The Open Questions with Massimo Colombo

Transcript

• 00:15Welcome back, this session is
• 00:17being recorded. Thank you.
• 00:27It's my pleasure to welcome our next
• 00:30speaker doctor Massimo Colombo.
• 00:32Who is head of the liver Center
• 00:33and general medicine at Saint
• 00:35Raphael Hospital in Milan,
• 00:36Italy and the Tadlow?
• 00:38This talk will be the open question.
• 00:40Doctor Colombo please go ahead.
• 00:42Thank you very much. Mr.
• 00:43Chairman Nadler chair.
• 00:45I would like to thank of course Doctor
• 00:48Michael Nathanson and Mario Strazza
• 00:51Busko for inviting me to be part of
• 00:54such a a terrific celebration of
• 00:57the 75 years of the Yale hepatology.
• 01:02I spent a couple of years in New
• 01:04York with Professor Hans Popper
• 01:06and to me in those years it was
• 01:08actually between 74 and 75.
• 01:11Professor Jar Casting was a myth
• 01:15completely that was often quoted
• 01:18during our leaving meeting,
• 01:20so it's a great honor to me.
• 01:22Be part of this celebration.
• 01:24Next line, please.
• 01:27And these are my conflicts next.
• 01:30I was asked the challenging task
• 01:32of discussing the open question,
• 01:35and in fact the selected 5 topics
• 01:37to discuss with you and the very
• 01:39first one an easy one in my opinion.
• 01:42A public health strategy for
• 01:44various petite is elimination.
• 01:46Next please.
• 01:51As you know, as you know,
• 01:52the World Health Organization in 2016
• 01:55through the World Health Assembly
• 01:57urge W join nation to cooperate in
• 02:00order to implement an articulate.
• 02:02The program of screening,
• 02:04prevention and treatment of various
• 02:06petitions with the aim of curbing
• 02:08delivered consequences of our appetites,
• 02:10including cancer liver cancer
• 02:12that were in at those times.
• 02:15There were approximately 5,000,000
• 02:17of people developing acute.
• 02:19That is the end of the year annually.
• 02:231.75 million of acute infection with the PC.
• 02:25Half of them PWD, which of course,
• 02:27poses challenges in terms
• 02:29of the risk of reinfection,
• 02:31and there was going to project that
• 02:34the tools slow down the rate of new
• 02:38infections down to 470,000 in 2030 and
• 02:43175,000 in 20-30 of appetite, etc.
• 02:45So 90% reduction through
• 02:48an articulated strategy of.
• 02:50Prevention and and therapy that was meant
• 02:53to lead a substantial reduction of mortality,
• 02:57including mortality caused
• 03:00by liver cancer next.
• 03:04Unfortunately, this goal,
• 03:05in my personal opinion,
• 03:07seems hard to reach out because of the huge
• 03:12burden of chronic carriers of hepatitis B&C,
• 03:16which is fueling the new
• 03:19cases of viral appetites,
• 03:22particularly located in those areas of
• 03:25the world where public health policies
• 03:28are lacking in those specific areas.
• 03:31In fact,
• 03:32the proportion of chronicle.
• 03:34Infected patients are very high
• 03:37compared to the Western area,
• 03:39and even more so challenging is the
• 03:42fact that only a tiny minority of
• 03:45the very few patients that have been
• 03:47diagnosed as carriers of appetite is B or C,
• 03:50are receiving appropriate antiviral
• 03:53therapy for hepatitis B or hepatitis C.
• 03:56This means that we are dealing with
• 03:59more than 250 millions of chronically
• 04:02infected hepatitis B carriers and 51.
• 04:05Offer hepatitis C which are a little
• 04:08bit less than those predicted in the
• 04:11very beginning of the program because
• 04:15following the introduction of DAA
• 04:18therapy but currently the target of 2030,
• 04:22elimination in the range of 90% reduction,
• 04:26diagnosis and 80% of treatment appears
• 04:30to me unlikely to be reached next,
• 04:33please.
• 04:34In fact,
• 04:35if you look at this map of the
• 04:40worldwide distribution of the policy.
