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Liver Cancer: One or Many Different Cancers?

December 20, 2021
  • 00:00Funding for Yale Cancer Answers
  • 00:02is provided by Smilow Cancer
  • 00:04Hospital and Astra Zeneca.
  • 00:08Welcome to Yale Cancer Answers with
  • 00:10your host doctor Anees Chagpar.
  • 00:12Yale Cancer Answers features the
  • 00:14latest information on cancer care by
  • 00:16welcoming oncologists and specialists
  • 00:17who are on the forefront of the
  • 00:20battle to fight cancer. This week
  • 00:22it's a conversation about liver cancer
  • 00:24with doctors Amy Justice and Tamar Taddei.
  • 00:26Dr Justice is the CNH
  • 00:28Long professor of Medicine and Doctor
  • 00:30Taddei is associate professor of
  • 00:32medicine at the Yale School of Medicine,
  • 00:34where Doctor Chagpar is a
  • 00:36professor of surgical oncology.
  • 00:39So maybe I'll start with you doctor Taddei,
  • 00:42tell us a little bit more about
  • 00:44yourself and what you do.
  • 00:46So I'm a hepatologist and my research
  • 00:49focuses on outcomes in liver disease
  • 00:51and liver cancer as well as in
  • 00:53clinical trials and prevention
  • 00:55and detection of liver cancer.
  • 00:58So that's sort of me in a nutshell.
  • 01:00OK, what about you doctor Justice?
  • 01:03So I'm a clinical epidemiologist and
  • 01:05I have spent my career harnessing
  • 01:08the national electronic health
  • 01:10record system that the VA has to
  • 01:12try to study important clinical
  • 01:14phenomenon like liver cancer.
  • 01:16Also, HIV, hepatitis C,
  • 01:18and a number of other conditions
  • 01:20using that national database.
  • 01:22And so I mean, it seems like the two of
  • 01:25you would have obvious research synergy,
  • 01:28but one of the things that's always
  • 01:31exciting and interesting to me is to see
  • 01:33how people from arguably different fields.
  • 01:36One an epidemiologist 1A hepatologist
  • 01:39kind of collide to come up with
  • 01:43interesting research ideas.
  • 01:45So Doctor Daddy tell us a little
  • 01:47bit more about how you met and about
  • 01:50how this collaboration started.
  • 01:53So I wouldn't call it a collision.
  • 01:55I actively. I actively sought
  • 01:57Amy's mentorship so Amy has
  • 02:00more than 20 year history of
  • 02:03developing cohorts in the VA in VA.
  • 02:06Data to carefully develop
  • 02:09clinical phenotypes of disease
  • 02:11specifically around HIV and aging,
  • 02:14and many other diseases.
  • 02:16Because a lot of this work
  • 02:19in HIV patients has also,
  • 02:21you know HIV patients commonly
  • 02:22have hepatitis C, for example.
  • 02:24They commonly have metabolic disorders.
  • 02:26And so she's really built a research
  • 02:29environment that can study systems
  • 02:32related diseases in a way that
  • 02:35was incredibly intriguing to me.
  • 02:37As a young person who wanted to
  • 02:40develop a cohort of patients with
  • 02:43cirrhosis at risk of liver cancer.
  • 02:45And so I sought her advice,
  • 02:47and this was in somewhere around 2011, 2012.
  • 02:51I asked to meet with her and I said,
  • 02:53look, you know, I've I've seen your work.
  • 02:55I want to know how to do this.
  • 02:57I think I'm going to need a
  • 02:58lot of handholding,
  • 02:59and there began a decade of a
  • 03:02phenomenal mentorship for me,
  • 03:03so that's that's how we met.
  • 03:06And doctor Justice tell us a
  • 03:08little bit more about kind of
  • 03:10the ideas that were generated.
  • 03:12The projects that you've designed,
  • 03:14and what the Genesis was of that.
  • 03:18Well, I'm a general internist,
  • 03:20so I think broadly,
  • 03:22which is sort of complementary to
  • 03:24and being an epidemiologist because
  • 03:26epidemiologists also think fairly broadly.
