The Unmet Clinical Needs with Norah Terrault

Transcript

• 00:15Welcome back after this session,
• 00:17we'll take a break for lunch.
• 00:19Please feel free to watch the
• 00:20prerecorded videos under the thank
• 00:22You Video tab or connect with other
• 00:24attendees using the attendee tab tab.
• 00:26This session is being recorded. Thank you.
• 00:33Hi everyone, it's my distinct pleasure
• 00:36to welcome Doctor Nora Toro who
• 00:38is going to be our next speaker.
• 00:40She's professor of medicine and chief
• 00:42of the division of GI and Liver and the
• 00:45NEO capitalist chair in liver disease
• 00:47at Keck School of Medicine at USC.
• 00:50Doctor thorough, please go ahead.
• 00:53Wonderful, well I want to first
• 00:54of all thank the organizers for
• 00:56this very very kind of itation.
• 00:58I'm excited to be here.
• 01:00And I'm hoping that you can see my screen.
• 01:06Hang on one SEC.
• 01:10OK, great all right.
• 01:12Can you all see my screen?
• 01:14I'll put it up on the big screen, OK?
• 01:17Right, so first of all,
• 01:18thank you and I really enjoyed
• 01:20listening to the talks before me.
• 01:22You're going to see that as I give you
• 01:24my view as a clinician here on the unmet
• 01:28clinical needs that there's a lot of
• 01:30a lot of what was presented already.
• 01:32Sort of speaks to already understanding
• 01:35these clinical needs and and
• 01:36carving a path forward in terms
• 01:38of research to address them.
• 01:40But I definitely put on my my clinician
• 01:43hat here to put together this talk for
• 01:46you and I'm going to start by just.
• 01:48Focusing on really the disease burden of
• 01:51the future and shown here in this study
• 01:54that was actually done out of Ontario,
• 01:56Canada using a provincial
• 01:58database but very much,
• 02:00I think mirrors what we're seeing
• 02:02here in the United States and often in
• 02:04other countries and what they did in
• 02:06this study was they looked at incident
• 02:09rates of cirrhosis by etiology,
• 02:12using a validated algorithm for
• 02:14identifying new cases of cirrhosis.
• 02:16And they looked at observed data
• 02:19from 20 to 2017.
• 02:20And then use that to project what the
• 02:22liver disease burden in the future
• 02:24is going to be and not a surprise
• 02:26to anyone in in this conference,
• 02:28is the overall incidence of
• 02:30cirrhosis is on the rise.
• 02:33And most impressively non-alcoholic
• 02:35fatty liver disease really
• 02:37is dominating the picture,
• 02:39as we can see as we move
• 02:41on more towards 2040,
• 02:42and they projected in the study that
• 02:45if we look towards 2040 police,
• 02:4875% of the liver disease.
• 02:51Burden in terms of incidence,
• 02:52cirrhosis is going to be from non
• 02:56alcoholic fatty liver disease and
• 02:57if we look at non alcoholic and
• 03:00alcohol associated liver disease,
• 03:01over 90% of liver disease burden,
• 03:04this is related to cirrhosis is
• 03:05really what we're going to be
• 03:07facing in 2040 that really served
• 03:09as a strong backdrop to what I'm
• 03:11going to be presenting today,
• 03:13which you'll see is quite focused
• 03:15on these two disease entities
• 03:17where the clinical needs are in
• 03:19terms of patients with NAFLD.
• 03:21And those with alcohol associated
• 03:24liver disease.
• 03:25So I'm going to start with Nash
• 03:27and what I'm going to try to do is
• 03:30just highlight which in the sort of
• 03:33day-to-day working of a hepatologist
• 03:35the things that are challenging for us,
• 03:37and I think the first is really
• 03:39managing the high disease burden.
• 03:41We projected that one out of
• 03:43every four patients has snaffled.
• 03:45There's clearly not enough hepatologists
• 03:46in the world to see all of these patients,
• 03:48so on we know that we have to triage
• 03:51towards seeing those that have the
• 03:53more advanced stages of fibrosis.
• 03:55For liver related complications,
• 03:56there's been some work done on terms
• 03:59of defining algorithms that can be
• 04:01applied in primary care to help triage
• 04:04those that go towards hepatology.
