Good afternoon, dear colleagues. First of all, let me introduce myself. My name is Marcelo Silva. I'm the head of Hepatology and Liver Transplant Unit at Australian University Hospital in Buenos Aires, Argentina, and I'm the current president. With my co-chair, Professor Mauricio Lisker-Mellman, Director of Hepatology Program in the Division of Gastroenterology at Washington University in San Luis, Missouri, we're honored to chair the 2021 ASLDLA Joint Symposium entitled, The State of Modern Hepatology in the Americas. We have discussed in detail how to approach such a comprehensive scope in a region that is characterized by a wide disparities in education, disease prevalences, and access to care. We then decided to focus only in hepatitis B and AFD to high burden diseases in which we can clearly diminish impact with feasible interventions such as appropriate diagnosis, vaccination, and education programs. We also aim to compare the regional disparities to be able to understand whether these gaps are and how to overcome them. As you can see here, we have several learning objectives of the symposium that are to review the hepatitis B diagnostic, prevention, and treatment challenges that clinical hepatologists face in different countries and regions in the Americas. Also to contrast the strategies used to diagnose and decrease NAFLD burden in the Americas, and to evaluate differences between vulnerable and non-vulnerable populations with liver diseases. Finally, to discuss the type of interventions that need to be deployed in each region to overcome various disease care and improve liver problems outcomes. We assign a structure with short lectures addressing current different hepatitis B challenges and NAFLD strategies either in US and LATAM regions, followed by a 20-minute slot for an interactive discussion with you, the audience. We're honored to be accompanied by a highly qualified faculty team such as Dr. Jorge Gonzalez, who has a PhD in virology and he's the head of the viral hepatitis program in the Ministry of Health in Argentina. Dr. Mindy Nugent, Professor of Medicine in GI hepatology and epidemiology at Stanford University, also Director of the GI and hepatology and liver transplant programs at Stanford Medical Center. Dr. Marco Arese, MD, PhD, full Professor of Medicine at the Pontificio University Catolica in Santiago de Chile, and also head of the Department of Gastroenterology of the School of Medicine at the Seminary University. Finally, Dr. Mari Reynela, Professor of Medicine in Gastroenterology and Hepatology at Northwestern University, Fainberg School of Medicine and Director of the Northwestern Fatty Liver Program. Dear Jorge, it's your time. Please go ahead with your 15-minute lecture entitled, Hepatitis B Diagnosis, Challenges and Prevention Gaps and the LA Perspective. Thank you. Hi, everybody. I want to thank the organizers to give me an opportunity to present this subject. Especially to the coordinators of Dr. Neman and Dr. Marcelo Silva. We're going to talk today about the ABD diagnosis challenge and prevention gaps. I have nothing to declare. We can revise the epidemiology data in 2016 about the American region and you see that 3.9 million people were chronically infected. 0.5 percent of prevalence among general population. At that time, 10,000 chronic infection in this year and most of them 56 percent because of perinatal transmission. Prevalence among five years old was somewhere between 0.04 to 0.1 percent. 31,000 deaths yearly were estimated to be due to ABD in the Americas in the year 2015. Related to the cascade of care, you can see that from that 3.9 million people with chronic infection, only 23 percent were diagnosed and only 3 percent were on treatment. We need to remember also that in South America, in this region, we have a hyper-endemic zone, the Amazon Basin for ABD with chronic caries in indigenous population between 1 and 40 percent in different age groups. If we look at the published data in 2021 with data from 2019, again, the infected was 10,000 and the mortality was around 15,000. In looking for the cascade, you again see that only 80 percent were diagnosed and in treatment, only 3 percent. In brief, in the Americas at year 2019, 3 million people were living with the chronic hepatitis, and 125,000 will die for liver cancer and chronic disease because of cellulose. Well, going to more data about the survey that the PAHO did in 2016, we can see some aspects of the national policies and strategies for prevention and control for viral hepatitis in 2017. So this survey was sent to all the countries and the prevention strategy for key population was implemented in 45 percent of the 33 responding countries. Treatment guidelines in line with the WHO recommendation for ABD, 86 percent among the 22 responding countries. Prevention strategy for health care workers, 84 percent among 38 responding countries. And celebrating the worry of hepatitis A in 55 percent of the country among 27 of them. World elimination period in HIV, 43 percent among 28 responding countries. And national strategy and plan for prevention, care, and control for viral hepatitis at that year, 2019, 48 percent among the 37 responding countries. Another aspect was about in the survey asking how much of the country have a structured prevention and control for viral hepatitis within the Ministry of Health. And the majority of the country have established an organic structure within the Ministry of Health to coordinate the response to viral hepatitis, 21 out of 25 reporting countries. And 16 of them have integrated with the pre-existing AIDS program. And five report having it independent of the other. And four have not yet given any information about research. The other aspect very important is about the laboratory capacity for HIV and HIV infection in the Americas. And as you can see, 100 percent of the responding countries have serology tests. Seventy-three percent have been using rapid tests for HIV. And in respect for the nucleic acid test for diagnosis, confirmation, and monitoring of