  • 03:28But I realized early on that I
  • 03:30could not be an expert in every
  • 03:32one of the conditions that were
  • 03:34worthy of study using the VA data,
  • 03:36so I've always had my eyes out for a
  • 03:38young promising people who want to be
  • 03:40the experts in those particular domains
  • 03:43and tomorrow absolutely fit that Bill.
  • 03:45And part of what I think is really
  • 03:48exciting about doing this work is
  • 03:49that there are a number of cores
  • 03:51and work groups affiliated with the
  • 03:53cohort studies that I've created,
  • 03:54and each one of those cores in
  • 03:56workgroups has greater depth and
  • 03:57understanding of the clinical questions
  • 03:59that they are looking at than I do.
  • 04:01But what Ioffer is sort of the
  • 04:02connectivity among those groups so that
  • 04:04we can learn how to do a phenotype
  • 04:06once somebody develops diabetes
  • 04:07in the endocrine group and we can
  • 04:09use it in the liver group without
  • 04:11having to recreate another wheel so
  • 04:13that we are definitely more as a.
  • 04:16We are more than the sum of our parts
  • 04:18and I find that exciting and a lot
  • 04:20of fun coming into work every day.
  • 04:23So just for people who are not
  • 04:25familiar with your work when you're
  • 04:27talking about these different cores
  • 04:29and and kind of spanning research
  • 04:32phenomena across different groups,
  • 04:34tell us more about how that exactly works.
  • 04:38Can you contextualize that for us and
  • 04:40maybe give us a specific example? Sure,
  • 04:44so I'll talk about tomorrow's work
  • 04:45because that's most relevant to this.
  • 04:47Call so when Tamar came to me initially
  • 04:50she wanted to create her own cohort study,
  • 04:52which she did with aplomb.
  • 04:54But then, over time,
  • 04:55she realized that she could also benefit
  • 04:57from doing some analysis with some of
  • 04:59the databases that we had created.
  • 05:00The cohorts we created that were a
  • 05:02little bit more generic than only
  • 05:04people who had cirrhosis per say.
  • 05:06Not to mention that we had other
  • 05:07data that we had merged into our
  • 05:10cohort studies that wasn't yet
  • 05:11available to her in the other study.
  • 05:13So she wrote up a proposal,
  • 05:15which was a brief, suggest,
  • 05:16brief outline of what she wanted to do.
  • 05:19I reviewed it,
  • 05:19thought it had the critical
  • 05:21information that we needed it,
  • 05:22and then it went to the liver core,
  • 05:24which is a standing group of
  • 05:26people who are very interested in
  • 05:28liver research in the VA data bin.
  • 05:30Lorry is the head of that core,
  • 05:32along with Jan Tate,
  • 05:33who is the Methodologist Ben
  • 05:35Larae being the clinician.
  • 05:36They reviewed it.
  • 05:37They made suggestions to her.
  • 05:39Several people in the course said
  • 05:40they were interested in participating
  • 05:42and signed on to be on the writing
  • 05:44committee and we went from there.
  • 05:47And and so doctor Taty tell us a little
  • 05:49bit more about the questions that you
  • 05:52were trying to answer with these studies.
  • 05:55So the first question was really
  • 05:58how to understand via data.
  • 06:01So where do you go to develop a cohort?
  • 06:04How is it housed within the you
  • 06:08know V8 computing infrastructure?
  • 06:12How do you actually look at that
  • 06:13data in a way that makes sense
  • 06:16and ask the right question?
  • 06:17So just having the data doesn't really
  • 06:20lead you to the right endpoint.
  • 06:22You have to actually start with
  • 06:24a good question and sometimes.
  • 06:26Good questions actually require a
  • 06:28lot of effort to actually be able
  • 06:31to define your population properly,
  • 06:33and so in the beginning when
  • 06:34we set up the cirrhosis cohort,
  • 06:36which is called the vocal cohort,
  • 06:38I did this with my colleague
  • 06:40Dave Kaplan at Upenn.
  • 06:41There's a lot of parallels
  • 06:43between Upenn and Yale,
  • 06:44a lot of collaboration going on there,
  • 06:47and so we actually had to really define
  • 06:49severity of liver disease in that cohort,
  • 06:52which is hard to do,
  • 06:53and we took a lot of advice from from.