• 04:05I'm just showing you one very
• 04:08more recent paper that
• 04:11just used A-fib four and.
• 04:13Enhanced liver fibrosis or elf,
• 04:15in order to triage patients towards
• 04:18hepatology and you can see in the
• 04:20figure on the right that it successfully
• 04:23reduced the number of of unnecessary
• 04:26referrals from 92% down to 70.
• 04:27But I would argue that 70 is still
• 04:30a pretty big number in terms of
• 04:32inappropriate referrals and so clearly
• 04:34these kinds of algorithms which are
• 04:37really very fundamental to how we're
• 04:38going to be dealing with disease burden,
• 04:40remain to be optimized.
• 04:44And then the second thing has
• 04:46been highlighted by other talks.
• 04:48Is that clearly NAFLD is a
• 04:51very heterogeneous disease,
• 04:52we we lump it all under one umbrella.
• 04:55But we understand that within the Group
• 04:58of individuals who have NAFLD or Nash,
• 05:01that they they differ in terms
• 05:03of their metabolic risk factors,
• 05:04their genetic polymorphisms,
• 05:06whether they use alcohol and other factors.
• 05:10And even though we're we end up
• 05:11at the same place with Nash and
• 05:13fibrosis being the entity of greatest.
• 05:15Concern we understand that this
• 05:17is a very heterogeneous patient
• 05:19population and I think not refining
• 05:21our phenotyping of patients has
• 05:23actually contributed to some of the
• 05:25challenges we have in terms of both
• 05:27drug development and clinical care.
• 05:29So if you look on the left where
• 05:31I see us today,
• 05:32as we have all the individuals that
• 05:35meet a histological definition,
• 05:36for example of of Nash with significant
• 05:40activity and or fibrosis that
• 05:42we're targeting for interventions.
• 05:44And yet we know that.
• 05:46In the future,
• 05:46we really are going to have different groups.
• 05:48They're going to need a different
• 05:50kind of treatment,
• 05:50and I think there's a lot of interest
• 05:53and and work being done around
• 05:55doing both molecular and genetic
• 05:57genomic profiling of patients with
• 05:59NAFLD so we can actually get to
• 06:01that more refined phenotyping.
• 06:03That's going to allow us to do better
• 06:06clinical care and clearly do, you know,
• 06:09better drug development as well.
• 06:11You are are very aware that there
• 06:12are are near over 100 compounds
• 06:14that are somewhere between phase one
• 06:16and phase three drug development.
• 06:18For Nash,
• 06:19but we're challenging that there again,
• 06:22this heterogeneity may undermine
• 06:24the ability of those drugs to
• 06:26demonstrate efficacy.
• 06:27So I think if we have this more
• 06:30refined phenotype,
• 06:30this is really a high clinical need.
• 06:32But one also,
• 06:33that's very important for the
• 06:34clinical drug development,
• 06:35where we would hope,
• 06:37then with this refinement to see
• 06:38improved drug efficacy,
• 06:40better biomarker performance,
• 06:41and ultimately to be able to
• 06:43translate those things that we're
• 06:45learning from clinical trials
• 06:46into the clinic with greater.
• 06:48Efficiency.
• 06:51And then the other aspect of Nash is that
• 06:53we're coming to understand that Nash,
• 06:55cirrhosis and Nash disease is unlike
• 07:00the chronic liver diseases that we've
• 07:02been dealing with predominantly
• 07:04over the past two decades,
• 07:05which were largely hepatitis C.
• 07:07So in the past, hepatitis C
• 07:09was the dominant disease,
• 07:10and we knew a lot about Natural
• 07:12History related to viral hepatitis,
• 07:13and a lot of our our understanding
• 07:15of how we intervene timing of
• 07:18interventions was really based on.
• 07:20A history that's related to viral hepatitis,
• 07:23but Nash is is not like that in the
• 07:25sense that it's a multi system,
• 07:27a metabolic disease,
• 07:28of which the liver is only one
• 07:30of the organs affected,
• 07:31and in particular the coexistence
• 07:33of vascular disease.
• 07:35I think makes it very interesting from
• 07:37the point of view of understanding if
• 07:39what we know about Natural History,
• 07:40especially as they move towards roses
• 07:43and its complications is going to
• 07:45be the same because vascular disease
• 07:47that's related to their underlying metabolic.