treatment response of chronic infection at a high level for both HIV and HIV in 19 out of 21 reported countries. Okay, let's see what about the publicly funded HIV and HIV treatment in the Americas in 2017. As you can see in the map, in 18 countries out of 37 reporting countries, publicly funded treatment is available for both hepatitis B and C. Eight countries provide publicly funded treatment only for hepatitis B, that is in light blue. And 11 countries reported to have no viral hepatitis treatment funded by the government in orange, mainly in the Caribbean and Central America. So we arrived to World Day, if I like to say, in 2019, and the PAHO published what we already know as a poster, that in Latin America, two million people live with hepatitis B, and only three percent was given a treatment. And also proclaimed that the treatment saved lives, and you see the map where the countries who don't have publicly funded treatment, now is a big number in Central America, North and South America, and Guyana, and Suriname, and in the Caribbean, of course. The other aspect that this survey relevates was the strategy for HPV birth-dose vaccinations, and you can see that certified among 52 countries, the birth-dose for HPV vaccine is included in their immunization policies, and in 22 of them as a universal policy, and 13 as a target policy to infants born from chronically infected mothers, as you can see in the graphic. Also, policies and additional strategy for prevention of perinatal HPV in the Americas, 22 countries among 28 reporting countries were using the immune globally for HPV in infants exposed, and that's represented 79 percent. Twenty-four out of 31 responding countries were testing perinatal women for HPV, that represented 77 percent of the participants, and 12 among 28 reporting countries have established the goal of eliminating mother-to-child transmission, and this represented 43 percent. And particularly in this strategy of mother-to-child transmission, now it's called PLUS, because for the pre-existing strategy for HIV and syphilis now, hepatitis B is some, and also Chagas disease in some endemic countries. So, AMTCP is a milestone for the elimination of HPV as a public health problem by 2030, as has been proposed by WHO, building on established hepatitis B vaccination program, and using also antenatal screening, maternal antiviral, and immune globally for hepatitis B. Then came the COVID-19 pandemic, and what it will say about the prevention, diagnosis, and treatment for many diseases, and also for viral hepatitis, was interrupted because people had to face a quarantine, met the misinformation, the ignorance, and fears. So, as a result, many people stopped visiting public or private health establishments, and the impact of this situation is unknown with this attitude, but it's enormous, because people have neglected the fundamental chronic immunocompromises, and this can be seen if we look at the coverage of the first dose, the first dose of HIV in the Americas, and you can see in the map on the left, many countries have it below 80% coverage, so this is unacceptable if you want to have a successful immunization. And on the right-hand side, you can see that in the year 2015, the countries of the region of Latin America, the majority were above 90% of the coverage, and the year 2020, again, many countries are below 80%, that is not acceptable. So, if we look again to the global immunization strategy and the progress taken into account for intervention, taken into account in 2015 as a baseline, you can see that the progress does not have been equal to all the strategies, so the major gap, as you can see, are in HIV, the dose, harm reduction, and for sure, testing and treatment. So, we have to remember the global hepatitis framework with the four actions to correct this situation, and also remember the five interventions that for the WHO was important for low- and middle-income countries, as you can see in this paper published in 2019 by Lancet Global. And let me see, let me say, sorry, remember some key transversal actions, some others, like increase awareness, improve surveillance, increase strategic teaching, mainly for healthcare workers, big network, essential individual, and promote national programs, funding, because of funding, because of action plans, responsibility, and promote workshops with patients and NGO, essential individuals, and we can, in that way, to correct what is wrong in this role. So, in conclusion, since 2015, significant progress has been made towards 2030 targets. Because of such a wide and diverse region, in Latin America, it is difficult to pinpoint the real state of each country, but the COVID-19 pandemic has strongly affected healthcare around the world, and particularly in Latin America, the impact on the diagnosis and immunization of HIV has been important. But we all know that there is organizations, protocols, and technical teams training and committed to overcome this contingency. So, the region can quickly surpass the current challenges and gaps to return to the path of elimination by 2030. Thank you very much. Hello, I am Min-Di Nguyen, hepatology at Stanford University in California. I am charged today to review the challenges and prevention gaps in hepatitis B from the ASLD perspective. So, first, I would like to review the rates of current diagnosis and delayed diagnosis in North America, what is the current rate of state of linkage to care and prevention gaps, and most importantly, what can we do to improve the current situation? So, globally, out of 290 million total people infected with hepatitis B, only about 10% have been diagnosed and only 1.6% have received therapy. And it has been reported from many places around the world that the CHB populations are aging, having more comorbidities and complications, and more difficult to manage. So, early diagnosis is very important. So, first, I would like to review the data from the U.S. So, from administrative claims database in the U.S., patients with insurance, about 200 million people, it's estimated