  • 06:56Amy and from then and how to do that and
  • 06:59and so since the inception of that cohort,
  • 07:03we set that cohort cohort up in 2012.
  • 07:06We've published some probably 25 papers
  • 07:08now on cirrhosis and outcomes in
  • 07:11cirrhosis from everything to important
  • 07:14clinical questions around the use of
  • 07:16anticoagulants in these patients to
  • 07:18the burden of cost of liver cancer.
  • 07:21Care to you know,
  • 07:23all kinds of different questions
  • 07:25that are that are.
  • 07:27Well answered in a large cohort,
  • 07:29but I think one of the issues
  • 07:31that's very important is that when
  • 07:33you develop a population cohort,
  • 07:35you make a lot of assumptions, right?
  • 07:37You say, well,
  • 07:37I'm going to be looking at people
  • 07:39with cirrhosis, right?
  • 07:40And yet, cirrhosis happens over decades.
  • 07:43There are many risk factors
  • 07:45that lead to cirrhosis,
  • 07:46and while cirrhosis is the
  • 07:47single most important risk
  • 07:49factor leading to liver cancer,
  • 07:50I wanted to have a better
  • 07:52idea of what happens to people
  • 07:54before they develop cirrhosis.
  • 07:56And are we missing upstream risk factors?
  • 07:59Perhaps by selecting pre selecting
  • 08:02this population and because
  • 08:04I'm not an epidemiologist,
  • 08:06I really rely heavily on Amy's
  • 08:10Broadview because you know,
  • 08:11the more specialized you become
  • 08:13in in medicine.
  • 08:14The more blinders you have and and
  • 08:16sometimes you need somebody to sort of
  • 08:17shock you into saying wait a second,
  • 08:19you know,
  • 08:20don't look at that population.
  • 08:22Look at the whole population and
  • 08:24let's think about this rationally.
  • 08:26And so in in more recent work
  • 08:28we've been looking at the whole
  • 08:30VA population to look at upstream
  • 08:32risk factors for liver cancer
  • 08:34and what was important about that was
  • 08:37the realization that if you only if
  • 08:39you looked at cirrhosis and put that
  • 08:42in as the risk factor, it washed out.
  • 08:44All the factors that occurred
  • 08:46before cirrhosis occurred,
  • 08:47yet cirrhosis is hard to reverse
  • 08:50whereas fatty liver diabetes can
  • 08:52be addressed more effectively.
  • 08:54So it was very important to look
  • 08:55at the whole population and begin
  • 08:57to look at upstream phenomenon
  • 08:58like tomorrow was talking about.
  • 09:01Yeah, I mean, it seems that there's
  • 09:04a very heterogeneous population
  • 09:05that kind of all leads to the
  • 09:08same endpoint of of cirrhosis.
  • 09:10So tomorrow maybe you can tell
  • 09:12us a little bit more about.
  • 09:14The epidemiology of of cirrhosis
  • 09:17and of liver cancer. How?
  • 09:19How common is this anyways?
  • 09:22So cirrhosis is actually quite common.
  • 09:26And liver disease in the general
  • 09:28population is also quite common,
  • 09:30so there's at least thirty million
  • 09:33Americans living living with liver
  • 09:35disease with known liver disease.
  • 09:37And there's probably many more
  • 09:38millions that are at risk for
  • 09:40liver disease and don't know it.
  • 09:42OK, so the major risk factors
  • 09:45for liver disease are viral,
  • 09:48hepatitis, hepatitis, B&C, alcohol,
  • 09:52excessive or unhealthy alcohol use and then.
  • 09:55What we call fatty liver disease,
  • 09:59which can be alcohol associated and
  • 10:01non alcohol associated and and that's
  • 10:04part of a bigger metabolic syndrome
  • 10:06that we actually see being sort of
  • 10:08a canonical risk factor for cancers.
  • 10:10All kinds of cancers in fact,
  • 10:13and our epidemiology in in liver
  • 10:15disease and liver cancer is
  • 10:17shifting fairly quickly because we
  • 10:19now have a cure for hepatitis C.