• 07:50Disease may alter the presentation or
• 07:52management of portal hypertension,
• 07:54and we are seeing clues and evidence of
• 07:55this in the studies that are coming forward,
• 07:58but I think this is an important
• 08:00clinical need that we want to know
• 08:02that the established interventions for
• 08:03cirrhosis that we've been utilizing
• 08:05for the last many decades that were
• 08:07done primarily in non Nash populations
• 08:10can now be applied equally to Nash
• 08:13patients or whether we need to refine
• 08:16our clinical management algorithms.
• 08:19So in terms of now,
• 08:20I think some of the key there's many,
• 08:21but the key unmet clinical needs would
• 08:25be to importantly have screening
• 08:27strategies that allow the appropriate
• 08:29patient to land in the hepatologist
• 08:31office and get the right kind of care.
• 08:33Clearly we need to be thinking about now.
• 08:35That sort of broadly and how
• 08:37we're doing prevention,
• 08:37but from the point of view
• 08:39of the hepatologist,
• 08:39that's an important aspect.
• 08:41I've highlighted this need to
• 08:42do improved phenotyping,
• 08:44so we really have not one diagnosis,
• 08:46but really a diagnosis,
• 08:48but it has characterized by very.
• 08:50Different types of patients that
• 08:52then get a very different type of
• 08:54intervention and management clinically,
• 08:56and then again that idea that we should
• 08:59think carefully about whether the
• 09:01interventions from non Nash populations
• 09:02can be applied to our Nash populations.
• 09:05I'm going to have a little bit more about
• 09:07Nash to say as I cover a few other areas,
• 09:09but I'll leave Nash for now and
• 09:10focus on the other major liver
• 09:12disease that we're going to be
• 09:14faced with in the next two decades,
• 09:16which we're already dealing with in
• 09:17a major way. And that is alcohol.
• 09:20So in this figure what I'm showing
• 09:23are the national vital statistics
• 09:26looking at deaths among individuals
• 09:28who have chronic liver disease.
• 09:30But looking at it by etiology,
• 09:33and this is based on ICD 9 codes from 2018,
• 09:36so a relatively contemporary
• 09:37snapshot of where we're at.
• 09:39And my point in showing you
• 09:41this slide was to
• 09:42emphasize that the striking thing about
• 09:45alcohol associated liver disease is that.
• 09:48It's associated with a very high mortality,
• 09:50so you can see that of those
• 09:52individuals who carried that chronic
• 09:54liver disease diagnosis in 2000,
• 09:55and 1882% of them died.
• 09:58This tells us two things.
• 10:00One is that and we know this
• 10:02from working in the clinic is
• 10:05that patients often present late.
• 10:06They present with advanced disease
• 10:08or the presenting with like severe
• 10:11alcohol associated hepatitis,
• 10:12so very severe disease with
• 10:15already associated high mortality.
• 10:17And so we're missing the
• 10:18opportunity to intervene.
• 10:19In a time where we might be able
• 10:21to reverse or prevent progression.
• 10:22So I think one of the major clinical
• 10:24needs in the realm of alcohol associated
• 10:27liver disease is to be able to
• 10:29identify disease at an earlier stage
• 10:31that we can take an opportunity then
• 10:33to to modulate that Natural History,
• 10:35and that means we both have to promote
• 10:37more screening for alcohol use disorder,
• 10:40which is the factor that sets them up
• 10:41for alcohol associated liver disease.
• 10:43But even among those who have AUD
• 10:45that were have appropriate screening
• 10:47strategies to identify those with.
• 10:49Ald before they get to these
• 10:53very advanced stages.
• 10:54And I,
• 10:55I think we we should also be aware
• 10:57that what the snapshot showed us
• 10:59in 2018 is is really not likely
• 11:01to be reflective of what we're
• 11:03going to see going forward,
• 11:05and one of the very striking things that
• 11:08occurred with the COVID-19 pandemic is
• 11:10the increase in alcohol consumption.
• 11:12That was well documented in
• 11:15epidemiological studies.
• 11:17We've seen really a spike in terms of
• 11:19the increase in alcohol use in 2019,
• 11:22more prominent younger.
• 11:24Individuals, women,
• 11:25minorities also affected and this
• 11:27study here is just to remind you
• 11:29of the impact of that one year
• 11:31increase in alcohol consumption.
