Liver Cancer Advances

May 03, 2021

Information

May 2, 2021

Yale Cancer Center

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email: canceranswers@yale.edu

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00:00Support for Yale Cancer Answers
00:02comes from AstraZeneca, dedicated
00:05to advancing options and providing
00:07hope for people living with cancer.
00:10More information at astrazeneca-us.com.
00:14Welcome to Yale Cancer Answers with
00:16your host doctor Anees Chagpar.
00:18Yale Cancer Answers features the
00:20latest information on cancer care by
00:22welcoming oncologists and specialists
00:24who are on the forefront of the
00:26battle to fight cancer. This week,
00:28it's a conversation about liver
00:30cancer with Doctor Mario Strazzabosco,
00:32Doctor Strazzabosco is a
00:34professor of medicine and clinical
00:36program leader of the liver Cancer
00:38program at the Yale School of Medicine,
00:40where Doctor Chagpar is a
00:42professor of surgical oncology.
00:46Mario, maybe we can start
00:47off by you telling us a
00:50little bit about liver cancers.
00:52So often people have different
00:54kinds of liver cancers.
00:56Sometimes cancers have started
00:57somewhere else and go to the liver and
01:01sometimes cancers start in the liver.
01:03Can you give us a
01:06framework of how to think about
01:08liver cancers?
01:10We distinguish cancers that start in the liver and
01:13we call them primary liver cancer,
01:16from cancer that goes into the liver with
01:19the primary cancer somewhere else.
01:23Those are called secondary liver
01:26cancer and in essence they are
01:29metastasis from a primary tumor.
01:32Today the topic will be
01:35cancer that happens
01:38in the liver as a primary site.
01:43And those are less common than the
01:45cancers that spread to the liver
01:48from other sites, is that right?
01:51That is right they are
01:52definitely less common,
01:54but it is true that
01:56primary liver cancer is actually one
01:59of the few cancers that are still
02:02increasing in terms of incidence
02:04and also in terms of mortality.
02:06So tell us a little bit
02:09more about primary liver cancers.
02:11Are there different types
02:12of primary liver cancer?
02:14Yes, there are several types.
02:17The two main types are
02:22hepatocellular carcinoma,
02:24which is the cancer
02:28that starts from the liver cells.
02:32It is the most common of them and the
02:37other is called cholangiocarcinoma
02:39and that starts from the bile ducts
02:42inside or outside of the liver.
02:45And this is less common.
02:46You mentioned that the
02:50incidences was increasing. What are
02:53the risk factors for getting liver cancer?
02:59This is a very important question.
03:03So liver cancer is increasing as a result of
03:06several worldwide epidemiological trends.
03:10The main risk factor is one, having liver disease.
03:15Two having hepatits c, three having
03:18hepatitis B, four, having an excessive
03:21consumption of alcohol, five, having
03:24what we call metabolic syndrome,
03:27which is the result of being obese
03:31or overweight or having diabetes,
03:34or having other cardiovascular risk factors.
03:38In addition to that,
03:40there is a 6th epidemiological
03:42trend which is very important,
03:45which is the poor access to care in certain countries.
03:55These are the main factors that
03:58contribute to increasing the
04:00incidence of primary liver cancer,
04:03and particularly of hepatocellular carcinoma.
04:06Of course, the combination of these factors
04:09changes according to the geographical area.
04:21It used to be that in the US,
04:24the incidence of HCC was lower
04:27for example, than Asia, Africa,
04:30or other places.
04:31But now with migration and other factors,
04:34it tends to become more equal in terms
04:38of distribution of risk factors and
04:41also the risk factors are changing,
04:43so we used to have a very big
04:47impact of hepatitis C.
04:49Now with the new treatments
04:53we see a rise in the
04:56hepatocellular cancer
04:57which is a consequence of the metabolic
04:59risk factor such as diabetes,
05:03so the incidence in the US vs Asia
05:06has increased.
05:09You mentioned that was due to in part to migration i.e.
05:13people from Asia moving to the US which
05:16might imply some genetic factors.
05:18So is there a genetic underpinning
05:21to some of these cancers as well?
05:25I think this is more exposure
05:27to viral hepatitis.
