Liver cancer has become the fastest increasing cause of cancer death in the United States. Now, several types of cancer can form in the liver. But the good news is, there are multiple treatment options.

We'll talk about those treatment options, prevention methods, and management of chronic liver diseases with a group of experts who are at the forefront of liver care. We'll take your questions and answer as many as possible. That's coming up now on At The Forefront Live.

[THEME MUSIC]

And today on At The Forefront Live, we have Dr. Pillai and Dr. Liao. Welcome to the program.

Thank you.

Thanks for having us

We'll get to your questions in just a moment. But first, we need to remind our viewers, the program is not designed it take the place of a visit with your physician. And let's just get started. And we can have each one of you tell us a little bit about yourself and what exactly you do here at UChicago Medicine.

Sure, of course. My name is Anjana Pillai. I'm a transplant hepatologist with the Transplant Institute. I direct-- I'm the Medical Director of our Liver Tumor Program, and I'm also the Co-director of our Living Donor Liver Transplant Program.

Dr. Liao?

And I'm Andy Liao, one of the medical oncologists at University of Chicago here. My focus is on liver and bile duct cancers. And together with Dr. Pillai, we run our multidisciplinary clinic here.

Dr. Pillai, let's start with you and just talk a little bit about the liver in general, and the functions that it performs for a person.

Absolutely. So many people may not know this, but your liver is actually your largest internal organ. It's pretty remarkable, and can sustain life when only about 10% to 20% of it is working, which is why many people actually don't know that they have advanced liver disease until they have symptoms.

Your liver does-- it actually does the most jobs of any organ in your body. It takes food and it breaks down the nutrients for energy. It stores many of your essential nutrients and minerals. It helps regulate blood sugar and produces blood sugar.

It helps-- it produces many of your clotting factors so that you heal from surgery or when you get a cut. It produces bile, which helps you metabolize fat. It helps you fight infections. And just as importantly, it also helps detoxify your body. So it helps break down chemicals and drugs you may injest, as well as alcohol.

Let's talk about liver cancer for just a moment. Is that becoming more common? I mentioned that in my intro, and it's something that I think a lot of people don't think about very much.

Yes, absolutely. So liver cancer is now the fourth leading cause of cancer-related death in the world. And in the United States, it's the fastest-growing cancer over the last several decades.

And so we have definitely noticed a rise in its incidence over all 50 states. It is the number 1 reason that patients are listed for liver transplant now in the United States. And in our own center, over 50% of our patients that are listed for transplant, it's due to primary liver cancer, or HCC.

And Dr. Liao, what are the different types of liver cancer?

So there can be many different types of cancer that happen in the liver. There can be primary liver cancer, meaning cancer arising from the liver cells. But inside your liver, there are also millions of bile ducts that help drain out the bile to help you digest. And there can be cancer arising from these bile duct cells.

And that's what's called bile duct cancer, or cholangiocarcinoma. And actually, the most common type of cancer that can go to the liver is actually-- it comes from somewhere else. For instance, colon cancer that goes to the liver, or lung cancer, or breast cancer, et cetera.

Dr. Pillai, you mentioned that the cancer death rates, liver cancer death rates, are increasing. Why do you think that's happening? Why are we seeing this?

Yeah, I think there's a few reasons. So just so we all orient ourselves, liver cancer, I'll refer to as HCC, is the primary liver cancer. Because Dr. Liao did mention there's several types of cancers that occur in the liver. But HCC often occurs in the background of cirrhosis, which is advanced liver disease.

So about 80% to 90% of cases occur because you have end-stage liver disease. And the most common reasons are alcoholic liver disease, hepatitis C, or fatty liver disease. So the reasons that we're seeing an increase is also-- because there's an increase in cirrhosis.