• 11:33So this is a modeling study,
• 11:35but a very novel way of kind of helping
• 11:37us to understand the impact of COVID-19.
• 11:40So what they did is they modeled
• 11:42that the increase that we've
• 11:44seen in Elkins consumption.
• 11:45If it just happens for one year and then
• 11:47they go back to where they were before,
• 11:49that still would lead to an increase in the
• 11:52total number of alcohol related deaths.
• 11:53Decompensation.
• 11:54And HCC and and the longer that
• 11:57they're drinking at these higher
• 12:00levels the the greater the impact.
• 12:02So COVID-19 itself is now
• 12:05contributing more cases of alcohol,
• 12:07associated liver disease,
• 12:08and the consequences of that are
• 12:10is really this aftershock meaning.
• 12:12We're going to be dealing with
• 12:14it in the next two to three,
• 12:15next one to two decades.
• 12:17In terms of that in terms of impact.
• 12:22And then I I would be remiss in saying
• 12:24that I think one of the critical elements
• 12:27for alcohol associated liver diseases.
• 12:28We don't have a drugs to to treat
• 12:31it as a chronic liver disease.
• 12:33So as I always like to to compare it to to
• 12:37Nash or NAFLD where there are near as I said,
• 12:41over 100 compounds that are different
• 12:43phases of development for individuals who
• 12:45have chronic liver disease due to Nash.
• 12:48But I went to clinicaltrials.gov
• 12:50earlier this week.
• 12:51And looked up the drugs that are available
• 12:53for alcohol related liver disease,
• 12:55not alcoholic hepatitis,
• 12:56which actually has actually a
• 12:58sort of a recent surge in terms
• 13:00of new drug opportunities.
• 13:02But for those that have
• 13:04chronic liver disease from LD,
• 13:06really it's a very short list
• 13:07and most of them are nutritional
• 13:10type interventions and and part
• 13:11of this is because the evidence
• 13:14shows that if they're abstinence,
• 13:16that's really the intervention of choice.
• 13:18And I couldn't agree more.
• 13:19And definitely we all strive to achieve.
• 13:22It's an individual to have
• 13:23alcohol associated liver disease,
• 13:25but I think what in putting that as
• 13:27being the treatment I think it has
• 13:30somewhat diminished efforts to help
• 13:32these individuals in managing their
• 13:34chronic liver disease while they're
• 13:36striving to achieve abstinence.
• 13:37And I think the other thing is,
• 13:40given the burden of disease that
• 13:41hepatologists are dealing with,
• 13:43we have to acknowledge that we're
• 13:45not experts generally in treating
• 13:46alcohol use disorder,
• 13:48and perhaps we either have to
• 13:49partner with those who can do it
• 13:52or become more expert ourselves.
• 13:53And even drugs that help with treating
• 13:56alcohol use disorder have been not
• 13:57well studied in patients who actually
• 13:59have alcohol associated liver disease,
• 14:01especially those with more
• 14:04advanced liver disease.
• 14:05All of these things,
• 14:06I think,
• 14:07limit our ability as hepatologist
• 14:09to be able to help the patient with
• 14:11alcohol associated liver disease,
• 14:13enjoy sort of improvements in
• 14:15Natural History because we don't
• 14:18have drug therapies to offer,
• 14:20and we ourselves are not the
• 14:22experts in terms of helping to
• 14:25manage the underlying cause.
• 14:27And then a Massimo actually
• 14:29highlighted this already,
• 14:31and I just want to say that you know,
• 14:32we've all seen this rise also in alcohol,
• 14:35associated hepatitis,
• 14:36and the use of liver transplantation
• 14:38as a therapy therapy for those that
• 14:40have the severe form of alcohol,
• 14:42associated hepatitis.
• 14:44And again the effective COVID
• 14:47is played a role here.
• 14:49So this is a very nice study
• 14:51just looking at the relative
• 14:53absolute change in individuals
• 14:54with alcohol associated hepatitis.
• 14:56Were either waitlisted for liver
• 14:59transplantation in orange who
• 15:01underwent liver transplantation
• 15:02in black and you can see that
• 15:04since sort of a pandemic started,
• 15:06there's been a exponential rise,
• 15:09particularly in the number of
• 15:12liver transplants performed.
