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S2-E55 – Day Three at the 2021 TLMdX From AASLD

Profs. Scott Friedman and Michelle Long, Dr. Naim Alkhouri and Global Liver Institute DIrector of Global NASH Programs Jeff McIntyre join Louise Campbell and Roger Green to review some of the most important and exciting presentations from the first three days of the 2021 TLMdX, the annual meeting from AASLD.

Each panelist chose 1-2 presentations or posters from the 2021 TLMdX from AASLD that they thought conveyed a major topic or question in the meeting.

Scott Friedman focused on the emerging realization that microbiome and gut microbiota are important to the development and resolution of liver disease on several different levels.

This focus paired neatly with Naim Alkhouri’s discussion of the increasing prevalence of alcoholic and non-alcoholic Fatty Liver disease among adolescents and young adults in the US.

And  in a different way, with Louise Campbell’s review of a presentation from Vicki Shah demonstrating that an Advanced Practice Provider (APP) pathway achieves more effective weight loss in NAFLD compared to standards of care.

Roger Green contrasts two supposed “failed” trials: aldafermin and pegbelfermin.

Michelle Long reviewed Dr. Tamaki’s paper discussing the longitudinal association between MRE scores and, separately, liver-related and CVD-related events in NAFLD.

Jeff McIntyre reviewed Donna Cryer’s talk this morning titled “Grit, Grace, Gratitude, and Resilience: What You Wish Your Doctors Knew about You.”

As usual with SurfingNASH, the conversation was interspersed with challenging insights and comments, debate, and laugher.

Highlights include:

5:27 – Introducing tonight’s panelists
15:27 – Naim Alkhouri discusses “The Prevalence of Alcoholic and Nonalcoholic Fatty Liver Disease in Adolescents and Young Adults in the US” (Parallel 5)
20:33 – Group discussion
28:56 – Louise Campbell discusses “An advanced practice provider (APP) pathway achieves more effective weight loss in NAFLD patients compared to standards of care” (Parallel 2)
37:40 – Group discussion
46:28 – Scott Friedman discusses “The influence of host genetics on liver microbiome composition in patients with NAFLD” (Poster #`1654)
48:39 – Scott transitions to “The influence of host genetics on liver microbiome composition in patients with NAFLD” (Poster #1781)
50:31 – Scott ties these two results together in addressing the importance and complexity of microbiome: “I say that …in part based on the work of Marty Blazer…an infectious disease doctor, who’s sort of convinced me that epidemiologically it’s very hard to explain how a disease showed up on our radar screens in a 20 to 30 year period, uh, that didn’t exist before…Certainly, our genes haven’t changed over hundreds, if not thousands of years, to any extent. And so something external has changed. It comes back to the environment,” and dietary changes.
52:53 – Group discussion
58:48 – Michelle Long discusses “Longitudinal association between MRE and liver-related events and CV events in NAFLD” (Sunday Presidential Plenary session)
1:07:56 – Group discussion
1:09:08 – Group discussion shifts toward the question of whether and when FDA might move away from biopsy as the requisite endpoint in drug trials
1:15:03 – Roger shares the audience’s question on probiotics and NAFLD. Scott provides a primary answer
1:16:37 – Jeff discusses Donna Cryer’s talk on “Grit, Grace, Gratitude, and Resilience: What You Wish Your Doctors Knew about You” (Sunday Patient Forum)
1:22:53 – Group discussion starts by considering the best word to describe the optimal provider: patient interaction (“partnership” emerges as a preferred choice)
1:28:23 – Roger discusses “Topline Results from the Alpine 2/3 Study,” a Phase 2b trial evaluating 3 doses of the FGF19 Analogue Aldafermin,(Sunday Presidential Plenary session) and “Efficacy and Safety of Pegbelfermin in Patient with NASH and Stage 3 Fibrosis: Results from the Phase 2b FALCON 1 study.” He connects these results by saying “What was striking is that if all you were doing was scoring the balls and strikes, then you’d say that those were both the same thing because neither one of them was going to point to a commercial success in the launch.” However, he continues, “the differences between the two vastly outweigh the similarities” in that pegbelfermin demonstrated minimal ability to differentiate from placebo while aldafermin clearly differentiated from placebo but might not have presented a strong enough commercial profile given other drugs in development.
1:33:07 – Group discussion
1:36:25 – Scott adds one comment on the importance of digital pathology if we are to continue relying on biopsy.
1:37:04 – Final question: “What’s the one thing that you hope that the part of the community that you touch most directly is going to take out of this meeting?”

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