Hi everyone, I want to welcome you today to our patient debrief. This is the second ever ASLD patient debrief. And I have the honor of introducing Stacey Trueskin, who will be leading us through this debrief. And Stacey had the monumental task of trying to summarize and highlight some top findings from the liver meeting this year that are relevant to our patient and advocate audience. And I just want to thank ASLD for having a great patient and advocate track this year and for including this debrief. I had the honor of doing this last year, and so I'm passing the baton on to Dr. Trueskin. And let me introduce Dr. Trueskin to you. She is the Chief Medical Officer and Director of Viral Hepatitis Programs at Philadelphia FITE Community Health Centers, and is a faculty member of the Infectious Diseases Division at the University of Pennsylvania. Dr. Trueskin received her MPH in Public Health from Yale University, her PhD EPI from Rutgers School of Public Health, and her MD from the University of Medicine and Dentistry in New Jersey at the Robert Wood Johnson School of Medicine, go New Jersey. Dr. Trueskin specializes in infectious diseases, HIV medicine, HIV and hep C co-infection, and internal medicine. She has an interest in public health, particularly the epidemiology of hep C and identifying and overcoming barriers to testing and treatment. She completed a three-year term of service as a member of the ASLD IDSA Hep C Treatment Guidance Panel, and currently serves as the Chief Medical Advisor to NBHR, and is a member of the Technical Advisory Board of the Coalition for Global Hepatitis Elimination. So with no further ado, because we have a jam-packed debrief that she'll be presenting, I will now hand it over to Dr. Trueskin. Go ahead. Thank you so much, Dr. Wang. It really is a pleasure to be here with you all today and an honor. I'm going to go ahead and get started, because as Dr. Wang said, we do not have a lot of time. Here are my disclosures. And now that I shared my disclosures, I want to share a disclaimer. There were 2,142 abstracts that were presented at the liver meeting over the last few days. And at this point, we have about 28 minutes. There is some really incredible groundbreaking scientific work that simply will not be covered today because of lack of time and scope. And so today, my goal is to highlight just some of the work that will be meaningful from a patient or advocate's perspective. And those topics are going to include the impact of the COVID-19 pandemic on liver health. I want to highlight just a couple of promising therapeutic areas, a couple of noteworthy diagnostics, and then leave the last little bit to focus on public health and advocacy work. So let's begin. The COVID-19 pandemic has certainly impacted the health and wellness of all of our communities. And those of us living with liver disease are no exception. So I want to first highlight two vaccination studies. The first study aims to determine the overall and COVID-19 related mortality in patients with cirrhosis post-vaccination. This was a retrospective review of about 3,200 unvaccinated and 254 partially and fully vaccinated adult patients with cirrhosis who were subsequently diagnosed with COVID-19. This study defined fully vaccinated individuals as those who got COVID-19 for at least 14 days after the second dose of either the Pfizer Moderna vaccine or the single dose of Janssen or J&J vaccine. Partially vaccinated was to have COVID-19 diagnosed somewhere around seven days after the receipt of the first dose of any of the above, but prior to being fully vaccinated. And the outcomes that were assessed were the COVID-19 testing or death. And so the results of this study did show a reduced risk of death among those with post-vaccination COVID-19 infection. And you can see here, the blue line are those who received vaccine compared to the red, those who were the control group. The take-home point here is those cirrhotic patients can develop breakthrough COVID-19 post either complete or partial vaccination. Those infections do have a reduced risk of mortality. Now moving on to vaccination in liver transplant recipients. The aim of this study was to look at the association between COVID-19 vaccination and infection and mortality in post-transplant patients. Of course, there's some concern that individuals who are immunosuppressed post-transplant may not have a robust immune response to vaccination. And this study tried to get to the heart of that. The methods here were to look at liver transplant recipients from 2008 to 2020, all of whom were greater than 18. And to define fully vaccinated here, it's a little bit different from the prior study of seven days post the second dose of either Pfizer or Moderna or 28 days post the Janssen or J&J vaccine. The study period was in these COVID times, 12, 15, 2021 to April. And the outcomes here also were a positive COVID test or death. And the results here involved 1900 plus eligible patients, 41% of whom were fully