Can you give me an introduction to your clinical practice and research interests?

Great. I just want to kick this off by understanding a bit more about AH. There was a 2018 article publishedby Dr. Emily Hughes about survival from alcholic hepatitis. They looked at 77 studies published between 1971 and 2016 and concluded that overall mortality from AH was 26% at 28 days, 29% at 90 days, and 44% at 180 days after hospital admission. These numbers are pretty stunning to me and I had no idea they were so high. Is thatpretty aligned with what you see in your practice?

I want to understand what the typical admission looks like. Like, how much of it is after a severe binging episode vs long term alcohol use. And what would you say drives patients to be admitted, is it acute jaundice or something else?

What % of patients who are admitted would you classify as severe vs moderate/mild (mdf >32)

Since Covid, have you found the admissions to increase, or is it about the same

After a patient is admitted, how do you make the diagnosis? Usually through biopsy?

I want to get an idea of how patients are treated, in particular, how many end up on corticosteroids or liver transplants, ECAD, plasmapheresis

Moving onto larsucosterol, for the inclusion criteria, they are enrolling patients with MDF scores >32 and MELD scores between 21 and 30, which to my understanding is pretty severe. What 90 day mortality would you expect in that general population based on that criteria?

Do you believe there are patient characteristics which yield better outcomes? Like age, overall health, sex, ethnicity, smokers, etc?

In the phase 2a trial they showed 100% survival for an open label, with a n of 19, with 12 of those being severe. All of them survived, with 8 of those 12 severe patients being discharged in 4 days or less after a single dose. Lille score was 0.19. So obviously this data is inherently limited by its open label nature and small n, but what are your thoughts about these results? Can you think of any other reasons all the patients may have recovered?

What do you make of the epigenetic mechanism? Do you find it concerning that this mechanism hasn't been published on in well-known medical journals, to my knowledge?

Assuming the drug did work, is there a % survival at 90 days you would like to see before you use it, or would you just try to put a patient on it as long as it is stat sig over placebo given lack of options?

Would you consider using it in all comers, off-label, or would you keep it to severe AH patients?

Something I found interesting was that bilirubin > 8 mg/dL had a median reduction over 28 days by nearly 50%. Is this something that happens naturally in terms of normal recovery?

The median lille score was 0.1 on larsucosterol and 0.41 on supportive care and corticosteroids from the university of Louisville, which had 16 AH patients. Do you think the 0.41 score is a pretty close representation of what to expect in a broader population on steroids and supportive care? Do you think the 0.1 lille score on larsucosterol is real or do you think the n is too small to make any meaningful guesses for efficacy?

in your recent article in NEJM, we couldn't help but notice there was no mention of larsucosterol, despite being the most advanced candidate in severe AH to my understanding. Is there any particular reason it wasn't included?

Are there any other drugs in development for severe AH you find interesting? Surrozen has a hepatocyte targeted R-spondin-mimetic (SWEETS), SZN-043, are you familiar with that one?

Dosing was halted after Grade 1 and 2 treatment-related asymptomatic liver transaminase elevations showed up, do you believe this is likely to be a dealbreaker?