  • 10:22And so while hepatitis C dominated as a
  • 10:24risk factor in the US for many decades.
  • 10:27We're able to cure it now,
  • 10:28and we're actually seeing more obesity
  • 10:32and alcohol associated liver disease
  • 10:34and liver cancer coming to the fore.
  • 10:37So these are major public health
  • 10:41issues that that really need to
  • 10:43be addressed at at a national
  • 10:45at a federal and state level.
  • 10:48And so Amy, when you think about you,
  • 10:51know fatty liver and obesity and alcoholism.
  • 10:56What proportion would you say of the VA
  • 10:59cohorts or of the cohorts in general
  • 11:02that you've looked at are at risk of one
  • 11:05of these such that you really wanted
  • 11:07to look at the global population? At
  • 11:10least 1/4 I'm depending on and
  • 11:12depending on how you define it more
  • 11:15than 1/4, possibly even up to half
  • 11:17and and for all of those
  • 11:20people is the mechanism and the
  • 11:22endpoint of cirrhosis the same?
  • 11:24In other words, both from a molecular
  • 11:28standpoint that you know there
  • 11:31is some sort of liver injury that
  • 11:33essentially then results in cirrhosis.
  • 11:36As well as the degree and
  • 11:37the type of cirrhosis,
  • 11:39are those of the same whether you
  • 11:42happen to have gotten to that
  • 11:44endpoint through obesity versus
  • 11:46a hepatite E versus alcoholism.
  • 11:50I'm going to let tomorrow address that
  • 11:52'cause she spent a lot of time on that
  • 11:53and it's a beautiful question.
  • 11:56So I think the question is,
  • 11:57do you want to make things sound
  • 11:59simple or do you want to just
  • 12:01embrace the complexity that's there?
  • 12:03You know Amy's always telling me.
  • 12:05Just embrace complexity, right?
  • 12:07And it's true.
  • 12:08I think cirrhosis is a final
  • 12:11common pathway of all of the
  • 12:13Cascades that lead to liver injury
  • 12:16and repair and aberrant repair.
  • 12:19You know, Yep, you can call
  • 12:21cirrhosis the final common pathway,
  • 12:23but that tells you very little about all
  • 12:25of the Cascades that happen to get there,
  • 12:28and I think actually we need to look
  • 12:30at liver disease and liver cancer
  • 12:32from an ideological standpoint.
  • 12:34Meaning what is it?
  • 12:35What's the etiology or the
  • 12:36'cause that brought you here?
  • 12:38Because there are different molecular
  • 12:41sort of biologies of those pathways
  • 12:44and then the cancers themselves.
  • 12:47You know,
  • 12:47even though we think about
  • 12:49two sort of dominant.
  • 12:50Primary liver cancers.
  • 12:52The 90% of these liver cancers
  • 12:55are are termed hepatocellular
  • 12:57cancer and they arise from the
  • 12:59liver cell from the hepatocyte.
  • 13:01But they look totally different
  • 13:02under the microscope.
  • 13:03So that begs the question,
  • 13:05are we dealing with so much
  • 13:07heterogeneity here that we're just
  • 13:08lumping these things into one name?
  • 13:10Liver cancer?
  • 13:12Yeah, so you know I I really want
  • 13:15to dive more into liver cancer.
  • 13:18The different types of liver cancer.
  • 13:20Whether the etiologies of these
  • 13:21cancers actually play a role in
  • 13:23terms of prognosis and treatment and
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  • 14:45Welcome back to Yale Cancer answers.
  • 14:47This is doctor a nice check part
  • 14:49and I'm joined tonight by my guests,
  • 14:51doctor, Amy Justice and Tamar Taddei.
  • 14:54We're learning about liver
  • 14:55cancer treatments and research,
  • 14:57and before the break we were talking a
  • 14:59little bit about cirrhosis and the different
  • 15:02pathways that people can get cirrhosis.
  • 15:04But I thought maybe we'd start
  • 15:07first with thinking about,
  • 15:08you know, doctor Justice.
  • 15:10Do all cirrhotics get liver cancer,
  • 15:14and does all liver cancer
  • 15:15come from cirrhosis?