• 15:14412% relative increase reflecting
• 15:15as highlighted before both the
• 15:18effects of more harmful alcohol
• 15:20use during the pandemic,
• 15:21but it's not just that,
• 15:23it's also reflecting the fact
• 15:25that transplant programs have.
• 15:26Have increasingly considered this as an
• 15:29indication for liver transplantation,
• 15:31and indeed. You're all very aware that
• 15:33that in highly selected patients that
• 15:35excellent outcomes can be achieved with
• 15:38liver transplantation for this indication,
• 15:40but the clinical needs the challenges
• 15:42here relate to how we select the patients.
• 15:46There's a lack of uniform selection criteria,
• 15:49and there's still a lot of liver transplant
• 15:52and insurance insurer variability in terms
• 15:54of approvals for liver transplantation.
• 15:57For this indication, and as a consequence,
• 16:00this indication for liver transplantation
• 16:01is 1, in which there's great.
• 16:04Disparities across the United
• 16:06States and this.
• 16:07There's a high clinical need for us
• 16:09to eliminate the disparity in terms of
• 16:12access for those appropriate patients.
• 16:16So to summarize,
• 16:17the key unmet clinical needs in LD,
• 16:19I would say biomarkers for early detection
• 16:22of LD among those with alcohol use
• 16:25disorder is an area that I think warrants.
• 16:28Great attention so that we can
• 16:30pick them up at an earlier stage.
• 16:32Hot effective therapies for the
• 16:34disease itself to be done concurrent
• 16:36with alcohol use, disorder,
• 16:38treatment and achievement of abstinence.
• 16:40We need validated and uniformly applied
• 16:43selection criteria for ADHD in the liver
• 16:45transplant setting and one final point.
• 16:48I want to point out is that we're seeing
• 16:51that alcohol use is also prevalent
• 16:54among those that also have risk factors
• 16:56for metabolic fatty liver disease.
• 16:58And in the past,
• 16:59we've sort of separated them out
• 17:01as being mutually exclusive.
• 17:02We we know that that's not true,
• 17:04and here's just one study that I
• 17:06want to highlight where you have to
• 17:08acknowledge that this dual diagnosis
• 17:10has its own Natural History and
• 17:12we need to be aware of it,
• 17:14and it probably needs a different
• 17:15form of therapeutic intervention.
• 17:17Or or perhaps more aggressive intervention,
• 17:19the patient who has a single diagnosis.
• 17:21And here's a study in which they took
• 17:23individuals who had an underlying genette.
• 17:25They took individuals who
• 17:27chronically used alcohol.
• 17:28They looked at risk.
• 17:30Else for fatty liver disease,
• 17:32P and PL3 and others and then also
• 17:34look at whether they had diabetes as a
• 17:37metabolic risk and then looked at what was
• 17:39the likelihood that those individuals.
• 17:42Would be at risk for liver related
• 17:44complications and you could see in
• 17:46chronic alcohol users that have the risk
• 17:47alleles it was increased at least threefold,
• 17:49but if you add it in diabetes on
• 17:51top of that then the risk for that
• 17:54complication went up tenfold.
• 17:56So clearly dual diagnosis are not
• 17:58rare and more attention to this dual
• 18:00diagnosis in terms of understanding it
• 18:02and it is important to meet a clinical need,
• 18:05which is that we see these
• 18:07patients very often.
• 18:10So I I not going to ignore viral hepatitis,
• 18:14but it really is the success story
• 18:16here and somebody who's been very
• 18:18invested in this for most of my
• 18:20career I I just sometimes love to
• 18:23just focus on how much we've achieved
• 18:25with both hepatitis B and hepatitis C
• 18:28are antiviral therapies have allowed
• 18:30us to achieve really very impressive
• 18:33results over the last two decades
• 18:35where we have impacted survival,
• 18:37reduced the rates of cirrhosis.
• 18:39And liver cancer.
• 18:41I'm really and preventing many patients
• 18:43from the need for liver transplantation.
• 18:46And indeed, we have all the tools in
• 18:48our toolbox to eliminate these viruses
• 18:51globally on the identification side,
• 18:53as we have very broad indications
• 18:55for testing,
• 18:55we have simple and accurate tests to do so.
• 18:59On the prevention side,
• 19:00we have a vaccine for hepatitis B.
