Liver Cancer: One or Many Different Cancers?

Transcript

00:00 --> 00:01Funding for Yale Cancer Answers
00:01 --> 00:03is provided by Smilow Cancer
00:03 --> 00:05Hospital and Astra Zeneca.
00:07 --> 00:10Welcome to Yale Cancer Answers with
00:10 --> 00:12your host doctor Anees Chagpar.
00:12 --> 00:13Yale Cancer Answers features the
00:13 --> 00:16latest information on cancer care by
00:16 --> 00:17welcoming oncologists and specialists
00:17 --> 00:19who are on the forefront of the
00:19 --> 00:21battle to fight cancer. This week
00:21 --> 00:23it's a conversation about liver cancer
00:23 --> 00:26with doctors Amy Justice and Tamar Taddei.
00:26 --> 00:27Dr Justice is the CNH
00:27 --> 00:30Long professor of Medicine and Doctor
00:30 --> 00:32Taddei is associate professor of
00:32 --> 00:34medicine at the Yale School of Medicine,
00:34 --> 00:35where Doctor Chagpar is a
00:35 --> 00:37professor of surgical oncology.
00:38 --> 00:42So maybe I'll start with you doctor Taddei,
00:42 --> 00:44tell us a little bit more about
00:44 --> 00:45yourself and what you do.
00:46 --> 00:48So I'm a hepatologist and my research
00:48 --> 00:51focuses on outcomes in liver disease
00:51 --> 00:53and liver cancer as well as in
00:53 --> 00:55clinical trials and prevention
00:55 --> 00:57and detection of liver cancer.
00:57 --> 00:59So that's sort of me in a nutshell.
00:59 --> 01:02OK, what about you doctor Justice?
01:02 --> 01:05So I'm a clinical epidemiologist and
01:05 --> 01:07I have spent my career harnessing
01:07 --> 01:09the national electronic health
01:09 --> 01:12record system that the VA has to
01:12 --> 01:14try to study important clinical
01:14 --> 01:16phenomenon like liver cancer.
01:16 --> 01:17Also, HIV, hepatitis C,
01:17 --> 01:19and a number of other conditions
01:19 --> 01:21using that national database.
01:22 --> 01:25And so I mean, it seems like the two of
01:25 --> 01:27you would have obvious research synergy,
01:27 --> 01:30but one of the things that's always
01:30 --> 01:33exciting and interesting to me is to see
01:33 --> 01:36how people from arguably different fields.
01:36 --> 01:38One an epidemiologist 1A hepatologist
01:38 --> 01:43kind of collide to come up with
01:43 --> 01:45interesting research ideas.
01:45 --> 01:47So Doctor Daddy tell us a little
01:47 --> 01:50bit more about how you met and about
01:50 --> 01:51how this collaboration started.
01:52 --> 01:54So I wouldn't call it a collision.
01:54 --> 01:57I actively. I actively sought
01:57 --> 02:00Amy's mentorship so Amy has
02:00 --> 02:03more than 20 year history of
02:03 --> 02:06developing cohorts in the VA in VA.
02:06 --> 02:08Data to carefully develop
02:08 --> 02:11clinical phenotypes of disease
02:11 --> 02:14specifically around HIV and aging,
02:14 --> 02:15and many other diseases.
02:15 --> 02:18Because a lot of this work
02:18 --> 02:20in HIV patients has also,
02:20 --> 02:22you know HIV patients commonly
02:22 --> 02:23have hepatitis C, for example.
02:23 --> 02:25They commonly have metabolic disorders.
02:25 --> 02:29And so she's really built a research
02:29 --> 02:32environment that can study systems
02:32 --> 02:35related diseases in a way that
02:35 --> 02:37was incredibly intriguing to me.
02:37 --> 02:40As a young person who wanted to
02:40 --> 02:42develop a cohort of patients with
02:42 --> 02:45cirrhosis at risk of liver cancer.
02:45 --> 02:47And so I sought her advice,
02:47 --> 02:50and this was in somewhere around 2011, 2012.
02:50 --> 02:53I asked to meet with her and I said,
02:53 --> 02:54look, you know, I've I've seen your work.
02:54 --> 02:56I want to know how to do this.
02:56 --> 02:58I think I'm going to need a
02:58 --> 02:59lot of handholding,
02:59 --> 03:01and there began a decade of a
03:01 --> 03:03phenomenal mentorship for me,
03:03 --> 03:05so that's that's how we met.
03:05 --> 03:07And doctor Justice tell us a
03:07 --> 03:09little bit more about kind of
03:09 --> 03:11the ideas that were generated.
03:11 --> 03:13The projects that you've designed,
03:13 --> 03:16and what the Genesis was of that.
03:18 --> 03:20Well, I'm a general internist,
03:20 --> 03:21so I think broadly,
03:21 --> 03:23which is sort of complementary to
03:23 --> 03:25and being an epidemiologist because
03:25 --> 03:28epidemiologists also think fairly broadly.
