global liver institute

Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. For the #NASHDay Wrap-up Panel, Global Liver Institute invited NASH Tsunami co-hosts Jörn Schattenberg, Louise Campbell and Roger Green to join NASH Programs Director Jeff McIntyre to discuss themes of the day and major issues in the Fatty Liver community.

This conversation includes the last fifteen minutes of the GLI NASH Day wrap-up panel. Jeff McIntyre asks two questions to the group. First, he asks each panelist to respond to the slogan “#StopNASHNow and its implication that for patients, it might be enough simply to arrest the progression of fibrosis, and therefore we should devote some of our research and regulatory energy to stopping the progression instead of focusing entirely on regression. For his last substantive question, he asks each of us to discuss something that puts a twinkle in our eyes as we consider the next 3-5 years of progress in the fight against Fatty Liver disease. Great questions that yield interesting and diverse answers from the three Surfers.

Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. To celebrate the occasion, Stephen Harrison joined Jörn Schattenberg, Louise Campbell and Roger Green to celebrate the event and comment on one crucial trend or event most signified what the last year has meant in the Fatty Liver community.

This conversation includes three sections:
• First, Roger discusses the Law of Unintended Consequences in the context of the FDA Complete Response Letter to Intercept Pharmaceuticals over obeticholic acid, an event that many feared would bring all momentum around Fatty Liver disease to a standstill but, two years later, has driven real bursts of creative energy and innovative problem solving centered around the disease rather than a drug.
• Second, Stephen’s and Jörn’s impassioned statements that the providers will never give up on addressing the challenges of NASH, both because, as Stephen describes, it is not in their character and because, as Jörn describes, “this disease is not going away.” As long as people are dying too young from the effects of NASH and HCC, he contends, the fight will continue.
• Finally, Roger asked the panelists for bold predictions about what will have changed before we come together a year from now to celebrate the 6th International NASH Day.

Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. To celebrate the occasion, Stephen Harrison joined Jörn Schattenberg, Louise Campbell and Roger Green to celebrate the event and comment on one crucial trend or event most signified what the last year has meant in the Fatty Liver community.

This conversation is about collaboration. It starts with Jörn Schattenberg noting the increasing momentum for groups to work together and proceeds to explore two observations from Louise Campbell:
• One about the rapidly expanding rate of change in the development of key products with particular emphasis on NITs
• A second on the increasing momentum behind broad approaches to the NAFLD pandemic, including the expansion of patient advocacy organizations around the world to the increasing energy all the various stakeholders and medical specialties to collaborate in an integrated attack on NAFLD and NASH. She notes that this energy needs to translate to a global set of local conversations sensitive to how healthcare operates in countries and regions.
From there, Jörn notes how Louise’s prior work in Hepatitis C gives her an experience the NASH physicians will not have and Stephen lists big items with tremendous progress, momentum and potential to a crescendo. 

Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. To celebrate the occasion, Stephen Harrison joined Jörn Schattenberg, Louise Campbell and Roger Green to celebrate the event and comment on one crucial trend or event most signified what the last year has meant in the Fatty Liver community.

This conversation consists mostly of reactions from Jörn Schattenberg, Louise Campbell and Roger Green to Stephen’s initial statement, followed by other thoughts from Stephen. The other Surfers are all impressed by the trial design. In response to a comment from Roger, Stephen comments enthusiastically on the unprecedented collaboration between sponsors, academics, regulators – the entire range of stakeholders – to resolve this issue. He goes on to note other questions – for example, the name of the disease – where the community is demonstrating unparalleled collaboration. All of this, he says, is leading to a proliferation of new research so vast that no one can keep up with all of it. 

There are three more points in this conversation:
• Jörn raises Quentin Anstee’s comments from Episode 26 that we need to develop a standard set of NITs to use in the evaluation process as another area where collaboration will be key
• Stephen points out that we may see our first drug approval in 2023, which will add new levels of energy and resourcing to the development and education processes
• Jörn begins to discuss his issue, which is the convergence between conferences to cover a range of issues that look past simple drug development to improve key questions from drug evaluation to clinical care pathways and inter-specialty collaboration to treat patients

Thursday, June 9, marked #NASHDay 2022, the 5th annual celebration of International NASH Day by the world's largest liver patient advocacy organization, the Global Liver Institute. To celebrate the occasion, Stephen Harrison joined Jörn Schattenberg, Louise Campbell and Roger Green to celebrate the event and comment on one crucial trend or event most signified what the last year has meant in the Fatty Liver community.

