Scott Webb (Host): Hepatocellular Carcinoma or primary liver cancer is the ninth leading cause of death in South Carolina and nationally. My guest is here today to tell us more about primary liver cancer and the importance of lowering our risk factors and being diagnosed early. I'm joined today by Dr. Derek DuBay. He's a Transplant Surgeon with PRISMA Health.

This is Flourish, the podcast brought to you by PRISMA Health. I'm Scott Webb.

Host: Doctor it's so great to have you here today. We're essentially going to talk about liver cancer but really Hepatocellular Carcinoma, the most common type of primary liver cancer, but risks, symptoms, prevention, you know try to get as much information as we can out there. So let's start there today what is Hepatocellular Carcinoma?

Derek DuBay, MD, MPH: Hepatocellular carcinoma is the most common primary liver tumor. When I say primary that means a tumor that arises from within the liver. You know, within the liver there's many different cell types but the most common are your liver cells and then your bile duct cells and this is a cancer that arises from your liver cells, your hepatocytes, thus the name, hepatocellular carcinoma. You know, overall the incidence of all cancers that occur anywhere in the body has actually been decreasing over the past several years with three exceptions. And this is one of the big three exceptions of cancers that is fastly rising in incidence is hepatocellular carcinoma. Hepatocellular carcinoma is the ninth leading cause death in South Carolina.

It's the ninth leading cause of death in the United states as well. It's interesting too, when people die, the CDC, the Centers for Disease Control, they categorize all deaths into these discrete, uh, areas and you know the number one is cardiovascular. Number two is cancer. But hepatocellular carcinoma is one of the only cancers that I'm aware of that's not categorized in the cancer cell death, despite it being a cancer. And that's because hepatocellular carcinoma is so intimately associated with liver dysfunction that the the etiology of death that the CDC categorizes is liver failure and hepatocellular carcinoma. And again, it's the ninth leading cause of death in South Carolina. It's the ninth leading cause of death in the United states.

Host: Yeah and I know we could do an entirely separate podcast on cancer that spreads to the liver and maybe we'll do that, a second part to this; but today we'll stay focused on this primary liver cancer. What are the main risk factors for developing this liver cancer and does alcohol abuse contribute to the disease?

Derek DuBay, MD, MPH: Historically, the main risk factor for developing liver cancer was Hepatitis C. One of the great breakthroughs in medicine in the past decade has been very effective treatment for Hepatitis C and Hepatitis C is very treatable and has largely been eradicated in most patients. The biggest risk factors for developing a Hepatocellular Carcinoma is alcohol use and abuse and and the metabolic syndrome. So the metabolic syndrome, if I can start there, is also increasing significantly in incidence throughout the United States. The metabolic syndrome is a syndrome uh, characterized by obesity, especially around the waist, uh, high BMI, some dyslipidemia, we call it, which is high triglycerides and low cholesterol.

So some doctor terms for abnormal blood fats, fats high blood pressure, but the, the mainstay is, either diabetes or pre diabetes, in that setting for it right there. So this is you know very common throughout the United States and it's increasing in frequency. Unfortunately at the same time, alcohol use disorder has just skyrocketed throughout the United States, especially since COVID.

It's certainly becoming more and more socially acceptable for you know social consumption of alcohol on a frequent basis and I would say just from a societal standpoint what is, you know socially acceptable, that bar seems to move every year and took a big move with the onset of COVID. You know, alcohol use disorder is, you know, significantly associated with development of hepatocellular carcinoma.

Now, interestingly enough, we often see that alcohol use disorder and the metabolic syndrome frequently occur in concert. And that's a very significant problem for the development of hepatocellular carcinoma. The liver is thought to have a two-hit hypothesis, meaning that a lot of times it will tolerate one insult, but when you have two separate insults, in this case, alcohol use disorder and a metabolic syndrome, it can push it over the edge.

Host: Yeah it is interesting. I'm wondering if there are any early signs and symptoms like do people know that they have a problem with their liver or that they potentially have hepatocellular carcinoma, or is it something that's often you know in the course of regular blood tests or diagnosed because you're looking for something else? Like how's that work?