03:28 --> 03:29But I realized early on that I
03:29 --> 03:31could not be an expert in every
03:31 --> 03:33one of the conditions that were
03:33 --> 03:35worthy of study using the VA data,
03:35 --> 03:37so I've always had my eyes out for a
03:37 --> 03:40young promising people who want to be
03:40 --> 03:42the experts in those particular domains
03:42 --> 03:45and tomorrow absolutely fit that Bill.
03:45 --> 03:47And part of what I think is really
03:47 --> 03:49exciting about doing this work is
03:49 --> 03:50that there are a number of cores
03:50 --> 03:52and work groups affiliated with the
03:52 --> 03:53cohort studies that I've created,
03:53 --> 03:55and each one of those cores in
03:55 --> 03:57workgroups has greater depth and
03:57 --> 03:58understanding of the clinical questions
03:58 --> 04:00that they are looking at than I do.
04:00 --> 04:02But what Ioffer is sort of the
04:02 --> 04:03connectivity among those groups so that
04:03 --> 04:05we can learn how to do a phenotype
04:05 --> 04:07once somebody develops diabetes
04:07 --> 04:09in the endocrine group and we can
04:09 --> 04:11use it in the liver group without
04:11 --> 04:13having to recreate another wheel so
04:13 --> 04:15that we are definitely more as a.
04:15 --> 04:18We are more than the sum of our parts
04:18 --> 04:19and I find that exciting and a lot
04:19 --> 04:21of fun coming into work every day.
04:22 --> 04:25So just for people who are not
04:25 --> 04:27familiar with your work when you're
04:27 --> 04:29talking about these different cores
04:29 --> 04:31and and kind of spanning research
04:31 --> 04:34phenomena across different groups,
04:34 --> 04:37tell us more about how that exactly works.
04:37 --> 04:40Can you contextualize that for us and
04:40 --> 04:43maybe give us a specific example? Sure,
04:43 --> 04:45so I'll talk about tomorrow's work
04:45 --> 04:47because that's most relevant to this.
04:47 --> 04:49Call so when Tamar came to me initially
04:49 --> 04:52she wanted to create her own cohort study,
04:52 --> 04:54which she did with aplomb.
04:54 --> 04:54But then, over time,
04:54 --> 04:56she realized that she could also benefit
04:56 --> 04:58from doing some analysis with some of
04:58 --> 05:00the databases that we had created.
05:00 --> 05:02The cohorts we created that were a
05:02 --> 05:03little bit more generic than only
05:03 --> 05:05people who had cirrhosis per say.
05:05 --> 05:07Not to mention that we had other
05:07 --> 05:09data that we had merged into our
05:09 --> 05:11cohort studies that wasn't yet
05:11 --> 05:13available to her in the other study.
05:13 --> 05:14So she wrote up a proposal,
05:14 --> 05:16which was a brief, suggest,
05:16 --> 05:18brief outline of what she wanted to do.
05:18 --> 05:19I reviewed it,
05:19 --> 05:20thought it had the critical
05:20 --> 05:21information that we needed it,
05:21 --> 05:24and then it went to the liver core,
05:24 --> 05:25which is a standing group of
05:25 --> 05:27people who are very interested in
05:27 --> 05:30liver research in the VA data bin.
05:30 --> 05:32Lorry is the head of that core,
05:32 --> 05:33along with Jan Tate,
05:33 --> 05:34who is the Methodologist Ben
05:34 --> 05:36Larae being the clinician.
05:36 --> 05:37They reviewed it.
05:37 --> 05:38They made suggestions to her.
05:38 --> 05:40Several people in the course said
05:40 --> 05:41they were interested in participating
05:41 --> 05:43and signed on to be on the writing
05:43 --> 05:45committee and we went from there.
05:46 --> 05:49And and so doctor Taty tell us a little
05:49 --> 05:51bit more about the questions that you
05:51 --> 05:54were trying to answer with these studies.
05:55 --> 05:58So the first question was really
05:58 --> 06:00how to understand via data.
06:00 --> 06:04So where do you go to develop a cohort?
06:04 --> 06:08How is it housed within the you
06:08 --> 06:11know V8 computing infrastructure?
06:11 --> 06:13How do you actually look at that
06:13 --> 06:15data in a way that makes sense
06:15 --> 06:17and ask the right question?
06:17 --> 06:20So just having the data doesn't really
06:20 --> 06:22lead you to the right endpoint.
06:22 --> 06:23You have to actually start with
06:23 --> 06:25a good question and sometimes.
06:25 --> 06:27Good questions actually require a
06:27 --> 06:30lot of effort to actually be able
06:30 --> 06:32to define your population properly,
06:32 --> 06:34and so in the beginning when
06:34 --> 06:36we set up the cirrhosis cohort,
06:36 --> 06:38which is called the vocal cohort,
06:38 --> 06:39I did this with my colleague
06:39 --> 06:41Dave Kaplan at Upenn.
06:41 --> 06:42There's a lot of parallels
06:42 --> 06:44between Upenn and Yale,
06:44 --> 06:46a lot of collaboration going on there,
06:46 --> 06:49and so we actually had to really define
06:49 --> 06:51severity of liver disease in that cohort,
06:51 --> 06:53which is hard to do,
06:53 --> 06:56and we took a lot of advice from from.
