The Future of Academic Hepatology with Scott Friedman

Transcript

• 00:10Welcome back. To the Yale Liver
• 00:13Diamond Jubilee, this session
• 00:15is being recorded. Thank you.
• 00:22Good morning and welcome back and.
• 00:25No, next speaker is doctor Scott Friedman,
• 00:28who's professor and chief of liver diseases
• 00:30and Dean for therapeutic discovery
• 00:32at Icahn School of Medicine at Mount
• 00:35Sinai and the title of his talk will
• 00:37be the future of academic pathology.
• 00:39Dr. Friedman. Please, go ahead.
• 00:42Thank you Doctor Dozier and just want to
• 00:44thank the organizers Michael and Mario,
• 00:47and Jim. It's really a deep honor to
• 00:49be included in this August presentation
• 00:52celebrating an extraordinary milestone
• 00:54in an extraordinary institution.
• 00:56I need to thank and wish to thank the
• 00:59funders who've kept me continuously
• 01:01funded since 1986, primarily the NDK,
• 01:03as well as the NI AAA.
• 01:06Uh, I thought that it would be
• 01:08informative to define what we mean
• 01:10by academic hepatology.
• 01:11Since we use this phrase a lot and
• 01:13it's the focus of my own comments,
• 01:15I define it as the science practice
• 01:18or advancement of liver disease
• 01:20by an academic Medical Center,
• 01:22and this can include of course,
• 01:23all the elements you've already
• 01:24heard about that,
• 01:25so epitomized the Yale Liver
• 01:27Program research, clinical practice,
• 01:30education, advocacy, outreach,
• 01:32and collaboration.
• 01:36I have some links to yell that may
• 01:38not be obvious to even my friends
• 01:41at Yale who I've known for decades.
• 01:43Name Sheila Sherlock,
• 01:44who was closely connected to Yale
• 01:46and whose name was mentioned by
• 01:47Dean Brown early this morning,
• 01:49actually hosted me for a
• 01:51student elective in 1977.
• 01:52I was very proud of that.
• 01:54It consolidated my deep passion
• 01:56for liver disease and of course
• 01:58indirectly linked me TL more directly.
• 02:01I've been a member of the Yale Liver
• 02:03Center External Advisory Board since 2006.
• 02:05I've been chair, I think since around 2014.
• 02:08I have to be Frank and saying it's one of
• 02:10the absolute highlights of my academic year.
• 02:12I love hearing about the science.
• 02:14Love interacting with the senior and
• 02:16junior members of the Yale Liver Center
• 02:19and hearing the latest and greatest,
• 02:21which has been a continuous
• 02:23stream of extraordinary science
• 02:25and clinical achievement.
• 02:27My own academic research started at US UCSF.
• 02:30This is a paper that described
• 02:32the first isolation of what we
• 02:35then call to Patrick Lipocytes,
• 02:37and now are commonly known as a paddock.
• 02:39Stellate cells,
• 02:39I show this in part because it was presented
• 02:42at the UCSF Liver Center Advisory Board,
• 02:45a member of which was Jim Boyer.
• 02:47So thanks Jim,
• 02:48I'm sure you had some positive things to say.
• 02:50I got my pilot feasibility funding and
• 02:53that led to this story and also to NIH.
• 02:57Funding.
• 02:57On the other hand,
• 02:59academic hepatology isn't always
• 03:00a better roses, and I share this.
• 03:03My first critique,
• 03:04which was actually a K award submission,
• 03:06sent concurrently with an
• 03:07R1 on the same topic.
• 03:09They had completely divergent reviews,
• 03:12and here's the agony of academic
• 03:14hepatology or academic medicine.
• 03:16This is what the reviewer said
• 03:18after I had established a method
• 03:19for isolating stellate cells.
• 03:21The major weaknesses of this application
• 03:23cast doubt on the validity of any
• 03:25data obtained and may impair Dr.
• 03:27Friedman's ability to compete for research.
• 03:28Running as an independent investigator.
• 03:31Thankfully I had great support in
• 03:32the form of my mentor Monty Bissell,
• 03:35and he encouraged me to just
• 03:37move on and things went well.
• 03:39That and other paths in my career
• 03:41have been highlighted by this article
• 03:44published in Hepatology in 2015,
• 03:46for which I also need to thank Jim Boyer
• 03:49since he was the editor of the series
• 03:51who invited me to write this piece.