Derek DuBay, MD, MPH: Yeah, unfortunately, early signs and symptoms of hepatocellular carcinoma are completely lacking. The patients rarely develop them. However most hepatocellular carcinoma, 95 percent or 19 out of 20 times, it arises in a setting of cirrhosis. Okay. So cirrhosis is irreversible scarring of the liver. And when you have cirrhosis, you have a significant risk, annual risk of developing hepatocellular carcinoma.

On that risk, uh, there's several different studies that try to quantify what is the risk if you have cirrhosis and it's, it's somewhere between one and 4 percent per patient per year. So you can do the math. If you have cirrhosis for a decade, your chance would be between 10 and 40 percent chance of developing this cancer, which is very, very common.

We know that the, if you have cirrhosis and liver dysfunction, that your risk goes higher, probably closer to that 4%, maybe even higher per year. Whereas if you have cirrhosis but no liver dysfunction, your risk is lower, probably even less than 1 percent per year. The problem is most people who have cirrhosis, surprisingly enough, do not realize they have cirrhosis. So when people are diagnosed with cirrhosis for one reason or another, and it's commonly diagnosed in the setting of getting a CAT scan or MRI for an alternative reason, like a kidney stone or whatever and it's recognized like, wow, they have cirrhosis. It's important to be in a surveillance program for hepatocellular carcinoma where you would get yearly, or sometimes even twice yearly imaging to look for early hepatocellular carcinoma because it is asymptomatic.

Host: Yeah, it's interesting. Would be so much easier Doctor if everything just had signs and symptoms you know and we could just go. Oh, yep that's what it is. But that's one of the tricky parts of course about all of this and why we need experts like yourself. So what's the or what type of screening is there for liver cancer?

Derek DuBay, MD, MPH: Yeah. So the indications for screening for liver cancer is the setting of cirrhosis. Cirrhosis is irreversible scarring of the liver. For people that do have cirrhosis; the recommended screening is to get an ultrasound every six months. If there's any abnormality seen on the ultrasound. It's the, uh, preferred imaging technique is either CAT scan or the gold standard is a MRI.

Host: All right, so you give us a sense there of the types of screening, gold standard being MRI. Uh, the $64,000 question of course Doctor is always, you know, is there treatment available for hepatocellular carcinoma or primary liver cancer and if so what options do patients have?

Derek DuBay, MD, MPH: Yeah so liver cancer is quite interesting. I often describe it to patients that it's, it's analogous to the rabbit and the turtle that are running the race. It's the turtle and the fact that it's a fairly indolent cancer, but it gets to the finish line. So it's, it's slow growing and it's, it's very treatable up front. Hepatocellular carcinoma is quite interesting in the fact that it oftentimes arises in several spots at once. So if you look at other common cancers such as colon cancer, lung cancer, breast cancer; the probability of those cancers arising in more than one spot at the same time is less than 1 percent of the time. With hepatocellular carcinoma, 40 percent of the time it will arise in two spots or more of the liver at the same time. And to be clear, it's not one cancer that's spread to one or more other sites. It's two separate cancers that arise at the same time.

And if you biopsy them and look at them, they're very similar but different cancers for it there. So the take home point is that there's a field defect that occurs in a cirrhotic liver that involves the entire liver. The treatment for hepatocellular carcinoma, I would say, three fold. The best treatment up front is what we call liver-directed therapy and that's predominantly administered not through surgeons, not through even medical oncologists, but is administered through interventional radiologists. The classic treatment is to stick a needle into one of these tumors and to cook it. We call that ablation. There's different ways that you can heat up the liver tissue to actually cook and kill the tumor, not even cutting it out. The other way to treat it is actually to, stick a micro catheter into somebody's artery and feed that into the liver artery and then finally into the arteries that go into the tumor and inject medications directly into the tumor that cause those tumors to die. There are other different techniques, but those are the two most common either to ablate the tumor or to what we call embolize the tumor through the artery for it there. And that's very, very effective at treating the tumors up front. The problem is even if you eradicate the hepatocellular carcinomas, the probability of them coming back, is about 85%.