• 04:44The activities,
• 04:46including the prevention of transmission,
• 04:50screening and treatment programs
• 04:52you see here,
• 04:53the red circles define those areas
• 04:58in which policy are in place,
• 05:01the data being collected.
• 05:03So we are aware exactly the burden
• 05:05prevention of transmission is in
• 05:07place and screening and treatment
• 05:09is being carried out and the red
• 05:12circles are mostly concentrated.
• 05:13In the resource rich areas of the world,
• 05:18whereas in most places in Asia and in Africa,
• 05:23they are significantly lacking,
• 05:25and these are exactly the regional
• 05:27where the burden of our appetite,
• 05:29this is so I it is not hard to
• 05:33me to predict that by 23rd 30
• 05:36the goal of our expertise,
• 05:39elimination or elimination of the new
• 05:41cases of acute have to be UFC would be an.
• 05:45Are the goal to reach next
• 05:47and on the top of this?
• 05:50It is a useless to remind us that the COVID
• 05:54pandemic has played a negative role.
• 05:57I'd like to present this paper,
• 06:00which is a little bit outdated
• 06:02compared to the very last one that
• 06:04have been published more recently,
• 06:05but that was interesting contribution
• 06:07because was based on a sub selecting
• 06:11individual for civil society
• 06:13organization and frontline and
• 06:15protected service providers have been
• 06:17interviewed in many parts of the world.
• 06:21Actually, 32 WHO regions can significant
• 06:24presence of the US regions that clearly
• 06:28demonstrate that in the context of
• 06:31apatite C elimination that has been
• 06:33reduced access of individuals to
• 06:36testing for a variety of reasons,
• 06:39including the fact that the testing
• 06:41facilities have been closed here
• 06:43and there and the lack of treatment
• 06:45access in many parts of the world,
• 06:47with people uncertain whether to.
• 06:51To to target or not treatment size.
• 06:54So pulling all this contributed to a
• 06:58further slowing down of the program
• 07:01of our procrastination and my comment
• 07:04on about this open question whether
• 07:07marketization would be reached by
• 07:102030 is that we definitely need
• 07:14more political will.
• 07:15The lack of political will is
• 07:18the main driver of Unsuccess.
• 07:21In this program, at least in my opinion next.
• 07:27The second topic I would love to
• 07:29discuss with you is that the evolving
• 07:32landscape of legal transplantation
• 07:33with the aim of reconceptualizing the
• 07:37criteria for listing next slide please.
• 07:42A couple of months ago there has
• 07:46been a very interesting and,
• 07:49in my opinion, timely meeting.
• 07:52Discussing the update of BCSC staging system.
• 07:56As you know, the BCSC staging
• 07:58system has been largely adopted
• 08:00by the Western liver societies,
• 08:03including easel and ASLD for
• 08:08staging patients with LEAP with
• 08:10primary liver cancer HCC actually.
• 08:13And guiding to the more appropriate
• 08:17treatment choice over the past year,
• 08:20there have been a tremendous step
• 08:23forward in the treatment of our
• 08:25appetites BC which led to refining
• 08:28the criteria for treating patients
• 08:30with early detected liver cancer
• 08:32with non transplant approaches,
• 08:35therefore limiting a little bit of the
• 08:37indication for liver transplantation.
• 08:40But such an indication for listing.
• 08:43Has been revitalized by the application
• 08:47of a new modalities for downstaging
• 08:51patients with the greater burden of liver.
• 08:56Restricted the agency C in the
• 09:00meaning that those patients with an
• 09:03intermediate stage of liver cancer
• 09:05that have been successfully now stage
• 09:08through days or radio and motivation
• 09:11are now more more often offer listed.
• 09:14The list of liver transplantation
• 09:16with a success which is comparable
• 09:18to patients who were as historically
• 09:20defined by Mazzaferro some 30 years ago
• 09:23listed on the basis of the Milan criteria,
• 09:26this.
• 09:26Has led obviously to a reshuffle of
• 09:29the listing criteria here and there.
