections, meaning that they have been sentenced and they have actual like a sentencing in a location where they're going to be and an anticipated, obviously, a release date. As you can see, the majority of those in our corrections facility are in the DOC. And then if you look at sex, which is not surprising, the majority are male. The majority in the state of Louisiana or African-Americans, next. And then also, if you look here at the next slide, you can see that the majority of those who are in the Department of Corrections, go back one, please, are actually in local parish jails. If you can go back for me to the census information, go back one more, please, then yes, here you can see that 52% are in local jails and only 48% are actually in DOC facilities. So this is something I think you need to think about and ask the complexities of treating in the Department of Corrections. It's not clear to me if other states are the same, but in Louisiana, a large percentage of those who are incarcerated are actually physically located in parish jails and not in the DOC facilities. And so that makes things complicated. Next slide. So what about hepatitis C screening and treatment in the Department of Corrections? So you can continue going with the next few bullets. You'll see that newly incarcerated persons screened are screened for hepatitis C with reflex testing and then other infections that I mentioned. And all of this is done at intake. So for those who are already incarcerated, we sent out a phlebotomy team to screen at each of the eight DOC facilities. And then actually when they have discharge planning, if that's needed, that's discussed during the clinic visits because you can imagine people may be released, but we know those release dates. And based on the release dates, if individuals are released during treatment, they're actually supplied with all of the medication they need to complete therapy. And they're also given an instruction card that's given to them where they can identify community locations to get follow-up in terms of labs, as well as additional care that they may need. Next. And then it's also important to know that because people are moving through the DOC facilities, we do have a process for monitoring their movement. Please go back one. And go back one more. And so as you can see here, this is kind of a flow. So there's a treatment form that's actually filled out on each person that's been diagnosed with hepatitis C. Like you might imagine their hepatitis B status is on there, if they're treatment experienced, treatment naive. Then they have an in-person appointment at the DOC facility, and then they have a second appointment usually after treatment. Medication is typically dispensed as scheduled at a pill call or by nurses. And occasionally it was keep on person, especially during COVID. And then there's testing for sustained virologic response or cure at the DOC facility. And then persons are released from the DOC facility. Then they're automatically given Medicaid. So that's a nice way they have continued health care. Next slide. And you can build this out until you will see again the flow of work at the parish jails. So on the parish jail levels, our parishes are like counties. And so you can imagine there are jails all over the state. So Louisiana Department of Health does the mass testing at the jails to get everyone screened for hepatitis C. But as of their new intakes, then the jail is responsible for doing the screening. And once the jail identifies those who are diagnosed with hepatitis C, the DOC is then notified so that treatment can begin. So these visits at the parish jails, because there's so many of them, they're done by telemedicine. But the provider doing the telemedicine visit has to be based at the DOC because of the 340B pricing. And then obviously movement of those who are incarcerated is monitored between the DOC and the parish jails. The workflow is still the same. There's an intake form. The only difference really is that telemedicine is done. And then medicine obviously is dispensed at pill call. And then they get labs there for the sustained virologic response. If individuals are released to the parish jails, they're also immediately placed on Medicaid. So next slide. So what does this look like? So all of the screening has been done in the eight DOC facilities between 2019 and 2022. And as you can see, we screened 17,231 individuals. So 94% of all the DOC facilities were screened. And that manuscript is coming to talk about the prevalence. And that hopefully has been accepted and will be published soon in the Journal of Viral Hepatitis. And then we ended up treating 1,794 individuals who were in the eight DOC facilities, getting 89% of those individuals treated. And we're working on that manuscript now. So when it comes to the parish jails, you can see we started that initiative after getting the eight DOC facilities screened and treated. We've been able to screen 4,268 individuals in the parish jail. So 32 facilities have completed screening. And that's within 29 parishes. So that's pretty ambitious. You can imagine just when you're at a hospital system with three or four campuses, that can be hard to manage. Well, imagine trying to go out to all of these parish jails. Obviously telemedicine has been very important in that. We have at least 57 other facilities or parish jails that need to be screened. And of those that have been screened, so far, of those who've been diagnosed, we've treated around 302 individuals in the parish jails. So I still think that's pretty amazing because you can see kind of the complexities of this system. Next slide. Well, what are the keys to kind of implementing this type of work? So certainly controlling costs. So that's key. Whether it's through the subscription model or 