• 03:53God, I hate to interrupt you,
• 03:54but if you could put your
• 03:55slides into presentation view,
• 03:56they're not advancing.
• 03:57I can't hear you,
• 03:59sorry if you can put your slides
• 04:01into the presentation view.
• 04:02They're not advancing right now,
• 04:04there you go.
• 04:06Better yet,
• 04:06just hit that button one more
• 04:08time that presentation view.
• 04:14The screen down at the bottom.
• 04:17There is no screen at the bottom.
• 04:19The little that looks like a.
• 04:22Yep, that right there OK?
• 04:25So I'll use this to advance Sharon, OK?
• 04:29OK, so you can still hear me everybody.
• 04:35Yes yeah, thank you.
• 04:36OK, so let let me now really focus
• 04:39on the on the major elements I was
• 04:41invited to opine about by Michael and
• 04:43Mario and Jim and before we move to
• 04:46the future of academic hepatology,
• 04:47I think it's worth reviewing the past,
• 04:50much of which has been highlighted
• 04:52by the previous speakers.
• 04:53There are tremendous organizational
• 04:55successes. And remember,
• 04:56I started in the field as a fellow in 1982,
• 05:00and so I've been blessed to
• 05:02see many of the developments,
• 05:04both academic, organizational,
• 05:05and scientific that have already
• 05:07been highlighted by others.
• 05:09But the field or the world of academic
• 05:12hepatology is a is a great success story,
• 05:15both in terms of government and foundations.
• 05:18I think collectively the field
• 05:20established during this period.
• 05:21Hepatology is a discrete discipline
• 05:23based on the initial leadership of
• 05:26Jerry Klatskin as well as Hans Popper,
• 05:28Fenton Schaffner and many others.
• 05:30The emergence of N IDK digestive
• 05:32disease centers and research networks,
• 05:35some of which you heard about from
• 05:37Jay Hoofnagle just a moment ago.
• 05:38The growth of foundations of many types
• 05:41supporting patients and research in
• 05:43really advancing both visibility and
• 05:45progress and liver disease and more
• 05:48recently the development or establishment
• 05:50of a liver focused study section.
• 05:52HBP that at least allow the
• 05:54appropriate level of expertise to be
• 05:57reviewing grants and liver disease.
• 05:59On the organizational side of
• 06:02the professional association,
• 06:04path has exploded with growth
• 06:06of professional organizations.
• 06:08Of those who see listed here,
• 06:09exceptional quality peer
• 06:11reviewed publication.
• 06:12Very strong representation
• 06:14of women already ASO's.
• 06:1640% of the members are women.
• 06:1850% of committee members.
• 06:2055% of the current governing board
• 06:23and increasing outreach to patients
• 06:25in underserved communities as well as
• 06:27international consortium partnering.
• 06:29I've also characterized.
• 06:30Some of these facets of growth.
• 06:33Don't want advancing,
• 06:34so we're going to pull them up for you.
• 06:36OK, Madison's gonna pull them up for you.
• 06:38OK.
• 06:41Just let her know which slide.
• 06:43Once she pulls it up, OK.
• 06:47Yeah, they were advancing
• 06:47on mine, so I apologize.
• 06:48I'm not sure what the problem is.
• 06:50I'm in Chrome. I please advance ahead.
• 07:23OK, great, so I'll pick up from here.
• 07:25Apologies again.
• 07:26I'm not sure what the problem was,
• 07:27but we'll forge on. So, as I noted,
• 07:30I've been in the business for 40 years.
• 07:33I think you heard a little
• 07:34bit about this earlier,
• 07:35but I think Jim reviewed some of this.
• 07:38Basically, when I was a fellow we had,
• 07:40in my view, for treatments and
• 07:42plus maybe cholestyramine,
• 07:43Lasix, Lactulose, aldactone,
• 07:45and Prednisone the best we had
• 07:47was an HBV vaccine was imminent.
• 07:49In fact, I was vaccinated
• 07:51and during the end of my.
• 07:52First year as a fellow next please.
• 07:58Look at 2022 next.
• 08:01Curative HCV treatment.
• 08:03Suppressive hepatitis B&D treatments.
• 08:05Liver transplantation and I'll
• 08:07return to that in a minute.