06:56 --> 06:59Amy and from then and how to do that and
06:59 --> 07:02and so since the inception of that cohort,
07:02 --> 07:05we set that cohort cohort up in 2012.
07:05 --> 07:08We've published some probably 25 papers
07:08 --> 07:10now on cirrhosis and outcomes in
07:10 --> 07:13cirrhosis from everything to important
07:13 --> 07:16clinical questions around the use of
07:16 --> 07:18anticoagulants in these patients to
07:18 --> 07:21the burden of cost of liver cancer.
07:21 --> 07:22Care to you know,
07:22 --> 07:25all kinds of different questions
07:25 --> 07:26that are that are.
07:26 --> 07:29Well answered in a large cohort,
07:29 --> 07:31but I think one of the issues
07:31 --> 07:33that's very important is that when
07:33 --> 07:34you develop a population cohort,
07:34 --> 07:36you make a lot of assumptions, right?
07:36 --> 07:37You say, well,
07:37 --> 07:38I'm going to be looking at people
07:38 --> 07:39with cirrhosis, right?
07:39 --> 07:43And yet, cirrhosis happens over decades.
07:43 --> 07:44There are many risk factors
07:44 --> 07:45that lead to cirrhosis,
07:45 --> 07:47and while cirrhosis is the
07:47 --> 07:48single most important risk
07:48 --> 07:50factor leading to liver cancer,
07:50 --> 07:52I wanted to have a better
07:52 --> 07:54idea of what happens to people
07:54 --> 07:56before they develop cirrhosis.
07:56 --> 07:59And are we missing upstream risk factors?
07:59 --> 08:01Perhaps by selecting pre selecting
08:01 --> 08:03this population and because
08:03 --> 08:06I'm not an epidemiologist,
08:06 --> 08:09I really rely heavily on Amy's
08:09 --> 08:11Broadview because you know,
08:11 --> 08:12the more specialized you become
08:12 --> 08:13in in medicine.
08:13 --> 08:15The more blinders you have and and
08:15 --> 08:17sometimes you need somebody to sort of
08:17 --> 08:19shock you into saying wait a second,
08:19 --> 08:20you know,
08:20 --> 08:21don't look at that population.
08:21 --> 08:23Look at the whole population and
08:23 --> 08:25let's think about this rationally.
08:25 --> 08:27And so in in more recent work
08:27 --> 08:29we've been looking at the whole
08:29 --> 08:31VA population to look at upstream
08:31 --> 08:33risk factors for liver cancer
08:34 --> 08:36and what was important about that was
08:36 --> 08:39the realization that if you only if
08:39 --> 08:41you looked at cirrhosis and put that
08:41 --> 08:44in as the risk factor, it washed out.
08:44 --> 08:46All the factors that occurred
08:46 --> 08:47before cirrhosis occurred,
08:47 --> 08:49yet cirrhosis is hard to reverse
08:49 --> 08:52whereas fatty liver diabetes can
08:52 --> 08:53be addressed more effectively.
08:53 --> 08:55So it was very important to look
08:55 --> 08:56at the whole population and begin
08:56 --> 08:58to look at upstream phenomenon
08:58 --> 08:59like tomorrow was talking about.
09:00 --> 09:03Yeah, I mean, it seems that there's
09:03 --> 09:05a very heterogeneous population
09:05 --> 09:08that kind of all leads to the
09:08 --> 09:10same endpoint of of cirrhosis.
09:10 --> 09:12So tomorrow maybe you can tell
09:12 --> 09:14us a little bit more about.
09:14 --> 09:16The epidemiology of of cirrhosis
09:16 --> 09:18and of liver cancer. How?
09:18 --> 09:20How common is this anyways?
09:21 --> 09:25So cirrhosis is actually quite common.
09:25 --> 09:28And liver disease in the general
09:28 --> 09:30population is also quite common,
09:30 --> 09:32so there's at least thirty million
09:32 --> 09:34Americans living living with liver
09:34 --> 09:36disease with known liver disease.
09:36 --> 09:38And there's probably many more
09:38 --> 09:40millions that are at risk for
09:40 --> 09:41liver disease and don't know it.
09:41 --> 09:45OK, so the major risk factors
09:45 --> 09:48for liver disease are viral,
09:48 --> 09:51hepatitis, hepatitis, B&C, alcohol,
09:51 --> 09:55excessive or unhealthy alcohol use and then.
09:55 --> 09:58What we call fatty liver disease,
09:58 --> 10:01which can be alcohol associated and
10:01 --> 10:03non alcohol associated and and that's
10:03 --> 10:05part of a bigger metabolic syndrome
10:05 --> 10:08that we actually see being sort of
10:08 --> 10:10a canonical risk factor for cancers.
10:10 --> 10:12All kinds of cancers in fact,
10:12 --> 10:15and our epidemiology in in liver
10:15 --> 10:17disease and liver cancer is
10:17 --> 10:19shifting fairly quickly because we
10:19 --> 10:21now have a cure for hepatitis C.