340B pricing, you have to keep costs controlled because obviously there are limited resources in the Department of Corrections. You have to have collaborations between the Department of Health and Department of Correction. In addition to buy-in from stakeholders and leaders in the Department of Corrections, they don't have to necessarily do this. So they have to see the reason to do it, the advantages to doing it. Along with the parish jails, there are different administrators in the jail system that aren't necessarily employed by the DOC. And so you have to get buy-in from them. Phlebotomy was something that was actually challenging for us initially to get people, a team, into the jails to safely do that during COVID and to have a consistent team. And then obviously you want to train providers and use telemedicine as a resource. And then you need a process for tracking persons moving through the system and arrangements for follow-up when released. Next slide, and this will be the last slide, to kind of go through kind of what does this mean, what are the public health implications, what are some of the challenges. So, I mean, I like to think that it can be done, and that's what I'm most excited about is that this is a population of patients that are at high risk for hep C. There's a high prevalence of hep C in those who are incarcerated. If we're going to really truly move towards hepatitis C elimination, then we have to make sure that we are screening and treating this population, and we screen 94% of those in the Department of Corrections, and 89% of those, you know, 89% were treated in the Department of Corrections at those eight facilities. Screening and treatment, like I said, is needed if we're going to eliminate hep C. Certainly, just like the World Health Organization estimates, we also anticipate that we'll have a decrease in chronic hepatitis C incidence and prevalence, along with the decrease in liver-related health outcomes in terms of, you know, cirrhosis, hep C cancers related to hep C, need for transplantation, death, all of those outcomes of which, you know, time will only tell when we have that information. Then there's also personal satisfaction. A number of these persons who are incarcerated felt like they were denied care, and so they're really grateful to finally have access to treatment. But the challenge is that you have to have the will, because this is a complex system that came together, and so you have to have people who want to figure out a way to make it affordable and figure out a way to really build relationships between departments. You have to have a plan for the movement within corrections and then outside of corrections, and then also dealing with persons who are incarcerated in jail. It's more complex, because again, not everyone at the jail is also in the DOC. Jail is kind of a revolving process, so some of those individuals have not been sentenced yet, and there are different administrators, different priorities, and different resources. It can obviously be more complicated, because when we have complicated patients at the jail, often we're having to transfer them to one of the eight DOC facilities for additional care, and there has been dissatisfaction of those individuals for being transferred from the jail to the DOC facilities. But the DOC facilities have better capability of anything that needs to be done routinely, so the jails can't really do repetitive testing if needed or repetitive imaging, so those individuals do have to be transferred. So I just want to thank you for your time and your patience. Sorry for some of the technical difficulties. We had some technical issues with Zoom this morning, so someone else had to advance the slides for me, but hopefully you got the information and you see all the work that we've done here in the state of Louisiana. I hope that you too will kind of think about what's being done in your states and move the agenda forward to make sure that we're getting persons who are incarcerated treated for their hep C. I also want to thank those that I work with in the Department of Health at Johns Hopkins who's been working with us on this initiative, as well as in the Department of Corrections. So thanks again for your time and attention. Thank you so much, Dr. Landry. That was really, really interesting and incredible, and we thank you for your efforts in Louisiana. I saw many of the components of your work being incorporated in our national legislation towards hep C elimination, so thank you for spearheading all of that. Okay, so hi everyone. My name is Callie Zhou. I'm an assistant professor and transplant hepatologist at the University of Southern California, and it is my distinct pleasure to introduce Dr. Tatiana Kushner. She's an associate professor in the Division of Liver Diseases at the Eichmann School of Medicine at Mount Sinai and has a joint appointment in the Department of Obstetrics and Gynecology, and she has been very instrumental in spearheading a lot of efforts on hep C in pregnancy. She is a member of the ASLB IDSA HCV Guidance Committee. She is a founder and director of Mount Sinai Women's Liver Clinic, which is a co-located clinic in the OB department, providing dedicated care to individuals living with viral hepatitis during pregnancy and postpartum. She has a research and clinical focus on addressing hep C in pregnancy and has helped to shift practice from risk-based universal hep C screening in pregnancy and is currently a co-investigator on a study of DAAs during pregnancy, so I'm very excited to hear from her and what she's done for this very unique population. Take it away. Thank you so much, Callie, and thank you to the organizers for the invitation to be part of this session and for everyone for joining today, so I will be shifting to another