population screening

You’re young. You’re healthy. Would you open Pandora’s box and take a DNA test to find out your risk of a serious disease?  Scientists say widespread DNA screening of young people will save lives — but who will pay the price?  And if you discovered you carry a high-risk gene for breast or prostate cancer, what can you do with that information, and who else might use it? Could insurance companies or prospective employers discriminate against you on the basis of your genes? Natasha Mitchell and guests — including Kara who took a test — dive into the science, ethics and economics of population DNA screening.

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).

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.

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.

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.

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.

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."

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.

Episode 10 dives into recent NAFLD and NASH Prevalence studies in the US, UK and Germany and explores what this can tell us about who to screen for NAFLD and NASH, when to screen first and how often to screen after that.

This wrap-up conversation wrestles with the question who to screen, when to start and how to reckon with the dual challenge that the early effects of Fatty Liver disease are more about metabolism than liver per se and that there are not enough hepatologists to treat everyone with Fatty Livers. The group's conclusion: we need to test more and earlier, but do not have enough data yet to tell us exactly how to implement this very, very high level statement.

Episode 10 dives into recent NAFLD and NASH Prevalence studies in the US, UK and Germany and explores what this can tell us about who to screen for NAFLD and NASH, when to screen first and how often to screen after that. This conversation focuses on the paper Screening for undiagnosed NAFLD and NASH: A population-based risk factor assessment using Vibration-Controlled Transient Elastography (VCTE), which was published last November in the refereed journal PLOS ONE.

Lead author Wayne Eskridge describes the study and presents key findings. In this conversation, two of the striking points he raises about the study are: (1) that relatively high percentages of study participants, volunteers with no previous history of liver disease, exhibited different levels of liver fat and even disease; and (2) that many of these were patients in their 40s as compared to the 50s and 60s where we more conventionally think about disease. After the group shared some concepts and numbers, participants agreed that the number of adults exhibiting some level of fatty liver with an accompanying metabolic challenge is 3 in 8.

Episode 10 dives into recent NAFLD and NASH Prevalence studies in the US, UK and Germany and explores what this can tell us about who to screen for NAFLD and NASH, when to screen first and how often to screen after that. This conversation focuses on the paper Prevalence and Risk Factors of Advanced Liver Fibrosis in a Population-Based Study in Germany, which was published last Saturday in Hepatology Communications. 

Last author Jörn Schattenberg presents results of the paper, after which panelist Ian Rowe and Wayne Eskridge ask the role that FIB-4 played in the study and analysis and Roger Green asks Professor Schattenberg what significance to apply to a Fatty Liver Index >60 in 3/8 of the sample.

This episode looks at four different sources of data estimating NASH and NAFLD prevalence in population subgroups the US, UK and Germany. All four suggest that the share of people living with NAFLD might be as high as three in eight. This is far too high a screening burden for the hepatology community to manage on its own. However, it should have broader implications for overall treatment pathways.

If the liver is the "canary in the (metabolic) coal mine," as Stephen Harrison frequently argues, then everyone in the metabolic disease cascade should be interested in screening patients to prevent the various metabolic diseases before they manifest as serious conditions.

The data sources include a German population study that was accepted for publication last week (Jörn Schattenberg, last co-author), the SUNN study that Wayne Eskridge has shared previously on this podcast, and data and insights from Ian Rowe's extensive study of the Leeds, UK population. Also, Louise Campbell discusses some raw data she has compiled from Tawazun work and Roger references the two studies that Stephen and colleagues conducted at the San Antonio Medical Military Center.

Louise Campbell convenes  liver nursing and nurse educator experts Kathryn Jack, Michele Clayton, Pam O'Donoghue and Patrizia Kunzler to consider where liver nurses and advanced nursing practitioners should fit into treatment and communication paradigms and what support they will need. Stephen Harrison joined to offer a different viewpoint.