that only 18% have been diagnosed, and among those with cirrhosis, only one-third have received antiviral therapy, and among those with liver cancer, only about half have been treated with antiviral therapy. And this data is fairly closely approximate, the data from the NHANES population survey. About 15% are aware of having any liver disease. And the data from provincial Ontario database in Canada also show very concerning data that out of the patients with hepatitis B diagnosis presenting with complications, less than half have been diagnosed. About half have been diagnosed within six months of complications. So, it shows that these patients have no chance of preventing these complications because they didn't get diagnosed and treated early enough, and there has been no significant improvement over time between 2003 and 2014. And institutional databases study, like this study here from Stanford Mayo Clinic and a few centers in Korea and Taiwan, show fairly similar data as the data that we saw in nationwide U.S. study claims database. So, only about half of the patients with HCC have been diagnosed here, and at the time of HCC diagnosis, only 17% have received antiviral therapy. So, pretty similar to and would agree with the data from Canada that many are diagnosed late when complications already develop. And in the U.S., we also need to be mindful that many of our hepatitis B patients are immigrants, and among immigrants from Africa, the diagnosis of HCC occur at a younger age. 30 to 50% of the patients with HCC born in Africa present younger than 50 years of age. So, what can we do to improve this situation? So, as I alluded to already, the majority of hepatitis B patients in the U.S. are foreign-born, so racial, ethnic, cultural diversity create language and health literacy barrier, fear of disclosure, and they're culturally-driven belief system that we need to be sensitive, be aware of, and we have to develop a culturally sensitive approach, and there have to be more health disparity research looking into these areas. And then there are programs to improve education and access, but these have been existing for one or two decades already, and we still have a very poor situation, a low HPV diagnosis rate. So I believe that a more simplified, a more universal, semi-universal approach to HPV diagnosis would be necessary to improve the status quo here. So as many or all of us here know, the various organizations from the CDC, the ASLD, and the U.S. Preventive Task Force have proposed very comprehensive detail and very good recommendation for HPV screening. And this is not new. The CDC recommendation to screen people born from areas with 2 percent or higher HPV prevalence has been around since 2008. The rest generally are based on very specific risk exposure, and some of these can be stigmatizing to patients, and the details of this comprehensive list may be difficult to recall or remember in routine practice for many physicians, primary care physicians especially, because they have to remember many cancer screening guidelines. So adherence is poor, and that's why the diagnosis rate remains poor, in my opinion. So can we have a universal screening for Hep B like we have for Hep C, but then maybe it's not cost-effective because Hep B prevalence in the general population in the U.S. is much lower than Hep C. So can we employ a semi-universal, semi-targeted approach to HPV screening that may be more cost-effective? So this is a recent attempt by our group to see if we can just use very simple data points, data that are widely available in any medical records that could be employed in EMR, electronic medical records base. So if we use sex, birth year, race, ethnicity, and whether the patient was born in the U.S. can we create a model that can diagnose or screen most of the Hep B population in the U.S. with reasonable sensitivity and specificity? So in this model, we found a sensitivity of about 87 percent and specificity about 80 percent. So we believe that this gives a reasonable first-step approach to a semi-universal, semi-targeted approach. And to improve this sensitivity, then we can complement it with the risk-based recommendation that had been proposed by the CDC ASOD. But at least with this, we can catch the bulk of the patients. And I advocated for this because EMR has been shown to work, and this is a work by Dr. Louis Roberts and his group in Mayo Clinic, and they looked at the patient who should be screened and were not screened here and make intervention via EMR, and the screening rate of eligible patient really improved significantly during the intervention period. So it can work, but we would have to make it simple, something that is practical. Now, how about beyond HPV diagnosis, vaccination rates in high-risk people, evaluation and monitoring of people already diagnosed, and treatment rate among people who meet the treatment criteria for antiviral therapy? So, vaccination for hepatitis B has been recommended, available, and covered by almost all insurance in the U.S. for decades. So we have seen in the past few decades that the vaccination rates have been going up consistently in the general population between 1999 and 2016. However, among the high-risk people as defined by the CDC, the rates actually have not consistently up during this same time period, and only about 69 percent, and 69 percent of them have undetectable immunity. And you can see that by 2013 and 2014, about four or five years ago, about 70 million high-risk people in the U.S. are still unprotected for hepatitis B. So there are more work especially targeting the high-risk people in the U.S. Among the community of hepatitis B patients already diagnosed, so this is the database, a claims database of about 200 million U.S. people, and of these we identify 55,000 hepatitis B patients. And if we define adequate evaluation to include an ALT, DNA, and e-antigen within about six months from the first hepatitis B diagnosis, then we found here only 38 percent of those patients with some GI and ID visits. Now, they may