population, and that is really what are the key issues in terms of moving the field forward in addressing hepatitis C in individuals who are pregnant, so I think any talk about hepatitis C elimination starts with what Gia started with as well, which is we are all aware that we are working towards a World Health Organization goal for viral hepatitis elimination by the year 2030, and I think what's notable here is that in the identified priority populations within these elimination efforts, pregnant and breastfeeding women are identified as a distinct and important priority population, and that's really because if you look at the proposed interventions in the World Health Organization goals, many of them really directly apply to the pregnant population. Some of them are in bold here, so obviously prevention of vertical transmission. If we want to work towards elimination, we want to eliminate vertical transmission so that we decrease ongoing spread of infections to future generations. Prevention and treatment and care for children and adolescents with hepatitis C and vertical transmission is the leading cause for hepatitis C among children. Partner notification services, and oftentimes when you interact with pregnant individuals, there's a discussion, of course, about partners and risk in partners of individuals with hepatitis C, and so really many of these World Health Organization proposed interventions are really specific to pregnant individuals, and when we think about working towards elimination, this is an editorial written by Dr. Jhaveri, who's also leading the way in studying hepatitis C in pregnant people and children. When we think about elimination, elimination means everyone, and it's critical to include pregnant patients and infants in elimination efforts. Of course, when we think about elimination, a central facet of elimination is treatment, and so we should not be excluding individuals during pregnancy in terms of interventions such as treatment that can benefit them. I'll discuss this population as we think about the whole cascade of care as we move from prevention to screening diagnosis, treatment, and linkage to care and where we are in terms of each of these steps in pregnant individuals and where we can perhaps do better in terms of addressing hepatitis C there. So to start a little bit about epidemiology in the U.S. with hepatitis C, particularly in pregnancy, really in parallel with what we're seeing with hepatitis C in non-pregnant settings, we're actually seeing an increase in young individuals in hepatitis C, and this applies to hepatitis C diagnosed in pregnant people. So this is a study that looked at data from the National Center for Health Statistics at all U.S. births from 2009 to 2019, and over that decade, we actually saw more than doubling of hepatitis C being diagnosed in pregnant individuals. And this more recent data that was just published earlier this year looks at a high-risk area in Appalachia, and this is data from a single center study looking at hepatitis C in pregnant individuals, and they found that hepatitis C infection rate of almost 12 percent. So this is a similar rate to what was just described in the incarcerated patient population, and furthermore, this rate here is 35 times the national rate and also five times the rate of hepatitis C reported in pregnant people in West Virginia in 2014. So of course, this is a really high-risk part of the country, but what's concerning is that rather than seeing a decrease in hepatitis C in pregnancy, we're actually seeing an increase in really impressive high numbers here. And when we think about pregnancy, a central aspect that we think about is mother-to-child transmission or vertical transmission of hepatitis C. And when we talk about the rates of hepatitis C transmission, perhaps the most cited study is this large systematic review that looked at over 100 studies of individuals with hepatitis C in pregnancy and identified a risk of vertical transmission of about six percent, and in those who are HIV co-infected, that risk is almost double at 11 percent. And so although these numbers are not as high as, for example, with what we see with hepatitis B vertical transmission, at the moment, as we'll see, there's not really a specific approach to decreasing the risk of transmission. Furthermore, we're learning that similarly to hepatitis B, there are specific risk factors and perhaps viral load cutoffs that may identify individuals who are at higher risk of transmission. We conducted a study in the ICES cohort in Ontario where it was a large database with paired mother-infant data, and we looked at individuals with hepatitis C in pregnancy and tried to identify if there are specific viral loads that could be used as a cutoff for higher risk of vertical transmission. And we did find that maternal HCV RNA levels over six logs were associated with increased risk of vertical transmission. Similarly, in a study published last year from the Maternal Fetal Medicine Unit Network, they also found that HCV RNA titers greater than 10 to the 6 IUs per, logs IUs per ml, were associated with increased risk of transmission and also identified another risk factor of antepartum bleeding as a risk factor of transmission. So as we move forward and we begin to really think about implementation of hepatitis C treatment in the pregnancy context, we may also want to think about those individuals who are at highest risk of hepatitis C transmission and perhaps target those individuals initially. But can we do anything to prevent mother-to-child transmission? So again, with hepatitis B, we have very defined protocols for what we can do to decrease risk of transmission. In terms of obstetric management for individuals with hepatitis C in pregnancy, there's not really specific interventions that