Roger's first question was for each panelist to describe a major event that took place since the 4th International NASH Day last June. Stephen Harrison answers first by discussing major advances in clinical trial design. This conversation consists of his answer.

Stephen Harrison describes two related areas where we have made what he describes as “real, granular progress in drug development” in terms of rethinking the design of Phase 3 clinical trials and endpoint assessment related to this redesign. Historically, sponsors conducted a single, very large, very long trial that sought first to achieve conditional approval based on sub-part H endpoints in fibrosis and then to achieve full approval based on outcomes developed as the initial trial group progresses to cirrhosis. The new idea is to conduct the fibrosis and cirrhosis elements in parallel, thus shortening the time to approval, simplifying endpoints and reducing the cost of the overall trial process. It is a vision of breathtaking scope…and, Stephen reports, it’s almost ready to launch.

Today, June 9, was the 5th International NASH Day (#NASHDay). Global Liver Institute (@GlobalLiver), the largest liver patient advocacy organization in the world, and 200 partner organizations held a day of education, awareness and motivation for Fatty Liver stakeholders the world around.

For its wrap-up panel, GLI invited the SurfingNASH co-host team to sit with Jeff McIntyre and review some of the day's major themes as well as major developments since the last International NASH Day. Like a typical SurfingNASH episode, there were equal parts big picture thinking, references to recent events, and laughs. Listen for a fast-paced discussion of big-picture items, most of which are different from the Episode 28 discussion.

On May 27 and 28, Surfing the NASH Tsunami covered the 5th Global NASH Congress, which discussed a wide range of topics related to Fatty Liver disease. In this conversation, Louise Campbell, who attended the conference for Surfing the NASH Tsunami, discusses presentations she found of particular interest. Jörn Schattenberg and Roger Green, who did not attend, ask questions about the presentations and raise issues that come to mind as they listen.

Two major themes emerge from this conversation. The first centers on Fatty Liver science, particularly liver structure. In the first keynote of the congress, Sven Franque discussed the vascular alternations even small amounts of liver fat can cause. During one of the congress's most anticipated presentations, Madrigal Pharmaceuticals Founder, Chief Medical Officer and President of R&D Rebecca Taub discussed the idea that different prospective Fatty Liver modes of action affect liver volume differently. Of specific interest, she noted that liver volume increases disproportionately to increases in liver fat. She also noted that the MAESTRO series of trials for resmetirom revealed a larger effect on liver volume than one might have predicted based solely on resmetirom's impact on liver fat levels. In the discussion, Jörn makes two key observations: (1) the liver vascular bed is unlike the vascular beds of other organs and (2) it has been reported that the impact of NASH on vasculature is different than that of liver fat from other causes.

When discussing patient advocacy, Louise notes that when she attended this meeting in 2019, there were no patient advocates involved, whereas this year, representatives from the Global Liver Institute and the European Liver Patients Association gave talks. Louise stated that the presence of patients changed the entire tone of the discussion, leading people who work with the theory of drug development and drug effects to consider what patients truly need as they listened to the various presentations.

The entire Fatty Liver community benefits from NASH Patient Advocacy and the work of our advocates, but relatively few of us understand what advocates do or how we benefit from their work. Leading German patient advocate Achim Kautz and Global Liver Institute Vice President of Policy and Public Affairs Andrew Scott discuss how they came to Fatty Liver patient advocacy, their priorities and activities that support our community, and the unique challenges of their fascinating work.

This episode starts with Roger Green inviting Achim and Andrew to discuss a specific success they have had in order to help listeners understand the nitty-gritty details of how their jobs work. After Achim shares a story about bringing patients with multiple metabolic diseases together for advocacy. Before Andrew can answer, Jörn Schattenberg invites Louise Campbell to comment on the disease and target population. She notes the breadth of the Fatty Liver community, from early-stage asymptomatic patients who have never been told they have disease along the spectrum to patients with advanced fibrosis and cirrhosis. Andrew and Achim acknowledge the breadth of patients in the Fatty Liver disease community and describe the process as a delicate balancing act given that the largest number of patients with unhealthy livers have early-stage disease they do not acknowledge or even know about, while the patients with late-stage disease are the ones who seek help most aggressively.

This conversation includes part of a more extended discussion that Donna Cryer had with Louise Campbell and Roger Green when she stopped by the virtual SurfingNASH.com studios to discuss her recent work.