• 08:09Gene therapies, some of which
• 08:11are being approved as we speak,
• 08:13refined immunosuppressives
• 08:14for immune liver disease.
• 08:16Go ahead FXR agonist approved for
• 08:19at PBC and being tested in Nash.
• 08:22And medical and immunological
• 08:24therapies for liver cancer.
• 08:26So an extraordinary breadth
• 08:27of of progress in a single
• 08:29career and single interval,
• 08:31and Yale has been at the
• 08:33forefront of virtually all
• 08:34of these these areas next.
• 08:40So let's look to the future.
• 08:42If we think about academic
• 08:43hepatology in the future,
• 08:44there are really two elements next.
• 08:471st is the scientific future
• 08:49which based on the trajectory of
• 08:51progress till now I think is a
• 08:53very bright and sunny outlook.
• 08:54On the other hand,
• 08:56next the organizational future I
• 08:58believe continues to have storm clouds,
• 09:00not because of scientific reasons
• 09:02but because of uncertainty and
• 09:05inconsistency and how hepatology
• 09:07is organized within departments
• 09:09and divisions and how their
• 09:11important work is supported next.
• 09:14So let me first start with the good news,
• 09:16the scientific future next.
• 09:20It's, I think almost axiomatic to
• 09:22remind us that hepatology really
• 09:24lies at the crossroad of science.
• 09:26That's the Times Square.
• 09:27If you will of of medicine.
• 09:29In my view, all of these major biologic
• 09:33advances and biologic movements,
• 09:36shall we say are really hard
• 09:38at the heart of liver disease,
• 09:40pathobiology and the homeostasis
• 09:42in particular, regeneration,
• 09:44which still remains quite mysterious,
• 09:47but of course holds the key to.
• 09:50A lot of progress, I'm sure next
• 09:53and without going into much detail,
• 09:54I think as much as we can expand our
• 09:57minds to think about the future,
• 09:58I don't.
• 09:59I believe we we can't even
• 10:01accurately predict all the ways
• 10:03the these fields will advance and
• 10:05intersect and ultimately improve
• 10:07the lives of our patients next.
• 10:12So next.
• 10:15In terms of the some of
• 10:17the specific successes,
• 10:18I want to highlight a couple of areas.
• 10:19One is diagnostics next.
• 10:22There's pathology and
• 10:24increasing reliance on AI.
• 10:25Artificial intelligence
• 10:27driven biopsy analysis next.
• 10:30There are noninvasive diagnostics
• 10:31and I'm going to highlight one in
• 10:33particular in the subsequent slide,
• 10:34but there are imaging advances,
• 10:36proteolytic profiling
• 10:37and function tests next.
• 10:41And let me highlight for you one
• 10:43of those advances that illustrates
• 10:45how engineering is converging
• 10:47on liver disease diagnostics.
• 10:48This is a an evolving but not yet
• 10:51approved diagnostic Full disclosure.
• 10:53I consult for the company.
• 10:54Their name is Glympse bio.
• 10:56I'm fascinated by their technology
• 10:58because what they effectively do
• 11:00is create a series of mass barcoded
• 11:03protease substrates hooked to a peg
• 11:05carrier and administered to the patient.
• 11:07And as those substrates are cleaved by
• 11:09specific enzymes in the liver they generate.
• 11:12Mass in mass bar code that mass bar coded
• 11:16peptides that can be assessed by mass
• 11:19spectrometry to yield a signature next.
• 11:22And so in that way one can look next.
• 11:25One can look to correlate specific
• 11:28RNA expression with the activity
• 11:31of the proteases that encode them.
• 11:34Or is that are encoded by them and at
• 11:36least in one phase in phase two study?
• 11:39This looks like a very promising technique.
• 11:41I'm not showing this really so much
• 11:44to highlight this technology as much
• 11:46to under score the convergence of new
• 11:49technologies that are really driven
• 11:51by bioengineers as in this case that
• 11:53will certainly look to the liver
• 11:55for insights and applications next.
• 11:59Next in terms of treatments,
• 12:03a whole list of emerging therapies next.
• 12:06Nash therapies, which I'll review shortly,
• 12:08and a fibrotic S for parenchymal and
• 12:11biliary fibrosis gene therapies for Nash.
• 12:14Next,
• 12:14regenerative medicine is in forms
• 12:16that we can't even envision.