can be done. In regards to mode of delivery, C-section versus vaginal delivery, there's no decreased risk with one mode of delivery versus the other. There is some not great data that suggests that invasive fetal monitoring or prolonged rupture of membranes are associated with increased risk. And so counseling is recommended in those settings to individuals to let them know that perhaps they're at increased risk. But generally speaking, that would not guide a management or change management if those interventions are needed. And finally, with breastfeeding, there's no association with hepatitis C transmission. So we should be very clear in our message and speaking with patients that they should breastfeed if that's their choice and that there's no increased risk of transmission. So if we don't really have defined methods for decreasing vertical transmission at the moment, why is it important to identify hepatitis C in pregnant individuals? Well, I think there are a few key components here. The first is that for women of childbearing age, pregnancy is often the initial and perhaps only encounter with the healthcare system. So really, this becomes an opportunity to screen for hepatitis C, diagnose them perhaps for the first time and link them to care while they're engaged in healthcare. In addition, we're learning more about how having hepatitis C in pregnancy is actually associated with adverse pregnancy outcomes. And so as we have data that shows that there's a specific influence of hepatitis C viremia on pregnancy outcomes, it is important that we counsel individuals who have hepatitis C in pregnancy that they may be at increased risk of outcomes such as intrahepatical stasis of pregnancy, for example, which you can intervene to decrease its severity and perhaps progression. In addition, even though we may not have defined methods to decrease risk of mother to child transmission, it is important to educate the moms that there is a risk of transmission and that children should be tested for mother to child transmission, linked to care, and treated if it occurs. And finally, really, it's an opportunity, again, because of the unique engagement in healthcare to link individuals to care for treatment, even if the treatment does not happen during pregnancy. It's an opportunity to link to care after pregnancy delivery. So recognizing this in conjunction with the change, the epidemiology where we're seeing actually an increase in hepatitis C in individuals of childbearing age and during pregnancy, the guidance has really been updated over the past five or so years where, although in the past it was risk-based screening that was recommended in pregnancy, now pretty much all of the major societies have come on board with the recommendation that all individuals should be screened during each pregnancy. The ASLD IDSA guidance was the initial guidance body to recommend universal screening, although did not necessarily change practice because much of the screening is done in the obstetric context. But as we move on, we saw that USPSTF, CDC, and eventually ACOG and SMFM, which are the obstetric societies, have also agreed that all individuals should be screened for hepatitis C during pregnancy, ideally with the initial prenatal panel. So how are we doing with this screening during pregnancy? Is everyone on board? Well, this is data using the National Quest Laboratory data set, which looked at incorporation of hepatitis C testing into the routine prenatal care panel across the country in health systems that use Quest. And we see that with updated recommendations, we see that there's an increase in hepatitis C testing over time. However, if you look at 2021, and hopefully these numbers have improved since then, but as of 2021, still less than half of individuals were actually being screened for hepatitis C in pregnancy. And there also were differences in individuals with commercial versus Medicaid insurance and suggesting that there are differences in practices based on insurance status. So despite progression in pregnant person screened for hepatitis C, current testing rates fall short of universal recommendations. And I think this is a place that we can really work to spread the word to make sure that obstetric practices across the country are implementing these recommendations, and that we are actually screening all people who present for care during pregnancy. So if we screen, what can we say about treatment of hepatitis C? And I think part of that hesitation initially with uptake for screening during hepatitis C was, well, if someone screens positive, what can we do if we can't treat them during pregnancy? So what are the current recommendations for treatment of people who have hepatitis C in pregnancy? And here I show the current recommendations from the ASLD IDSA guidance, as well as from the SMFM. If you look on the left, the ASLD guidance says that despite the lack of a recommendation, treatment of hepatitis can be considered during pregnancy on an individual basis after a patient-physician discussion. So this guidance really emphasizes the importance of joint decision-making in determining whether to initiate hepatitis C treatments. If you look at the SMFM guidance, they say that we recommend that DAA regimens only be initiated in the setting of a clinical trial, suggesting that really they think that hepatitis C treatment in pregnancy should be in the research context. Well, should we consider hepatitis C treatment in pregnancy? We have these highly effective DAAs. Can we incorporate their use in the context of pregnancy? And I think it's an evolving field, but there are really two perspectives. The potential benefit is that we can, of course, cure the moms. These are very effective agents, and pregnancy should not interfere with the effectiveness of these