Donna starts her conversation by saying that she is bringing three pieces of news with her. The first: with support from Novo Nordisk, the National Committee for Quality Assurance has released a white paper titled, "A Rallying Cry: Improving Coordinated Care for People with Nonalcoholic Steatohepatitis." The second: the American Heart Association has released a paper discussing the link between NASH and heart disease. The third is the initiation of GLI's "Liver Health is Public Health" campaign.

This episode focuses on all three of these developments, along with the Barcelona conference next month and the reality that socially underserved elements of the population have suffered more during the pandemic than those who are better off economically. The conversation moves too fast and with too many digressions to capture accurately, but it is a great, brief listen.

Episode 13 looks at the NICE Draft Guidance Evaluating FibroScan use in Community and Primary Care settings. This conversation focuses on underlying tensions between a methodology designed to assess big-ticket spending on critical moments of disease and a population screening approach that centers on wellness care more than illness care.

This conversation starts with Roger Green noting an inherent tension between short-term health economic tests driving a decision not to compensate and longer-term healthcare priorities that rely on patients who cannot afford the test being able to take it. Ian Rowe describes this as a tension inherent in the UK system and therefore, not a "real issue." In contrast, Jörn Schattenberg notes a significant structural issue in that, as Ian noted earlier, NICE relies on companies to provide the necessary data, but the costs of providing that data might be excessive for a small diagnostics company like Echosens, although not for a major drug company. Jörn goes on to raise the issue of reimbursing wellness vs. illness; this is an economics of illness analysis done for a process that enhances wellness. Louise Campbell suggests a parallel analysis of the cost of expensive HCC drugs like sorafenib that are highly costly but provide only 3-6 months added longevity. In the end, Roger Green asks one thing each participant would like to see vs. something they are confident they will see. Answers vary, but they suggest that the current system is not a particularly effective way to assess this kind of analysis and that, beyond that, this specific analysis might benefit from some different looks at data. In the end, Louise Campbell notes that the comment period ends on March 9 and invites as many people as possible to comment before then.

Episode 13 looks at the NICE Draft Guidance Evaluating FibroScan use in Community and Primary Care settings. This conversation focuses on the real impact of a decision not to compensate at this time, with most discussion centering in some form around the idea that a positive NAFLD screen leads to what Chris Estes of the Center for Disease Analysis Foundation describes as a "Cascade of Care." 

Jörn Schattenberg leads this conversation by asking whether we can use an entry test or some other method to enrich the test and thereby speed development of the data necessary to answer the question. Chris Estes points out that the right analysis will require assessment of the entire care cascade, with all its tests and care for people who test positive. Roger Green asks Chris whether such data exists in another setting where we can extrapolate to this situation, to which Chris notes that the FibroScan studies are fairly early and done only in tertiary care centers. Louise Campbell asks Chris whether any post-COVID modeling has been done given that the downstream burdens COVID is placing on the healthcare system due to diseases being diagnosed later in course of disease. Chris refers to some viral hepatitis analysis that suggests that while analysts initially assumed a two-year lag in care due to COVID, the actual impacts on care and costs appear to last far longer. The rest of the discussion bounces back and forth between the question how to apply data that lead to clear inferences but is not directly applicable to this case and the lack of the continuum of data necessary to make clean comparisons. At the end, Louise Campbell suggests that a decision not to compensate will way most heavily on economically burdened and rural patients. Roger Green asks whether this becomes one more health burden on people who already have not received enough care and Chris Estes describes this combination of inability to travel and incur costs of care with COVID, the dramatic increases in opioid addiction in this population, and well-noted increases in drinking and obesity to create a "perfect storm" of risk factors.

Episode 13 looks at the NICE Draft Guidance Evaluating FibroScan use in Community and Primary Care settings. This conversation focuses on some of the data issues surrounding this evaluation, ranging from the lack of the long-term data necessary to make the wellness case to narrower, more case-specific flaws in how costing data was developed. 