And the average time between the initial tumors and the recurrent tumors is about 2 years. So the gold standard treatment for hepatocellular carcinoma is a liver transplant, and the reason for the liver transplant is because it's a field defect in the entire liver, so the best treatment is to remove the entire liver and put a non-cirrhotic liver back into the patient. So I can give you a little bit of data. If you take 100 people, or maybe 200 people and divide them into two groups. The first group just gets the liver-directed therapy. Their one year survival approaches 100%, but their five year survival is only 30 percent if you just treat with a liver-directed therapy.

Conversely, if you have the group of 100 patients who get the liver-directed therapy up front, followed by liver transplantation, their one year survival actually goes down significantly. Down to 94%. So, 6 percent of people would die from liver transplant complications in the first year, but their long term survival, their five-year survival, is 75%. So liver transplant is front loaded on risk, but it has the absolute best long term survival.

Now, I mentioned that there's three treatment modalities for liver cancer. I mentioned liver-directed therapy and liver transplantation. The other one is chemotherapy and immunotherapy and we've tried different chemotherapy for years

with liver cancer and had very minimal success with that. But there are new agents that are much more effective. And especially the new immunotherapy medications that have entered the market appear to be especially effective for liver cancer. But these are primarily indicated for patients that have advanced liver cancer that is not amendable to liver-directed therapy or liver transplantation. And they've been shown to significantly prolong somebody's life but they are not curative in themselves.

Host: Yeah, it's a lot to take in and I'm sure we're just kind of scratching the surface here. I've heard and talked to some experts about immunotherapy. Again we may, we may have uncovered that we could do a couple more podcasts, but for today you know focusing on hepatocellular carcinoma, primary liver cancer just want to finish up. Is there anything we can do to reduce our chance of developing liver cancer? Is it really just about addressing the risk factors so as you went through that whole list of things uh, that could put us at higher risk. Is it about lowering our risk factors, uh, limiting our drinking uh, I'll let you in the words of an expert final thoughts.

Derek DuBay, MD, MPH: Yeah, from a population based standpoint the most important thing is for the metabolic syndrome, diet and exercise especially exercise, rigorous exercise that I think most of us know we should get, but not a lot of people carve out the time and their weight to actually attain. So diet and exercise to reduce your metabolic syndrome. I should note metabolic syndrome is strongly associated not only with cancer development but also heart disease and stroke.

With regard to alcohol use disorders, reducing or ideally eliminating alcohol ingestion is critically important and I think this is most important again for this category of patients that have both metabolic syndrome and alcohol use disorder. So from a population standpoint, diet and exercise and moderate to minimal alcohol consumption. For people that have cirrhosis and know they have cirrhosis, even if they feel fine, which is the majority of people with cirrhosis, they're like, well, I have cirrhosis, but I have no symptoms from it.

That's the most common scenario. Lots of people like that walking around that may or may not even know they have cirrhosis. But if you know you have cirrhosis, you should be in a screening program. And that, also is difficult with regard to patient compliance because you've got to go get imaging done, there's co-pays, time off from work for that and the best scenario is like hey we didn't even need this. I don't see anything and it's hard to get people to adhere to a regimen like that but it's so important because if you catch hepatocellular carcinoma in its early stages, it's very treatable. When you have advanced hepatocellular carcinoma, there's not a lot you can do.

Host: Yeah it seems I never have an expert on who says ah, you can wait on the diagnosing of cancer, right? It's always about early detection, early diagnosis, early treatment is best and as you say in the case of hepatocellular carcinoma chances of survival much higher if it's diagnosed and treated earlier. I really appreciate the education today Doctor. I appreciate your expertise. Thank you so much.

Derek DuBay, MD, MPH: Thank you.

Host: For more information and other podcasts just like this one, head on over to prismahealth.org/flourish. This has been Flourish, a podcast brought to you by PRISMA Health. I'm Scott Webb. Stay well.