therapies. So we can cure the mom while she's engaged in healthcare and has health insurance, and this is an opportune moment to do so. There's a potential that if you treat hepatitis C in pregnancy, we will lower the risk of vertical transmission, decrease further community transmission, and perhaps even optimize pregnancy outcomes by decreasing hepatitis C-associated adverse pregnancy outcomes. On the other side, though, many providers would say that we really need to have very robust safety data before offering any medication during pregnancy, and also that if vertical transmission does occur, children can be treated starting at age three, so perhaps it's okay if there's vertical transmission if you can treat the child later. What do patients and providers think about this idea? Because I think it is very important to know the patient perspective, particularly, and the provider perspective, particularly if we're recommending joint decision-making as the ASLD guidance recommends. So when we conducted a survey of women with a history of hepatitis C at UCSF and the Women's Interagency HIV Study, we found that 60% of women said that they would consider taking DAAs during pregnancy if they lowered the risk of vertical transmission, and this was a few years back before really there was any data on hepatitis C medication in pregnancy. In a more recent study, there was a qualitative investigation of obstetricians and patients regarding their views of treatment of hepatitis C in pregnancy, and you see that there's some overlap in terms of their thoughts about what would be potential barriers to treating pregnant people, including cost and access, insufficient obstetrician knowledge, and of course safety, I think, is always the top concern about hepatitis C or any medication during pregnancy. So do we have any data? Well, very exciting that we actually do have data that is emerging about the use of DAAs in pregnancy, and I think this is a rare setting where actually we're evaluating medications in pregnant individuals. There are very few health conditions overall where we're actively studying medication use in pregnancy, and this is a summary of the data that is currently available. There's a published study using Harvoni in pregnancy. This was a phase one study, Lidipasvir-Sebastivir, that was published in 2020. Nine patients who completed treatment, all with SVR with no significant adverse events reported. There's also a recently completed phase one study of Cepasivir-Velpatisvir that was presented at CROI and will hopefully be published soon. And there's also a large phase four study underway called the STORC study. This is a multi-center study where we hope to recruit a hundred patients during pregnancy and offer treatment during second and third trimester of pregnancy with interim results that were just presented as a late breaker at ASLD this year. And finally, there's the IMPACT study group, which actually will be studying Glicepavir-Prebrentisvir that also during pregnancy, this will be a phase one, phase two study that hopefully will be underway soon. In addition, there's a coalition for global hepatitis elimination spearheaded registry, which is called the TIP-HEP-C registry, which is a registry specifically dedicated to collecting data on DAA exposure in pregnancy. And therefore, as we accumulate real world data, hopefully that will also contribute to our knowledge about safety and efficacy of these medications in pregnancy. I realize I'm running a little bit short of time, but there's also real world data that we have. This is data from our center where we were treating patients in our women's liver clinic, and we offer treatment during pregnancy through and with a joint decision-making approach as recommended by ASLD. I eventually treated seven individuals during pregnancy and eight during the postpartum period. And what we found was that this co-located approach was feasible and helpful, but really what we saw was that there was a significant drop-off in the postpartum period, and many individuals who were treated did not come to their SVR-12 visit, really highlighting the challenges of not even just offering treatment during pregnancy, but maintaining engagement in the postpartum period. And this study really emphasizes this point. This is a large retrospective cohort study using data from six states in the Medicaid Outcomes Distribution Research Network, and they specifically looked at individuals who are pregnant and diagnosed with opioid use disorder in pregnancy. These are the highest risk patient population. And they looked at how many of these individuals had testing and or follow-up or medication for hepatitis C during the 60 days postpartum and then the six months postpartum. And in this very high risk patient population, less than 10% of women with opioid use disorder in pregnancy who are at risk for hepatitis C got care in the six months after delivery. Again, highlighting really the challenging time postpartum where many people are lost to care. We need systems in place that help to make sure that hepatitis C treatments can be delivered if it wasn't done so in pregnancy. This is a study from New England where they worked on this issue and they developed a dedicated linkage consult for individuals with hepatitis C during pregnancy, as well as a co-located model where mothers and children can be treated together with multidisciplinary approach with social work and addiction medicine treatment located all in the same place. And even with this very integrated care model, they had significant improvement, but only then documented that about a third of individuals achieved SVR. So these programs are very helpful, however, still highlight the challenges that are inherent in this postpartum period. And I'll just end also about the piece