The previous conversation looks at how NICE analyzes procedures and ways this approach might conflict with the economics of NAFLD screening. This conversation starts with Ian Rowe noting that NICE depends on the manufacturer to provide data for the analysis, but Echosens only presented one year data. Louise Campbell asks if advocates could put forward some of the Hepatitis C data to address the issue, but, as Ian points out, FibroScan is the index diagnostic for NAFLD; in contrast, it was used for disease staging in Hep C. Jörn Schattenberg joins the conversation to note ways in which Germany and the UK are similar in terms of the relationship between reimbursement and use and other ways in which they are different. Eventually, Jörn points out, we will have 10-year data, but he asks how this can benefit patients today. Louise suggests that data and analyses exist in other settings that can help address these issues for NICE, particularly if we consider biopsy (and its costs) as the option. Ian Rowe asks "a couple of questions from the NICE perspective," which make the point that this kind of screening probably is desirable but must be carefully managed because once tests are made available more widely, people will sign up quickly, backlogs will ensue and practices will be challenged and may wind up needing to add staff. Louise acknowledges all this and notes that this analysis places a higher training burden on the manufacturer than Phillips or GE face with ultrasound.

Episode 13 looks at the NICE Draft Guidance Evaluating FibroScan use in Community and Primary Care settings. This conversation focuses on the basic way that NICE approaches issues like this one and tensions between that approach and the health and wellness outcomes this kind of screening might provide.

As Roger Green mentions when starting this conversation, Surfing the NASH Tsunami usually advocates for early prevention and wellness care as key strategies for fighting the coming NASH pandemic. The issue is that NICE answers relatively specific questions using rigorous cost analyses. At this point in time, the caliber of longitudinal data necessary to make the optimal case for FibroScan simply does not exist.

After Roger describes the underlying issue, Ian Rowe focuses the conversation by discussing the approach that NICE takes to health economic analysis. Along the way, he notes that in cases like this one, the correct application of this generally valuable analysis might not lead to the best outcome in terms of the health of patients. Louise Campbell goes on to discuss three ways that this particular analysis fails to capture the situation accurately: (i) the test was viewed in a vacuum instead of in the context of the care it would trigger; (ii) the testing frequency was based solely on tests done in radiology departments, which appear to account for a small percentage of all FibroScan tests done in the UK; and (iii) it assumed uniform costing for FibroScan tests done in a radiology department, whereas Louise was able to point through personal experience to the deviations (both from the analysis and from each other) from the numbers used in the analysis. This conversation ends with Chris Estes discusses the idea that this should be a model of long-term inputs and outputs reflecting not only the cost of the test but also the costs and benefits of the downstream care that would result from testing.

The UK's National Institute for Health and Care Excellence (NICE) issues health economics-based decisions on whether therapies and diagnostics should be reimbursed by the British government. In a recent draft guidance titled FibroScan for assessing liver fibrosis and cirrhosis outside secondary and specialist care, NICE has stated that "there is not enough certainty for [using FibroScan to assess liver fibrosis or cirrhosis for adults in primary or community care] to recommend it as a clinically effective and cost saving option for routine use." This episode centers around understanding the draft guidance and what it means for out of hospital screening.

In addition to Louise, Jörn Schattenberg, Ian Rowe and Roger, this panel includes a first-time: lead modeler and epidemiologist Chris Estes of the Center for Disease Analysis Foundation. Chris has been lead modeler on some of the 2015-2030 projects previously discussed on the podcast.

The question driving this episode is: what about the NICE decision makes sense and what might not. Ian started by providing context about NICE: its mission is to "allow 'rational' in inverted commas decisions to be made about health care spend, mostly from a cost effectiveness and clinical effectiveness perspective." He noted that this decision revolves around a fairly narrow target: FibroScan in a community or primary setting, as compared to its delivery or secondary care. Ian goes on to note that two sets of data that would help drive a decision are scarce: how well the test works and, separately, how well learning test results causes patients to improve their health. Against that backdrop, he noted that a decision not to fund might be "regrettable" and not in the interest of patients, but a logical outcome of the presenting question, organizational mission and lack of existing data.

Louise Campbell followed Ian and question some specifics of how the analysis was conducted and the source and nature of cost data NICE used. On the "nature of data" issue, she noted that the NICE review team presented FibroScan costs as a single, fixed variable, whereas in the "real world," the ways and amounts that different institutions charge vary widely.

Roger Green then broadened the question to ask what the outcome might be with a broader question or approach the economics of the situation. Chris Estes discussed the direct and indirect costs that would go into a complete calculation and then to note that if you could prevent disease before it began (by addressing obesity or early NAFLD, this would be the most cost effective strategy. Ian noted it was also one on which the manufacturer seemed unable to provide data.