05:29For example, one of the main factors
05:32in hepatitis B
05:34which is a direct oncogenic virus
05:37and it used to be lower here and higher
05:41for example, in the Mediterranean
05:43countries and in Asia.
05:45And changes in the
05:49worldwide population may change that.
05:51But one peculiar thing in the
05:54US is actually the increase
05:57of metabolic risk factors.
05:59Cancer associated with obesity
06:03and diabetes and one important thing
06:06to understand in terms of liver cancer
06:09is that whereas we try to focus on
06:12one risk factor as a matter of fact,
06:15patients with liver cancer,
06:16have several risk factors. It is not unusual
06:19to find a patient that is
06:21overweight, maybe is diabetic,
06:23which goes with being overweight and
06:25he didn't know he had hepatitis C
06:29so lived a normal life with
06:32drinking more than his liver could stand,
06:35and so here we are and maybe
06:38even he was smoking.
06:40So just a regular guy that had
06:43accrued four risk factors for liver cancer.
06:45So this is very important to understand
06:48when they add to each
06:51other the increasing the risk factor
06:53is exponential.
06:54I want to pick up on the viral
06:57hepatitities which increase the risk
06:59of developing hepatocellular cancer.
07:02So hepatitis B and hepatitis C,
07:05interestingly, as we're living
07:07through Covid right now, another
07:09viral disease for which we have a vaccine,
07:14it's important to understand that
07:17there are vaccines for hepatitis B&C.
07:21Have those vaccines had any
07:23impact on reducing the rates
07:26of hepatocellular cancer?
07:29We have vaccination available
07:31for hepatitis A&B. Hepatitis A is not
07:34associated with liver cancer, it is the
07:37hepatitis that is actually acquired
07:41through eating shellfish,
07:43or seafood. Hepatitis B,
07:48we have a vaccine which is extremely
07:52efficient and we have data showing that,
07:55for example, in some country in Africa
07:59where they had a very high incidence
08:02of a hepatocellular cancer because of the
08:06maternal fetal transmission of hepatitis B,
08:09they implemented a mass
08:12vaccination program there.
08:14And the incidence of liver cancer dropped
08:17dramatically, so yes,
08:19it is there and we can decrease the
08:22incidence with vaccination and in fact
08:25most people in the younger generation
08:29are vaccinated for it.
08:33Unfortunately we never made it with
08:36trying to find a vaccine for hepatitis C because of
08:39this high variability of the virus.
08:42But we were lucky because
08:45we were able to devise
08:48pharmacological treatment and so now
08:50we have very effective ways to eradicate
08:54the virus using small molecule compounds.
08:58And that is important information.
09:01And overall I think one message
09:03that it would be very important
09:06to get through to the public, is that
09:09most formal liver disease and therefore
09:12also liver cancer are preventable.
09:14And also treatable in terms of liver disease.
09:18So you can
09:20prevent risky behavior for viral
09:23hepatitis, you can use vaccination.
09:26You can treat the virus
09:30if you realize you are
09:33infected before having a cirrhosis.
09:36Avoid, of course,
09:42excessive use of alcohol.
09:43You can act on the lifestyle if you
09:47have diabetes. If you are
09:50obese,
09:53you can lose weight.
09:54You can increase your exercise.
09:57You can control those factors and so
09:59all of them are actually preventable,
10:02acting both at a personal level
10:05and public health action.
10:08Let's pick up on on that.
10:11You mentioned a
10:14number of preventative measures,
10:16so if somebody gets vaccinated
10:19against hepatitis B, for example,
10:22and never contracts hepatitis B,
10:24it's understandable then that
10:26they've eliminated that risk factor,
10:29but if they get hepatitis
10:32C and are treated for it,
10:35does that eradicate the risk of
10:38developing hepatocellular carcinoma?
10:40Or is the fact that they already had
10:44hepatitis C even though it was treated,
10:48does that still increase their risk?
10:58Number one, there's a lot of
11:01people that have hepatitis C
11:03and don't know it, particularly
11:06in the so called baby Boomer.
11:09#2 this drug that I was mentioning,
11:16DAA, direct active antivirus,
11:19are extremely
11:23good and can eradicate
11:25the virus in most cases.