that's related to pregnant people, of course, which is the follow-up for infants. And in order to evaluate infants for mother to child transmission, there was a, there's a recommendation to screen children born to mothers with hepatitis C. And this study showed that even among individuals who are engaged in pediatric well child services, only 30% were screened for hepatitis C with the previously recommended testing approach of testing at 18 months of age. But fortunately, just as of this past November, the CDC has updated their recommendations for testing for infants to now recommend earlier testing at two to six months of age with HCV RNA in order to help to minimize this loss to follow up and hopefully keep people engaged in care to make sure that perinatally exposed children are actually tested for mother to child transmission. So I will end here. This is just my summary slide and I will turn it over to Callie and Mary to start the discussion. Thank you so much for your time. Both those talks are really great. So I have a lot of questions, but I'm going to start with one of the questions from the Q&A. So this is for Dr. Landry. So this person asked, do you mind sharing your experiences treating those who are incarcerated in jail without a sentence? Sometimes we were told by jail administrators that a patient is predicted to be incarcerated for a while, but then released shortly after and unable to reach continued treatment post-release. Do you mind expanding more on your experience with this complex patient population? Yeah, that's a, it's a tough situation and that's what's hard about the jails. And that's why we haven't fully kind of gone into treating persons who are in jail, who are not in the Department of Corrections because the Department of Corrections, we know they're at least sentenced. We know that what their release date will be, and that's unlikely to change and unlikely to change quickly. Unlike those who are in parish jails, where there are some people there for hours, literally, and some people days and weeks. But the way that I would think about that is similar to what we do in the DOC is just having processes in place ahead of time. So we're fortunate enough if needed to be able to get all 84 days of the authorized generic clues available. So if you're able just to give, you know, person's medications when they leave, no matter when they're released, then that could be very effective. You know, these medications are so safe, safer than I feel like a lot of antibiotics that we use, especially as, you know, a hepatologist, we see more augmented related injuries than, you know, abuser related issues. So if you could have the medication up front so that if they are released unexpectedly, they could still have all the medication, that will be a huge public health impact, because we know that most likely they're going to get cured of their hep C, even if you don't see that person again, or can't contact them. So if you could educate, give them the medicine. And then, again, that's why it's helpful to have some type of linkage to care coordinators who could try to be responsible for staying abreast of that person. And then their goals is just to get that person to the first follow-up visit. And after that, their work is done. And so I think that could be helpful. And then again, the third thing is if you're able to set up in your state to make sure that that person does have access to Medicaid, at least you ensure that they have some type of access to health insurance afterwards, so that even if you can't find them, they at least have insurance. So when they need to access healthcare systems, they can. So that would be kind of my three biggest things, being able to give individuals all the medicine they need, you know, when they're released. And then also having some type of linkage to care person available, and then Medicaid access once released. Can I ask a follow-up question? I'm curious, is there any opposition from those individuals? Like, you know, the stigma thing always comes up. So do any of them choose not to pursue hepatitis C treatment, because they don't want to be seen picking up the pills or whatever? Yeah, so that's a really good question. Because you might wonder, like, why I said we only screened like 94% or only treated 89%, right, when everyone had the option, especially in the DOC, to be screened or treated. But yes, there are just a percentage of people who say, no, thank you. And you have to respect that. So the majority wanted, as you know, kind of I showed you from what we've done. But yeah, there are people who maybe they allow to be screened. And even after diagnosed, they say no to the treatment, actually. Or in the jails, we have situations where people start treatment and then just stop, you know, just like, okay, you know, I don't want to be on treatment anymore, or have some other side effects for why they say they want to stop treatment, and then just stop. So that is an issue and does come up. But the vast majority are really grateful, and really grateful to have the opportunity to receive screening and to receive treatment. So we'll continue with Dr. Landry, and then we'll move over to pregnancy in a second. So one of our attendees had a question about where the funding from treating incarcerated population comes from. I think that's quite important, as we, you know, try to enact the same thing in other states. Yeah, so the funding is also coming from the Louisiana Department of Health in conjunction with Department of Corrections is where the funding is coming from, from both with helping together to kind of manage and treat this population. Would you see opposition from others? I mean, obviously, you're focused on Louisiana, but do you think that Louisiana is unique in some ways that perhaps other