• 19:02You could argue that there's a
• 19:04clinical need for a hep C vaccine,
• 19:06but at least we have a lot of prevention
• 19:08activities around viral hepatitis.
• 19:10And of course therapeutics are
• 19:12safe and highly effective, but.
• 19:15You know this is still an example of where
• 19:19having all the tools doesn't necessarily
• 19:21mean you get to where you want to go,
• 19:23and it highlights the importance of the
• 19:26implementation sciences in allowing us
• 19:28to take what we learned from clinical
• 19:30research and from clinical trials,
• 19:32and then really enacting it to
• 19:34make big differences in terms
• 19:36of patients and public health.
• 19:37And this is a very recent estimation of
• 19:40how we're doing with hep C elimination,
• 19:43and it shows on the left.
• 19:46Is what we've achieved up and up
• 19:48in in 2015 and then on the right
• 19:51is the snapshot of where are we in
• 19:53in 2020 and what you can see is.
• 19:55While the overall number of prevalent
• 19:57cases has gone down from 64 to 60 million,
• 20:00there's still huge gaps in terms
• 20:03of many patients not yet being
• 20:05diagnosed in a very modest proportion
• 20:08that have been treated.
• 20:10So I would say there's a clinical need here,
• 20:12and the clinical need is not only
• 20:15globally but very very specifically.
• 20:17Of the United States,
• 20:18where what we need are models of
• 20:20care that allow us to both diagnose
• 20:22and deliver this highly effective
• 20:23therapy and the same cascade
• 20:25issue exists for hepatitis B.
• 20:27We know how to diagnose this.
• 20:28We have highly effective therapies,
• 20:30but still we are not always getting
• 20:31it to the patients that need it.
• 20:36And I think the the most interesting
• 20:38and and and put a pressing clinical
• 20:40need from from the point of view of
• 20:42where I think science still needs
• 20:43to come and help us out there.
• 20:45It's not just around implementation
• 20:47but really more work needs to be
• 20:50done is an understanding how to
• 20:51reduce the already low risk of cancer
• 20:54to even lower among individuals
• 20:55in whom they are virally treated.
• 20:58So for the patient who's has
• 21:00hepatitis C and achieved SVR but
• 21:02the patient who has hepatitis B and
• 21:04is fully suppressed on antiviral.
• 21:06Therapy.
• 21:06We know that in those scenarios the
• 21:08risk for liver cancer and generally has
• 21:11reduced about 70% with antiviral therapy.
• 21:14And yet there still remains enough
• 21:16risk that we have to continue
• 21:19surveillance in these patients lifelong.
• 21:21And So what?
• 21:22I think the clinical needs are,
• 21:24can we take these patients and get that
• 21:26risk even lower such that we could
• 21:29stop surveillance and along the way,
• 21:30can we come up with a better risk
• 21:32stratification so that we don't have
• 21:35to survey everyone that we have a?
• 21:37A group that maybe low enough
• 21:39already that we don't have to do so,
• 21:41but I think this is where I'm
• 21:42I'm excited about.
• 21:43The possibility,
• 21:44for example,
• 21:44to take a patient who's been cured of
• 21:47hepatitis C but who may have cirrhosis.
• 21:48Can we do antifibrotic therapies that
• 21:51might allow us to reverse the fibrosis
• 21:53so that we do eliminate race for HCC?
• 21:56Or can we change the Intrapac mill use such
• 21:59that it's a less prone to carcinogenesis?
• 22:02And in the case of hepatitis B,
• 22:03of course the Holy Grail is to
• 22:05really not only suppress virus,
• 22:07but to eliminate it by eliminating both
• 22:10CCC DNA and integrated forms of DNA.
• 22:14But I think this is a high clinical need.
• 22:16This would substantially take us sort of
• 22:18to the finish line with these individuals
• 22:20who have had hep C or have happy,
• 22:23but we want to get them to the point
• 22:25where HCC is no longer a risk for them.
• 22:29And while I'm on the subject of HCC,
• 22:32I think the other clinical challenge is
• 22:35is HCC surveillance in patients with Nash.
• 22:39And as you know,
• 22:42there's increasing evidence that Nash.
• 22:45Is one of the conditions in which we can
• 22:48see HCC in the absence of cirrhosis.