11:27Then the question becomes
11:30at what stage did you apply that treatment?
11:32Did you have just a minor
11:37chronic hepatitis or were
11:40you already progressed to have
11:44more fibrosis and cirrhosis.
11:47And the risk decreases in
11:49a different way whether you
11:51treated hepatitis before becoming
11:54cirrhotic or when you were already
11:57cirrhotic?
11:59In this second instance,
12:01the decrease in the risk is less important.
12:06The thing that we learned after treating
12:09many patients and erradicating
12:11the virus is that the risk of
12:15having liver cancer was decreasing,
12:17but was not zero.
12:19So there is still a substantial risk,
12:22even if it is, let's say halved.
12:29And there is a big controversy in the literature,
12:32but I won't go into that,
12:34but I think that one of the problems is,
12:39the timing in the Natural History
12:41of disease in which you apply the
12:44treatment and just to go back to
12:48the beginning of this conversation,
12:50we said most patients
12:53with liver cancer
12:54have more than one risk factor.
12:57So if I only eliminate the
12:59virus and eradicate it,
13:01I decrease a very important risk factor.
13:04But I don't zero the risk factor
13:07because the patient
13:09may be diabetic, the patient may be overweight,
13:12but the patient may be drinking
13:14or go back to drink because
13:16now he doesn't have the virus.
13:18So again,
13:19one of the important messages
13:25is that liver cancer is a very
13:29comprehensive approach.
13:31Eliminating the virus is just step one.
13:33We're going to pick
13:35up on how we deal with all of the other
13:38lifestyle factors right after we take
13:41a quick break it for a medical minute.
13:44Please stay tuned to learn more
13:46about advances in liver cancer with
13:49my guest doctor, Mario Strazzabosco.
13:51Support for Yale Cancer Answers
13:53comes from AstraZeneca, working to
13:56eliminate cancer as a cause of death.
13:58Learn more at astrazeneca-us.com.
14:01This is a medical minute
14:03about smoking cessation.
14:05There are many obstacles to
14:07face when quitting smoking,
14:08as smoking involves the potent drug nicotine.
14:11But it's a very important lifestyle change,
14:14especially for patients
14:15undergoing cancer treatment.
14:17Quitting smoking has been shown to
14:19positively impact response to treatments,
14:21decrease the likelihood that patients
14:23will develop second malignancies,
14:25and increase rates of survival.
14:27Tobacco treatment programs are
14:29currently being offered at federally
14:31designated Comprehensive cancer centers
14:33and operate on the principles
14:35of the US Public Health Service
14:37clinical practice guidelines.
14:39All treatment components are evidence
14:41based and therefore all patients are
14:43treated with FDA approved first line
14:46medications for smoking cessation as
14:48well as smoking cessation counseling
14:50that stresses appropriate coping skills.
14:53More information is available at
14:55yalecancercenter.org you're listening
14:57to Connecticut Public Radio.
14:59Welcome back to Yale Cancer Answers.
15:02This is doctor Anees Chagpar and
15:05I'm joined tonight by my guest
15:08doctor Mario Strazzabosco.
15:09We're discussing the care of patients
15:12with liver cancer and right before
15:15the break Mario you were telling us
15:18about this plethora of factors that
15:20increase people's risk of
15:23liver cancer and the fact that
15:26while we do have interventions for
15:29hepatitis there frequently are other
15:32factors that are are involved.
15:35You mentioned a few that I'm
15:37going to lump together,
15:40which are metabolic syndrome.
15:43So obesity and diabetes,
15:45as well as alcohol which
15:47can lead to fatty liver.
15:50So can you tell us a little
15:53bit more about fatty liver,
15:56and whether that impacts the development
16:00of liver cancer and whether
16:02there's any quote safe amount
16:05of alcohol that we can consume?
16:14What we call fatty liver is
16:17a very common condition which
16:20is identified by an increased
16:22deposition of fat in the liver cells.
16:25Fatty liver can be the result of several
16:31problems, but most likely it's due to
16:37the effect of obesity,
16:39the affect of diabetes, hyperlipidemia,
16:42and what we call metabolic syndrome,
16:46which is a complex of
16:50changes that are increasing
16:52the risk of cardiac disease.
