S2-E57 - AASLD 2021 Wrap-up: Looking Back on an Eventful TLMdX Surfing the MASH Tsunami

Manal Abdelmalek, Jörn Schattenberg and Ian Rowe join regulars Stephen Harrison, Louise Campbell and Roger Green to recap this week's just-concluded TLMdX 2021, the AASLD annual liver meeting. 

When AASLD announced that the 2021 TLMdX would be held as a purely virtual meeting, attendees and observers feared a loss of focus and the kind of amplifying energy that comes from being with colleagues. That did not happen. Instead, the breadth, quality and novelty of the meeting's presentations generated exceptional positive energy despite the virtual setting. 
4:10 - Roger starts by saluting Manal for giving the NAFLD Wrap-up Talk at TLMdX 2021, then introduces other panelists
6:58 - Icebreaker question: Where did this meeting "make the biggest dent" in Fatty Liver disease?
12:21 - Manal discusses how she organized and prepared for talk and describes "somewhat surreal" feeling of seeing semi-quantitative histology fail in trials where so many non-invasive markers suggested proof of efficacy
16:13 - Jörn points out the inherent tension between needed accelerated endpoints and being tied to a severely flawed "gold standard" of biopsy
17:15 - Stephen's simplest solution: capitalize on existing study results to link MRE, fibrosis and outcomes
18:56 - Manal counters: this assumes  biopsy is the gold standard, when we know it is seriously flawed
21:02 - Stephen: it's time to "reach a common ground on what it takes to achieve replacement of histology with an NIT"
24:02 - Ian suggests that the FALCON trial history will strengthen FDA's attachment to biopsy
26:13 - Stephen's key to moving beyond biopsy: strengthening the data that supports credibility of NITs
28:13 - Jörn: having a combination of NITs that each reflect different elements of the disease makes effort easier and more credible
28:45 - Ian: controlled cirrhosis studies might allow quick validation and acceptance
29:35 - Manal: we know how to design better trials now,  cites story of ALPINE 2/3 as proof
32:17 - Stephen: the path to the data-driven future explodes when the first drug is approved
33:32 - Lars Johansson (Antaros Medical)  joins from audience to ask Stephen whether we can reanalyze spleen volumes from old trials  and reanalyze imaging data possibly with AI
34:52 - Stephen salutes Lars's "very good insight" about the potential to reanalyze the "huge" bodies of data from older trials
35:54 - Jörn agrees, but cautions that we need to keep primary focus on getting a drug approved
38:41 - Lars returns to audience
39:25 - Manal returns to Louise's  thought that one thing coming from meeting has to do with genomics, citing Million Veteran database
40:16 - Manal describes how single cell RNA data will shape the future of diagnostics and treatment in Fatty Liver diseases
41:10 - Louise refers back to various talks involving the patient-treatment impact of genomics and others implicating genetics as a possible reason for high variability in placebo response between trials.
43:42 - Stephen raises the diversity inherent in microbiome data as playing a role in making Fatty Liver so complex to characterize and treat
45:10 - Jörn points out that any drug that can "elevate above all these thresholds" and complexities will have to be "quite robust"
46:23 - Stephen envisions the day when drugs are approved based on MRE and the scarcity of MREs around the world creates a new set of challenges
47:37 - Manal observes that "precision medicine has been hot and heavy," which spurs Roger to note that all the key advances mentioned in the meeting are tied to advances in computing and modeling power
48:12 - Closing question: The biggest story a year from now? Stephen, Manal and Ian focus on "Phase 3 results." Jörn, Louise and Roger focus on ways patient empowerment will focus attention on better patient solutions.
57:05 - Business section