There's an increase in the number of patients that are now living with hepatitis C that have progressed to cirrhosis. We have better medications available, so people with cirrhosis are living longer. And also, because of the rise of fatty liver disease, alcohol, and diabetes, which also contribute to cirrhosis, there's an increase in all those different ideologies that all lead to the risk of liver cancer.

Dr. Liao, what were some of the symptoms that a person might experience if they do have a liver cancer?

So a lot of times, it's kind of non-specific, vague symptoms like feeling more tired, fatigued. Unexplained weight loss, or loss of appetite. Sometimes, if the liver function is impaired, patients might notice symptoms like swelling in their legs and having bloating in their abdomen, so fluid filled up inside their abdominal cavity, et cetera.

I'm sorry, but--

Go ahead.

--can I just build on what Andy said?

Sure.

That's exactly right. Patients often don't present until they have symptoms. And so by that time, many times, we don't have a cure.

And I know we're going to talk more in detail about that. So this is why-- where surveillance comes in. It's important to undergo surveillance and look for risk factors that may potentially put you at risk for liver cancer.

And can you talk about some of those risk factors? What would people need to be aware of? Obviously, you mentioned alcohol intake and obesity.

Yeah, absolutely. So 90% of liver cancer happens in the background of cirrhosis. So anyone with cirrhosis, which is advanced liver disease, or scarring of the liver, should undergo liver cancer screening.

There is guidelines from the US societies, from societies around the world, including Europe, Asia-Pacific, and they all recommend an ultrasound every six months for anyone with cirrhosis. Also, that includes patients with hepatitis B, many of whom, or at least 20% of whom, don't necessarily need cirrhosis to have liver cancer. So that subset of patients should also undergo regular screening. And there's guidelines for age related to that and when they should go undergo screening.

So Dr. Liao, if we go through the screenings and it's caught early, is it treatable?

Yeah. And in fact, it's curable if it's caught early. And that's why screening is so important.

What are some of the treatments that people might go through?

So there-- we've actually come a long way in how we treat liver cancer, how we treat primary liver cancer, hepatocellular carcinoma. So for patients with localized disease, options include surgery or even a liver transplant, which we'll talk about in a little bit. And then there are ways to directly treat the liver.

For instance, they can go in and burn off with our-- we call it radiofrequency ablation, but burn off small liver tumors. There are ways to microwave the small liver tumor. And then there's ways to go indirectly the liver with a catheter and plant radiation seeds in there to treat localized liver tumors that way. And then there are a lot of new treatments that treat the whole body for patients with more advanced cancers, cancers that spread outside the liver. These include targeted therapies and also immunotherapies.

That's interesting. And immunotherapy is one of those areas that we've talked about quite a bit recently. What happens in that case with the patient?

So immunotherapy is a very different way of treating cancer, and it's been-- has generated quite a lot of excitement in cancer treatment. And not just liver cancer, but in many different other kinds of cancer. And it's actually been approved in liver cancer and other kinds of cancer by the FDA.

So the way, in general, it works is that it tricks your body to go after-- so essentially, it's like your body doing the job of attacking the cancer cells. So normally, your body's immune system is very good at detecting bad cells.

So if you go out to the beach and get a sunburn, you don't immediately get skin cancer. And that's because your body's immune system recognizes that there are damage cells, and sends those damaged cells to go away. So for a cancer to grow in your body undetected by your immune system, it must have somehow come up with ways to escape from your immune system's surveillance.

And so a lot of these new immunotherapy treatments that we have essentially un-hides this cancer from your immune system. And then your immune system goes after it. And studies in liver cancer have shown that it's provided significant benefits in liver cancer patients.

That's fascinating. And I love the sunburn analogy. I've never really thought of it that way, but that makes perfect sense. I mean, your body does do a lot of the work to prevent some of these things--

Absolutely.

--you can't always. That's fantastic. So let's talk about some of the other treatment options. You mentioned them briefly, but what are the more common treatment options? And what should people expect?