• 09:32There are some areas,
• 09:34geographical areas in which many
• 09:37centers are reluctant to expand
• 09:40beyond Milan criteria,
• 09:42but I would say that there are other
• 09:44Centers for instance in the Far East.
• 09:45Next slides please where?
• 09:50Pushing the envelope.
• 09:51A liver transplantation is being
• 09:53offered also for advanced liver
• 09:56cancer like the better cellular
• 09:58castronova developing with portal
• 10:00vein Thrombosis Limited to the 1st
• 10:02and the 2nd degree portal vein,
• 10:06including of course those with
• 10:09thrombosis of the main trunk.
• 10:11Support that trunk and as you see
• 10:14here the overall survival rate
• 10:16are rather interest.
• 10:17Of course these are not ideal.
• 10:20But if you compare this with the
• 10:24classical reception approach,
• 10:26you would appreciate the.
• 10:29Go beyond the 50% survival at the Year 5.
• 10:34Possibly some of them at least,
• 10:36and they are possibly reaching out
• 10:39to the 50% survival at five years,
• 10:42which means that I could be
• 10:44considered a viable option.
• 10:46Obviously in my personal opinion
• 10:49this should be limited and restricted
• 10:53to trials could not be considered
• 10:57to be a viable option.
• 11:00For every day and the main reason
• 11:03is that we still are dealing
• 11:06with restricted availability of
• 11:09donor organs next light list.
• 11:13The second area I wish to touch
• 11:17regarding the evolving landscape of
• 11:20liver listing is alcohol and here
• 11:24we would enjoy the presence of Nora.
• 11:28Professor Nora, the road,
• 11:30who has contributed a lot to this.
• 11:32The pioneer was Phillip Maturana,
• 11:35who in 2011 published in New
• 11:38England at Peppa,
• 11:40where he was able to
• 11:42demonstrate that that listing.
• 11:44Through early transplantation,
• 11:47patients with a severe acute.
• 11:50Alcoholic appetite is not responding
• 11:53to steroid therapy resulted in a
• 11:56significant increase of survival
• 11:59compared to untreated patients.
• 12:01Actually untreated patient had the
• 12:04mortality rate of approximately 75%
• 12:07in six months compared to long term
• 12:10survivors of transplanted patient
• 12:12of the 7475 and these fit into the
• 12:17story domain of the alcoholic.
• 12:21Liver disease being transplanted in many
• 12:24parts of the world beyond the classical
• 12:28indication of listing for cirrhosis.
• 12:31Acute alcohol severe alcoholic patis
• 12:33is becoming more and more frequently
• 12:37transplanted even in our geographical
• 12:40region where historically cirrhosis was
• 12:43the endpoint of chronic alcoholic abuse.
• 12:47However, in Italy,
• 12:48and also in the Mediterranean basin,
• 12:51the prevalence of severe alcoholic
• 12:54patis on the rise following a change,
• 12:59a dramatic change in the pattern.
• 13:01Working with this binging ranking
• 13:03of the juvenile population.
• 13:05Of course, listing for acute, severe,
• 13:08acute colitis is a challenge because he has
• 13:13to fight against the stigmas and of course,
• 13:16also the reluctant of listing such
• 13:21a populations population versus
• 13:24other classical indication in a area
• 13:28where again the scarcity of the.
• 13:31Resources that,
• 13:32in terms of a donor organs,
• 13:35is persisting there.
• 13:38Despite the fact that the organizations
• 13:42and the leaves society do not endorse
• 13:46the six month rule of abstinence
• 13:50of sobriety to list patients with
• 13:54alcoholic related liver disease,
• 13:57early liver transplantation for a severe
• 14:01alcoholic hepatitis is experiencing
• 14:04some difficulties here and there.
• 14:07To be accepted as a routine approach,
• 14:12I understand that in America the
• 14:15transplantation of severe alcoholic
• 14:17hepatitis accounts for 2% of
• 14:21all the liver transplant that
• 14:24are performed in the US regions.
• 14:27Next slide,
• 14:28please.