16:54This is how we recognize this
16:58at the beginning and we used to think that fatty
17:02liver was a relatively benign condition,
17:06but now we
17:08understand that some patients
17:11with fatty liver
17:13will develop an
17:18inflammatory condition of the liver
17:20that is not any more benign but can
17:24lead to chronic liver disease like
17:26cirrhosis and can be associated with
17:29the development of liver cancer.
17:31Clearly the amount of people that are
17:35affected by this condition is very high, so
17:41the question is how do we
17:43follow those patients?
17:44What do we do?
17:51It would be important to try to prevent it,
17:55and so how do you prevent it?
17:58There is data that shows if you lose
18:0210% of your body weight the risk decreases.
18:05This 10% of your body weight
18:08should be lost in your
18:11abdominal fat because this
18:13is a fact that is more
18:17associated with this complication.
18:25An increase in physical activity is going to play a role.
18:29We see that with patients that
18:32have this predisposition,
18:33a low carbohydrate diet is preferred.
18:36They should avoid sodas and so on.
18:41I do understand this is
18:45a change in lifestyles which
18:49are very very difficult to achieve.
18:53But addressing this metabolic factor is
18:56really part of the constellation of medical
19:02action that we need to take.
19:11I mean it seems like this really,
19:15that constellation to
19:18exercise more, lose weight, eat right,
19:21that's really a constellation for good
19:24health in general, and it has so many
19:27really important health benefits.
19:29But one question that people
19:32may be wondering about is,
19:35if I've been overweight
19:38all my life and we know that there is
19:41an uptick now
19:45even in childhood obesity.
19:47So if somebody has been overweight, obese,
19:50they then lose a bunch of weight,
19:53is the damage to their liver already
19:56done such that you're
19:58having a relatively small impact on
20:01reducing hepatocellular carcinoma?
20:03Or is this really reversible?
20:11If you eliminate the
20:15damaging condition to the liver,
20:17you can to a certain extent
20:21reverse the chronic damage.
20:23We learned this when we started
20:25to treat patients with hepatitis B and antivirals.
20:30They were very effective in suppressing
20:33the virus and that patient
20:36went from a complete cirrhosis
20:38to an incomplete cirrhosis.
20:40So yes, there is a remodeling of your
20:42liver and this is not
20:44complete in how much it happens.
20:47It depends how far you went,
20:49but there is to a certain extent
20:52a remodeling or the liver and
20:54we saw that happening in patients
20:56that stopped drinking alcohol.
20:58All of them have an improvement.
21:01And we saw that with patients
21:03treated for hepatitis.
21:04Now to what extent this is going to impact
21:09the natural
21:10history of metabolic liver
21:11disease is less certain,
21:13but it's very likely that we can,
21:17for example, if you
21:18decrease your body weight,
21:20your risk decreases.
21:21Now the trick is that when
21:23you decrease your body weight,
21:26you don't need to get it back,
21:29So it's very easy to decrease 10%
21:31of your body weight,
21:33but what it counts is 2 years after.
21:37Did you maintain that 10%
21:39decrease because that is what
21:41counts in terms of
21:44risk reduction.
21:46So you want to
21:48make sustainable lifestyle changes now.
21:50One of the things that you
21:52mentioned was that you've seen the
21:55fact that you can reduce risk in
21:57people who have stopped drinking,
22:00so abstained from alcohol,
22:01but some people may be wondering,
22:05is there any quote safe limit for alcohol?
22:08So if you used to drink 4 drinks a night,
22:12is it OK to drink one drink a night?
22:16Is there any safe level of
22:20alcohol to which the damage to your
22:23liver is minimal and the risk of
22:28hepatocellular carcinoma is minuscule?
22:30Or is all alcohol going to be
22:33somewhat toxic to your liver?
22:40We used to think that there
22:42was a threshold, and
22:44this is being kind of revised,
22:46but it's very well known that a little
22:49amount of alcohol can actually
22:52improve your metabolic risk.
22:54However, how little is enough,
22:56it doesn't really depend on a fixed dose.
22:59It depends what your
23:02genes are and what your history is.
