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Throughout this podcast, panelists uncovered a large set of actions that might improve NASH care for those Black Americans who have the disease while suggesting a range of solutions, some more realistic or faster to achieve than others. In this conversation, each panelist is asked to mention one thing they believe might actually improve within the next year. A few focus on 3-5 year fixes, but most offer a progress steps that can be attainable within the next year if enough of the right people dedicate focus to them.

Suggestions include: looking at epigenetics to determine whether there are non-Hispanic Black American families with genetic markers for disease and how these may be addressed through diet and other lifetsyle issues (Zaki Sherif); organizing a disciplinary group inside NIH to fund a multi-center study on this issue (Donna Cryer); ensuring that NAIL-NIT and other trials that are currently in recruitment phase include a large enough subsample to study this population (Louise Campbell); developing and beginning to implement plans for specific activities that will reduce health inequity (Ani Kardashian); separately, (i) for drug companies to invest in learning the specific issues related to NASH that affect this community and (ii) empowering patients through education and outreach (Yani Adere); and enable Global Liver Institute and other organizations to become "clearinghouse[s]" for good ideas to flourish in efforts that attract groups with common interests and focus to this larger conversation (Roger Green).

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With so many major clinical trials for Fatty Liver drugs recruiting over the next couple of years, we have an opportunity to study effects on Black Americans from inception, instead of assuming these drugs work the same in different racial groups only to find, some years later, that we were wrong.

This conversation explores historical reasons for underrepresentation and shares possible reasons or steps to remedy this issue in a timely fashion. It starts with Ani Kardashian echoing points that other panelists made earlier in the episode about the need to enrich clinical trials with larger shares of non-Hispanic Black patients so that we can learn about how the disease is different in this group than in other sub-populations. In response to a question from Roger Green, Donna Cryer traces a chain of actions to address the issue: corporate drug developers ask their CROs how to ensure large enough representation in the sample. CROs reach out to community groups that have credibility with community leaders and members to recruit. "People who look like me" take researchers into their communities to certify the researchers' credibility. Louise Campbell confirms this vision by discussing research with Aborigines in Australia. The rest of the conversation centers around three topics: (i) the role International NASH Day can play in providing education on this issue, (ii) the challenges that occur because front-line physicians in hospitals with large proportions of non-Hispanic black patients do not screen patients for Fatty Liver, and (iii) challenges, opportunities and strategies involved in attempting to screen patients for Fatty Liver when they visit hospitals and clinics for other diseases.

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Factors that make treating NASH and NAFLD a unique challenge for non-Hispanic Black Americans range from Social Determinants of Health (SDOH) to omics suggesting that the disease in Black Americans may be different than in Caucasians or a range of behavioral elements (for example, smoking) that are more closely associated with Black Americans.

This conversation begins with Stephen Harrison noting that a combination of lower incidence of Fatty Liver disease within this population and an historically appropriate trust deficit that non-Hispanic Black Americans feel toward medical trials leads to study samples without enough sample to tell us whether a given diagnostic or course of therapy works better or worse in a non-Hispanic Black American population. As a result, he notes, we do not know how negative health behaviors like smoking or alcohol, genomic patterns and comorbidities affect liver health in this population. Later on, Zaki Sherif notes that in omics work in HCC, he and colleagues identified metabolites that upregulated in Caucasians and down-regulated in Blacks. All this culminated in Donna Cryer's point that this is an historic moment to enrich non-Hispanic Black American populations in these trials so that from the moment we begin using these drugs in the general population, we will know how these drugs work among Blacks instead of simply "assuming" they work as they do with other racial groups, only to lear 5-10 years later than this is wrong.

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How do you discuss a disease with no history during Black History month? Surfing the NASH Tsunami asked, "What challenges exist for non-Hispanic Black Americans in the areas of NAFLD and NASH, given how low incidence is?" In this conversation, a corporate executive, not-for-profit patient champion and academic researcher discuss some of the reasons it is so important to identify and address these issues today.