10:21 --> 10:24And so while hepatitis C dominated as a
10:24 --> 10:26risk factor in the US for many decades.
10:26 --> 10:28We're able to cure it now,
10:28 --> 10:31and we're actually seeing more obesity
10:31 --> 10:34and alcohol associated liver disease
10:34 --> 10:36and liver cancer coming to the fore.
10:36 --> 10:41So these are major public health
10:41 --> 10:43issues that that really need to
10:43 --> 10:45be addressed at at a national
10:45 --> 10:47at a federal and state level.
10:48 --> 10:51And so Amy, when you think about you,
10:51 --> 10:55know fatty liver and obesity and alcoholism.
10:55 --> 10:58What proportion would you say of the VA
10:58 --> 11:01cohorts or of the cohorts in general
11:01 --> 11:04that you've looked at are at risk of one
11:04 --> 11:07of these such that you really wanted
11:07 --> 11:10to look at the global population? At
11:10 --> 11:12least 1/4 I'm depending on and
11:12 --> 11:14depending on how you define it more
11:14 --> 11:16than 1/4, possibly even up to half
11:17 --> 11:19and and for all of those
11:19 --> 11:22people is the mechanism and the
11:22 --> 11:24endpoint of cirrhosis the same?
11:24 --> 11:28In other words, both from a molecular
11:28 --> 11:30standpoint that you know there
11:30 --> 11:33is some sort of liver injury that
11:33 --> 11:35essentially then results in cirrhosis.
11:35 --> 11:37As well as the degree and
11:37 --> 11:38the type of cirrhosis,
11:38 --> 11:41are those of the same whether you
11:41 --> 11:44happen to have gotten to that
11:44 --> 11:46endpoint through obesity versus
11:46 --> 11:49a hepatite E versus alcoholism.
11:49 --> 11:51I'm going to let tomorrow address that
11:51 --> 11:53'cause she spent a lot of time on that
11:53 --> 11:55and it's a beautiful question.
11:55 --> 11:57So I think the question is,
11:57 --> 11:59do you want to make things sound
11:59 --> 12:01simple or do you want to just
12:01 --> 12:03embrace the complexity that's there?
12:03 --> 12:04You know Amy's always telling me.
12:04 --> 12:06Just embrace complexity, right?
12:06 --> 12:07And it's true.
12:07 --> 12:10I think cirrhosis is a final
12:10 --> 12:13common pathway of all of the
12:13 --> 12:16Cascades that lead to liver injury
12:16 --> 12:18and repair and aberrant repair.
12:18 --> 12:20You know, Yep, you can call
12:20 --> 12:22cirrhosis the final common pathway,
12:22 --> 12:25but that tells you very little about all
12:25 --> 12:27of the Cascades that happen to get there,
12:27 --> 12:29and I think actually we need to look
12:29 --> 12:31at liver disease and liver cancer
12:31 --> 12:33from an ideological standpoint.
12:33 --> 12:34Meaning what is it?
12:34 --> 12:36What's the etiology or the
12:36 --> 12:38'cause that brought you here?
12:38 --> 12:41Because there are different molecular
12:41 --> 12:44sort of biologies of those pathways
12:44 --> 12:46and then the cancers themselves.
12:46 --> 12:47You know,
12:47 --> 12:48even though we think about
12:48 --> 12:49two sort of dominant.
12:49 --> 12:52Primary liver cancers.
12:52 --> 12:55The 90% of these liver cancers
12:55 --> 12:56are are termed hepatocellular
12:56 --> 12:59cancer and they arise from the
12:59 --> 13:00liver cell from the hepatocyte.
13:00 --> 13:02But they look totally different
13:02 --> 13:03under the microscope.
13:03 --> 13:04So that begs the question,
13:04 --> 13:06are we dealing with so much
13:06 --> 13:08heterogeneity here that we're just
13:08 --> 13:09lumping these things into one name?
13:09 --> 13:10Liver cancer?
13:12 --> 13:14Yeah, so you know I I really want
13:14 --> 13:17to dive more into liver cancer.
13:17 --> 13:19The different types of liver cancer.
13:19 --> 13:21Whether the etiologies of these
13:21 --> 13:23cancers actually play a role in
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14:45 --> 14:47Welcome back to Yale Cancer answers.
14:47 --> 14:49This is doctor a nice check part
14:49 --> 14:51and I'm joined tonight by my guests,
14:51 --> 14:53doctor, Amy Justice and Tamar Taddei.
14:53 --> 14:55We're learning about liver
14:55 --> 14:56cancer treatments and research,
14:56 --> 14:59and before the break we were talking a
14:59 --> 15:01little bit about cirrhosis and the different
15:01 --> 15:03pathways that people can get cirrhosis.
15:03 --> 15:06But I thought maybe we'd start
15:06 --> 15:08first with thinking about,
15:08 --> 15:10you know, doctor Justice.
15:10 --> 15:13Do all cirrhotics get liver cancer,
15:13 --> 15:15and does all liver cancer
15:15 --> 15:16come from cirrhosis?