23:05So if you're drinking alcohol but
23:07you have hepatitis C, it's zero,
23:09there's no even smelling it.
23:12So it's a difficult question to reply.
23:22In general your advice is
23:25abstinences is the gold standard.
23:28It depends on what your
23:30overall risk profile is.
23:32But let's say if you drink once in a while,
23:36that is clearly not a problem,
23:38But if it's your habit,
23:42it may become a problem.
23:46This doesn't say that if
23:48you go out for dinner,
23:49you can drink a glass of wine.
23:51Of course you can,
23:53even eating a candy is OK.
23:57But not OK if you have diabetics.
24:00This brings us to the point
24:03of surveillance of the liver, right?
24:06How can we tell how damaged our liver is,
24:10whether it's from diabetes,
24:11or whether it's from obesity,
24:13or whether it's from alcohol,
24:15or whether it's from hepatitis.
24:17As you mentioned before the break,
24:20we may not even know that we have.
24:23Are there ways of looking
24:25at the liver?
24:28Yes, so everything starts
24:30from understanding whether
24:32you liver is damaged or not,
24:34so you may for any reason do
24:38some laboratories tests that
24:39include liver function tests.
24:41You may get an ultrasound or
24:43you may get tested for hepatits
24:46C for example if you
24:52were born a baby boomer,
24:54so if you had a risky behavior
25:00anything that may increase risk,
25:04then a way to understand how
25:06chronic is your damage,
25:08you can use a fiber scan so it's like
25:12a machine that
25:14looks like an ultrasound,
25:16but it is not ultasound because this
25:19measures how elastic is your liver and
25:21that can give us an estimate whether
25:24you have significant fibrosis or not.
25:27Or you can do an MRI, there are
25:30several ways to understand if you
25:32liver disease, and
25:34then if you have chronic liver
25:37disease with significant fibrosis,
25:38the current guidelines are that
25:40you should be doing an ultrasound,
25:44every six months.
25:47And there is very good evidence that
25:50this can help diagnose liver cancer
25:54in early stage and therefore in a
25:58stage when the treatment can be successful.
26:01There are other patients that may
26:03need screening, like patients
26:05mainly from Asia that have hepatitis.
26:12and are less than 40 years of age.
26:20Or for example, a patient with hepatitis C that
26:23has been treated,
26:26but they have significant fibrosis.
26:33So the screening is a very important
26:36component of our strategy, but
26:39still we see patients coming to the
26:43clinic with advanced stage cancers.
26:47Or cancer that is beyond curative options.
26:52And that is a failure of screening,
26:55but of course you can have the
26:58situation in which the patient
27:00didn't know he had liver disease,
27:02because a lot of times liver disease
27:05can be significant but not
27:07symptomatic.
27:13So still the amount of patients that come
27:16with advanced liver disease is too high
27:18because we do have again
27:22ways to prevent the cancer, ways to screen
27:25to get an early diagnosis and it
27:29is important because we now have
27:31several ways to approach liver cancer
27:34and therapeutic approaches
27:38are increasing every year.
27:42So it's very important to get diagnosed
27:44and to go to a center where you have a
27:48multispecialty program so that all
27:50aspects of the care can be addressed
27:53at the highest professional level.
27:55And it brings back one of the other
27:58risk factors that you mentioned
28:00which was access to care people who
28:02don't have good access to care,
28:05and I wonder whether you
28:06mentioned that as a risk factor.
28:09Because if you don't have access to care,
28:12you can't get appropriate screening,
28:14is that right?
28:16You cannot and appropriate care
28:21is something that we will be
28:24investigating next because it's really
28:26a pity that you have ways to prevent it,
28:28way ato treat it, but people don't
28:31even get close to that opportunity.
28:33It's really saddening.
28:35Doctor Mario Strazzabosco is a
28:37professor of medicine and clinical
28:39program leader of the Liver Cancer
28:41program at the Yale School of Medicine.
28:44If you have questions,
28:45the address is canceranswers@yale.edu
28:47and past editions of the program
28:49are available in audio and written
28:51form at yalecancercenter.org.
28:52We hope you'll join us next week to
28:55learn more about the fight against
28:57cancer here on Connecticut Public Radio.