The rest of the episode focused on issues such as how this question would be treated differently in Germany, what data sources or facts might drive a different decision and how to research or acquire this data. Louise noted several examples of areas where she felt the costing analysis might not have reflected the realities of the market and patient care cases. The conversation jumps from one topic to another. Toward the end, Jörn notes that while our primary focus should be to support wellness, the easier economics to evaluate are those of treating illness and it becomes clear that this tension between illness that provides hard data and wellness that is a softer measure but clearly of greater benefit to society is a significant source of friction that tends to undercut long-term thinking.

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.

Global Liver Institute Founder and CEO Donna Cryer and Key Opinion Leader Professor Scott Friedman joined Roger Green at NASH-TAG 2022 for a far-reaching conversation on drug development and scientific advances in Fatty Liver disease.

This episode includes the entire discussion, plus a shorter one with Roger and  SurfingNASH co-host Louise Campbell on some of the lessons emerging from NASH-TAG's first day.

Timestamps: 
2:17 – Roger Green introduces the agenda for today’s episode
5:42 – Donna Cryer: “Favorite phrase” from the NASH-TAG Day 1 is “lessons learned”
7:02 – Scott Friedman on NASH-TAG Day 1: equal parts sobering and promising, with a major conceptual change
7:34 – Scott’s “sobering” points: highly anticipated clinical trials “did not pan out;” “we don’t know where this disease starts” or where to start treating it; and “we tend to approach the disease as one size fits all”
9:06 – Scott’s “promising” points: digital histopathologies, gene regulation and epigenetics, diagnostics, organoid technologies and more
11:33 – Roger: We need to think of “combination” treatment strategies not only as static same-time combinations but also sequencing of medications as replacements or add-ons 
12:58 – Donna: To de-risks trials, include patients throughout objective setting and trial design
14:42 – Roger: Patient feedback may provide greater value to smaller companies with less margin for error
15:28 – Scott: Another consideration is patients’ disappointment "when things don’t work.”
16:20 – Donna: Patients realize the first drug “doesn’t have to be perfect”
17:13 – Donna: Interdisciplinary discussions at NASH-TAG are a very hopeful development
18:04 – Scott: We have a great deal to learn about underlying biology, but the efforts to do so make me hopeful
19:10 – Scott: Weight loss reverses a biology we can’t seem to accomplish with NASH drugs, which is promising
20:18 – Donna: We need multidisciplinary, multifaceted complete care approaches that do not rely on patients’ willpower and work for different types of patients
22:24 – Scott: “Personalizing” is not just about therapy, but also how the patient copes with the disease
23:02 – Donna: I remember early in my care being jealous of cancer patients for the holistic care they were able to receive that liver patients weren’t
25:55 – Donna: Will pruritis continue to be an ultra-rare indication when it exists with so many liver diseases?
26:25 – Scott: New, more elegant biologic definition of pruritis processes should lead companies to develop better therapies
28:59 – Donna: When they are approved, NASH drugs will be prescribed in as polypharmacy.  Patients have multiple healthcare costs. I hope manufacturers will act responsibly
30:14 – Donna: Pricing for pruritis agents might inspire a backlash. Patient advocates will not support current pricing
31:01 – Roger: Keep in mind that modeling comes from finance departments and targets cash management and budgeting issues
31:34 – FINAL QUESTION: What do you believe will change and hope will change in the next year?
31:40 – Scott: Hope to see a drug trial result that will points to approval. Expect to see advances in NITs and digital histopathology
32:41 – Donna: Hope and expect two things: alignment between advocates, researchers, manufacturers and regulators on what mark we need to hit and what will happen once we hit it, and clarity around best use of NITs
33:31 – Roger: Expect to see adoption of digital histopathology in 23, maybe even end of next year. Hope to see widespread acceptance that stabilizing fibrosis is a perfectly acceptable clinical outcome for drugs
34:33 – Scott: We’ve known all along that FDA considers non-progression from advanced fibrosis to cirrhosis an acceptable endpoint
36:03 – Louise and Roger chat about fine points from NASH-TAG sessions and the first part of S3 E2
45:55 – Business Sect

SurfingNASH is covering each day of NASH-TAG 2022. This episode is a "morning after" conversation with Stephen Harrison, Louise Campbell and Jörn Schattenberg reviewing key points of the Day Two discussions, with particular focus on the two "fireside chats" that wrapped up the program.