• 14:31In America, guided by Doctor Nora,
• 14:35the road the American Consortium
• 14:37Overlay Transplantation pump is this
• 14:40paper that provides robust data,
• 14:44sponsoring the utilization of liver
• 14:47transplantation and early liver
• 14:50transplantation in patients who fail to
• 14:54be compliant with the abstinence window.
• 14:5712 Centers enrolled in eight units region.
• 15:01147 patients down in the controlled
• 15:06population not being transplanted,
• 15:07mortality was in the range of 70% at
• 15:11month 6 and the survival they were
• 15:13able to achieve the following liver
• 15:16transplantation was 84% with the
• 15:18better rate of survival for those
• 15:20who are in had remained abstinent
• 15:23after liver transplantation.
• 15:25Compared to those 70% that have some
• 15:30level of recidivism of alcohol use after.
• 15:34Liver transplantation.
• 15:39Sorry, here is minus A plus.
• 15:41Obviously that's is inverted next.
• 15:45Next slide please.
• 15:47The third topic to be discussed in
• 15:51the RECONCEPTUALIZING criteria of
• 15:53listing is liver transplantation
• 15:55for colorectal metastasis that
• 15:58are primarily indicated to liver
• 16:00transplant 2 liver section.
• 16:03Some years ago, colleagues in Oslo,
• 16:05Norway where they can enjoy
• 16:09a sufficient number of donor
• 16:12organ to test the other options.
• 16:15This was published they they were
• 16:18able to publish a paper in which
• 16:21the patients with normal selectable
• 16:24leading role in the testis,
• 16:26well defined with some response to
• 16:30chemotherapy and the time from the.
• 16:33Where is the liver fraction greater
• 16:35than one year to avoid the patients with
• 16:39an early metastasis from colorectal cancer,
• 16:41were able to demonstrate the
• 16:43benefit of liver transplantation.
• 16:45Now the Sakas second study was
• 16:50published a couple of years ago,
• 16:52demonstrating and convalidation
• 16:54validating those initial reports
• 16:56with an overall survival,
• 16:59which is considered to be very appealing.
• 17:03In this patient population,
• 17:06and particularly in those who have no
• 17:10evidence of liver disease and the survival,
• 17:14was definitely much better for
• 17:16those with the lowest score,
• 17:17the so-called form clinical risk
• 17:20called that accumulates some anatomical
• 17:23characteristic of the tumor,
• 17:25which is a greater than 200
• 17:29nanograms and the.
• 17:31Metastasis occurring after one
• 17:36year from primary cancer detection.
• 17:40All in all,
• 17:42this is is going to show us that
• 17:45there are other avenues to for
• 17:48treating patients were not responding
• 17:52to classical reception,
• 17:54although it is common belief that this
• 17:58should be retained in the context of.
• 18:01Control establish next slide please.
• 18:07And this is the algorithm
• 18:08that is being proposed,
• 18:09which is published in last telling
• 18:12us that there is a group of patients
• 18:15that are that should be evaluated
• 18:18for their biological behavior before
• 18:21being listed to liver transplantation,
• 18:24and then some of them are coming
• 18:27from the sacraments.
• 18:28Disease as we said.
• 18:30But also patients with
• 18:31the synchronous disease,
• 18:33provided they are biologically
• 18:35reactive can be listed.
• 18:37Liver transplantation,
• 18:38obviously in the context of a
• 18:43control studies only next slides.
• 18:48This is telling us the four
• 18:51that the liver transplantation
• 18:53is experiencing new avenues,
• 18:55but of course of limited application
• 18:58owing to the fact that the.
• 19:01Restriction of the donor
• 19:04organs everywhere it occurs,
• 19:07the the point that I wish to
• 19:09discuss with you is something
• 19:11that has particularly to do with
• 19:13Europe rather than with America.
• 19:14The struggle for HCC as planning to join
• 19:17the European umbrella of cancer screening.
• 19:20Next slide quite recently.
• 19:24Quite recently the European
• 19:28Commission released.