states would have more opposition? Does it relate to prevalence of hepatitis C that they're seeing perhaps or other factors? And this is where I think buy-in kind of from the top down becomes really important. So, you know, when our initiative started, our Secretary of Health at the time, Rebecca Gee, was very committed to this, and really extended a lot of her energy and efforts and focus during her time at working on this initiative. And so that's why I say the will has to be there. And so when it comes to these type of things, you can't just do it alone. So there has to be political will, which can be a little bit more complicated in some states. If you look at our data, the majority of people that were able to get treated was because we expanded Medicaid. So then another question becomes like, had we not expanded Medicaid, would we have had the funds, right? Because you need the funds in combination, like the last question asked between the Department of Corrections and the LGH kind of helping to support and shore up these resources for obviously more testing, which, you know, comes into why sometimes testing isn't done, because you don't have the resources or the money to test. And then if you test, then you're kind of more obligated to do something with that testing, which then requires more money. So you have to have, you can't do this outside of understanding that there's political components that go into it as well, as well as the different departments, and finding additional resource, and there has to be a commitment, you know, towards that. And that will be different for every state based on what every state is kind of dealing with, which is why I think the imperative is so much more that we get together and push a national initiative. Because if we have a national initiative, then it doesn't become as dependent on the states to figure some of these things out. But if there is a model that, you know, which is what they're looking for, like kind of fixing costs, you know, we want to get kind of a rapid test created, kind of all of these things that need to be done to effectively eliminate Hep C, we can have a national push, I think it will bring along a lot of other states where some of these other things may be more challenging. And then we have another question for Dr. Landry. So do you have periodic hepatitis C testing for those who tested negative entry into the DOC? The comment is we see a lot of hepatitis C transmission in our prisons in New Mexico. Correct, that's right. So we know that people are getting infected in the prison, which is why we're hoping to see a difference kind of in some of those incidence and prevalence numbers as we're getting people treated. But currently, we don't have yet assistance to go back, you know, kind of in rescreen, we're just trying to get through the initial screening of all the DOC of all those in the DOC. But that would be, you know, something that we will consider in the future. Once we get through this, do we go back and try to kind of either rescreen everyone or certain populations. And then obviously, there's still providers in the DOC who are very well versed and have seen at any time can then, you know, initiate screening on an individual basis. But we have not set that up yet from a universal or mass screening perspective. And Dr. Landry, you guys treat acute hep C, or is it only chronic? We are treating only chronic and according to like the initiative, but on a case by case basis, yes, we're treating, we'll treat acute hep C as well. Okay, perfect. And then we have another question about do you have any difficulty with disruptions and treatment or gaps in medication due to movement in the DOC between facilities? Or have you been able to successfully have these patients stay in one location during treatment? The comment here is despite medical holds, often patients in our facilities move on treatment and the meds are delayed. Correct. I mean, it's surprising to me that I learned that even in the DOC, once they know their sentence, they are moving, like in between facilities. So we've been very good. We have a system it's called CAGE and that can really keep up with those movements. And because obviously, we're been intentional about the initiative, there doesn't cause too many disruptions in therapy. So persons who are in the DOC, whether they go to the jail or come out of the DOC should really be able to maintain therapy without much disruption of care. Yeah. So that hasn't been so much of an issue, even though people are moving. So it's not that they're not moving, we are able to really monitor them. And it has just been interesting that we've, like I said, we've had to move some people from the jails to the DOC facilities, because even if just a diagnosis of cirrhosis, separate from them being treated, they need more regular just surveillance. And those types of things just aren't possible or as easy to do in the parish jails. I have one more question for Dr. Landry, and then we'll move on to Dr. Kushner. Are any other states, I know you're proposing that this should be kind of a national model, are there any other states that are following this? And then, you know, all states will have some, most states have some private correction facilities. Is this being done at all in any of the private correctional systems? Yeah, so you can imagine the private side, it's not going to be done as much. I mean, right, it's some of these, it's kind of a business perspective, just how much money do you have? What resources do you have to put to that? You know, obviously, you know, screening, treating can be more expensive. So not as much on the private side, certainly would love for it to extend there. Because like we've mentioned, I think it does have important public health implications to prevent