  • 15:17So the answer is that not all
  • 15:20cirrhotics develop liver cancer,
  • 15:22but cirrhosis by itself has a pretty
  • 15:25poor prognosis associated with it.
  • 15:27So you want to avoid
  • 15:29cirrhosis if at all possible.
  • 15:31And it is possible to develop
  • 15:33liver cancer without cirrhosis.
  • 15:35Most classically,
  • 15:36if you have hepatitis B viral infection,
  • 15:39you can go directly to liver cancer
  • 15:42without passing through cirrhosis.
  • 15:43But more typically the vast majority
  • 15:46of people who develop liver cancer
  • 15:48or at least have had a cellular liver
  • 15:50cancer have had cirrhosis previously
  • 15:54and and doctor Taty.
  • 15:56If you have cirrhosis.
  • 15:59How is cirrhosis diagnosed
  • 16:01so cirrhosis has to be suspected
  • 16:04and that's the problem.
  • 16:06So your liver is your largest
  • 16:07solid organ and it regenerates,
  • 16:10which is marvelous.
  • 16:11But it doesn't tell you
  • 16:13it's sick until it's very,
  • 16:15very sick, and that's a problem.
  • 16:17So we would love to detect cirrhosis in
  • 16:20that early stage where patients don't feel
  • 16:24any different and their counts are still OK,
  • 16:27and there's still more or less healthy.
  • 16:29But more often than not,
  • 16:31we detect cirrhosis when people present with.
  • 16:34Signs of early liver failure,
  • 16:36like jaundice or bleeding or
  • 16:38very low platelet counts.
  • 16:39This is already very,
  • 16:40very advanced and it very much limits what we
  • 16:42can offer that patient in terms of treatment.
  • 16:44If they do have a liver cancer.
  • 16:47All patients with cirrhosis should
  • 16:49have screening for liver cancer in the
  • 16:52form of an ultrasound every six months.
  • 16:54And it's really important to talk to
  • 16:57patients about the fact that your body may
  • 16:59have problems even if you don't feel it.
  • 17:02And I think this is something that
  • 17:04people have a hard time wrapping their
  • 17:06head around that you could actually be
  • 17:09harboring a chronic illness and really
  • 17:11not notice any change in how you feel.
  • 17:13Which is why people really do need
  • 17:15to go to the doctor regularly.
  • 17:16It's it's an important thing to have
  • 17:18a physical and to have an established
  • 17:21rapport with a primary care doc who
  • 17:23knows you and has looked at you over
  • 17:25time and can see subtle changes when
  • 17:27they come up before you even feel them
  • 17:30doctor justice talk a
  • 17:31little bit more about that.
  • 17:32I mean, we talked about some of the
  • 17:34things that can lead to cirrhosis,
  • 17:36and I think some of us might be thinking.
  • 17:39You know, maybe I am a little bit overweight.
  • 17:41Maybe I do enjoy a couple of
  • 17:44drinks every now and then.
  • 17:46If these are factors that
  • 17:48potentially can lead to cirrhosis,
  • 17:50and cirrhosis is silent except
  • 17:52for when it's pretty late and
  • 17:55can affect my blood work,
  • 17:57how is that diagnosed?
  • 17:58I mean, should should I be going to the
  • 18:02doctor and getting an ultrasound of my
  • 18:04liver to see if if I have cirrhosis?
  • 18:07And would cirrhosis even show up
  • 18:09on an ultrasound or a CT scan?
  • 18:12Well again it depends on at
  • 18:14what stage you're talking about.
  • 18:15So very early signs of liver injury that
  • 18:18could lead to cirrhosis and may maybe
  • 18:21an early harbinger of cirrhosis is the
  • 18:25ratio of AST aspartate transaminase to
  • 18:28alanine transaminase and platelets,
  • 18:30which is also called FIB 4,
  • 18:32and that's a very routine test of patients.
  • 18:36Get it very frequently when
  • 18:37they see their doctors.
  • 18:38It's part of the the routine panel of
  • 18:40tests that are sent for blood work.
  • 18:42And if that test is abnormal
  • 18:45or not rock solid normal,
  • 18:47then it would be very reasonable
  • 18:48to have a conversation around.