Timestamps:
2:42 – Roger introduces session
4:07 – Louise starts discussion
5:37 – Stephen reviews patient case
12:10 – Panel introductions 
22:33 – FIRST QUESTION: health discrimination and quality of care
24:58 – Michele: 2012-3 report stated that patients admitted with alcohol-related liver disease lacked HEP access, received poor treatment. We have made some progress but see similar issues today with COVID-19
27:59 – Patrizia: in Switzerland, liver patients come to care late in disease.  Nurses provide excellent care but are not involved in prevention. Doctors drive the entire decision hierarchy
29:24 – Michele: Similar issue in UK;  where nurses need decision input and greater investment in specialists, particularly in rural areas
31:47 – Kate: Agreed. We lose too many opportunities for nurses to inform and educate
32:40 – Pam: HCC patients on wards present "extremely unwell", in late stages. Nursing “short-staffed.” Not enough time to coach patients. 
33:43 – Pam: I did recordings so I could work with one patient while another consumed recording. We also worked with patients in groups 
36:06 – Stephen: We’re getting closer to our first NASH drug, which will reduce frequency of NASH-HCC if we can treat early enough in disease progression. Also, we need to create a communication model that combines nurses and doctors
37:33 – Stephen: Another target: podiatrists. They  check patients' liver enzymes before Lamisil therapy,  see dysfunction and don’t know what to do. And  which other specialties? Obesity? Cardiology? ENDO? GYN? KEY: two “foundational pillars of education” - doctors and nurses - working collectively to develop and share content
39:38 – Pam: This requires trust between doctors and nurses. Trust takes time
41:24 – Kate: In prisons, once patients are diagnosed, we arrange conversations in person or video. Harder to build rapport without in person. With rapport, everything flows smoothly
43:15 – Kate: We have a system for GPs to refer patients for FibroScan, which is an excellent communication opportunity for nurses
44:58 – Michele: Some UK universities offer liver education, most do not. This is a global challenge
47:07 – Pam:  We should invest some of this billions we spend on HCC systemic therapies in education before and early in  disease progression
48:43 – Michele: Liver "blindsided" countries and planners who focused on renal,  CV and cancer
49:34 – Louise: We spend heavily on expensive late-stage drugs but lack funds to locate and educate at-risk people early in  process or steer them to clinical trials
50:39 – Louise: How can we use the Lancet Commission's  competency documents better?
51:15 – Michele: Others have local competency documents in their own languages
53:25 – Patrizia: Not certain about Swiss association 
54:15 – Stephen: Not aware of a common framework in US
57:48 – FINAL QUESTION: something you would like to see in next 2 years
58:46 – Michele: More global action from/for nurses
58:58 – Kate: Engage other specialties. New UK competency criteria around Fatty Liver
1:00:07 – Kate: More inclusive trial recruitment based on communication in patients' own languages
1:03:14 – Patrizia: Collaboration matters, but support/fund nurses today in research  and publication
1:04:18 – Pam: Encourage British Liver Trust to be more aggressive;  they can be quite effective
1:05:10 – Louise: Bring all the liver disease competencies we have to bear on NAFLD
1:06:53 - Business report

The Innovations in NAFLD Care 2022 Series includes a recent webinar and a hybrid meeting planned for Barcelona in May. This new event is a key new element in the effort to drive more holistic multi-specialty approaches toward diagnosis, treatment and management of patients with NAFLD and NASH. In this conversation, Stephen Harrison, Louise Campbell and Roger Green join Professors Schattenberg and Lazarus to consider innovative elements for this and future programs and to discuss the outcomes they would like this program (and others like it) to produce.

The Innovations in NAFLD Care 2022 Series includes a recent webinar and a hybrid meeting planned for Barcelona in May. This new event is a key new element in the effort to drive more holistic multi-specialty approaches toward diagnosis, treatment and management of patients with NAFLD and NASH. In this conversation, Stephen Harrison, Louise Campbell and Roger Green join Professors Schattenberg and Lazarus in discussing structural issues and social determinants of health that are shaping the growing Fatty Liver pandemic and why education is so important to combatting the pandemic.

The Innovations in NAFLD Care 2022 Series includes a recent webinar and a hybrid meeting planned for Barcelona in May. This new event is a key new element in the effort to drive more holistic multi-specialty approaches toward diagnosis, treatment and management of patients with NAFLD and NASH. In this conversation, Stephen Harrison, Louise Campbell and Roger Green join Professors Schattenberg and Lazarus in reviewing the program scope and agenda elements with an eye toward the most important ways to increase patient awareness of NAFLD and NASH.

The Innovations in NAFLD Care 2022 Series includes a recent webinar and a hybrid meeting planned for Barcelona in May. This new event is a key new element in the effort to drive more holistic multi-specialty approaches toward diagnosis, treatment and management of patients with NAFLD and NASH. In this 10-minute conversation, Professors Schattenberg and Lazarus outline the social and health system factors that motivated them to create this program.