• 19:30A statement where by the wishes to
• 19:33apply screening to other types of cancer
• 19:37with respect to the classical breast,
• 19:40cervical and colorectal cancer that
• 19:43will be offered in a very in a very
• 19:49expanded manner by 2025 and to this end,
• 19:52the European Association for the Study
• 19:54of the Liver is being interviewed
• 19:57to give an answer on this and here.
• 20:00And my understanding is there
• 20:02there are conflicting opinions.
• 20:04Next slide please.
• 20:08Quite recently, let's say a couple of
• 20:11months ago there has been a very successful
• 20:14joint meeting between ASD and Esther
• 20:16regarding the endpoint liver cancer
• 20:18and then Doctor Natalie again, Carrie.
• 20:23Provide me with this slides that summarize
• 20:26these thought and these comments.
• 20:30And she puts a light on this
• 20:35controversial aspects of screening,
• 20:37due mainly to the fact there is no
• 20:41evidence that is cost effective
• 20:43in overall next light and to the
• 20:46point that the colleague of ours,
• 20:49Doctor Peter Jefferson,
• 20:50wrote a nice article telling that we
• 20:54need a stronger evidence for deciding
• 20:57to run the Protostellar casino.
• 21:00Slides, please.
• 21:03I wish to remind you that here in
• 21:05America there are modeling studies
• 21:07indicated that there is a rise in the
• 21:10HCV incidence among patients with
• 21:12the SVR and this might represent the
• 21:15next ideal target for screening.
• 21:18Next lines and it has been in fact
• 21:21predicted that in a few years this will
• 21:24represent the majority of patients
• 21:26requiring screening next slides, please.
• 21:29And the recent paper and modeling
• 21:31is telling us that for SVR patients
• 21:35with advanced fibrosis and those with
• 21:37roses screening is cost effective.
• 21:40But with the warning that perhaps
• 21:43the annual surveillance should be
• 21:46stopped at the age of 60 in the in,
• 21:49those who are cured and have advanced
• 21:53fibrosis versus those with Serositis whose
• 21:56age can be use surveillance program can be.
• 22:01Running up to the age of 70,
• 22:03I'm not sure that this model would
• 22:05apply to the European Mediterranean
• 22:07for this situation where commuted,
• 22:10the tightest causes serious at
• 22:12an advanced age,
• 22:13and most patients are older than those seen,
• 22:16for instance, in America's next slides.
• 22:21In the end, they calculated
• 22:23that doing this way screening
• 22:25is cost effective. Next slide.
• 22:30The four topping is the expanding
• 22:32the liver exposure man.
• 22:34Whether pathology should care about
• 22:36their pollution. Maximize this.
• 22:40You are aware that there are a
• 22:42number of experimental studies
• 22:43modeling demonstrating that the the
• 22:45components of air pollution may
• 22:48cause liver disease that various
• 22:50levels through different mechanisms.
• 22:51Here they are listed, including muffled
• 22:55deal method and Type 2 diabetes.
• 22:58Some of the mechanism causing
• 23:01hepatotoxicity are similar to those that
• 23:04are acting enough of the generated by
• 23:08labor labor lipotoxicity next slides.
• 23:11This is an interesting study that I
• 23:14would leave to Michael Trainer and
• 23:16Jim Boyer to comment where a group
• 23:18of scientists demonstrated that
• 23:20the components of a polluted air
• 23:23are able to interact with biases
• 23:25and lipid metabolites to generate
• 23:28liver inflammation and exasperate
• 23:31the progression method. Next slide.
• 23:35Next please, but there is also no no.
• 23:39Can you go back sorry, thank you,
• 23:42but there is also epidemiological
• 23:44evidence coming from China.
• 23:45This large area in China where with
• 23:49the satellite analysis we're able
• 23:51to measure the air concentration of
• 23:55pollutants and correlate the findings
• 23:57with the prevalence of muffled
• 24:00in the population that were part
• 24:03of the registry and then ongoing.
• 24:05Prospective studies and there were
• 24:07demonstrated to find a direct correlation,
• 24:10although not with the linear correlation
• 24:14between exposure to air pollution,
• 24:18pollution,
• 24:19and muffle,
• 24:20the incidents in those areas next.