  • 18:50Well, how much do you drink?
  • 18:51How long have you been drinking?
  • 18:53OK, let's look at your BMI,
  • 18:54which is an indication of what your
  • 18:56risk for fatty liver disease might be.
  • 18:58What's your family history?
  • 19:00You know those sorts of questions
  • 19:02can be explored,
  • 19:02and if enough of them are positive,
  • 19:04then yes,
  • 19:05an ultrasound would make some sense.
  • 19:07I'll let tomorrow talk a little bit
  • 19:09more about what would happen when
  • 19:10I refer the patient over after.
  • 19:12Ordering the ultrasound to the hepatologist,
  • 19:15but as the primary care doc.
  • 19:17Yes,
  • 19:17I would consider getting an ultrasound
  • 19:18on someone who I considered to
  • 19:19be at high risk.
  • 19:20So tomorrow just to to kind of
  • 19:22pick up the conversation there.
  • 19:25One of the things that you both
  • 19:27mentioned was that cirrhosis in and
  • 19:29of itself is not is not something
  • 19:32that you should aspire to have.
  • 19:35I mean, not only does it increase your
  • 19:38risk of of Pato cellular carcinoma,
  • 19:41but in and of itself.
  • 19:43It it can have problems.
  • 19:45You mentioned that the liver was
  • 19:47an organ that can regenerate.
  • 19:49If you do have cirrhosis.
  • 19:51If your blood work is abnormal,
  • 19:54is there a way that you can reverse that?
  • 19:57Can you lose weight?
  • 19:59Stop drinking,
  • 20:00you know you mentioned drugs
  • 20:03that can cure hepatitis C.
  • 20:05Now, can that reverse cirrhosis?
  • 20:09Or is is it the case that once
  • 20:11you have a cirrhotic liver?
  • 20:13You have a cirrhotic liver.
  • 20:15It depends on how how significant
  • 20:17the scarring is of the liver.
  • 20:19So very, very early cirrhosis.
  • 20:22We're beginning to think more and more
  • 20:24can be reversed if you take away the
  • 20:27whatever is insulting the liver, right?
  • 20:29So if it's viral hepatitis
  • 20:30you treat the hepatitis.
  • 20:31If it's alcohol, you stop drinking.
  • 20:33There are people who can have
  • 20:36their fibrosis reverse even very,
  • 20:39very early cirrhosis.
  • 20:40But once you have a lot of
  • 20:42scar laid down and a lot of.
  • 20:44Thick trabeculae we call them
  • 20:46sort of thick bands of collagen
  • 20:48deposition in the liver.
  • 20:50The liver really can't repair itself anymore,
  • 20:53and so there is.
  • 20:54There is a point at which you
  • 20:56cannot turn back the clock,
  • 20:58and so Amy, from an epidemiologic standpoint,
  • 21:01and we we kind of touched on this a
  • 21:03little bit before the break, but I just
  • 21:05want to unpack it a little bit more.
  • 21:08Is the rate at which you develop cirrhosis.
  • 21:11If you have had any of these different.
  • 21:16Sources of injury, whether it's alcohol,
  • 21:18whether it's a hepatite E, whether it's.
  • 21:22You know being obese is the rate
  • 21:26at which you develop cirrhosis,
  • 21:28different in in those different etiologic
  • 21:31factors and is the potential to develop
  • 21:36hepatocellular carcinoma based on those.
  • 21:40Our priority risk factors different
  • 21:43in amongst each of those risk factors.
  • 21:46So obviously drinking a little
  • 21:48alcohol versus drinking a lot of
  • 21:50alcohol is going to influence how
  • 21:52quickly you might develop cirrhosis.
  • 21:53You know if you,
  • 21:55if you are drinking extremely heavily
  • 21:57cirrhosis can occur much earlier
  • 21:59than if you're drinking fairly
  • 22:01heavily for a longer period of time.
  • 22:03We actually have studied this in HIV,
  • 22:06which is a risk factor also
  • 22:08for cellular cancer.
  • 22:10And we were able to show using the VA
  • 22:12data that people who were able to suppress
  • 22:15their HIV get their virus undetectable.