• 12:19I'm going to talk a little bit more
• 12:21about car T therapy and Nash therapies next.
• 12:24And of course,
• 12:25Geno Transplantation,
• 12:26which I will have a few words to
• 12:28say about next please.
• 12:32So without going into much detail,
• 12:34this shows the vibrancy of
• 12:36the the therapeutic space.
• 12:37For non alcoholic steatohepatitis
• 12:39these are the targets that are
• 12:41represented by different therapies
• 12:42and approaches that are currently
• 12:44in phase two or phase three trials.
• 12:47They can include efforts to reduce liver fat,
• 12:49improve insulin resistance,
• 12:51treat inflammation,
• 12:53improve the oxidant state of and
• 12:55health of the hepatocyte as well
• 12:57as direct acting antibiotics.
• 12:58So look at all these therapies and
• 13:00appreciate these are all born on the back.
• 13:02Or on the the hard work of basic and
• 13:05translational science that is already
• 13:06now translating into enormous potential
• 13:08for patients with this disease.
• 13:10Next, and in particular,
• 13:12currently there are at least as
• 13:15of a little over a year ago there
• 13:17were 73 drugs in phase two and
• 13:20nine drugs in phase three.
• 13:21For Nash, none have been approved yet,
• 13:24but I'm not at all daunted by this.
• 13:25I think we're closing in on the key
• 13:28pathways that drive Nash and the
• 13:30prospects long term for for therapies.
• 13:33For this disease and other
• 13:35fibrotic disorders is extremely
• 13:36price right next please.
• 13:40Let's let's skip this slide, please.
• 13:48Next slide. So let me talk a
• 13:52little bit about a novel therapy
• 13:54that is utilizing car T cells,
• 13:56which is chimeric antigen receptor T
• 13:58cells and focus in particular next on
• 14:01the role of the senescent stellate cell.
• 14:04So what you're looking at here is
• 14:06a template that we created many
• 14:08years ago that has provided a great.
• 14:10I would say insight into how the
• 14:13hepatic stellate cell generates scar.
• 14:15The cells are activated from injury signals
• 14:18from hepatocytes primarily or from calandria.
• 14:21Sides in the case of biliary disease,
• 14:23and it leads to a perpetuation phase that is
• 14:26comprised of several phenotypic changes that,
• 14:28collectively I would say,
• 14:30conspire to make scar next, please.
• 14:33Now what we've learned over the last few
• 14:36years is that Stella cells can disappear,
• 14:38and they can also regress
• 14:40so they can deactivate,
• 14:42and they can undergo apoptosis.
• 14:44And in particular,
• 14:45more recent studies show that they can
• 14:48also transition to a senescent phenotype
• 14:50that is thought to be especially pro.
• 14:52Inflammatory and pro fibrotic and
• 14:54so others have thought have sought
• 14:57therapies to deplete these pro fibrotic.
• 15:00So, in essence,
• 15:01cells let me show you one approach that
• 15:02we've been peripherally involved with.
• 15:04Next please.
• 15:06So this is a study that was really
• 15:09developed and pioneered by the lab of Scott.
• 15:13Lowe had a peripheral role,
• 15:15but it was really his and Michelle
• 15:17sidelines efforts that generated a
• 15:19totally new approach to treating
• 15:21liver disease and what they did
• 15:23is they generated specific car
• 15:24chimeric antigen receptor T cells by
• 15:27identifying a receptor on stellate
• 15:29cells that you par receptor.
• 15:31That seems to characterize only
• 15:33the senescence stellate cells and
• 15:35these accumulate and create a pro.
• 15:36Inflammatory pro fibrotic environment
• 15:38so they showed in this animal model
• 15:40either CL4 or also a Nash model
• 15:42that if they induce the disease and
• 15:44then at six weeks they administer
• 15:46these U PAR directed car T cells
• 15:48that had a dramatic impact.
• 15:50What you can see on the different
• 15:52boxes on the right is that the Sirius
• 15:55red staining in the untreated was
• 15:57dramatically reduced when the stellate
• 16:00cells senescent cells were depleted,
• 16:02as was the beta gal staining which
• 16:05is a marker of senescence next.
• 16:07And that's correlated with these
• 16:10quantitative readouts of decreased fibrotic
• 16:12area and decreased beta gall expression.