• 24:25There is a conundrum I pick up.
• 24:27This paper demonstrated that we
• 24:29are being overexposed to methane,
• 24:32which is of course an esthetician
• 24:34gas which of course is toxic to us
• 24:37because displaces oxygen for there.
• 24:39But interestingly enough there are
• 24:42experimental eclinical data suggesting
• 24:44that nothing has a protective action against.
• 24:50Liver inflammation,
• 24:50so to some extent is counterbalanced,
• 24:53and to end up in my presentation next.
• 24:58Whether artificial intelligence is going to
• 25:00be a game changing impact those buttons.
• 25:03Practice next. If you if you next.
• 25:09If you read this interesting paper where
• 25:11it is summarized what artificial what we
• 25:14should expect from artificial intelligence,
• 25:17OK, respected benefit replicating
• 25:18the judgment of expectation,
• 25:20by the way, or discovering impactful
• 25:22inside finalized volume of data,
• 25:24too large and complex for human to perceive.
• 25:27It has been extensively utilized in
• 25:30radiology based image recognition,
• 25:33but here next slides I would like to
• 25:35draw your attention to pathologist.
• 25:37You know ballooning cell.
• 25:39Is the pillar of a diagnosis of
• 25:42Nash the Nash in fact can only be
• 25:45diagnosed by stogy probably next.
• 25:47In this nice paper,
• 25:499 pathologists were challenged to look
• 25:52at the number of slides from Nashua
• 25:56Persian having ballooning that were
• 25:59digitized and then were after three
• 26:02months challenged to review those lies
• 26:05that were in parallel scrutinized
• 26:08by secondary money generation 2
• 26:11photon excitation fluorescence
• 26:13microscopy to identify the cells.
• 26:15Next slides and the result of this verdict
• 26:18arresting studies was that overall,
• 26:20interobserver agreement for presence
• 26:21absence of baloney was very good.
• 26:23This,
• 26:24with a lot of internal classic consistency
• 26:26given the moderate agreement on ballooning,
• 26:30the artificial intelligence versus
• 26:32pathology pairwise from corpus was wide.
• 26:3519 dash 42% and need larger was the gap for
• 26:39inter pathologist there was some corpus.
• 26:42Since ballooning is a pretty definite.
• 26:45The target in trials to decide whether
• 26:48the drug is active or not against Nash
• 26:51ballooning is considered to be a spectrum.
• 26:54Those objecting for his presence or complete
• 26:57absence to be unequivocally determined as
• 26:59a trial and point and the very last slides,
• 27:03is a nice editorial.
• 27:05Comes from an editorial in lost it that
• 27:08I read that a couple of last weeks,
• 27:10actually,
• 27:11that illustrate the concerns related.
• 27:16With the application intelligent,
• 27:19the charisma between artificial intelligence
• 27:22and the documentation is a concern.
• 27:24The input data are drawn from
• 27:27outside the health setting and
• 27:28that the algorithm performance,
• 27:30source code and input data
• 27:32are not available to review.
• 27:34That's important point.
• 27:35Conservative algorithm with thirst
• 27:37and validated using retrospective in
• 27:40silico data that might not reflect.
• 27:42They are worth clinical practice
• 27:44and clinician.
• 27:46Receiving artificial intelligence
• 27:47generated decision rarely have oversight
• 27:50of the data points used to reach
• 27:53a specific decision contributing.
• 27:55The so-called algorithm aversion, unclear.
• 27:58Who, among developer companies,
• 28:01researchers,
• 28:01clinician or hospitals should
• 28:04accept responsibilities for the
• 28:06adult decisions altogether?
• 28:08This is what we need to improve to
• 28:10brief the child's between artificial
• 28:13intelligence and implementation.
• 28:15I thank you for your attention.
• 28:16And I apologize for being that long.
• 28:22Thanks very much. You know,
• 28:23really interesting talk and
• 28:24many things to think about many
• 28:26questions and and see how you
• 28:29can move forward. Thank you.