A. Ruth He, MD, PhD: Risk factors including viral hepatitis (hepatitis C, hepatitis B infection), alcoholic liver disease, and NASH from the metabolic syndrome—I think all of those can cause chronic inflammation, eventually leading to cirrhosis, which increases the risk of having HCC develop in the liver.

Ghassan K. Abou-Alfa, MD: That’s very important. We just heard about the 4 key risk factors for HCC—hepatitis B, which is a DNA virus, so it really is very nonforeign to our own DNA; hepatitis C, which is an RNA virus; the heavy alcohol use; and, of course, the new one that we’re seeing more and more, which is nonalcoholic steatohepatitis leading to nonalcoholic fatty liver disease. Manish, are you seeing quite a bit of NASH nowadays?

Manish R. Sharma, MD: We are. Oftentimes, it’s sort of the diagnosis of exclusion, right? You see the patient. By the time they get to me, they already have HCC. You go through the list. “OK, no viral hepatitis. No heavy alcohol history.” You start narrowing it down, and you discover that they are probably someone who fits this metabolic syndrome picture. They may be a diabetic patient. They may be obese. They may have hypertension or things like that. So that kind of fits. We don’t necessarily have a biopsy of “healthy” liver showing the fat, but I think that’s oftentimes a presumed diagnosis. At the end of the day, in many ways, the way we treat the disease is not dependent on the underlying etiology. It’s oftentimes sort of an academic discussion regarding how this came about.

Ghassan K. Abou-Alfa, MD: It’s interesting that you’re bringing this up. Amit, are we dealing with the same disease for a patient with hepatitis B, versus hepatitis C, versus alcohol, versus nonalcohol, or is it like 4 different diseases?

Amit Singal, MD: I think that hepatitis B is definitely a different disease. You’re talking about a DNA virus that integrates. And so you can actually develop HCC in the absence of cirrhosis. I think that we could all agree that hepatitis B is its own beast. I think that hepatitis C is also different from alcohol and nonalcoholic fatty liver disease. When you take a look at this, it really breaks down into, at least in my mind, viral-mediated HCC and non—viral-mediated HCC. I think alcohol and nonalcoholic fatty liver disease are 2 diseases that start in terms of fat accumulation by different means, but you end up on 1 pathway. So these 2 diseases are very similar.

Mark W. Karwal, MD: I’ve seen several cases of hemochromatosis that have been treated with phlebotomy without cirrhosis and still get HCC.

Ghassan K. Abou-Alfa, MD: Absolutely.

Amit Singal, MD: If you have hemochromatosis, you’re at the highest risk for developing HCC among all the risk factors. The issue is that hemochromatosis, while it’s one of the most common genetic diseases among Caucasians, is a relatively rarer cause compared with these other 4 that we just listed.

Ghassan K. Abou-Alfa, MD: I totally agree. And so, if we look at any practice, and look at the common risk factors that are seen among patients with HCC, they’re going to be hepatitis C, hepatitis B, alcohol, and nonalcoholic fatty liver disease. That’s really what we are seeing day to day. But you’re right—there are many other risk factors that can definitely be brought up, among which, of course, hemochromatosis and others that we don’t necessarily see for any common reason.

Mark, you have a patient with HCC. Would you read your treatment plan differently if they have hepatitis C versus hepatitis B?

Mark H. O’Hara, MD: At this point, I don’t think we have a definitive answer to that. I think there are some clinical trials that show that some patients with hepatitis C might respond better to one therapy over another. We can talk about that later in the treatment section. That’s being looked at in subset analyses of clinical trials. We don’t have any definitive proof right now.

Ghassan K. Abou-Alfa, MD: That’s fair. So, we still read it, at least for now, as 1 disease.

Amit Singal, MD: It’s important for all of us to consider whether there are new therapies for hepatitis C or relatively new therapies for hepatitis C. Even when we talk about hepatitis C today, most of the HCC that’s developing will be in the setting of cured hepatitis C. Even when you cure hepatitis C, if these patients have cirrhosis, they remain at high risk. If we don’t continue to screen this population, we’re going to see more and more advanced HCC present in this population. It’s an important subgroup of the hepatitis C population that will be one of the main risk factors as we move forward.

Ghassan K. Abou-Alfa, MD: I’m happy you brought that up. If anything, I can conclude that at the moment, our current understanding of the demographics and risk factors in HCC is evolving. I would refer everybody to the excellent paper that was reported in the Journal of Clinical Oncology in July of 2016 that showed that the population is doing extremely well in regard to the fact that there is already a vaccination for hepatitis B for the Asian population in the United States. There is definitely a lower risk for HCC in that population.

Transcript Edited for Clarity