So I think, as Dr. Liao said, it really depends at the stage in which you're diagnosed. So again, just going back to the importance of surveillance, by the time-- if you present with symptoms, some of the symptoms that Dr. Liao. described earlier, oftentimes, your cancer is advanced. And oftentimes, it's not curable.

So this is why we have surveillance for liver cancer, because the whole idea of surveillance for any cancer, really, is if you have the options of curative options if the cancer is detected early. So if you undergo proper surveillance, if you have cirrhosis or if you have hepatitis B and you detect a small lesion that's localized, meaning it hasn't spread, it's a certain size or a certain number, the curative option includes resection. So taking-- removing that tumor, which we work very closely with our transplant surgeons, our hepatobiliary surgeons, and then transplant.

So as I stated earlier, a liver transplant is a curative option, and it's the number 1 reason many of our patients-- I'm sorry. Rather, liver cancer is the number 1 reason many of our patients are on the liver transplant list nationally. So both those things are 100% curative.

And then some of the other treatments that Dr. Liao recommended, such as-- so we call it "liver-directed therapy." So unlike most cancers, we're able to direct treatment right into the tumor itself, often through a catheter through your groin area. And that's either radiation seeds, or it's chemotherapy beads.

We can also microwave, or ablate, that lesion. And then if it's more advanced, that's when the combination of either doing a local or regional therapy, or adding systemic therapy, which are many of the newer medications, come into play. For liver cancer, interestingly, until 2008, we only had one--

Right, yeah.

--systemic therapy.

So the next question from one of our viewers. If a lesion can't be biopsied, what are my options?

A lesion can be biopsied. It absolutely can. However, for liver cancer, we don't recommend a biopsy if it's classic because there-- over the years, what we've learned is liver cancer has a very characteristic appearance on cross-sectional imaging, which is when you get a CT scan or MRI.

But it has to be with contrast. That means there has to be a dye that goes into your IV. And if you have the right test, it looks very specific. And if it meets all those guidelines, then you do not need to be biopsied. If--

Yeah. Saves you an invasive procedure.

Absolutely.

Yeah.

However-- and we review all these things, and we have a tumor board where we review every patient and their case. However, if we are concerned that it might not be classic for liver cancer, or we're concerned that it could be a bile duct cancer, or some cancers are mixed, then we will biopsy.

Right. And then for patients that we're considering other newer forms of therapy, patients with more advanced disease, nowadays, we're getting smarter about personalizing each person's treatment. And so sometimes, to consider patients for newer treatments, clinical trials, et cetera, sometimes we would want a biopsy in that setting to see what kind of genetic changes there are in the tumor cells, and see if we can find new targeted therapies or clinical trial options for that patient.

Can we talk about the tumor board for just a minute, and explain to viewers what that is and what that does? Because I think that's very important in your jobs.

Can we talk about our tumor program first?

Absolutely.

[LAUGHS]

[LAUGHS]

So Andy and I are both part of our multidisciplinary Liver Tumor Program. We're very proud of it at the University of Chicago, because we are one of few centers in the Chicagoland area that really have it. And it's a one-day clinic where there is a transplant hepatologist, a transplant-trained surgeon, an oncologist, an interventional radiologist could all see the patient if they need to.

And again, this is because liver cancer often happens in the background of liver disease. So you'd need expertise in liver disease. And you also need expertise in oncology.

And so when our patients come, we really try to determine, OK, who do you need to see? And to the best of our ability, we will see patients together in-clinic. Our interventional radiologist will come up, or their nurse practitioner will come up. Our surgeons are almost always available in-clinic for us. And it really helps enhance the patient experience because they get quite a lot of time with all of us.

Yeah. It's like one-stop shopping. And it really just highlights-- because we have so many different treatment options nowadays for liver cancer, it's so important for every specialist to come together and deliver the best treatment plan-- individualized treatment plan for each patient.