• 16:15Now,
• 16:15what was probably more exciting to me
• 16:18is the last bar graph you see there,
• 16:21where in fact there was an almost doubling
• 16:23of the serum album of these animals,
• 16:25which speaks to a relationship we
• 16:27don't really understand well about.
• 16:29The connection between more
• 16:31fibrosis and less regeneration,
• 16:33or conversely when fibrosis goes down,
• 16:35regeneration and liver function
• 16:36may improve and so that.
• 16:38Represents an incredibly important
• 16:40future area of investigation that
• 16:43hopefully others will return to next.
• 16:48So this car T cell approach has
• 16:51also been utilized by a lab run
• 16:54by Jonathan Epstein at Penn.
• 16:56Interestingly, for those who were
• 16:58connected to the Harvard Medical Complex,
• 17:01Jonathan's dad was Frank Epstein.
• 17:04He happened to be my chair
• 17:05at the Beth Israel,
• 17:06and it was an iconic renal scientist,
• 17:08and Jonathan is an equally
• 17:11extraordinary cardiology scientist,
• 17:13and let me summarize this paper,
• 17:15which really represents a new approach,
• 17:17not necessarily for liver fibrosis yet,
• 17:19but certainly applicable there next.
• 17:22And what Jonathan did is.
• 17:25What he Jonathan did is he worked with
• 17:28the M RNA vaccine experts at Penn,
• 17:31and rather than administer the car T
• 17:34cells following transduction ex vivo.
• 17:35What he and his collaborators did is
• 17:38they created lipid nanoparticles not
• 17:40unlike the Moderna and Pfizer vaccines
• 17:43in which this was a administered to
• 17:46animals with cardiac fibrosis and the
• 17:49lipid nanoparticles effectively program
• 17:51T cells to make and car cells in vivo.
• 17:55The CARS T cells were directed to a
• 17:57protein called the FIBROBLASTIC activation
• 18:00peptide and it cleared fibrosis.
• 18:02As you see in the third panel of
• 18:04the fibrotic heart on the right,
• 18:05so we're into a whole new world now where
• 18:08in vivo Carty therapies may be useful,
• 18:11using lipid nanoparticles,
• 18:12which are of course very safe
• 18:14and well tested in the COVID
• 18:16vaccines to deplete specific cells,
• 18:17whether they're pro fibrotic or others.
• 18:19So stay tuned to this area of growth,
• 18:22it could impact not only fibrotic
• 18:24diseases but other diseases.
• 18:25Where there are specific clones of
• 18:27cells that are disease causing next.
• 18:32Next and let's skip this slide
• 18:35and the next one. I apologize.
• 18:37I had added these slides after I sent
• 18:40them on to you folks at the let's
• 18:43clear this great next slide. Good.
• 18:46So what about xenotransplantation?
• 18:50We heard about this incredible advance
• 18:54with a Pickard transplanted into an
• 18:56American man at University of Maryland.
• 18:58Only about six weeks ago.
• 19:00Interestingly, it was highlighted not
• 19:02only in this journal artificial organs.
• 19:04But literally there is a journal
• 19:06called Pig Progress.
• 19:07And of course it's interesting
• 19:09to the pig industry as well,
• 19:10but more in the mainstream.
• 19:12Next, the New York Times
• 19:13highlighted this as well next.
• 19:17And and highlighting the man received the
• 19:20heart from a genetically altered pig. So I,
• 19:23without getting into much of the science,
• 19:26remember that the the scientific basis
• 19:28of this is to use CRISPR technologies
• 19:31to effectively delete any genes that
• 19:35could drive immuno intolerance and
• 19:39could also lead to transmission of
• 19:42any pig endogenous retroviruses.
• 19:44So with the advent of CRISPR.
• 19:47Technology comes the prospect
• 19:49of actually humanizing a pig not
• 19:51only to be used for heart,
• 19:53but of course for liver as well,
• 19:54and that hasn't been described yet,
• 19:56but I believe it represents
• 19:58a potentially transformative
• 20:00technology that could change our,
• 20:02translational and clinical
• 20:03world at hepatology.
• 20:05Next, please.
• 20:05So what are the what would the impact
• 20:08of liver transplantation be next?
• 20:11First of all,
• 20:11lives would be saved for patients
• 20:13dying of end stage liver disease
• 20:14because it would in principle
• 20:16no longer be a supply shortage,
• 20:17which of course limits access
• 20:20to transplant the next.