the spread even within those facilities. And we all know that financially caring for patients with advanced liver disease is quite expensive. So in the long run, we certainly hope that there will be some economic, you know, cost effectiveness to treating, but in the short term, in some of the private facilities that hasn't been done yet. And then in terms of models for doing it, I know, you know, we know there are other states that are working now on statewide elimination, but I have not seen all of them kind of incorporating the infarcerated piece as much. And so I don't I don't want to speak incorrectly, but I know like Washington, Louisiana and Washington states were kind of with a one and two to get these things started. But I don't know that corrections was focused on as much as we've been doing here in Louisiana. All right, perfect. Thank you. So we have a couple minutes left. So we're going to shift over to Dr. Kushner. So we have a question about safety of direct action agents during lactation and breastfeeding. If there's any data to speak to about that. So not too much data. I mean, of course, we have animal safety data, both during pregnancy and exposure and breast milk. But of course, we can't apply that necessarily to humans. But there is there was one small abstract that was presented at CROI this year, which was looking at the pharmacokinetics of cephosphere, velpatysphere or plusa in breast milk. And they looked at four patients that were participants in some of these other studies and looked at exposure to these medications and breast milk and found that there was a very, very low amount of drug I think they calculated that was just pulling it up as I'm looking, it was point 7% of the daily dose in an adult and a child adjusted to weight. So very, very low amounts of the drug are actually transferred into the breast milk and thus very low exposure in the infant. And so looking at that data, I think that we can say at least from cephosphere velpatysphere, it appears to be safe and there's very low exposure in the breast milk. And then if you extrapolate, and we're really considering treatment in pregnancy, probably the exposure during pregnancy is as high or similar to what would be in breast milk. So at least in the stork study, the approach is of course, we hope to initiate treatment during second and third trimester of pregnancy. But if they deliver early, then we do continue with breastfeeding. We don't say do not breastfeed because you're on the drug. So from what we know, which is there's limited data, it does appear to be safe in breastfeeding. What are the potential risks or like real risks to the fetus if the mom was taking hepatitis C meds during pregnancy? I know a lot of it is just pregnant women, pregnant people, and it's just scary to do the medication, but and there's just, it's great that they're actually studying this. That was a good point to bring up that most often it's just, it's not done. But what are the things that you would counsel a patient about if they wanted to stay on their medication? Like if they got pregnant while they're incidentally going to go and treat it? Yeah. So I think there's a distinction between first trimester exposure of medication and then later pregnancy exposure, which is what we're doing in these studies, really targeting the end, you know, second and third trimester for treatment. Why is that? Well, you know, it's a finite duration of treatment, so we can easily finish it during third trimester. But also that organogenesis, you know, the fetal development happens early in pregnancy. And we think that the potential risk is really minimized with later exposure. Now the question about if they are on DAAs and they become pregnant, that of course introduces the first trimester exposure. And so in that setting, the guidance is not quite clear. And if it were my patient, for example, I would probably consider stopping treatment and then treating them later in pregnancy just because we don't have that data. I think that again would be a case by case basis, joint decision making. But ideally, if we are to plan treatment in pregnancy, we would offer treatment later in pregnancy where it's, you know, there's no potential risk to organogenesis. Now, when we're looking at, you know, endpoints in, you know, the large stork study, really the endpoint of interest that we're looking at is preterm delivery. And we don't know if treatment during pregnancy will actually increase or decrease the risk of preterm delivery because hepatitis C itself appears to be associated with preterm delivery. And perhaps the medications will actually decrease that. Or perhaps medications, maybe there is some impact that can contribute to preterm delivery. But we don't actually know which way the data will look. So late pregnancy exposure should not be associated with like congenital defects and the things that we are really worried about with medication exposure, for example. All right. That sounds good. And then, Sally, there's a question about if the recording of the seminar will be available, if you could address that, and we'll close for the day. Yes, the recording will be available. It's going to be up on the website probably within the next 48 hours. Okay. And they don't believe there's CME, correct? No CME. All right. Well, thank you, everyone, for joining. Thank you, Dr. Christian. Thank you, Dr. Landry. Mary and I are so excited to have you guys and so great to see a good turnout for this. Thank you so much. Thanks so much. Thanks. Thanks for having me. Have a good day, everyone.

Dr. Mary Thompson

Dr. Gia Landry

hepatitis C treatment

pregnant individuals

incarcerated individuals

Louisiana Correctional System

universal screening

direct-acting antivirals

pregnancy and breastfeeding

integrated care models