And so once we have that, once we see that patient in that clinic, then we have all discussed who sees the patient. And then we have a tumor board every Thursday. So all those patients go on that tumor board, where again, all of us are present. There's about 15 to 20 physicians that specialize in liver disease from different disciplines that come to the tumor board.

And then we make recommendations for treatment, follow-up, future treatments, transplants. All of that's done. And then it goes into the medical records. The patients are called. So it's a very step-wise, streamlined procedure-- process that we have implemented over the last two years. And we're very proud of it.

Yeah.

So we have another question from a viewer. Is the AFP tumor blood test accurate?

That's a very good question. So the AFP is the Alpha-fetoprotein. So it was, up until very recently, part of the surveillance. So we kept talking about surveillance, but I don't think we talked about what that entails.

So surveillance means if you have cirrhosis of the liver, or if you have hepatitis B, and you are an Asian man greater than 40, or if you're an Asian woman greater than 50, or an African, not African-American, Africans with hepatitis B greater than 20, you should be screened for liver cancer. And that includes an ultrasound of your abdomen at minimum every six months. And going back to the AFP, AFP was the tumor marker that was also recommended in addition with the ultrasound.

The issue is, not all tumors produce AFP. Only about 60% do. So it is a tumor marker that can help us prognosticate and help us in surveillance. But because it's not seen in all tumors, if you just get an AFP, you may miss 40% of tumors.

So one of the questions we had on the list was, how long can you live with liver cancer before you actually need a liver transplant? You don't obviously always need a transplant, but--

Yeah. Again, I think it really depends on the stage at which you present. So if you undergo surveillance and it's caught before symptoms, it's caught early, of course, you are going to be more amenable to curative options. Like we said, taking the tumor out or the transplant.

Now, of course, that depends on the health of your background liver and your overall functional health yourself. Now, if you have more advanced cancer-- there's a lot of timelines that say once it's metastasized, or goes outside the liver, or goes into any of your major blood vessels, your five-year survival is lower. It's about 10%.

However, that's before many of these new treatments came out. And keep in mind, these treatments just came out, really, in the last two years. So now we are seeing people that live longer. And so if they live longer, there's also newer treatments coming out.

So that's where the idea of sequential therapy, meaning you start one treatment. If they fail, there's a second-line treatment. There's a third-line treatment.

Or we go back and we reconsider the local regional therapy. We didn't have any of those options just even two years ago, which is why these statistics were so poor. Now, I'm not saying that we're anywhere close to where we would like to be to cure advanced liver cancer, but I do think that we have many more options than we did just a few years ago.

And Dr. Liao, one of the advantages that we have here-- as an academic medical center, we do a lot of research and clinical trials. Can you talk to us a little bit about some of the clinical trials, the research, that may be happening in this area?

Yeah. So as I said, immunotherapy has generated a lot of excitement, and there are a few drugs that already have been FDA-approved for liver cancer. But we're always trying to improve upon current standards in immunotherapy. So a lot of the next-generation in clinical trials that are coming up are focusing on these next-generation immunotherapy approaches, where they're combining immunotherapy with a different kind of immunotherapy, or combining immunotherapy with targeted therapy, or using immunotherapy in an earlier setting. For instance, starting patients on immunotherapy right after surgery.

And some of the trials we have here-- one of them we have is very cool. It's called an oncolytic virus. So basically, we hijack a virus to infect the tumor. So it's a kind of immunotherapy in that way. And we've seen some pretty dramatic responses to that.

We also have trials combining current immunotherapies with what's called "targeted therapy." So these are drugs in general pills that target different ways that the cancer uses to grow. For instance, a lot of these target how cancer cells make new blood vessels, so prevents them from growing or spreading by inhibiting their ability to make new blood vessels. We also have studies looking at what's called "metabolic therapy," meaning depleting key nutrients in the liver tumor microenvironment to make them more responsive to conventional treatments, and make the immune environment more favorable. So lots of exciting things going on.