• 22:50Traditionally that's been reserved really
• 22:52for our thinking about hepatitis B patients,
• 22:55but we now understand that
• 22:56that's also true for Nash.
• 22:58There was a recent meta analysis that
• 23:00suggested that the prevalence of HCC and
• 23:03non cirrhotic Nash was 38% compared to
• 23:06other etiologies where it was only 14%.
• 23:09And even when we look at population based
• 23:11cohorts which is shown in the bottom,
• 23:13this is looking at a Swedish cohort and.
• 23:15That they looked at individual,
• 23:16histologically defined navile and
• 23:19then followed them prospectively.
• 23:21Patients that had fibrotic Nash
• 23:23but was noncirrhotic still.
• 23:25Had you know a 2 1/2 fold higher
• 23:28risk of getting HCC so all of this
• 23:30is to say is that I don't think it's
• 23:33a sporadic finding that this is real
• 23:35and I think we clinicians are chronic
• 23:37grappling with what do we do about this?
• 23:39There's no specific guidance yet
• 23:42around doing surveillance,
• 23:43but we recognize that this is sort
• 23:45of the coming tsunami.
• 23:47In terms of potential cases of ATC and
• 23:49so a high clinical need is in terms
• 23:53of identifying how we would best do
• 23:56surveillance among these patients.
• 23:58And then of course,
• 23:59I can't leave the the topic of surveillance
• 24:01without kind of circling back and saying,
• 24:04you know, again,
• 24:05you can have the tools you should.
• 24:06You can know who to screen,
• 24:07but yet you're implementation
• 24:09can let you down,
• 24:10and there's still so much
• 24:12work to be done in terms of
• 24:14implementation of HCC surveillance.
• 24:16And this is just one of many studies
• 24:18that have highlighted that simple things
• 24:19can make a difference in this case.
• 24:21What they did was they just used a
• 24:24simple mail reminder as an outreach
• 24:26mechanism to try to improve.
• 24:28For surveillance and you can see in
• 24:30the table that compared to usual care,
• 24:32they were able to increase the proportion
• 24:35of patients that were getting their
• 24:37semiannual surveillance from 30 up to 40%.
• 24:40But clearly 40% of individuals getting
• 24:43their annual surveillance is still
• 24:44far short of where we want to be,
• 24:46and I think we're very challenged in
• 24:49the realm of HCC of having surveillance
• 24:51that that depends upon implementation
• 24:54of radiology on a regular basis.
• 24:57So novel strategies to help us.
• 24:59These surveillance again further
• 25:01risk stratifications that we could
• 25:03maybe think about it in in a more
• 25:05select group of patients to be more
• 25:07intense than others is important.
• 25:09Clinical areas of need.
• 25:10So just to summarize the strategies
• 25:13to improve adherence are needed.
• 25:15The risk stratification might be
• 25:17particularly useful as we have more
• 25:19and more individuals that might need
• 25:21surveillance and thinking about.
• 25:22How do we use resource in resource
• 25:24constrained areas?
• 25:25How do we apply our surveillance
• 25:27to those most at
• 25:28risk and most likely to benefit?
• 25:30And then I think,
• 25:31very excitingly is the opportunity
• 25:33for novel biomarkers that may bail
• 25:35allow us to move away from imaging as
• 25:38a required element for surveillance,
• 25:40and perhaps just be a simple
• 25:42blood test that could be more
• 25:45easily repeated and where we would
• 25:47anticipate that surveillance in
• 25:49terms of HCC would be easier to to
• 25:52implement on a population basis.
• 25:57And then I just want to close
• 25:59with liver transplantation.
• 26:00I'm first and foremost a transplant
• 26:03hepatologist so you know to be part of
• 26:06a A to be part of a discipline that has
• 26:09transplantation available for those
• 26:11individuals in whom are therapeutic
• 26:13interventions have failed and now
• 26:14we have someone with complications
• 26:16that warrant a new liver is just
• 26:18great to be operating in a time where
• 26:20that is an available therapy and
• 26:22it's highly successful with you know
• 26:24one to five years survival rates.
• 26:26Which are excellent,
• 26:28but everybody here knows that the demand
• 26:30persistently is greater than supply.