vaccinated. And it compared the vaccinated to unvaccinated patient populations. Two patients in the vaccinated group and 15 in the control group did develop COVID-19 infection. There were no deaths in those who were vaccinated versus two deaths in the control group, both of which were COVID-19 related. The study did find that full vaccination with a COVID-19 vaccine was associated with a 75% reduction in COVID-19 infection or death. Take home point here is that full vaccination is in fact associated with a decrease in COVID infection or death in liver transplant recipients. Now let's look at the impact of the pandemic on liver transplants as a whole in the United States. The aim of this study was to analyze the impact of the pandemic. The methods here were retrospective analysis of UNOS data of outcomes in the adult liver transplant recipient population. They compared the COVID period, which was March to September of 2020 to pre-COVID period in 2019. The results here compared to the pre-COVID period, 4% fewer liver transplants were done in COVID times. Alcoholic liver disease was the most common primary diagnosis with a significant increase from the pre-COVID period. 90 day graft and patient survival was in fact lower during the COVID period. And programs really did attempt to preemptively lower immunosuppression during COVID-19 pandemic. And that led to more rejection episodes prior to discharge. The take home point of this study is that during the COVID-19 pandemic, the rates of liver transplant did decrease slightly and outcomes related to 90 day graft survival, patient survival, and early rejection were also impacted here. So let's take a shift in gears, removing from the COVID-19 pandemic to just touching on some promising therapeutics. And again, we're just touching the surface here of a few studies that I think might be meaningful to those who either have lived experience with liver disease or are advocating on behalf of people living with liver disease. So in light of the fact that alcoholic hepatitis had increased rates of, were made up the largest number of individuals who received liver transplant in COVID times, I thought it was important to highlight this study, which looks at the efficacy of lactobacillus therapy and reducing heavy drinking among heavy drinkers diagnosed with moderate alcohol associated hepatitis. The method here was a double blind prospective study that looked at LGG versus placebo in patients with moderate alcohol hepatitis. The results were that individuals who were treated with LGG had a significant reduction in drinking to the level of less than four drinks per week, which is either considered a social drinking or, or absent in drinking at the six month mark compared to placebo. And you can see the results in the graph on the slide. It's pretty stark and compelling. So six month LGG did in fact reduce heavy drinking levels in this pilot study, which is promising for the future, most certainly. Now shifting away from alcohol hepatitis to primary biliary cholangitis. So this study looked at the, the effect of obatocolic acid on time to occurrence of first liver transplant or death in patients who are living with PBC. Okay. This method, we used a Cox regression model comparing time to transplant or death in patients who were treated with OCA versus those who were not. And you can see in the graph that I've put on this slide that in fact, none of the confidence intervals cross one. So OCA treated patients did in fact have a significantly lower risk of transplant or death. And this could be really meaningful for people living with primary biliary cholangitis at the potential therapeutic area. The next therapeutic area is for refractory ascites. And so as, as many of you may know, individuals with decompensated cirrhosis will often have refractory ascites that will require either placement of tips or serial parasentesis for removal of ascites fluid. So this study, the aim was to evaluate the safety of a tunneled peritoneal drainage in a large cohort of patients with decompensated cirrhosis and refractory ascites so that individuals could manage their refractory ascites essentially at home. The methods here compared, um, looked at 223 patients with refractory ascites who had a contraindication for tips implant. Study looked at 90 day survival incidents of hyponatremia and incidents of spontaneous bacterial peritonitis. And they were compared to a group of patients who received the standard of care, which is serial parasentesis. And you can see here from the results section, there, there were 53 explants with a mean of 72 days to explant. The most common cause for explantation was, um, was infection. SBP incidents was in fact similar to that of the standard of care, but hyponatremia was more common in those who had this tunneled peritoneal drainage system in place. The take home here is that tunneled peritoneal drainage is in fact an alternative treatment option in patients with refractory ascites and a contraindication