15:17 --> 15:20So the answer is that not all
15:20 --> 15:22cirrhotics develop liver cancer,
15:22 --> 15:24but cirrhosis by itself has a pretty
15:24 --> 15:26poor prognosis associated with it.
15:26 --> 15:28So you want to avoid
15:28 --> 15:31cirrhosis if at all possible.
15:31 --> 15:33And it is possible to develop
15:33 --> 15:35liver cancer without cirrhosis.
15:35 --> 15:35Most classically,
15:35 --> 15:39if you have hepatitis B viral infection,
15:39 --> 15:41you can go directly to liver cancer
15:41 --> 15:43without passing through cirrhosis.
15:43 --> 15:45But more typically the vast majority
15:45 --> 15:47of people who develop liver cancer
15:47 --> 15:50or at least have had a cellular liver
15:50 --> 15:52cancer have had cirrhosis previously
15:53 --> 15:56and and doctor Taty.
15:56 --> 15:59If you have cirrhosis.
15:59 --> 16:00How is cirrhosis diagnosed
16:01 --> 16:03so cirrhosis has to be suspected
16:03 --> 16:05and that's the problem.
16:05 --> 16:07So your liver is your largest
16:07 --> 16:09solid organ and it regenerates,
16:09 --> 16:10which is marvelous.
16:10 --> 16:12But it doesn't tell you
16:12 --> 16:14it's sick until it's very,
16:14 --> 16:17very sick, and that's a problem.
16:17 --> 16:20So we would love to detect cirrhosis in
16:20 --> 16:23that early stage where patients don't feel
16:23 --> 16:26any different and their counts are still OK,
16:26 --> 16:29and there's still more or less healthy.
16:29 --> 16:30But more often than not,
16:30 --> 16:34we detect cirrhosis when people present with.
16:34 --> 16:35Signs of early liver failure,
16:35 --> 16:37like jaundice or bleeding or
16:37 --> 16:39very low platelet counts.
16:39 --> 16:40This is already very,
16:40 --> 16:42very advanced and it very much limits what we
16:42 --> 16:44can offer that patient in terms of treatment.
16:44 --> 16:46If they do have a liver cancer.
16:46 --> 16:49All patients with cirrhosis should
16:49 --> 16:51have screening for liver cancer in the
16:51 --> 16:54form of an ultrasound every six months.
16:54 --> 16:56And it's really important to talk to
16:56 --> 16:59patients about the fact that your body may
16:59 --> 17:01have problems even if you don't feel it.
17:01 --> 17:03And I think this is something that
17:03 --> 17:06people have a hard time wrapping their
17:06 --> 17:08head around that you could actually be
17:08 --> 17:11harboring a chronic illness and really
17:11 --> 17:13not notice any change in how you feel.
17:13 --> 17:14Which is why people really do need
17:14 --> 17:16to go to the doctor regularly.
17:16 --> 17:18It's it's an important thing to have
17:18 --> 17:20a physical and to have an established
17:20 --> 17:22rapport with a primary care doc who
17:22 --> 17:25knows you and has looked at you over
17:25 --> 17:27time and can see subtle changes when
17:27 --> 17:29they come up before you even feel them
17:29 --> 17:30doctor justice talk a
17:30 --> 17:31little bit more about that.
17:31 --> 17:34I mean, we talked about some of the
17:34 --> 17:36things that can lead to cirrhosis,
17:36 --> 17:38and I think some of us might be thinking.
17:38 --> 17:41You know, maybe I am a little bit overweight.
17:41 --> 17:43Maybe I do enjoy a couple of
17:43 --> 17:45drinks every now and then.
17:45 --> 17:47If these are factors that
17:47 --> 17:49potentially can lead to cirrhosis,
17:49 --> 17:52and cirrhosis is silent except
17:52 --> 17:54for when it's pretty late and
17:54 --> 17:56can affect my blood work,
17:56 --> 17:58how is that diagnosed?
17:58 --> 18:01I mean, should should I be going to the
18:01 --> 18:04doctor and getting an ultrasound of my
18:04 --> 18:07liver to see if if I have cirrhosis?
18:07 --> 18:08And would cirrhosis even show up
18:08 --> 18:10on an ultrasound or a CT scan?
18:12 --> 18:13Well again it depends on at
18:13 --> 18:15what stage you're talking about.
18:15 --> 18:18So very early signs of liver injury that
18:18 --> 18:21could lead to cirrhosis and may maybe
18:21 --> 18:24an early harbinger of cirrhosis is the
18:24 --> 18:27ratio of AST aspartate transaminase to
18:27 --> 18:30alanine transaminase and platelets,
18:30 --> 18:31which is also called FIB 4,
18:31 --> 18:36and that's a very routine test of patients.
18:36 --> 18:37Get it very frequently when
18:37 --> 18:38they see their doctors.
18:38 --> 18:40It's part of the the routine panel of
18:40 --> 18:42tests that are sent for blood work.
18:42 --> 18:44And if that test is abnormal
18:44 --> 18:46or not rock solid normal,
18:46 --> 18:48then it would be very reasonable
18:48 --> 18:49to have a conversation around.