Day Two of NASH-TAG included presentations of new data on wet markers, imaging and combination therapy, discussion of novel targets and advances in our understanding of basic science. All this led up to the meeting's climax + denouement: David Shapiro's talk on why the current trial and approval system is unsustainable and places unnecessary burden on patients, developers and investors, followed by two "fireside" chats that were, in fact, calls to action to rethink the appropriateness of clinical trial endpoints driven by so-called "semi-quantitative" histopathology reads driven by liver biopsy.

The day produced bold arguments, exceptional images, and some compelling new facts and perspectives. It was also long: Roger, Stephen and Louise started with a 6:15a MST SurfingNASH recording session and went through until the 8:15p MST program adjournment (for Louise in the UK, the cirrhosis fireside chat ended after 3:00a Sunday morning!) The next morning, the group met to review the speeches, slides and impassioned moments of a compelling, powerful day.

In the process, they revisited some of the day's high points, culminating in powerful statements on the problems with current clinical trial endpoints articulated by Stephen Harrison for non-cirrhotic trials and Vlad Ratziu for cirrhotic trials and supported by a powerful statement by Global Liver Institute Founder and CEO Donna Cryer focusing on how the current trial endpoint system places patients under undue burden and unnecessary, sometimes mortal, risk.

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. 

This conversation is part of SurfingNASH's 2021 NAFLD Year-In-Review. Co-host Dr. Stephen Harrison joins Louise Campbell and Roger Green to review five key NASH themes that emerged in 2021, while simultaneously discussing the year for Surfing the NASH Tsunami.

It seems fitting that the first SurfingNASH event of 2022 should include Stephen, Louise and Roger. In this thoughtful, fast-moving conversation, Stephen identifies what he considers five key areas where the Fatty Liver community has progressed in the past year:
1. Call to action -- 2021 saw two separate, vitally important calls to action to share the scope of the upcoming NASH pandemic with the medical community at large and begin to create forums and processes to develop an agenda and care practices that would reach far beyond hepatolotgy all the way to primary care and other specialties that have historically had little to do with the liver. Jeff Lazarus work with colleagues at Wilton Park and in over 100 countries to evaluate the current status of NASH diagnosis, treatment and screening around the world and to being developing a public health agenda. At around the same time, a multidisciplinary panel of US opinion leaders organized by AGA published a general call to action and a specific Clinical Care Pathway, starting at diagnosis, that included multiple specialties and, for the first time, set out to define a way specialties can work together in identifying patients at risk, screening them for disease, and then treating as appropriate.
2. Natural History -- 2021 saw publication of two major papers on the natural history and progression of the disease. One paper produced by Stephen, Naim Alkhouri and a range of associates, evaluated a large group of seemingly healthy middle-aged men who receive treatment at the San Antonio Military Medical Center and mirrored a smaller study 10 years earlier. The two studies were fairly consistent in determining that slightly over one adult in three has demonstrable NAFLD and one in seven or eight has documentable NASH. The difference in the populations was that while approximately 2% of the 2011 sample exhibited F2 or F3 NASH, that number almost tripled ten years later. These papers and Dr. Arun Sanyal's work published later in the year in the New England Journal of Medicine indicated that we can project a steadily increasing trend line for cirrhosis cases, with growth in most major markets at 10-12% per year.
3. Drug Development --news here was mixed, although Stephen points out that we have learned from each failed trial. SurfingNASH discusses this topic frequently, so suffice it to say that as the year ends, three medications recruiting or conducting Phase III trials and several other exciting, innovative agents have already demonstrated some positive Phase II results.
4. Weight loss surgery -- Stephen feels that the SPLENDOR study, which we discussed recently on the podcast (S2 E60), merits notice because of what it suggests about the ability of dramatic weight loss to halt or reverse cirrhosis. There are drugs in development right now that appear capable of producing the same levels of weight loss shown with bariatric surgery, which provides hope that we can eventually stabilize and perhaps regress fibrosis levels in cirrhotic patients.
5. Non-invasive testing -- Several different modes of non-invasive testing have made progress during the year, ranging from liquid tests that received FDA approval and/or enhanced their commercialization capabilities to published research suggesting that MR Elastography (MRE) has compiled much of the data necessary to prove outcomes with greater clarity and confidence than biopsy. Stephen shared his belief that 2022 will be the year when academics, drug developers and regulators begin to align around a strategy to move beyond biopsy with deliberate speed.

None of these items are new, but the way Stephen organizes them is clearly worth a long listen.