Yeah, it sounds like the research is really booming on this. There's very exciting things happening in the world of science when it comes to liver tumor and cancer. So that's good news for all of us. So interesting question. A colonoscopy, can that help detect?

You know, we get this all the time. I do colonoscopies. I'm a gastroenterologist that self-specializes in transplant medicine. But, no. So a colonoscopy looks at your colon. And many people always ask me if their liver looks OK.

[LAUGHS]

And I say, you never want me to see your liver while I'm doing a colonoscopy--

You're not going that far, yeah.

--because that means I went through your perineum. [LAUGHS] So no, I don't see your liver when I do a colonoscopy. What it can tell us if there's any masses.

So colon cancer, of course, is the reason we do colonoscopies. Colon cancer surveillance. And that is one of the cancers that do go to the liver.

And we are-- we do see those types of patients in our clinic. And we're seeing these patients present younger. So a colonoscopy is important.

You should get colon cancer surveillance as well, which we have guidelines for. So in that regard, it's very important. But it's not a way to detect primary liver cancer.

Interesting. Is there such thing as a benign liver tumor? And if so, does it hurt you at all? Can you live with it?

Yes. So no, it does not hurt you. And yes, there are benign liver tumors. So I actually give this lecture quite often.

And the way that I look at liver tumors is benign lesions that never need follow-up, benign lesions that need follow-up, and then malignant things, like what we're talking about with liver cancer and bile duct cancer. So because we get cross-sectional imaging or a CT scan for so many reasons, we see all these new things-- or, we see all these things pop up in the liver that you may have had your whole life that never will have any impact. So hemangiomas are the most common things, which is abnormal collection of blood vessels.

You can see cists. You can see flocculonodular hyperplasia or adenomas. All of these are-- they have different-- they're different subsets of benign tumors. Some never need to be followed, and some need to be followed, or your lifestyle modified a little bit. But absolutely. You don't need to chase every lesion that you see in the liver.

So if you do have liver cancer, are you automatically added to the transplant list? And if so, how long does it usually take?

Yeah. Thank you for that question too, because then I can plug this Donate Life, which is very important--

That is very important, yes.

- --to all of us. So you have-- so you don't automatically get on a transplant list, no matter what. There is a pretty extensive work-up our patients go through. So in addition to an indication, which is often the advanced liver disease, or in this case, I should say a liver cancer, we have to make sure the liver cancer is not too advanced, because then we can't offer a cure with the liver transplant.

And then-- but we also have to make sure you fit all the other criteria for a liver transplant. That you're medically otherwise stable. That surgically, the surgeons can do it. That you have good support system.

That you don't have any psychological issues that bar treatment. That you don't have substance abuse issues. These are all just as important to get on that list.

And once you get on the list, the time is very variable. The United States is divided into 11 regions by the United Network of Organ Sharing, which kind of controls this. And we're region 7.

And so for our region, it can go anywhere from 6 to 18 months once you're put on the list for liver cancer, as to when you would get a liver. And so for that reason, we also have a Living Donor Program at the University of Chicago Medicine. So if you have relatives that could potentially donate, or close friends, or community members, altruistic donors, that is also an option. And I know we're over time--

It's OK.

--but I just think that purpose of organ donation-- the issue is, we want to give livers to our patients. The problem is, there's about only 6,000 to 8,000 livers that we do a year, and there's about 16,000 patients waiting on the liver transplant list. So just not enough supply for the demand that we have.

Well, you guys were fantastic.

Thank you. This was so much fun.

Thanks so much.

And both so young.

[LAUGHS]

Thank you, thank you.

That's all the time we have for the program. Thank you for being on the show, and thank you for your wonderful questions. If you want more information, you can visit our website at uchicagomedicine.org, or you can call 888-824-0200. And also, remember to keep an eye on our Facebook page for more events and live programs that will be coming up soon. Thanks for watching, and have a great week.