18:49 --> 18:50Well, how much do you drink?
18:50 --> 18:52How long have you been drinking?
18:52 --> 18:54OK, let's look at your BMI,
18:54 --> 18:56which is an indication of what your
18:56 --> 18:58risk for fatty liver disease might be.
18:58 --> 18:59What's your family history?
18:59 --> 19:01You know those sorts of questions
19:01 --> 19:02can be explored,
19:02 --> 19:03and if enough of them are positive,
19:03 --> 19:04then yes,
19:04 --> 19:06an ultrasound would make some sense.
19:06 --> 19:08I'll let tomorrow talk a little bit
19:08 --> 19:10more about what would happen when
19:10 --> 19:12I refer the patient over after.
19:12 --> 19:15Ordering the ultrasound to the hepatologist,
19:15 --> 19:16but as the primary care doc.
19:16 --> 19:16Yes,
19:16 --> 19:18I would consider getting an ultrasound
19:18 --> 19:19on someone who I considered to
19:19 --> 19:20be at high risk.
19:20 --> 19:22So tomorrow just to to kind of
19:22 --> 19:24pick up the conversation there.
19:24 --> 19:27One of the things that you both
19:27 --> 19:29mentioned was that cirrhosis in and
19:29 --> 19:32of itself is not is not something
19:32 --> 19:34that you should aspire to have.
19:34 --> 19:37I mean, not only does it increase your
19:37 --> 19:40risk of of Pato cellular carcinoma,
19:40 --> 19:42but in and of itself.
19:42 --> 19:44It it can have problems.
19:44 --> 19:47You mentioned that the liver was
19:47 --> 19:49an organ that can regenerate.
19:49 --> 19:51If you do have cirrhosis.
19:51 --> 19:54If your blood work is abnormal,
19:54 --> 19:56is there a way that you can reverse that?
19:56 --> 19:59Can you lose weight?
19:59 --> 20:00Stop drinking,
20:00 --> 20:02you know you mentioned drugs
20:02 --> 20:05that can cure hepatitis C.
20:05 --> 20:08Now, can that reverse cirrhosis?
20:08 --> 20:11Or is is it the case that once
20:11 --> 20:13you have a cirrhotic liver?
20:13 --> 20:14You have a cirrhotic liver.
20:14 --> 20:16It depends on how how significant
20:16 --> 20:19the scarring is of the liver.
20:19 --> 20:22So very, very early cirrhosis.
20:22 --> 20:24We're beginning to think more and more
20:24 --> 20:26can be reversed if you take away the
20:26 --> 20:28whatever is insulting the liver, right?
20:28 --> 20:29So if it's viral hepatitis
20:29 --> 20:30you treat the hepatitis.
20:30 --> 20:33If it's alcohol, you stop drinking.
20:33 --> 20:36There are people who can have
20:36 --> 20:39their fibrosis reverse even very,
20:39 --> 20:40very early cirrhosis.
20:40 --> 20:42But once you have a lot of
20:42 --> 20:44scar laid down and a lot of.
20:44 --> 20:45Thick trabeculae we call them
20:45 --> 20:48sort of thick bands of collagen
20:48 --> 20:49deposition in the liver.
20:49 --> 20:53The liver really can't repair itself anymore,
20:53 --> 20:54and so there is.
20:54 --> 20:56There is a point at which you
20:56 --> 20:57cannot turn back the clock,
20:58 --> 21:01and so Amy, from an epidemiologic standpoint,
21:01 --> 21:03and we we kind of touched on this a
21:03 --> 21:05little bit before the break, but I just
21:05 --> 21:07want to unpack it a little bit more.
21:07 --> 21:11Is the rate at which you develop cirrhosis.
21:11 --> 21:15If you have had any of these different.
21:15 --> 21:18Sources of injury, whether it's alcohol,
21:18 --> 21:21whether it's a hepatite E, whether it's.
21:21 --> 21:25You know being obese is the rate
21:25 --> 21:27at which you develop cirrhosis,
21:27 --> 21:31different in in those different etiologic
21:31 --> 21:36factors and is the potential to develop
21:36 --> 21:39hepatocellular carcinoma based on those.
21:39 --> 21:42Our priority risk factors different
21:42 --> 21:45in amongst each of those risk factors.
21:46 --> 21:47So obviously drinking a little
21:47 --> 21:49alcohol versus drinking a lot of
21:49 --> 21:51alcohol is going to influence how
21:51 --> 21:53quickly you might develop cirrhosis.
21:53 --> 21:54You know if you,
21:54 --> 21:56if you are drinking extremely heavily
21:56 --> 21:59cirrhosis can occur much earlier
21:59 --> 22:01than if you're drinking fairly
22:01 --> 22:03heavily for a longer period of time.
22:03 --> 22:05We actually have studied this in HIV,
22:05 --> 22:08which is a risk factor also
22:08 --> 22:09for cellular cancer.
22:09 --> 22:12And we were able to show using the VA
22:12 --> 22:15data that people who were able to suppress
22:15 --> 22:18their HIV get their virus undetectable.