  • 22:18Had a much slower progression
  • 22:20to hepatocellular cancer than
  • 22:22the people who were not.
  • 22:24So I think that's actually a pretty good
  • 22:26template for a lot of these phenomenon.
  • 22:28If you can manage these risk factors,
  • 22:30try to get them as low as possible.
  • 22:32You can modify how rapidly someone
  • 22:34is going to develop cirrhosis,
  • 22:36and that's a very important
  • 22:37modification in terms of their
  • 22:39risk for hepatocellular cancer.
  • 22:41So do we know just to follow up on that?
  • 22:43Amy, do we know, for example,
  • 22:46that whether if you have a history
  • 22:49of hepatitis C that that's
  • 22:51worse in terms of developing?
  • 22:54Cirrhosis and subsequent Pato
  • 22:56cellular carcinoma. Then,
  • 22:58if you were a heavy drinker or you know,
  • 23:01being a heavy drinker is a little bit
  • 23:04worse than having a BMI of 30 do.
  • 23:06Do we have any kind of ideas about the
  • 23:09relative risk of each of these risk factors?
  • 23:12So hepatitis B is probably the
  • 23:15strongest individual risk factor.
  • 23:17Thankfully, the prevalence of hepatitis
  • 23:18B in the United States is relatively low.
  • 23:21When you talk about things like hepatitis C,
  • 23:24alcohol, fatty liver HIV,
  • 23:28it's not one size fits all.
  • 23:30It really depends on how severely you
  • 23:32have those problems or conditions,
  • 23:34and so it's it's not true to say that
  • 23:36one is much worse than the other.
  • 23:38It really depends on how
  • 23:40out of control they are.
  • 23:43Yeah, and so Tim are picking up on
  • 23:46what Amy had kind of lead us to.
  • 23:49You know if if you're referred to patient
  • 23:53who's got a suspicion for cirrhosis,
  • 23:56they come to you and they they've
  • 23:59had an ultrasound or a CT scan.
  • 24:03What's the next step in terms of you know,
  • 24:06checking to see whether they
  • 24:08have hepatocellular carcinoma?
  • 24:10So if they come to me with an ultrasound,
  • 24:12usually that ultrasound is sufficient
  • 24:15to look for large tumors in the liver
  • 24:18tumors over 2 centimeters, for example.
  • 24:20But we know that ultrasound in and of itself
  • 24:22is a very insensitive screening modality,
  • 24:25which is why there are studies underway to
  • 24:27look at more sensitive screening modalities.
  • 24:30When I'm refer to patient,
  • 24:32I actually think very carefully about.
  • 24:34What brought them to me?
  • 24:36So I think about viral,
  • 24:38metabolic and inherited disorders of
  • 24:40the liver that can lead to cirrhosis
  • 24:43as well as autoimmune disorders.
  • 24:45So I think you know,
  • 24:47cirrhosis is stigmatized because people
  • 24:49associate it entirely with alcohol.
  • 24:51And actually there are many different
  • 24:54causes of cirrhosis and even alcohol.
  • 24:56Some people can drink very heavily
  • 24:57and never have liver disease.
  • 24:59And some people can drink fairly
  • 25:00modestly and get liver disease.
  • 25:02So I think you know there
  • 25:03really should be no stigma.
  • 25:04Associated with cirrhosis.
  • 25:05So I I look at all of the sort
  • 25:08of pathways that could have
  • 25:10gotten them to where they are,
  • 25:12and then we usually in the liver
  • 25:14in the liver clinic now have non
  • 25:17invasive ways of testing the liver
  • 25:19stiffness which is a marker of of
  • 25:21how fibrotic the liver is and those
  • 25:24those ways of measuring are called
  • 25:26transient elastography where we
  • 25:28measure the stiffness of the liver
  • 25:31and can give the patient right there
  • 25:33in the clinic an estimation of.