Yani Adere, NASH MSL at Novo Nordisk and the person who pitched the episode idea to Roger Green, kicks off this conversation by discussing issues that concern and motivate her, She notes that even with lower incidence than other racial groups, NASH is still the second leading cause of liver transplant in non-Hispanic blacks and that the course of the disease is similar in black and Caucasians. Next, Global Liver Institute Founder and CEO Donna Cryer notes that since NASH is a disease without much history, we can make Black History in realtime by introducing clinical trial protocols, treatment modalities and population screening programs that address specific challenges facing that community. Next, Dr. Zaki Sherif of Howard University notes that end-stage liver disease in non-Hispanic Black communities has two challenges: faster progression from cirrhosis to HCC than other groups and lower likelihood to receive a liver transplant. During the rest of this conversation, Dr. Ani Kardashian of the Keck School of Medicine at USC, Zaki and Donna comment on several addressable issues that explain why liver outcomes are lower for non-Hispanic Blacks than for other racial groups.

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In recognition of Black History Month, SurfingNASH looks at how the impact of NASH on non-Hispanic Black Americans differs from other groups. The episode includes Key Opinion Leaders not only in Fatty Liver disease but also, more broadly, social determinants of health like food insufficiency and clinical trial participation.

This episode was originally suggested by Dr. Yani Adere, a Medical Science Liaison at Novo Nordisk and long-time SurfingNASH listener. Yani set the stage for this conversation by noting that while incidence of NASH and NASH cirrhosis may be relatively low among non-Hispanic Black Americans, those who get the disease progress at the same rate as other ethnic groups and, in fact, Fatty Liver is the 2nd leading cause of cirrhosis in this population. She concludes by noting that Social Determinants of Health (SDOH) create undue burdens for Black Americans with liver disease as with other diseases.

Donna Cryer, Founder and CEO of the Global Liver Institute followed Yani. First, she noted that since NASH has a limited history as a disease, it offers the chance to create history by building health equity into clinical trials and patient treatment as initial protocols and guidelines come into force, "instead of waiting 5-10 years" as with other diseases.
Dr. Zaki Sherif of Howard University raised an important point about Liver Disease in this community: while non-Hispanic Black Americans progress from liver to cirrhosis slowly (as do other groups), the speed at which they progress from cirrhosis to HCC is faster...and Black Americans are less likely and slower to receive liver transplants.

Dr. Ani Kardashian of USC, a transplant hepatologist and national leader on the issue of food insufficiency, began her comments by nothing that while Fatty Liver disease is not as common in Black Americans, outcomes are poorer. Ani raises the issue that some of the poorer outcomes might result from lower levels of patients in clinical trials, which is a challenge with many diseases.

From here, the discussion heads off in several different directions, all of which confirm the point that the intersection of relatively low incidence, other diseases with higher prevalence and severe outcomes and the range of SDOH issue leads to a situation where patients receive less treatment and support than other sub-populations. The group discusses some of the major challenges and posits possible solutions.

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This wrap-up conversation of our NAIL-NIT episode provides greater detail on NAIL-NIT's research plan. The plan itself includes two elements: a retrospective analysis of data collected to date by drug developers in their own clinical development programs and a six-year prospective study currently estimated to include 1,000 - 1,300 patients, with major adverse liver outcomes (MALOs) anticipated to report in four years and final results in six.
In response to a question, Mazen Noureddin suggested that we might see some significant guidance to drug developers and manufacturers within a year on the topic of screen failure rates. Over time, the retrospective data will also afford the opportunity to test some of the newer composite test measures like FAST and MAST against larger samples of patients. Sen Sundaram expressed a different target for one-year results: guidance from one or more regulatory agencies about how many patients they will want to see in key clinical trial patient cohorts and sub-populations.

In terms of the prospective studies, Louise Campbell asked whether certain segments of patients who had screened out of previous studies would be appropriate for the prospective sample. Stephen Harrison noted that one particular clinical trial, North Sea Therapeutics, included over 100 patients with F3 and NAS of 3 but no balloon hepatocytes. He also noted that by using the Summit Clinical Trial network to recruit a significant share of patients, they would be recruiting a significant share of patients through community trial sites, which can produce patients faster than academic sites. In response to the closing question, NAIL-NIT panelists made a plea for more companies to join this effort.

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The conversation looks at how the NAIL-NIT program design improves on the quality of insight provided by the NAS score, both in terms of drug development and treatment of individual patients. Also, note that during this conversation, Mazen Noureddin thanks a relatively large group of individuals and companies supporting this project. 