22:18 --> 22:20Had a much slower progression
22:20 --> 22:21to hepatocellular cancer than
22:21 --> 22:23the people who were not.
22:23 --> 22:25So I think that's actually a pretty good
22:25 --> 22:27template for a lot of these phenomenon.
22:27 --> 22:30If you can manage these risk factors,
22:30 --> 22:32try to get them as low as possible.
22:32 --> 22:34You can modify how rapidly someone
22:34 --> 22:35is going to develop cirrhosis,
22:35 --> 22:37and that's a very important
22:37 --> 22:38modification in terms of their
22:38 --> 22:40risk for hepatocellular cancer.
22:40 --> 22:43So do we know just to follow up on that?
22:43 --> 22:46Amy, do we know, for example,
22:46 --> 22:49that whether if you have a history
22:49 --> 22:51of hepatitis C that that's
22:51 --> 22:53worse in terms of developing?
22:53 --> 22:56Cirrhosis and subsequent Pato
22:56 --> 22:57cellular carcinoma. Then,
22:57 --> 23:01if you were a heavy drinker or you know,
23:01 --> 23:03being a heavy drinker is a little bit
23:03 --> 23:05worse than having a BMI of 30 do.
23:05 --> 23:09Do we have any kind of ideas about the
23:09 --> 23:11relative risk of each of these risk factors?
23:12 --> 23:14So hepatitis B is probably the
23:14 --> 23:16strongest individual risk factor.
23:16 --> 23:18Thankfully, the prevalence of hepatitis
23:18 --> 23:21B in the United States is relatively low.
23:21 --> 23:23When you talk about things like hepatitis C,
23:23 --> 23:27alcohol, fatty liver HIV,
23:27 --> 23:29it's not one size fits all.
23:29 --> 23:32It really depends on how severely you
23:32 --> 23:34have those problems or conditions,
23:34 --> 23:36and so it's it's not true to say that
23:36 --> 23:37one is much worse than the other.
23:37 --> 23:39It really depends on how
23:39 --> 23:41out of control they are.
23:42 --> 23:45Yeah, and so Tim are picking up on
23:45 --> 23:49what Amy had kind of lead us to.
23:49 --> 23:52You know if if you're referred to patient
23:52 --> 23:55who's got a suspicion for cirrhosis,
23:55 --> 23:59they come to you and they they've
23:59 --> 24:02had an ultrasound or a CT scan.
24:02 --> 24:05What's the next step in terms of you know,
24:05 --> 24:08checking to see whether they
24:08 --> 24:09have hepatocellular carcinoma?
24:10 --> 24:12So if they come to me with an ultrasound,
24:12 --> 24:14usually that ultrasound is sufficient
24:14 --> 24:17to look for large tumors in the liver
24:17 --> 24:19tumors over 2 centimeters, for example.
24:19 --> 24:22But we know that ultrasound in and of itself
24:22 --> 24:24is a very insensitive screening modality,
24:24 --> 24:27which is why there are studies underway to
24:27 --> 24:30look at more sensitive screening modalities.
24:30 --> 24:31When I'm refer to patient,
24:31 --> 24:34I actually think very carefully about.
24:34 --> 24:35What brought them to me?
24:35 --> 24:38So I think about viral,
24:38 --> 24:40metabolic and inherited disorders of
24:40 --> 24:42the liver that can lead to cirrhosis
24:42 --> 24:44as well as autoimmune disorders.
24:44 --> 24:46So I think you know,
24:46 --> 24:49cirrhosis is stigmatized because people
24:49 --> 24:51associate it entirely with alcohol.
24:51 --> 24:53And actually there are many different
24:53 --> 24:55causes of cirrhosis and even alcohol.
24:55 --> 24:57Some people can drink very heavily
24:57 --> 24:58and never have liver disease.
24:58 --> 25:00And some people can drink fairly
25:00 --> 25:01modestly and get liver disease.
25:01 --> 25:03So I think you know there
25:03 --> 25:04really should be no stigma.
25:04 --> 25:05Associated with cirrhosis.
25:05 --> 25:08So I I look at all of the sort
25:08 --> 25:09of pathways that could have
25:09 --> 25:11gotten them to where they are,
25:11 --> 25:14and then we usually in the liver
25:14 --> 25:16in the liver clinic now have non
25:16 --> 25:18invasive ways of testing the liver
25:18 --> 25:21stiffness which is a marker of of
25:21 --> 25:23how fibrotic the liver is and those
25:23 --> 25:26those ways of measuring are called
25:26 --> 25:27transient elastography where we
25:27 --> 25:30measure the stiffness of the liver
25:30 --> 25:32and can give the patient right there
25:32 --> 25:35in the clinic an estimation of.
25:35 --> 25:37How serious this may be,
25:37 --> 25:39and then from there I try to figure out
25:39 --> 25:42if there's anything I can help remove
25:42 --> 25:44that could be stressing the liver,
25:44 --> 25:46and so there are some treatments for
25:46 --> 25:49some of these different causes obviously,
25:49 --> 25:51and then you know they I make sure
25:51 --> 25:53I go over what we call cirrhosis,
25:53 --> 25:55health maintenance with the patient,
25:55 --> 25:56you know what they can do to
25:56 --> 25:57protect their liver,
25:57 --> 25:59how often they need to be seen,
25:59 --> 26:00how to protect themselves
26:00 --> 26:01against other illnesses,
26:01 --> 26:03because when the liver has cirrhosis,
26:03 --> 26:06it sort of loses a lot of its.