to tips. Let's turn our attention to statins. This was a theme that I saw come up. The next two studies I'm going to share with you, look at the impact and potential advantages of statin therapy, um, which many of, of, of you in the patient population or advocates group may know is taken often to, to, um, reduce cholesterol and reduce the risk of cardiovascular events. This study aimed to look at the effect of statins on the risk of developing acute on chronic liver failure. And the methods used in this study were retrospective cohort study on patients with cirrhosis who attended the VA. And you can see from the graph that's up on this slide in the blue, the blue line, uh, is statin exposure compared to no statin. And you can see that cumulative statin exposure does in fact reduce the risk of developing acute on chronic liver failure. So there's some potential here as well. And then if we were to look at simvastatin, another statin that's used potentially in liver transplant donors to improve outcomes in liver transplant recipients, the aim of this study was to determine a simvastatin donor treatment is safe in preventing ischemia or reperfusion injury and effective to reduce graph loss at 180 days post-transplant. This was a double rhyme, double blind, randomized preoperative treatment of deceased donors with simvastatin on liver transplant recipient outcomes. They looked at 90 and 180 day outcomes, and they found that patient and graph survival rates were higher among the group that received simvastatin compared to the control group. So the take home here is that donor simvastatin treatment before liver transplant is safe, and it might just improve early graft and patient survival post transplant. So let's move on to, uh, to promising therapeutics in non-cirrhotic NASH with fibrosis. The aim of this particular study was to evaluate the safety and efficacy of cotadatide, a GLP-1 and glucagon receptor co-agonist peptide, looking at non-cirrhotic NASH, but with fibrosis. The methods here were randomized double-blinded placebo trial with cotadatide in obese patients with NASH with fibrosis. And you can see that cotadatide was given at two different doses from the graphs on the right, and compared to placebo, cotadatide treatment led to improvements across disease components of liver steatosis, inflammation, and fibrosis. The next two and final studies look at hepatitis B therapy. So this study is a phase 2A trial of a PD-L1 antibody, ASC-22, also known as envafolamab in patients with chronic hepatitis B. The aim of this study was to evaluate the safety and preliminary efficacy of ASC-22 in patients with chronic hep B after a single injection. And they used a single ascending dose study of three different doses with three patients per dose and a 12-week follow-up. And all of the chronic hep B patients were hepatitis B E antigen negative. They had surface antigen that was less than 10,000 and an undetectable hepatitis B DNA. The results included a single dose of ASC 22 up to 2.5 milligrams per KG was safe and well tolerated. And a single dose did induce a dose dependent reduction in hepatitis B surface antibody with, I'm sorry, antigen, which you can see on the graph on the right. So the take-home point here is that ASC 22 does indeed have the potential to cure chronic hep B patients in combination with other therapies. And this next study does look at co-administration. So combination therapy with one agent, VIR 2218 and PEG interferon alpha. And the aim of the study was to evaluate both the safety and efficacy of VIR 2218 alone and in combination with PEG interferon alpha for the treatment of chronic hep B. They looked again, similarly to the last study at virally suppressed participants who are receiving 200 milligram to subcutaneous injection of VIR 2218 every four weeks, six doses, either alone or in combination with interferon. And you can see from the graph that there was in fact, a substantial hepatitis B surface antigen reduction with the co-administration of VIR 2218 and PEG interferon alpha by week 24. And three participants actually achieved loss of their surface antigen by week 24. And we all, for those of you familiar with interferon, the, the adverse events were consistent or effects were consistent with known safety profile of PEG interferon alpha. So the take-home point here is that combination therapy may actually have the potential again, to cure chronic hep B. So I want to share with you now two noteworthy diagnostics that I think could have meaning for, for patient population, advocacy population. The first is serum MMP as a biomarker biliary atresia and a large U.S. cohort studies. So matrix metalloproteinase, otherwise known as MMP7 was studied here to look at the accuracy of it as a marker. The optimal cutoff was, was set to be identified and they wanted to compare MMP7 diagnostic performance to other clinical markers. The methods here used were a case control study, 399 cholestatic infants, 201 that had biliary atresia, 198 