see GI doctors for colonoscopy or for abdominal pain, but there would be an opportunity to evaluate for hep B because these patients have hep B diagnosis, but the rate is very low. And for patients who did not see GI or ID, the rate is even lower, 26 percent. Recently, their interest in hepatitis D screening, so I included the data here. So among these patients, the rate of hepatitis B antibody testing is really small, less than five percent, even among patients seen by GI or ID specialists. Now, encouragingly, I guess people are more worried about liver cancer or other reasons to get an abdominal ultrasound or imaging, so about 50 to 60 percent of patients with hepatitis B have an ultrasound or a CT in the first six months of hepatitis B diagnosis, so this is a bit better. Monitoring rates are even worse. Monitoring rates are even worse, so only 60 percent would have at least an annual visit, and this, you know, doesn't mean that it is for hepatitis B, so any visit, and only 40 percent had at least one ALT test and only 28 percent had at least one DNA test annually, so the evaluation is poor and the monitoring is also not anything that is close to the ASLD recommendation. Now, in another large nationwide database with lab data and ethnicity data, we were able to categorize the patients if they are treatment-eligible or not, so we found about 11 percent would meet ASLD criteria and 14 percent by ESO criteria using lab data because liver biopsy and fibroscan data are not available in this database, so this rate of treatment-eligible patients may be an underestimate. However, among these patients found or confirmed to meet the treatment criteria, only about 60-65 percent received antiviral therapy throughout the whole follow-up time, and there's no significant change in the last nine years versus the years before that, so it's a consistent theme. Data in the U.S. as well as in Canada, these situations have not really improved over time, and that's really concerning. And I want to mention again that the database that we use to look at these issues are from people with private insurance considered to be better insurance in the U.S., so the issues of funding or access may be less so than the general hepatitis B population, and that's consistent with a study that we did several years ago using reviewing records from patients in several clinics in the Bay Area in Northern California. Financial difficulties were cited to be only in a minority of patients meeting criteria for treatment and did not get treatment. So, I hope I have shown you the gaps and some of the potential things that we could do to improve the current screening diagnosis and disease management, and what I believe is that we have to make the guidelines and the recommendations simpler, more practical for the busy practitioner to use. And I want to call out to this recent study by the WHO group, this is a major effort reviewing the world literature in patients to see the percent of the patient meeting criteria and the treatment rate, et cetera, and the proposed actions, there's a short list, and I think very practical and very important that we need better data to support the guidelines that are stratified not just by cirrhosis, but also by disease activities among the patients with no cirrhosis, and the data should be disintegrated by study setting, because there are vast differences between community patients and patients seen at liver referral centers, in addition to the usual things that have been stratified for asex, race, ethnicity, and region. So, same for screening and diagnosis, we need to have a practical, simplified algorithm that can be easily applied with EMR or with the clinicians in practice, and we also need to have practical and simplified management algorithm to help guide the treatment and management of hepatitis B patients. With that, I would like to end, and thank you for your attention. Good morning. First of all, I would like to thank the ASLD for inviting me to speak in this symposium and to the government board of the Latin American Association for the Study of the Liver Alley for selecting me to deliver this talk on behalf of the association. I have a lot to say, but I will try to keep it short and brief, and I would like to thank on behalf of the association. I have no financial or other conflict of interest related with the content of this presentation. Non-alcoholic fatty liver disease is currently a global epidemic, which is burdening health systems worldwide. I would like to indicate that epidemiological data from Latin America is limited and likely inaccurate, and also would like to state that the region is characterized by important social, cultural, ethnic, and economic differences. This is probably the most cited graph of global epidemiological data related to NAF prevalence taken from the publication from Janus et al in 2016 and then republished in 2019. As I mentioned before, current NAF prevalence estimated from Latin America are imperfect because primary data from most of the countries in these regions are lacking. Available studies reporting data from Brazil, Chile, Mexico, and Colombia are studies that were performed more than a decade ago. Therefore, it is likely that NAF prevalence is currently higher. Other indirect estimates of NAF prevalence in Latin America, such an examination of epidemiological figures for obesity and diabetes, also indicate that countries of this region have indeed a high NAF prevalence, although the scenario is heterogeneous in our region. Prevalence of obesity in LATAM is very significant. These are the figures shown in the last report from the OECD databank, and you see that the prevalence are very significant, and adding pre-obesity and obesity, you can reach up to 70% of the population in countries like Mexico and Chile. Epidemiological trends in diabetes are also worrisome, and as shown in this recent publication, again, Chile and Mexico have very high prevalence of diabetes that reach between 12% and 13% of the population. Another estimate of the huge problem related