drugtrial

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.

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.

Program co-chairs Jeff Lazarus and Jörn Schattenberg join the Surfers to discuss their "Innovations in NAFLD Care 2022" series and how it promotes the broader NAFLD Public Health Agenda.

This far-ranging discussion focuses on the Innovations in NAFLD Care 2022 webinar and event series with the goal of understanding what makes this series special and why it is so important today. The NAFLD Public Health Agenda is challenged with high prevalence levels, year-on-year double-digit increases in the number of newly-diagnosed cirrhosis patients, worsening of diets and exercise regimens brought about by the COVID-19 pandemic and an array of issues stemming from the lack of efficacious and tolerable medicines approved for this indication.

Last weekend's NASH-TAG 2022 was the best attended event in the conference's six-year history, and probably the one that will have the greatest long-term impact on diagnosis, treatment and monitoring of Fatty Liver patients. In this wrap-up conversation, our seven-person panel (including two Pharma execs and one diagnostics entrepreneur) considers how two key stakeholders -- FDA regulators and patients -- might respond to changes in clinical trial protocols that remove or de-emphasize biopsy-generated data.

This conversation is a continuation of 4.2, which focused on the NASH-TAG "fireside chats." This one starts with Erin Quirk's observation that events of the past year (presumably COVID-19 approvals) demonstrate that FDA is not slow to act when presented with clear need and high-quality data. Erin goes on to confirm that the statements FDA made during the fireside chat demonstrated a "real openness" to dialogue, which is what agencies do to signal that they consider it important to improve processes and/or solutions. Next, she suggests that a patient representative should be on future years' panels. FInally, she harkens back to Dr. Toerner's referral to HIV as a model for relatively fast, data driven change. The conversation shifts to focus on competing views on how to act in the patient's interest, with Erin, Ian and Amy all expressing points of view. Toward the end of the conversation, Roger shifts to discuss the practical implications of Stephen's suggestion that studies should review 3 H & E slides per patient instead of the current number (one) and the two of them discuss practical implications on screen fail rates and its flipside, patient acceptance rates in terms of study cost, timeliness and ability to standardize and simplify placebo response analyses.

SurfingNASH invited four attendees to the NASH-TAG wrap up (three first-timers, two corporate executives) to focus on presentations and discussion from the fireside chats. Highlights include:
4:20 – Introduction of first-time panelists Amy Articolo (Novo Nordisk), Erin Quirk (Terns Pharmaceuticals), Rachel Zayas (AGED Diagnostics) and the returning Ian Rowe (University of Leeds)
12:55 – Opening question: what about NASH-TAG 2022  surprised you most?
13:04 – Consensus: energy and passion. Rachel mentioned the vast divergence in  balloon hepatocyte readings
16:19 – Led by Stephen, group discusses powerful single slides
22:51 – Question: What single presentation had a real impact on your thinking?
23:04 – Rachel: Single Cell Transcriptomics, which can identify disease drivers.
25:53 – Ian: Scott Friedman’s point about the need to balance blocking fibrosis with maintaining sufficient collagen for scar healing.
27:16 – Amy: Talks about upstream effects resonated because Novo Nordisk works to develop combination therapies.
28:53 – Erin: One “pleasant takeaway” was big companies sharing findings “shoulder to shoulder” with smaller ones.
30:04 – Roger: Rate reaction to fireside chats using 6-point scale. Erin, Amy, Rachel all say 5. Liked diverse viewpoints, high energy level. Ian says 4, maybe 3. Fears that following the path laid out in meeting will lengthen drug development.
36:06 – Stephen: We need to improve use of histopathology, design and implement a multi-year path to NITs as outcome drivers and develop NAIL-NIT, a multi-company, “agnostic” data repository to utilize everyone’s data to “ask the big questions” and drive large prospective trials. Also, we should provide analytics and perspective on unresolved issues that are delaying final FDA guidance document
47:02 – Amy: Key is to impact patients’ lives, which is more “function and feel,” less survival. We’ll look back on this as "The moment of change”
48:59 – Roger: FDA has becoming more open and encouraging since 01/21 webcast
50:33 – Roger: Stephen’s push to lower screen fail rates from 80% to 50% will drive 2.5x increase in eligible patients, thus shortening trials, reducing costs
52:35 – Stephen: This can also reduce placebo response rates, which are a major issue in interpretation
54:27 – Erin: Should we even be looking at liver tissue when pathologists are so mislaligned on balloon hepatocytes? Stephen: Eventually, perhaps not. But the ongoing trials today have to rely on histology
55:02 – Erin: Are we creating medications that patients actually will want to take, given that many choose not to participate in trials? Louise: Decision is individual, but those who take time to make it wisely have the greatest prospects for success
57:14 – Ian: Findings from trial populations and natural history populations can vary widely. Also, the NITs we use in trial need to work financially for the larger population
59:20 – Amy: Expanding trial population into primary care or OB/GYN would broaden target dramatically
1:01:02 – Question: something you hope to see that is different in a year and something you believe you will see
1:01:14 – Louise: Patients and advocates at future Fireside chats
1:01:29 – Rachel: Tests that look separately at the different NAS elements instead of creating composite scoring
1:02:02 – Erin: A positive Phase 3 study result
1:02:31 – Amy: Solid and actionable programs to create solutions to issues identified this past weekend
1:03:03 – Ian: Expect positive Phase 3 data. Hope to see discussion around NITs that correlate consistently with histology and drive changes in outcomes
1:03:21 – Stephen: Hope to report positive Phase 3 trial
1:05:04 – Roger: Believe AI histopathology will play larger role; hope this entails more than simply emulating human brain 
1:08:03 – Busines