The first section focuses mostly on what we can and cannot learn from a NAS score, and implications of its shortcomings on the drug development process. After this, Stephen Harrison notes the complex role the liver plays in energy transfer throughout the entire metabolic process. This suggests that the effects of Fatty Liver disease vary among individual patients and, as a result, drug development and patient diagnosis and treatment should provide sufficient insight to optimize each patient's therapy. As the conversation closes, Mazen Noureddin is responding to a question from Louise Campbell about what we will learn about optimal testing strategy. Mazen suggests there is unlikely to be a single "winning" test but, instead, a combination of NITs probably will be necessary to answer all the questions necessary to optimize therapy.

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NAIL-NIT is both a response to the challenges of histopathology and an effort to create a different vision of testing liver patients.

This episode starts with Stephen Harrison describing the events that came to demonstrate how challenging current histopathology approaches: a series of drug development failures that reflect shortcomings in methodology rather than in the developmental drugs themselves. Sen Sundaram notes that the difference between the NAIL-NIT approach and that of other consortia is that NAIL-NIT seeks to link NITs directly to outcomes rather than correlating them to histopathology-based measures. Mazen Noureddin discussed the frequency at which patients with obvious NASH and fibrosis fail to screen into studies due to inability to find balloon hepatocytes in the biopsy-derived slides and raises the human ethical implications of excluding these patients. Amy Articolo encourages us to envision a future in which drugs are available to treat patients and make sure we have the best possible testing to diagnose and prescribe the proper therapeutic regimens to patients. From there, the discuss shifts as Stephen Harrison and Sen Sundaram discuss the quality of data existing today that links NITs directly to outcomes. Sen notes that "if we think about the amount of data that we have" for NITs and outcomes, "we probably have more data now than is cited to support histopathology in a current guidance."

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NAIL-NIT is a new NAFLD consortium dedicated to exploring the direct relationship between non-invasive testing (NITs) and outcomes in Fatty Liver disease. In this opening conversation, study co-directors Stephen Harrison and Mazen Noureddin are joined by Steering Committee members Amy Articolo, Medical Director for NASH at Novo Nordisk and Senthil Sundaram, CEO of Terns Pharmaceuticals. 

One at a time, the four panelists describe their motivations for forming and becoming a part of this consortium. Mazen Noureddin talks about the group's common goal to produce data that will shape a shift from biopsy-derived drug approval analyses to NITs. Stephen Harrison describes the group's strategy and two main efforts: retrospective analysis of the significant amount of available data that link NITs and outcomes, and a prospective study to be conducted over the next 4-6 years designed to establish correlations and links to outcomes not only for individual tests, for also for combinations of NITs. Sen Sundaram discussed his earlier work with a similar consortium that asked the same kinds of questions about PBC and demonstrated that alkaline phosphatase could provide the analyses necessary for drug approval. Finally, Amy Articolo starts by noting that she has transitioned from a full-time treating OB/GYN to a corporate executive and brought with her a "passion" for "patient-driven, patient-centric care" and several ways that supporting analysis driven entirely by NITs can support support that passion. 

The NAIL-NIT initiative has potential to transform how we evaluate drugs for approval and patients throughout the course of their disease. This is an important episode (and conversation) for anyone with a personal or professional stake in simplifying the NASH/NAFLD drug development process while simultaneously improving the quality of data for regulators and treating physicians alike.

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Co-director Mazen Noureddin and Steering Committee members Amy Articolo of Novo Nordisk and Senthil Sundaram of Terns Pharmaceuticals join the Surfers (Stephen Harrison is also a co-director) to discuss the NAIL-NIT Consortium, an ambitious effort to link non-invasive testing (and specific tests) directly to outcomes.

 NAIL-NIT's activities include a prospective six-year study of 1,000 - 1,300 patients and, separately, retrospective analysis of thousands more cases to establish the best ways to make use of the growing array of non-invasive testing methods in the treatment, diagnosis, and monitoring of NASH patients.

Participants in this episode anticipate that the retrospective element will start generating elements within one year, and the prospective within four years. They describe the program's goals as being practical and business-like (better drug and NIT development), but also profoundly human (never denying a patient with clear F3 fibrosis access to a trial because the pathologist could not find a balloon hepatocyte on the cell.