26:06 --> 26:07You know immune surveillance
26:07 --> 26:09ability for certain pathogens.
26:09 --> 26:11You know they need to be up to
26:11 --> 26:12date with their adult vaccines,
26:12 --> 26:13that sort of thing.
26:13 --> 26:15And then you know if if the
26:15 --> 26:16liver disease is very severe.
26:16 --> 26:18We talk about things like
26:18 --> 26:19liver transplantation.
26:19 --> 26:21And certainly if the patient
26:21 --> 26:22comes to me with liver cancer,
26:22 --> 26:24as many of my patients come to me with,
26:24 --> 26:25you know,
26:25 --> 26:26newly diagnosed liver cancer,
26:26 --> 26:28that's a whole other conversation around
26:28 --> 26:31prognosis and treatment and all of that.
26:32 --> 26:34So, so in our last minute,
26:34 --> 26:37maybe we can just talk a little bit.
26:37 --> 26:39About prognosis and treatment of
26:39 --> 26:42liver cancer tell us more about
26:42 --> 26:43how that's treated and and what
26:43 --> 26:45the prognosis really is Amy.
26:46 --> 26:48Well, this is really tomorrow specialty,
26:48 --> 26:50but unfortunately because people present
26:50 --> 26:53so late the prognosis is quite grim.
26:53 --> 26:55With that I will hand it over tomorrow.
26:56 --> 26:57So tomorrow are there.
26:57 --> 26:59Are there new treatments that can
26:59 --> 27:01make that prognosis less grim?
27:02 --> 27:04Yes, so in the last five years we've
27:04 --> 27:07seen a number of new agents come to
27:07 --> 27:09the market for advanced liver cancer.
27:09 --> 27:11We'd still really like to detect
27:11 --> 27:13liver cancer at its earliest stages,
27:13 --> 27:15where it either can be removed by
27:15 --> 27:17surgery or treated ablative Lee.
27:17 --> 27:20And so I think it's important to
27:20 --> 27:21really raise awareness for people
27:21 --> 27:23to get screened if they have
27:23 --> 27:25been diagnosed with cirrhosis.
27:25 --> 27:26Certainly we're always looking
27:26 --> 27:28at screening and risk factors,
27:28 --> 27:30and whether there are other things
27:30 --> 27:31apart from cirrhosis that would
27:31 --> 27:33bring a person to screening.
27:33 --> 27:35Like chronic hepatitis B for example,
27:35 --> 27:38but the treatments are dependent on
27:38 --> 27:41stage and the overall survival in liver
27:41 --> 27:44cancer is about 18% at five years,
27:44 --> 27:45which is dismal.
27:45 --> 27:47But it's getting better because
27:47 --> 27:49we have new agents,
27:49 --> 27:50things that can really change the
27:50 --> 27:52course of a patient's life is,
27:52 --> 27:54you know, surgery to remove the tumor,
27:54 --> 27:56but also liver transplantation in
27:56 --> 27:58patients who have liver disease and are
27:58 --> 28:00perhaps too sick for those surgeries.
28:00 --> 28:01And so you know,
28:01 --> 28:03there are a number of different local
28:03 --> 28:05treatments that can be done for sort
28:05 --> 28:07of what we call intermediate disease.
28:07 --> 28:09But the most important thing is for
28:09 --> 28:11the patients case to be discussed
28:11 --> 28:13in a multidisciplinary tumor board,
28:13 --> 28:15because there are many people who
28:15 --> 28:17manage liver cancer and we all need
28:17 --> 28:19to come to the table to develop
28:19 --> 28:21a a clear plan for the patient.
28:21 --> 28:24And you know, to really think about that,
28:24 --> 28:25patient their unique circumstances
28:25 --> 28:27and what's best for them.
28:28 --> 28:30Doctor Tamar Taddei is associate
28:30 --> 28:32professor of medicine and digestive
28:32 --> 28:35diseases and doctor Amy Justices CNH,
28:35 --> 28:36Long professor of medicine at
28:36 --> 28:38the Yale School of Medicine.
28:38 --> 28:40If you have questions,
28:40 --> 28:42the address is canceranswers@yale.edu
28:42 --> 28:45and past editions of the program
28:45 --> 28:47are available in audio and written
28:47 --> 28:48form at yalecancercenter.org.
28:48 --> 28:50We hope you'll join us next week to
28:50 --> 28:52learn more about the fight against
28:52 --> 28:54cancer here on Connecticut Public
28:54 --> 28:55radio funding for Yale Cancer
28:55 --> 28:57Answers is provided by Smilow
28:57 --> 29:00Cancer Hospital and Astra Zeneca.

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December 19, 2021

Yale Cancer Center

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