to NAF in the region is the increase seen in the last decades of NASH-related cirrhosis. In this recent study published in Scientific Report, LATAM exhibits the highest age-standardized incidence rates of NASH-related cirrhosis, and when estimated as an annual percentage changes between 1990 and 2017, there is significant increase between 120% and 200% changes in that time frame in the region. There are several issues related to NAF diagnosis that are important in LATAM. First of all, there is a lack of awareness among non-specialists. This has been reported and documented in the U.S. and other countries, and is likely to present in LATAM, although hard data on that is not yet published. With lack of awareness, I refer to the lack of awareness among non-specialists, endocrinologists, cardiologists, primary care physicians, that see often patients with NAFLD but are not aware of the proper diagnosis, the proper recertifications, and also about the referral pathways that are applicable to these patients. In relation with this, the simple non-invasive tests like FIP4 and others are likely underused, either by not being known or for not being regularly applied to patients who are at risk of having NAFLD or advanced NAFLD. One other problem is the lack of availability of liver stiffness assessment with modern technology. The use of transient elastography is being widely accepted in the world for this purpose, but at present times, there is only 241 transient elastography apparatus in LATAM, which is a rather low figure for the needs of the patient community. Other issues that are related to this are that we need to increase the opportunities for continuous educations on topics related to NAF among non-specialists, such as the case finding and risk certification. We have also to procure that non-specialists screen for NAF at least at at-risk individuals such as obese patients and diabetes patients. This has been endorsed in the recently published LA guidance and by other expert groups as shown in this publication. We also need in this regard simple referral pathways because these are key for proper care. In this recent publication from Kanwal and collaborators, an updated scheme for identification of patients at risk is provided. This scheme, which is a summary of other published in the literature, include the use of FIFOR to try to classify patients in low risk and high risk, and if you have a proportion of patients that are in the indeterminate risk, they should be assessed by transient elastography or liver stiffness measurement in order to classify these patients and establish proper referral pathways to either keep the patients in the primary care setting or refer to a pathologist or eventually explore indications for treatment. This kind of referral pathway are needed to disseminate in our region and certainly in low resources setting, the availability of diagnostic tools including elastography is likely to be limited. In that setting, diagnosis will often require to make pragmatic choices and establish low cost solutions until a modern technology is available. When you think in the NAF challenge in Latin American region, I would like to show this slide because some of the ideas for facing the NAF challenge were delivered in a recent series of workshops conducted by the Economist Intelligence Unit and the ESEL Foundation, where a number of health professionals and leaders and primary care providers and dermatologists convened to discuss regional calls. In this slide, the calls for Latin Americans are presented and they are expected to provide a rallying point for stakeholders to align around in order to develop a road map for advancing NAF public health agenda. These proposals include to integrate NAF screening in health checkups in order to increase awareness of what means NAF in terms of risk of diabetes and liver disease and cardiovascular risk, try to decrease health system fragmentation, which is a barrier for the implementation of multidisciplinary teams, and try to efficiently use resources by task shifting between the health care team, meaning that the physicians have to reduce their load doing more patient care and nurses and allied professionals took some tasks, principally of education about the disease and its risk. Design and implementation of efficient and effective models of care for patients with NAFLD is crucial. We have to break paradigm and advance implementation of comprehensive models of care for NAFLD. Recommendations made by a group of experts published recently in Nature Reviews, Gastroenterology, and Hepatology, as shown in this slide, are, in my opinion, applicable to our region. This group of experts proposed eight points that are related to coordinate system to define the composition and structure of multidisciplinary care and develop guidance for diagnosis, screening, referral pathway. We have to articulate the roles and interaction between primary, secondary, and tertiary care providers, and establish local service in order to treat NAFLD and common comorbidities. In a companion publication in the same journal by the same group, a consensus statement about the global public health agenda for NAFLD was recently published. And in most of these concepts I have already mentioned, and in this consensus participates some LATAM experts, including Juan Pablo Ara for my group, agreed this agenda that we have to impose also in our region. With regard to public policies, there is a significant lack of public health policies addressing NAFLD and its health consequences in the Americas. Some modeling studies that were conducted in my department and are in the process of publications suggest that the establishment of public health policies on NAFLD-related conditions is associated with a lower burden of disease and resulting complications in the years to come. Some examples of public policies to address that are shown in this slide. Fiscal measures such as food taxes, using taxes and subsidies to promote healthier diet are important. Policies for the procurement and provision