This conversation is part of SurfingNASH's 2021 NAFLD Year-In-Review. Andrew Scott, Global Policy Lead for the Global Liver Institute joins Louise Campbell and Roger Green to discuss the growing energy and impact of NASH patient advocacy.
This episode focuses on the steps that have increased reach and effectiveness of NASH patient advocacy dramatically in 2021. Andrew starts by noting some of the pivotal steps this year through which patient advocates began or expanded collaborations with the medical community in 2021, and then describing the activities that resulted from these collaborations: Global Liver Institute's (GLI) US NASH Action Plan, the range of guidelines and recommendations emerging from medical societies, the externally-led Patient-Focused Drug Development (PFDD) meeting with FDA, and a range of legislative initiatives in the US Congress and many states. Andrew notes that much of this activity emanated from decisions GLI took in 2017 to promote the importance of NASH in the constellation of liver diseases. Also, he notes the importance of discussing not only Fatty Liver disease but also the constellation of non-communicable metabolic conditions linked to it.
Today, GLI focuses on providing appropriate therapeutic options and support for every stage of NAFLD. Activities like the PFDD meeting focus on the need for drug development and approvals. Others, like GLI's collaboration in building and promoting a nutrition app, focus on earlier stage disease and helping patients live healthier lives before they experience disease. All activities address the needs to educate stakeholders and develop products to support, diagnosis, treatment and management at every stage of disease progression.
The conversation shifts to the need to conceptualize Fatty Liver in a broader context. Louise notes the statement that the liver is a mirror on the metabolism, or perhaps the patient. Andrew states that GLI will increasingly focus on the idea that LIVER HEALTH IS PUBLIC HEALTH and on overall wellness.
This leads Roger to wonder why other patient advocacy organizations silo patients so that the focus is on an individual disease as compared to overall patient wellness. Andrew observes that focusing narrowly on a single disease and serving as advocate for patients with that disease has been extremely effective for some patient advocacy groups  in fund raising and public clout. However, Andrew notes, we are coming to a place in society where we need to view many of these issues in a more integrated way.
Louise observes from experiences in the UK that organizations competing for funds will not collaborate if they foresee an economic or PR downside. Andrew acknowledges this possibility, but reports that GLI has found success by collaborating with community liver groups to help them raise more money. This engenders good will and strengthens bonds within the community.
Roger shifts the conversation in the direction of metrics to point out that we do not yet have a concise, widely used and accepted test or metric to indicate success in slowing or stopping the growth in NASH. Andrew agrees and notes this is a particular challenge on Capitol Hill, where legislators are looking for hard numbers to demonstrate the need for (and later success of) programs. The GLI-supported NASH Care Act, which was initially entered in 2021 and will  hopefully be passed this year, creates a Task Force charged with determining what the national metric(s) should be.
The next phase of this conversation reverted to broader issues around the liver as part of a holistic health system. Andrew's key points: (i) GLI recognizes that given the diverse levels and settings in which it operates, there is no viable "one size fits all" approach; and (ii) GLI is finding effective strategies for working more closely with government regulators. 
Finally, Andrew's goal: To get a vote on the NASH Care Act sometime this year.

This conversation is part of SurfingNASH's 2021 NAFLD Year-In-Review. Professor Jeffrey Lazarus of ISGlobal and the University of Barcelona joins Louise Campbell and Roger Green to discuss the emerging NAFLD public health agenda.

Jeff Lazarus comes to the effort to create a global NAFLD Public Health agenda from his experiences spearheading similar efforts in HIV and Hepatitis C. The conversation begins with Jeff describing the path by which he shifted focus from each liver disease to the next. Just as reduction in HIV transition rates revealed the high level of Hepatitis C infections among HIV patients (particularly intravenous drug users), the reduction in Hepatitis C incidence following advent of the direct-acting antivirals revealed still-significant levels and growth rates of liver cirrhosis. This in turn revealed the degree to which NASH is driving the continuing growth of cirrhosis in the global population. It also revealed the degree to which efforts to reduce or eliminate NAFLD were lacking a strategy, an idea of the burden or sense of economic consequences.

From here, the discussion shifts to looking at similarities and differences between HIV and Fatty Liver Disease. One key similarity: a patient can have this disease for a long time before having to address it. A key difference: the steps one takes to combat infectious disease vs. what is more of a "lifestyle" disease.
Next, the group discussed  Jeff's path to help shape a global consensus around the need to treat Fatty Liver and an action plan regarding how to do so. The first key was to determine how many countries are prepared to deal with NAFLD. Answer: out of 102 the group explored, none were prepared. This led to a two-year process with 218 global stakeholders to develop a global consensus statement on goals and actions, which we discussed on S2 E59. With these pieces in place, the global stakeholder group is working on a framework of sustainable development goals.
In response to a question from Louise regarding the impact of COVID-19 on these efforts, Jeff stated public leaders have not and will not educate the public on the impact of diet and exercise on the disease.. As a result, NAFLD Public Health advocates need to educate leaders on why public safety and nutritious diets are goals for fighting Fatty Liver.
NOTE: It emerges that the countries with the best public preparedness for NAFLD are those that take guidance from hepatologists.
In response to a question from Roger, Jeff suggested the attitude that bad health behavior is an individual right but paying the costs of the result disease is a social cost is not new.  Specifically, he noted that this attitude is not different from what we see with tobacco or alcohol. He went on to discuss the importance of promoting public health, not only as a way to improve individual behaviors but also to create and focus advocates. Today, he states, we are failing both to diagnose the disease earlier and to invigorate providers, patients and social actors to behave in ways that reduce the rate and severity of what is in many ways a lifestyle disease.
A comment by Roger about the relationship between urgency and action leads Jeff to discuss the "terribly unsexy"attribution fraction, a statistical analysis that estimates the percentage of severe liver outcomes that are attributable to a specific disease (for example, NAFLD vs. Hep C.)
As the conversation closed, Jeff discussed his priorities for 2022: (i) to create and work with partnerships to take actions that give life and substance to the consensus recommendations; and (b) to create more consensus opportunities around the work of Wilton Park and possibly a similar meeting in the Americas.