• 20:22It would also present major ethical
• 20:24challenges around liver transplant candidacy.
• 20:27Does everybody who have advanced liver
• 20:29disease of any cause at any institution
• 20:32equally qualify because it would,
• 20:36potentially,
• 20:36you know,
• 20:37expand enormously the availability
• 20:39of donor organs.
• 20:41And that in turn next could have a
• 20:44major impact on how hepatologists
• 20:46and liver transplant surgeons
• 20:49interact next and could also have
• 20:51significant economic implications.
• 20:53And I can't really predict whether it would
• 20:55actually decrease or increase the cost.
• 20:57One could argue it could decrease
• 20:59the cost by transplanting patients
• 21:01before they have or require
• 21:03highly intensive care and lengthy
• 21:05postoperative stays in the hospital.
• 21:07On the other hand,
• 21:08the number of transplants could
• 21:09go up so precipitously that that.
• 21:11And impose a disproportionate
• 21:13burden on the health care costs for
• 21:16patients with liver disease next.
• 21:19Of course,
• 21:19it also is bad news for pigs next and
• 21:22in one of my favorite pseudo journals,
• 21:24The Onion I share with you this
• 21:28euphemistic headline that pig
• 21:30dies waiting for transplanted
• 21:31heart given to human.
• 21:33So there will be implications
• 21:35both for man and pig next.
• 21:39So let's look at the storm clouds,
• 21:42or at least the Gray clouds that I
• 21:44believe continue to hover over academic
• 21:46hepatology and some of the challenges,
• 21:48and maybe some of the solutions next.
• 21:52So first, let's think about funding.
• 21:55The NDK is a spectacular success story.
• 21:58Jay Hoofnagle highlighted that beautifully
• 21:59in this talk just a few minutes ago next,
• 22:02and you can open this whole slide, please.
• 22:06Right there, great.
• 22:07So if if we compare for example the National
• 22:09Cancer Institute and IDK and this is
• 22:12some back of the envelope calculations,
• 22:14the prevalence of cancer 18 and a
• 22:17half million which includes mostly
• 22:19survivors and new cases.
• 22:21The prevalence of liver disease
• 22:23around four and a half million
• 22:24mortality you see listed here,
• 22:26but if we effectively take the
• 22:28total funding for cancer AT10CI and
• 22:30normalize that per number of patients,
• 22:34the eighteen 5,000,000 and do the same
• 22:36calculation for liver disease patients,
• 22:38my calculation is that patients with
• 22:40cancer have on average almost twice
• 22:42the funding per patient of research
• 22:45dollars as those with liver disease.
• 22:47And so this really represents an inequity.
• 22:50And I think we all understand what the.
• 22:51Challenges are in public awareness
• 22:54and public perceptions around liver
• 22:56disease and liver disease research next.
• 22:59Another way to look at it in terms
• 23:02of NIH support is through the support
• 23:05of different centers and so the NCI
• 23:08has 71 designated cancer centers.
• 23:10There are broken down as you see here.
• 23:12Next,
• 23:13the NI AAA has 23 centers of three
• 23:15of which are directed to alcohol,
• 23:18associated liver disease.
• 23:19And as we know next.
• 23:23The and I the NDK supports 3 centers.
• 23:26Yale, of course being the premier center.
• 23:29But again, to my view,
• 23:32an inequity in terms of recognizing the
• 23:34unmet need and of course the return
• 23:37on investment that these centers
• 23:39and other one funded investigators
• 23:41yield for liver disease research and
• 23:44progress in the field and ultimately
• 23:46improve treatments for patients.
• 23:47Next slide please.
• 23:50So where are we currently in terms of how
• 23:53academic hepatology fits within the universe,
• 23:56or of an academic center?
• 23:58Almost all liver programs are within GI
• 24:00divisions with three to four exceptions.
• 24:02We at Mount Sinai, one of them.
• 24:04Traditionally,
• 24:04since our founding in the 1960s.
• 24:08The challenge is that hospitals
• 24:09and health systems reward clinical
• 24:11productivity and revenues,
• 24:12particularly transplant more
• 24:14than academic success, and so,
• 24:16as a result,
• 24:17freestanding liver divisions like
• 24:18ours really have a hard time
• 24:20generating a positive revenue
• 24:21stream based on their RV's.