of healthy food, particularly in the school, are important. Promote healthy diet and physical activity through mass media campaign. Analystic planning of non-communicable disease are important in this regard. Finally, I would like to make some remarks on research. Research output remains low in our area, in the area of NAFL, which is reflected in low publication rates in scientific journals as shown in this table taken from a recent publication from Alehe that show that the number of publication in the last decade is very low and is concentrated in few countries in the region. This have as a consequence that the information about important NAFL related issues are scarce or limited. The reasons include income disparities and no resources to do research, clinically oriented medical training with again, no capabilities to perform research and insufficient availability of research funding. Indeed, we have to work in more coordinated efforts in order to address the peculiarity of NAFL in the region. We have to procure institutional strengthening through North-South and South-South collaboration and articulation of multi-center consortia, which I think are relevant to conduct impactful research in NAFL. Collaboration with high income countries like the US or Europe through existing international network, as well as more extensive participation in large international clinical trials may also help in improving NAFL research in Latin America. Indeed, building large biobanks is important as we can characterize better our publication in terms of genetics, biomarkers, anomics information. And for that, scientific societies such Latin American Association for Study of Liver are key to promote this collaboration. In conclusion, ladies and gentlemen, Latin American countries face unique challenge and obstacles to addressing the growing burden of NAFL. The main challenge to improve care of people living with NAFL in Latin America include among others, lack of disease awareness, health system fragmentation, and the need for development of effective strategies for prevention and effective treatment of NAFL and comorbidities, including type two diabetes and obesity. Education efforts on NAFL and extensive collaboration between scientific societies, governments, non-governmental organizations, pharmaceutical industry, and other stakeholders are needed to advance the NAFL public health policies agenda. Thank you for your attention. Hello, my name is Mara Rinella, and it is my privilege today to speak on minimizing disease burden in NAFL at the ASLD Ale Symposium. These are my disclosures, none of which are relevant and none are active. So as you can see here, the scale of the problem in the U.S. and in Europe, and really globally, is quite substantial. The global population of about 24.7% of fatty liver EU combined, where 155 million people have fatty liver disease, 28.9 have NASH, and 5.8 million have advanced fibrosis-related fatty liver disease. So the increase in liver failure due to this is why this topic is so timely. Here you can see the increase in both alcohol and NASH, but the full change since 2002 is dramatic. It's five-fold compared to approximately two-fold for alcohol, as noted in the graph below. Focusing on the United States, the scale of the problem is quite significant, but more concerningly, predicted estimates from 2030 would suggest that the cases will overall increase to 100 million from 80 million, but more importantly, there will be 168% increase in decompensation, 178% increase in liver-related death, and 137% increase in HTC, so not only the number will change, but the concentration and percentage of more advanced disease will also increase disproportionately. One of the biggest challenges in the field remains how we might identify those who already have advanced disease or those who are at highest risk for progression. The majority of these are not seen in hepatology clinics, rather they're seen by a primary care provider who are typically unaware of the patient's disease risk. This is an example of an algorithm meant to help divert away those with low risk of advanced disease from hepatology and slightly refine the population that does get referred. However, algorithms such as this are not typically implemented and you can see that the basic screening tool that I have in this example, the FIB4, is based on parameters that are readily available, such as age, ALT, AST, and platelet count. So despite available data, patients are not triaged optimally. These are data from Northwestern where we sought to assess the extent of evaluation or risk stratification in the context of incidentally noted hepatic steatosis after the exclusion of those who had other liver diseases or a prior diagnosis of fatty liver disease by their primary care provider. They also needed to be followed in our system by a PCP. As just discussed, the first step in the evaluation is to use a FIB4, which is calculable from age, liver enzymes, and platelets, all readily available. Not surprisingly, the elements needed to calculate a FIB4 were readily available in 92%. However, FIB4 was not documented in any patient's record. When scores were calculated, we noted that they, a very low percentage, but equally distributed among low- and high-fibrosis-risk patients who refer to hepatology. So there's clearly room even in a tertiary care center for education and implementation of care pathways. NAVLD is complex and heterogeneous, making it difficult to predict disease progression and treat effectively. Individual, family, and societal factors interact and can provide barriers to successful intervention, and thus, they need to be carefully identified and focused on in an individualized manner. Thus, it shouldn't be a surprise that the optimal care model involves a multidisciplinary approach once the patient is identified and referred for specialty care. Here, you can see that if you have a NAVLD patient who has preferably been risk stratified from a primary care setting, there are numerous individuals or numerous treatments