In advance of NASH-TAG 2022 this weekend, Jörn Schattenberg joins the Surfers to answer a key conference question: are we ready to pivot toward non-invasive tests and better uses of histopathology? The group explores a range of questions and ideas that are likely to emerge during Saturday night's fireside chats.

The group explores a range of questions and ideas that are likely to emerge during Saturday night's fireside chats.

 Highlights include:
7:03 – Stephen Harrison begins to discuss NASH-TAG 2022
7:45 – Jörn Schattenberg: we’re not ready to move beyond biopsy in 2022. Hope that we will bring forward the right program by end of year
8:31 – Roger agrees
8:43 – Stephen agrees, but looks to determine how to resolve pivotal challenges
9:46 – Stephen lists discussants for the fireside chats, including regulators, researchers and industry representatives
10:30 – Stephen lists  key topics for his talk on non-cirrhotic trial endpoints
11:37 – Stephen lists “hurdles” biopsy  "needs to overcome" 
12:40 – Stephen’s key issue for histopathology : why we only score one H&E and one tri-chrome read per sample. He suggests three H & E and promises to reveal data on this in his talk.
15:08 – Jörn: "Why three?” 
16:08 – Stephen: no magic, three non-contiguous reads “just makes sense.” The goal is to is to find ballooned hepatocytes or clustering, which might not appear in one slide but will frequently elsewhere in the sample.
18:11 – Stephen: choose the slide with the strongest presence of disease
18:47 – Key benefit: we screen fail fewer people on ballooned hepatocytes
19:59 – Potential secondary benefit: reducing resolution scores in the placebo group
21:09 – Stephen: three companies looking at this. All see a major difference.
21:29 – Stephen: there are commercial issues as well: high screen fail rates inflate costs and take lots of time. This approach will save money and time.
24:13 – Stephen: I like Jörn’s idea about using AI here. It will enhance reproducibility.
24:52 – Stephen: another issue is the shift from one to multiple pathologists. Multiple pathologists turns out to drive screen fail rate higher. We need something to counter that.
26:49 – Louise Campbell: getting more tissue is beneficial for the patient
27:52 – Louise: a lot of NIT evaluation comes from pairing to biopsy samples. The more samples, the more opportunity to test NITs.
29:14 – Stephen shifts to getting beyond the biopsy. FDA issue: link an NIT to outcome. The cirrhosis chat gives us our first shot on goal.
30:55 – Stephen: one challenge with non-cirrhotics is that NITs are not included in the major Phase 3 trials
32:07 – Jörn: this is a pivotal issue and NASH-TAG is the right place to discuss it
33:33 – Louise: consider quality-of-life as a high value outcome measure
33:57 – Jörn: how do we explore stabilization of disease with NITs?
34:31 – Stephen: all these are reasons to “set the stage” with cirrhotic cohorts first, learn the lessons, then extend to non-cirrhotics
37:56 – Closing question: what will make 2022 successful to you in terms of moving this agenda forward?
38:17 – Jörn: data from the consortia
38:50 – Stephen: a clear idea of what will get us to a surrogate endpoint with NITs. Until then. improve histopathology practices.
39:54 – Louise: anything with histopathology that leads us toward NITs is good. Also, we will need to do more remotely as long as COVID keeps rearing its head.
40:51 – Roger: let’s learn more and make two cases one on economics and the other on data quality
41:17 – Stephen: one more thing: better economics and stronger data will motivate Big Pharma to invest
43:53 – Stephen: at the end of the day, it’s all about economics
44:53 – Roger: burnt money feels wasted, makes study investment feel like an expense
46:09 – Stephen: listen for more Saturday night
47:16 – Business report