• 26:32And when we look over,
• 26:34you know the last one you know
• 26:3710 to 20 years,
• 26:38while there's been a sort of steady increase
• 26:42in the number of transplants performed,
• 26:44there's been an equally steady
• 26:45rise in those that need them,
• 26:47and really over the last 20 years
• 26:49the number has been pretty static,
• 26:52that about 60% of waitlisted patients
• 26:54receive a liver transplant annually,
• 26:56and.
• 26:57The sad side side of this is that
• 27:00about 20% of them die annually
• 27:02because they get too sick to
• 27:04be offered a liver transplant.
• 27:06So I heard some very,
• 27:07you know you heard from prior speakers
• 27:09about really the exciting arenas here.
• 27:11No doubt this is high clinical.
• 27:13Need we need more organs and there
• 27:15are potentially many novel ways that
• 27:17are out there that are being looked
• 27:19at to to do so from bridge therapies
• 27:23to enhance ways of doing living
• 27:26donation met making better use of
• 27:29of the the organs of poor quality.
• 27:31Those that are stereotactic and
• 27:33then of course the very exciting
• 27:35areas of xenotransplantation.
• 27:36And and organoid transplantation.
• 27:41So I'm going to just close by saying
• 27:44that I've leaned pretty heavily here
• 27:46on on 2 diagnosis alcohol and and
• 27:49medic metabolic fatty liver disease,
• 27:51because these are going to be
• 27:53the diseases that dominate our
• 27:55landscape both in the outpatient and
• 27:57increasingly on the inpatient service.
• 27:59And I would highlight that both of
• 28:01them are currently diseases that
• 28:03don't have a liver specific therapy,
• 28:05and certainly for Nash,
• 28:06a very exciting and dynamic
• 28:08area for drug development.
• 28:09I would say that we would love to see that.
• 28:11Same thing happened for managing chronic
• 28:14alcohol associated liver disease.
• 28:16The other thing that's important
• 28:18about these two diseases is that we
• 28:20can't do it alone as hepatologist
• 28:21that these are both diseases in
• 28:23which multidisciplinary approaches
• 28:24are needed to optimize our outcomes,
• 28:27and so striving to provide a clinical
• 28:30care environment that can do so,
• 28:33I think, will yield important dividends.
• 28:36I've highlighted throughout my talk
• 28:38the importance of risk profiling or
• 28:40risk stratification as a way both to
• 28:42improve the way that we manage our patients.
• 28:44Clinically,
• 28:44it's going to be important for drug
• 28:46development and ultimately we all
• 28:48know that this will be the mechanism
• 28:50by which we're going to pave the way
• 28:51towards a more personalized form of medicine.
• 28:55I've also highlighted this,
• 28:57I think interesting concept of whether
• 28:59the Natural History of cirrhosis
• 29:01may need to be adjusted for Nash,
• 29:03since it's it's a sort of a unique
• 29:06disease and having both this more
• 29:10widespread metabolic complication profile.
• 29:13HCC clearly important.
• 29:14I could have really spent the entire
• 29:16talk talking about the clinical
• 29:17challenges around HCC but some exciting
• 29:19developments but we still have a lot
• 29:21more work to do in terms of first
• 29:24and foremost the surveillance viral
• 29:26hepatitis it it is the success story,
• 29:28but elimination is still quite a long
• 29:31way off so I'd say down but not out
• 29:34and then across my talk this morning
• 29:36I've I've highlighted that we can do
• 29:39great things in terms of our research,
• 29:42but ultimately.
• 29:42To to get the benefits we need good
• 29:45implementation science and I would say
• 29:47that that's true now more than ever.
• 29:50And with that I'd like to thank
• 29:51you for your attention.
• 29:52And again,
• 29:53congratulations Yale on your Jubilee and
• 29:56been really delighted to be part of it.
• 29:59Thanks very much Doctor.
• 30:00Thoreau,
• 30:00so a lot more to do still,
• 30:02but the future looks very bright so
• 30:05with that I would like to remind the
• 30:09audience that would join us again at 1:15.
• 30:13We now have a lunch break and you
• 30:15can join us by using the yield
• 30:17liver and world round table link.
• 30:18Which is on the all sessions page.
• 30:21And if you have time,
• 30:23please take a few minutes to watch
• 30:25your prerecorded videos under
• 30:26the thank You Video tab.
• 30:27And with that, we'll see you at at 1:15.
• 30:31Thanks very much.