that can be optimally provided in a team-based approach. Hepatology, while able to do the risk stratification for the risk stratification exclusion of other diseases, really should focus on liver-directed therapy and identify relevant comorbid disease. Co-management with endocrinology is critical because a lot of the comorbidities are endocrine or metabolic in nature, and their management may best be optimized either by an endocrinologist or a primary care provider with an interest or ability to do this. Nutrition is probably the most important interaction with a patient we'll have. This typically should be done on a very regular basis, at least monthly, in order to implement changes in diet and exercise level. And then in some patients, the incorporation of health psychology to help with behavioral therapy and optimization of underlying psychiatric disease really can provide the best multidisciplinary approach. So if this is the model, are we ready? So this concept was tested in a very nice study led by Jeff Lazarus. So the concept of needing a multidisciplinary clinic or multidisciplinary care in patients with fatty liver disease is not new. And here, what this study sought to do was to assess the level of preparedness for such an approach in Europe specifically. In general, indices provide benchmarks in health policy and public health that enable systematic assessment over time and among countries. Here, you can see how the various countries in Europe scored. And generally, it's quite clear that the level of preparedness is low. Additionally, when surveyed, if any of these countries had a written national NAFLD or NASH plan, the answer was 100% of the time that they did not. In fact, if you look at national or subnational NAFLD or NASH strategy, plus in the inclusion of fatty liver in any form in a national or subnational strategy of key diseases or conditions that are related to fatty liver disease, you can also see that this is dismally low and poorly represented. So we have clearly quite a lot to do. So can governmental policy make a difference? So this is an excellent example where the Australian government decided to focus on hepatitis C in an attempt to try to eradicate hepatitis C from Australia. What they did was they significantly vamped up screening and testing, looking at and then direct referral for treatment in addition to direct government investment in education, annual screening in patients with high-risk behaviors, incentives for developing management care plans and free testing. And what this did was it resulted in a very significant improvement in the identification of patients with hepatitis C. These consensus recommendations are the output of a consensus process led by Jeff Lazarus that involved 218 experts, including a few of us from ASLD. Through a Delphi process, this particular process developed 37 recommendations and 26 statements that covered various aspects needed to advance the NAFLD public health agenda. You can see here the areas of leadership for NAFLD public health is awareness, treatment and care, policy strategies and a whole society approach, patient and community perspectives and defining and implementing models of care. In the U.S., the Global Liver Institute and others work together to formulate an action plan that addresses many of these issues outlined by the NAFLD global consensus recommendations and center though on awareness and education, diagnosis, patient management and policy initiatives. Importantly, this was created with all stakeholders in mind and has really set the ball moving forward in the United States. Significant efforts have also been undertaken, many of which have been led by Donna Cryer and the Global Liver Institute that have bolstered awareness on multiple levels, including the establishment of International NASH Day. ASLD's Public Policy Committee is also working on several aspects and also in conjunction with GLI and other patient care organizations to heighten awareness and screening of NAFLD, help provide or seek funding for surveillance, focusing on populations at risk, disparities and focusing on surveillance activities and collaboration with agencies. And the ASLD Public Health Committee, which represents a diverse set of stakeholders, is currently drafting an opinion piece on behalf of ASLD, highlighting the priorities of this initiative. Importantly, collaboration with GLI has also been established with the NASH Care Act of 2021, which is highlighted here. This was initially introduced in the last Congress as H.R. 8658, proposing a national strategy for surveying, preventing, diagnosing and addressing NASH. The three areas of focus are one, to obtain data on the prevalence of pediatric and adult NAFLD or NASH in the United States. Two, to establish a multidisciplinary task force and develop recommendations for the prevention, screening, diagnosis and treatment of NASH and interrelated conditions. And lastly, to establish a national prevention program for diabetes, NAFLD and NASH and metabolic syndrome. GLI, ASLD and the CDC did a briefing on Capitol Hill just a few weeks ago, which we hope was successful in increasing awareness on these important issues. And this bill is planned to be reintroduced in the House of Representatives in October, so later October, 2021. So several health, public health priorities are needed to reduce disease burden, not just in the US, but worldwide. So to reduce disease burden, one must increase awareness. So currently there's no existing NASH policy for this common, silent, deadly and preventable disease. There are international efforts underway to increase visibility such as the NASH Care Act, International NASH Day and the NAFLD Global Consensus Recs. Societal change is also important to improve nutrition and activity. Increasing education is of paramount importance. There's poor understanding of the disease, identification and risks among primary care providers and specialists in addition to the general public. The increased, this would be alleviated or improved by increasing presence at