• 24:23Since we don't have any support at
• 24:25all from the transplant program,
• 24:27and these competing incentives
• 24:28have led to next several features,
• 24:31but I like to summarize it as the
• 24:34clinical tail wagging the academic dog,
• 24:37of course.
• 24:37This is different than every center
• 24:39and I may sound a little bit cynical,
• 24:41cynical based on my own experience,
• 24:43but it is challenging to get the
• 24:45attention of healthcare systems and
• 24:47hospitals when transplant is such an
• 24:49extraordinary resource in terms of
• 24:52revenues and and the need for resources next.
• 24:56So what is the solution?
• 24:58You can open this please.
• 24:59We need to align incentives between
• 25:02academic hepatology and transplant
• 25:04and create win win situations
• 25:06with shared success.
• 25:07I think we need to recognize the
• 25:09unique value value of academic
• 25:11hepatology as a source of creativity,
• 25:13knowledge and talent.
• 25:14We need to acknowledge the downstream
• 25:16positive financial impact of caring
• 25:18for patients with liver disease.
• 25:20Of course,
• 25:21improve awareness and funding of
• 25:23liver disease and engage the public
• 25:25something that the ASLD has really
• 25:27started to focus on tremendously,
• 25:29and I do believe that successful
• 25:31begets success.
• 25:31Meaning as more liver disease
• 25:33treatments emerge,
• 25:34we need to leverage these successes
• 25:36to highlight the return on
• 25:37investment by the public academic
• 25:39medical centers and founders next.
• 25:43So if I look to the future,
• 25:46I think on the scientific side
• 25:48we all agree that there will be
• 25:50unparalleled scientific success that
• 25:52will translate into new diagnostics and
• 25:54treatments to improve and save lives.
• 25:56And some of the obvious places where
• 25:59growth and success are most imminent
• 26:01include liver regeneration therapies,
• 26:03of which there are some in clinical trials,
• 26:05antibiotics and gene therapies,
• 26:07and treatment of monogenic and even
• 26:09complex genetic diseases that include
• 26:12Nash better cancer treatments.
• 26:13For primary liver cancer and
• 26:16cholangiocarcinoma, and of course,
• 26:17the prospect of revolutionary
• 26:19advances in transplantation and
• 26:21in particular xenotransplantation
• 26:23on the organizational style.
• 26:24A side I think we still face challenges
• 26:27within academic medical Centers
• 26:28for the discipline to find a model
• 26:31with stable financial footing that
• 26:32really recognizes the unique and
• 26:35deep contribution of hepatology to
• 26:37the success of an academic center,
• 26:40I think Mario Strasser Bosco showed
• 26:42how important the Yale liver.
• 26:44Center has been as a effectively a
• 26:46nucleating entity that has pulled in
• 26:49and generated success from departments
• 26:51all around the Yale Medical School,
• 26:54and so we need to recognize this,
• 26:55and of course rewarded as best we can to
• 26:58enhance progress and create synergies.
• 27:00Next,
• 27:01please.
• 27:02So if we look to the past or we
• 27:04look to the future,
• 27:05Yale Liver Center has been there
• 27:07both the past accomplishments that
• 27:09I and so many of the speakers have
• 27:12highlighted and the future successes
• 27:13that we surely can anticipate will
• 27:15be linked to the success of the
• 27:17Yale Liver program and importantly,
• 27:19the Yale Liver Center next.
• 27:21And so I want to close by acknowledging
• 27:24and congratulating the Yale liver program
• 27:26for their 75 years of leadership and success.
• 27:29It's one of the extraordinary
• 27:31success stories.
• 27:32In my career, I'm deeply honored to
• 27:34be involved as a member of the ABA,
• 27:37and especially honored as well to be
• 27:39included in this program this morning.
• 27:41So with that, I'll close and
• 27:42thank you all for your attention.
• 27:44Thanks very much Doctor Friedman and justice.
• 27:47Short comment.
• 27:48From Jim Boyle,
• 27:50who says he remembers your
• 27:51presentation as a fellow to the
• 27:52Advisory Board like it was yesterday,
• 27:54and he thanks for for your
• 27:56support of the saddle.
• 27:58So thank you very much for a great talk.
• 28:00OK, my pleasure.