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 Manal Abdelmalek of Duke University joins Louise Campbell and Roger Green to discuss the use of older drugs to treat cirrhosis patients today and her views on where NASH drug development is heading.

Manal begins by discussing the inherent tension between the research world, which reveals several promising modes of action and drugs in development but are unlikely to yield a first approval less than two years from now, compared to patient treatment, where people living with cirrhosis are looking for help today. Her talk focuses on the value of stabilization as a goal for cirrhotic patients being treated today and in part on the advances in basic disease knowledge and specific drug and diagnostic development will empower HCPs to prescribe the exact drug therapy that is right for the individual patient.

The last half of December marks our annual NAFLD Year-in-Review. Episodes 62-64 each include ~20 minute segments of longer interviews with Stakeholders who have made a dent in Fatty Liver disease in 2021. In this episode, Louise Campbell and Roger Green are joined by Manal Abdelmalek, Kenneth Cusi and Jörn Schattenberg.

Highlights:
3:26 – Manal Abdelmalek introduction and discussion: opportunities in the new drug pipeline and ways to treat using older agents until new agent arrive
5:06 – Manal: urgent to treat cirrhosis when it appears. Reversal may not be “achievable;”  but blunting progression can provide stability 
9:51 – We learn more about heterogeneity of cirrhosis patients all the time. Some day, genetics will pinpoint each patient's outcome to avoid so we can treat accordingly
12:20 – Louise: would a combined database of multiple cirrhosis drug study patients provide richer insights?
14:05 – Manal: let’s “shelf,” not "trash," drugs that had promising NIT results but missed in Phase 2b or 3 histology
18:57 – Louise: Manal does well to remind us how to use older drugs to stabilize cirrhosis patients.
21:05 – Manal: until new drugs become commercially available in 2-5 years, using older drugs better will be key
23:07 – Ken Cusi introduction and discussion: development of multi-disciplinary activities and clinical care pathways
24:10 – Ken: New data on prevalence and etiology of NASH cirrhosis spurred multi-specialty activities
24:41 – Key insight drivers: NHANES analyses, endorsements from medical societies and global journals, work of Jeff Lazarus and Wilton Park
27:01 – 2022 a “great year:"  new/updated guidelines, major Phase 3 trials progressing
 30:00 – Louise:  AGA critical care pathway work and collaboration among specialties pivotal, positive and extending to related consumer industries
 31:26 – Ken: 2-3 years from now, foresees “convergence of awareness” to expand FIB-4 and other simple tests to more patient risk subgroups.
33:25 – Study in progress: screening large number of patients to determine NASH prevalence among non-diabetic patients
35:34 – There was significant debate whether to include screening for T2D patients in  the 2018 AASLD guideline recommendations
37:03 – Louise: Fatty Liver disease has far broader implications than simply for the liver
38:41 – Roger: asks how liver testing and vigilance will fit in  schedules and practices of already overburdened providers
39:55 – Ken:  requires a of simple, inexpensive, easily accessible  Stage 1 tests like FIB-4, was key to its selection
42:22 – Jörn Schattenberg introduction and question: how are cost effectiveness analyses progression
44:25 – Jörn: 2021 has been “an exceptional year” for NASH
46:04 – Collaborated with Vlad Ratziu and others to produce cost of illness study published in Liver International in 2021
49:39 -Louise:  why does it feel like we study cost effectiveness only for expensive new drugs and never measure cost effectiveness of inaction?
50:38 – Jörn: value of monitoring relies on measuring related risks from cardiovascular and other systems
52:22 – Roger:  re Louise’s question, most cost effectiveness work evaluates a specific new expenditure, not a global “what if”
55:44 – Jörn: quality-of-life, which has clear economic costs, strongly associated with NAFLD
57:14 – Roger: Using HER to identify patients at risk might be a more palatable way to target education and information
59:50 – Jörn: An Optum database algorithm built by NIDDK provides a look at how to target
1:01:09 – Episode ends

This conversation is part of SurfingNASH's 2021 NAFLD Year-In-Review. Professor Alina Allen of the Mayo Clinic joins Louise Campbell and Roger Green to discuss the rapid progress the profession has made in improving user-friendliness and ease of interpretation of MRE and the coming expansion in the role that non-invasive liver testing will play in the years to come.