that did not enrolled in the childhood liver disease research network and serum MMP7 was quantified by antibody-based assay. And the results demonstrated that MMP7 was superior to GGT, a colic stool and obstructive features in liver histology in making the diagnosis and MMP7 cutoff of 67.4 nanograms per ml produced a high sensitivity and specificity and a negative predictive value of 95.4% for the diagnosis of biliary atresia. So the take-home message here is that MMP really did have a superior discriminatory value compared to other clinical markers and was able to rule out, rule out biliary atresia in patients with that negative predictive value. The next diagnostic I want to walk you through is the GALAD score. The aim here was to compare the performance of AFP and GALAD for the detection of hepatocellular carcinoma. They also wanted to determine the performance of AFP and GALAD in those who had to have an ultrasound or CT MRI to make that diagnosis of HCC. The methods here were a prospective cohort study about 1,500 patients all with cirrhosis and GALAD was tested blindly at diagnosis and six months prior to HCC diagnosis and the results indicated that GALAD had the best performance of any biomarker at HCC diagnosis and six months prior to HCC diagnosis. So this may in the future compete with or potentially replace AFP and it can also limit unnecessary diagnostic CTs or MRIs in the future which is great. So moving on to public health and advocacy, the next series of studies are larger studies that have larger public health impact and I think can also lead provide data to share with leaders, government, payers, etc. The first study that I want to share with you all is really evidence of ongoing racial inequities in the United States, certainly within our healthcare system. This study aimed to evaluate the relationship between cirrhosis status and hepatocellular carcinoma trends in both black and white patients with HCC. The study here was a retrospective cohort study of adults diagnosed with HCC at two different health systems in Indiana and North Carolina between 2009 and 2019. Fibrosis in this study was defined by a CIP4 score of greater than 3.25 and trends were compared both before and after the release of direct acting agents for HCV. The results here were certainly concerning. The odds of a black patient having non-cirrhotic HCC increased 34% per year whereas trends in non-cirrhotic HCC did not change significantly for white patients. And in those with a Fib4 category of less than or equal to 3.25, so no fibrosis or minimal fibrosis, in the DAA era rates of HCC still increased by 22% per year for black patients and only 12% per year for white patients. So the take-home here again is that rates of HCC in patients without cirrhosis are rising still in the DAA era which is certainly concerning but even more so disproportionately for black patients in the United States. If we look at NASH or non-alcoholic steatohepatitis in the U.S., according to obesity, find some really interesting information from this study. The aim was to model clinical and economic burden of NASH in the United States stratified by the presence or absence of obesity and certainly we know that as a country the United States continues to to get heavier so a study like this has great import when we think about policy making resource allocation. The methods here were a Markov model with one-year cycles and 20-year horizon and they applied estimated age obesity patterns from population-based data and what the authors of this study found was that over two decades obese NASH will have higher all-cause cardiac and liver-specific mortality compared to non-obese NASH and obese NASH had large estimates of liver transplant, decompensated cirrhosis, and years of hepatocellular carcinoma and I think that the overarching message here is with the growing prevalence of obesity in the United States and related NASH we're going to have some major clinical and economic impact in the U.S. that we should start planning for soon and advocating for resources for. The next study really has to do with liver transplantation. This is a one-year report for the assessing the impact of the acuity circle policy on liver transplant allocation. So the aim of this was to increase broader sharing of livers with a decrease in variation in median MELD score at transplant and no adverse effect to waiting list mortality. The methods here were a retrospective cohort of the OPTN waiting list and transplant data one year before versus post this policy was in place. The results were encouraging showed an average distance was increased from 154 to 199 nautical miles while variation in median transplant score by donor-specific antibodies decreased from 13 to 11.8 and you can see from the maps that are on the right hand side the dark areas for the median transplant score have become lighter post policy making the take-home point is that livers really are traveling a greater distance there's less variation in the