  • 25:35How serious this may be,
  • 25:37and then from there I try to figure out
  • 25:40if there's anything I can help remove
  • 25:42that could be stressing the liver,
  • 25:45and so there are some treatments for
  • 25:47some of these different causes obviously,
  • 25:50and then you know they I make sure
  • 25:51I go over what we call cirrhosis,
  • 25:53health maintenance with the patient,
  • 25:56you know what they can do to
  • 25:57protect their liver,
  • 25:57how often they need to be seen,
  • 26:00how to protect themselves
  • 26:01against other illnesses,
  • 26:02because when the liver has cirrhosis,
  • 26:04it sort of loses a lot of its.
  • 26:06You know immune surveillance
  • 26:08ability for certain pathogens.
  • 26:10You know they need to be up to
  • 26:11date with their adult vaccines,
  • 26:13that sort of thing.
  • 26:14And then you know if if the
  • 26:15liver disease is very severe.
  • 26:17We talk about things like
  • 26:19liver transplantation.
  • 26:20And certainly if the patient
  • 26:21comes to me with liver cancer,
  • 26:23as many of my patients come to me with,
  • 26:24you know,
  • 26:25newly diagnosed liver cancer,
  • 26:26that's a whole other conversation around
  • 26:29prognosis and treatment and all of that.
  • 26:32So, so in our last minute,
  • 26:34maybe we can just talk a little bit.
  • 26:37About prognosis and treatment of
  • 26:40liver cancer tell us more about
  • 26:42how that's treated and and what
  • 26:44the prognosis really is Amy.
  • 26:47Well, this is really tomorrow specialty,
  • 26:49but unfortunately because people present
  • 26:51so late the prognosis is quite grim.
  • 26:54With that I will hand it over tomorrow.
  • 26:56So tomorrow are there.
  • 26:58Are there new treatments that can
  • 27:00make that prognosis less grim?
  • 27:02Yes, so in the last five years we've
  • 27:04seen a number of new agents come to
  • 27:07the market for advanced liver cancer.
  • 27:10We'd still really like to detect
  • 27:11liver cancer at its earliest stages,
  • 27:14where it either can be removed by
  • 27:16surgery or treated ablative Lee.
  • 27:18And so I think it's important to
  • 27:20really raise awareness for people
  • 27:22to get screened if they have
  • 27:24been diagnosed with cirrhosis.
  • 27:26Certainly we're always looking
  • 27:27at screening and risk factors,
  • 27:29and whether there are other things
  • 27:30apart from cirrhosis that would
  • 27:32bring a person to screening.
  • 27:33Like chronic hepatitis B for example,
  • 27:36but the treatments are dependent on
  • 27:38stage and the overall survival in liver
  • 27:41cancer is about 18% at five years,
  • 27:44which is dismal.
  • 27:45But it's getting better because
  • 27:48we have new agents,
  • 27:49things that can really change the
  • 27:51course of a patient's life is,
  • 27:53you know, surgery to remove the tumor,
  • 27:55but also liver transplantation in
  • 27:56patients who have liver disease and are
  • 27:59perhaps too sick for those surgeries.
  • 28:01And so you know,
  • 28:02there are a number of different local
  • 28:04treatments that can be done for sort
  • 28:05of what we call intermediate disease.
  • 28:07But the most important thing is for
  • 28:09the patients case to be discussed
  • 28:12in a multidisciplinary tumor board,
  • 28:13because there are many people who
  • 28:16manage liver cancer and we all need
  • 28:18to come to the table to develop
  • 28:20a a clear plan for the patient.
  • 28:22And you know, to really think about that,
  • 28:24patient their unique circumstances
  • 28:26and what's best for them.
  • 28:29Doctor Tamar Taddei is associate
  • 28:31professor of medicine and digestive
  • 28:33diseases and doctor Amy Justices CNH,
  • 28:35Long professor of medicine at
  • 28:37the Yale School of Medicine.
  • 28:39If you have questions,
  • 28:41the address is canceranswers@yale.edu
  • 28:42and past editions of the program
  • 28:45are available in audio and written
  • 28:47form at yalecancercenter.org.
  • 28:48We hope you'll join us next week to
  • 28:51learn more about the fight against
  • 28:53cancer here on Connecticut Public
  • 28:54radio funding for Yale Cancer
  • 28:56Answers is provided by Smilow
  • 28:57Cancer Hospital and Astra Zeneca.