primary care provider, endocrine and cardiology and other meetings or the Obesity Society, for example. Updating guidance, which is currently underway. Cross-society NAFLD guidelines, which is also underway with ACE and incorporation into medical school curricula, which is critical if we're gonna train people who know about the disease and understand its importance. Low engagement of multi-stakeholders in the process is also important. It's an important deficit and thus engaging the NAFLD community is critical. This can be achieved at least in part by convening and collaborating with experts and organizations across sectors, including patient organizations, care providers, families and payers. And lastly, advancing the public health research agenda because there are really insufficient funds for research in NASH and obesity and other interrelated conditions. So focusing on increasing NIH funding, providing support for healthy initiatives in school, active lifestyle, et cetera, are all of very high importance. And collaboration across disciplines to establish care models. There is no uniform recommendation on optimal approach to care in this disease. And we need to start targeting high-risk groups, establish and disseminate best practice models so that the framework is there for people to take up and execute. So in summary, it's going to take a multi-pronged approach to decrease disease burden that starts with broadly increasing awareness across sectors. With that, I very much thank you for your attention and look forward to any questions. Thank you for your excellent presentations. Let me start my concluding remarks by presenting data that underlines some of our continental commonalities, but also why so many are still considering our North and South America relationship as if we are distant neighbors. North and South America are generally considered separate continents and taken together are called the Americas. Latin America and the United States are on the same side of the world. And undoubtedly, there is much we have in common. Both are continent-side geopolitical units comprising different states with their own histories, shades, and different political and economic outlooks. However, the United States of America is rich, while Latin America is comparatively poor. Let me give you some numbers. The gross domestic product or GDP in the United States was worth 20,000 billion US dollars in 2020, according to the official data from the World Bank, representing 18.5% of the world economy. In contrast, the combined GDP of Brazil, Mexico, Argentina, Colombia, and Chile averaged $660 million. It has been recommended that at least 6% of the GDP should be spent in health. The United States spent in 2020, 18%. In contrast, Brazil allocated 9%, Argentina, 5%, and Mexico, a meager 2.5%. As my colleagues and friends from Allen SLD have eloquently presented, both hepatitis B and NAFLD are not only world, but also regional health problems that affect a significant proportion of our populations. What about NAFLD? NAFLD is a complex disease with significant genetic and environmental factors. In the US, it is estimated that more than 80 million individuals suffer of NAFLD, and close to 17 million suffer of its more aggressive counterpart, NASH. The high economic burden of advanced disease associated to fatty infiltration and fibrosis is well known and is quite costly. There is a tenfold difference in cost when comparing well-compensated F4 patients with NASH versus those with NASH in stages one, two, and three. In South America, the situation is not better. The prevalence associated to obesity and metabolic syndrome in the general population is close to 50%, and we are world leaders in per capita silver consumption and childhood obesity. What do we need to transform the NAFLD public health agenda in the Americas? As we heard from Dr. Rinella and Dr. Arese, we need to impact on the awareness through increased NAFLD education, generate well-thought policy strategies, understand the health and economic burden of the disease, establish appropriate treatment and care schemes with the identification of sustained interventions, and develop leadership of ASLD and ALLE as a continental coalition to develop collaborative epidemiologic roadmaps and action plans. And what about hepatitis B? As you heard, hepatitis B is also a public health problem with significantly different hepatitis B surface antigen prevalence in our different regions. As adequately stated by the WHO, despite the significant burden it places on our communities, hepatitis has been essentially ignored as a health and development priority until recently. Dr. Wen and Dr. Gonzalez persuasively articulated the need of enhancing and expanding our hepatitis B vaccination programs, ideally starting early in life, prevention of mother-to-child transmission of hepatitis B with better antenatal diagnosis, smart use of antivirals in the third trimester, and widespread availability of hepatitis B vaccine and hepatitis B immunoglobulin, ensuring access of sterile needles and syringes in PWIDS, and effective drug-dependent treatment programs, and finally, effective access to early diagnosis, linkage to care, and antiviral treatments. However, there are several battles ahead to win. Leadership is unequal. Prevention programs are limited in scope and coverage. Diagnostic techniques and treatments remain scanned or highly prized. A public health approach in hepatitis is in its infancy, and hepatitis education must improve significantly. Finally, the COVID-19 pandemic has disrupted HPV programs and services in the U.S. and Latin America, which has further delayed our control and elimination efforts in hepatitis B and in other branches of our health system. The hepatitis B WHO 2030 goals of prevention, testing, and treatment remain a difficult-to-reach possibility in the next eight to nine years. Thank you for your attention.

ASLDLA Joint Symposium

modern hepatology

Americas

NAFLD

hepatitis B

public health

awareness

education

policy strategies

treatment options