median MELD score at transplant nationally and sicker patients are being transplanted faster which is all good news. I'd like to move on and touch base about viral hepatitis. The global hepatitis B cascade of care was presented at the liver meeting and I think gives us a overview or a snapshot of where we are in the global hepatitis B pandemic and exactly how far we are from the World Health Organization's elimination targets for 2030. So the aim of this study was to estimate the national regional and global cascade of care of hepatitis B 166 country-specific models estimated the 2019 global cascade of care for hepatitis B. The results here were the global prevalence of hepatitis B surface antigen was estimated to be 3.6 percent in 2019 and just 0.9 percent among five-year-olds which is still relatively high and you can see from the cascade of care that's on the right hand side is we have an incredible amount of work to still do. If you look at those individuals who are treatment eligible and of those who are diagnosed we have huge step-offs in the care cascade with just a very small proportion who are diagnosed and treatment eligible and even fewer who are on treatment. So we have a lot of work to do in terms of screening and treatment to accomplish those 2030 elimination targets. There was a very interesting cost-effectiveness analysis of treating all hepatitis B surface antigen positive individuals in the United States looking at the economic impact of that approach. Certainly we apply a treat-all strategy for things like HIV and other infections and this model proposed that we would do the same for hepatitis B. The methods were a Markov model to estimate the hep B related morbidity and mortality and the annual treatment cost for this model was estimated to be 5,400 per year U.S. dollars. The results found that a treat-all strategy was certainly found to be cost-effective. If the price were dropped to 2,000 U.S. dollars per year the scenario would be considered highly cost-effective and if the price were further dropped to 750 U.S. dollars per year the scenario of treating everybody with hepatitis B surface antigen would actually be cost-saving. So the take-home point is a treat-all strategy could could be beneficial from both an economic and certainly from a public health perspective if we were able to have all individuals have be brought down to an undetectable viral load. If we shift gears and we talk a little bit about hepatitis C prevalence and the cascade of care entering 2020 there were a few really compelling cascades that were presented at the liver meeting this past week. This one aimed to evaluate elimination progress and establish a new 2020 baseline for future elimination efforts globally. The methods here were 110 country and territory specific models used to estimate the prevalence and the cascade of care. The results included 56.7 million viremic infections remain in 2020 which is a decrease from the 63.7 million that were in existence at the beginning of 2015. However, less than a quarter of those current infections have been diagnosed and only five percent diagnosed were treated in 2020 and so you can look at this very compelling cascade of care. The gold bar shows how many current infections we have and a steep drop-off to that orange bar with how many are currently diagnosed with even fewer having been treated. So the take-home message here is that HCV prevalence has certainly declined since 2015 but there are really significant efforts that are needed to meet the 2030 elimination targets. And here's one way that we could do this. This is an elegant study that was was presented at the liver meeting that aims to evaluate the effectiveness of a simplified rapid treatment initiation with the goal being same day at confirmation approach to hepatitis C treatment to young people who inject drugs. This was an open label randomized control trial comparing the efficacy of a seek and test and rapid treatment model versus usual care and curing people who inject drugs. And the results here are shown in the graph. 64 percent of participants in the rapid treatment arm achieved a cure compared to just nine percent in the usual care arm and that was of course significant. And you can see that there are differences at each stage in the care cascade when you compare rapid treatment to usual care. The take-home message here is we should be advocating for same day low barrier simplified HCV care to achieve higher cure rates. So with that I am just about at the top of my 30 minutes and I want to thank again the organizers of the meeting for putting together a patient debrief this year and and having a patient track and an advocate's track at the liver meeting. I want to thank you all for your time and attention and I'm grateful to have had the opportunity to speak with you all today. Thank you so much.

liver meeting

COVID-19 impact

liver diseases therapies

hepatitis treatment strategies

racial disparities

public health efforts

research