Alina notes some specific new information about MRE and other non-invasive testing methods that have come to light in the past year. Key new points about MRE include (1) Alina's statement that "we an actually diagnose NASH" using MRE and MRI-PDFF, (2) Alina's comment that we can execute MRE in a five-minute session, and (3) there are demonstrated correlations and precision prediction data for MRE and cirrhosis. The predictive power of MRE on likelihood of progression allows a way to match pairs in clinical trials more accurately by adding the act of pairing by active and control groups. Alina also notes that the same probability metrics that allow researchers to match pairs in a trial will also power the treating physician to schedule the next MRE in 1-5 years depending on relative risk of progression. In the end Alina suggests that we do not need MORE biomarkers, but instead we need to determine the best way to explore the ones that have been developed in the last few years.

If you listen closely, you will hear Alina discuss some questions that will be answered and data that will be presented at NASH-TAG 2022.

SPLENDOR lead author Ali Amirian, the Surfers and audience member Shardool Jain of Altrix Bio debate whether and when bariatric surgery might become first line therapy for multi-morbid metabolic patients. 

Dr. Jain takes the position that for many patients with metabolic co-morbidities, drugs tends not to work over time, so why not go to bariatric earlier in therapy...even in first line? Panelists disagree to varying degrees. After Dr. Jain leaves, the group answers Roger's question about what they anticipate might be long-acting effects of this pivotal study.

The Surfers, joined by SPLENDOR lead author Ali Aminian, broaden their discussion into considering MACE and MALO patients into clinical trials.

After Roger Green notes that the percentage reductions in MACE (7.2%) and MALO (7.3%) were virtually identical, the group returns to explore the question of including co-morbid metabolic patients in clinical trials. To spur the discussion forward, Ali shares some additional insights on differences in how the bariatric surgery group performed in SPLENDOR vs. the group that did not receive surgery.

Lead author Ali Aminian shares key findings from SPLENDOR on the impact of bariatric surgery on Major Adverse Cardiovascular Events (MACE) and Major Adverse Liver Outcomes (MALO).

Top-line: over a ten-year followup period, bariatric surgery led to a fourfold decrease in MALO and almost a twofold decrease in MACE. This led Stephen Harrison to ask whether it makes sense to combine MACE and MALO as an endpoint in future studies and to comment on the oddity that most specialties seek to include patients with relevant co-morbidities in their clinical drug development trials but NASH drugs seek to exclude them.

NASH-TAG 2022 takes place in Deer Valley Utah and on-line from January 7-8, 2022. Join Surfing NASH to learn about the last three sessions of the meeting, which include multi-stakeholder "fireside chats" about how to make progress in non-invasive testing for non-cirrhotic NASH and NASH cirrhosis.

Co-chair Stephen Harrison leads the panel through key sessions from NASH-TAG. This conversation starts with a review of Session 7, which features presentations on PNPLA3 and HSD17B13 knockdowns and a range of novel targets. Discussion proceeds to Session 8, which includes presentations on several key basic science topics ranging from transcriptomics to integrin. Finally, Stephen leads the group through discussion of the two fireside chats, where collections of governmental, commercial and academic stakeholders discuss how to make progress in using novel tests for products designed to treat patients with non-cirrhotic NASH and, separately, NASH cirrhosis.

NASH-TAG 2022 takes place in Deer Valley Utah and on-line from January 7-8, 2022. Join Surfing NASH to learn about the important and innovative drug development and basic science talks in the meeting.

Co-chair Stephen Harrison leads the panel through each of the sessions during the conference's first morning. The session starts with Michael Charlton's annual "Year in Review" talk, includes discussions on an array of drug classes and ends with a session on the biologic basis of NASH progression. He pauses at the end of his review of each session, thus leaving Steering Committee member Jörn Schattenberg and Surfers Louise Campbell and Roger Green to comment on favorite presentations, ask questions and place this information in the context of what we are learning elsewhere about Fatty Liver disease and the drugs that are being developed to treat it.

NASH-TAG 2022 Co-chair Stephen Harrison and Steering Committee Member Jörn Schattenberg review the upcoming conference, focusing on major issues in NAFLD and NASH diagnosis, staging, treatment and monitoring.

NASH-TAG 2022 faculty, format and schedule suggest that this conference will produce breakthroughs in knowledge and consensus about NAFLD therapy. This week, NASH-TAG 2022 Steering Committee member Jörn Schattenberg joins the Surfers to discuss key presentations and critical issues in the conference. NASH-TAG co-chair Stephen Harrison walks the panel and audience through the entire NASH-TAG agenda, with Jörn, Louise Campbell and Roger Green contributing questions and comments throughout the session.

Highlights from the program:

8:54 – Stephen provides a little background on NASH-TAG
9:44 – Stephen begins to discuss Friday morning program
10:34 – Describing the first session, “A one-stop shop”
13:10 – Jörn Schattenberg comments on Session One
14:09 – Roger Green comments on Session One
15:10 – Louise Campbell comments on Session One
15:26 – Stephen discusses Sessions Two and Three, with comments on the oral presentations thrown in
18:24 – Louise comments specifically on the talk about why NASH-related HCC is resistant to treatment; Stephen agrees and amplifies
19:02 – Jörn comments on Sessions Two and Three
20:19 – Stephen discusses the break session and goes on to discuss Session Four
23:18 – Roger asks about which oral presentations will appear at the conference, Stephen demurs
23:55 – Jörn expresses enthusiasm that the LITMUS, NIMBLE and the NIH Cirrhosis Network
25:15 – Stephen discusses Session 5 
26:43 – Roger expresses enthusiasm for the entire afternoon program (Sessions 4 and 5)
27:09 – Stephen discusses the scope and scale of the efforts LITMUS and NIMBLE are making, and goes on to discuss recent progress against cirrhosis in the context of mentioning the cirrhosis network
28:29 – Jörn expresses positive outlook on the Path AI and HistoIndex presentations
29:05 – Stephen begins review of Day Two, Session Six.
]31:14 – Stephen: “This may be one of the most intriguing sessions”
32:25 – Roger begins comments on Session Six
33:02 – Louise comments on Session Six
35:07 – Stephen begins review of Session Seven
36:24 – Louise begins comments on Session Seven
37:06 – Stephen begins discussion of the second evening with Session Seven
37:56 – Jörn comments on Session Seven
38:22 – Stephen discusses the last two hours of the meetings – “fireside chats” with governmental, corporate and academic stakeholders about whether it is time to pivot away from semi-quantitative biopsy-based endpoints toward NITs.
40:04 – Roger agrees with Stephen’s exceptional excitement about the potential of the fireside chats; Stephen elaborates on what will make the chats so special
42:23 – Final question: one more thing each panelist would like to point out in the agenda?
42:34 – Jörn praises “great program,” wonders whether the fireside chats should have included a patient representative
43:04 – Louise echoes Jörn’s comments on program quality and wish for a patient representative in the fireside chats
43:50 – Roger asks whether talks on the PNPLA3 and HSD17B13 knockdowns presage a longer-term future for therapies
44:42 – Stephen is partial to the fireside chats, expresses belief that researchers will take away from this meeting something they can use in research
454:52 – Business section

Manal Abdelmalek, Jörn Schattenberg and Ian Rowe join regulars Stephen Harrison, Louise Campbell and Roger Green to recap NAFLD and NASH-related insights from the 2021 , the AASLD annual liver meeting. This conversation focuses on complexities and challenges NAFLD drug development and patient treatment will face in the future and ends with predictions about the biggest stories of the 2022 Liver Meeting (hopefully hybrid instead of only digital!).

The specific complications include microbiome, which has the potential to add a regional (or even individual) component to our understanding of NAFLD. Stephen Harrison speculates on how the scarcity of MRE machines will affect patient diagnosis if MRE becomes the dominant method for diagnosing/staging NASH and Roger Green notes that the advances in disease analytics and modeling have all resulted from continuing improvements in the quality and cost effectiveness of generating and analyzing data. Finally, panelists state when they expect to be the big story of the 2022 TLM, with the group divided evenly between those looking to Phase 3 results from ongoing trials and those who believe that the increasing presence of the patient viewpoint will drive significant changes in every element of how we diagnose, stage and treat patients in the future.