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Risk Factors for Hepatocellular Carcinoma

Panelists:Ghassan K. Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center; Richard S. Finn, MD, Geffen School of Medicine; Riccardo Lencioni, MD, Sylvester Comprehensive Cancer Center; Amit Singal, MD, UT Southwestern Medical Center
Published: Wednesday, Apr 27, 2016


Transcript:

Ghassan K. Abou-Alfa, MD:
There are probably what I would call the bulk risk factors, or the key risk factors, for HCC being hepatitis C, hepatitis B, alcoholic cirrhosis, and also nonalcoholic steatohepatitis (NASH). Tell us a little bit more about why you are that concerned nowadays about nonalcoholic steatohepatitis.

Amit G. Singal, MD: I think what we are going to see is a shift in the epidemiology of HCC, and I think that’s what you’re getting at. Let’s remember, worldwide, chronic hepatitis B is actually the most common risk factor for HCC, and that’s really outside the US. That’s in East Asia and Africa. In the United States currently, chronic hepatitis C is the most common cause for HCC, and this accounts for anywhere from 50%, in some centers even up to 65% to 70%, of HCCs that are being seen. As you know, there’s new effective agents for hepatitis C, and so we’re going to see cures being offered to many of the patients who currently have hepatitis C. And this should hopefully reduce the future burden of HCV-related HCC.

Unfortunately, as we continue to solve one problem, another one arises. So, we have increasing rates of obesity and increasing rates of diabetes, and patients who have underlying metabolic syndrome are at high risk for developing nonalcoholic steatohepatitis. It’s currently estimated that 30% of Americans actually have nonalcoholic steatohepatitis with approximately 2% to3% of the population actually having the form that can progress to cirrhosis and HCC. When you look at this from a population-attributable fraction, nonalcoholic fatty liver disease is actually one of the most common reasons that we’re going to be seeing HCC. So, I think that this is really the future of HCC.

Ghassan K. Abou-Alfa, MD: That’s, if anything, quite concerning because what we thought is hepatitis C—we’re going to talk a little bit more about the treatment—is a problem that will be resolved, and this is definitely great news in medicine. But, at the same time, the nonalcoholic steatohepatitis and the risk of obesity and diabetes are on the rise. As we heard, 30% of the population has some form of NASH. That’s quite concerning. Richard, do you attest to that? Are you seeing a shift in your clinic in regard to the patients with HCC? Are you seeing it?

Richard Finn, MD: Yes, I think, obviously, regionally across the country, we see differences in liver cancer etiology. Certainly, I think in the US, as you commented, hepatitis C dominates. I think probably in places like New York and Los Angeles, there’s a little more hepatitis B. In Los Angeles, we have a large demographic from Mexico, and there’s an increased risk of diabetes; probably in Dallas, as well. And we are seeing more nonalcoholic steatohepatitis–related liver cancer.

Ghassan K. Abou-Alfa, MD: That’s great. Going back to the story of the cirrhosis, and again let’s imagine that physician calling for an opinion to Richard or to Riccardo. You might ask like, or I need to know, how the liver is doing. So, the Child-Pugh score has been something we kind of carry on, but, at the same time, we protest sometimes and say it’s not necessarily the appropriate measure. Talk to us a little bit in regard to what Child-Pugh is.

Amit G. Singal, MD: So, Child-Pugh is a scoring system that’s based on five variables; the presence of ascites, the presence of hepatic encephalopathy, bilirubin, albumen, and INR. Using these five variables, you can get a score that goes anywhere from 5 to 15. And this has been used traditionally as a good marker of the degree of liver dysfunction. When you look at treatment algorithms for HCC, the Child-Pugh is actually what’s traditionally been built into there. Now, this has also been protested, as you said, by some people because the assessment of ascites and the assessment of hepatic encephalopathy can be quite subjective. And so there have been new scoring systems that have come up in terms of prognostic variables for patients with HCC, such as the ALBI score, which is based more so on albumen and bilirubin getting rid of the subjective ascites and encephalopathy assessments—which can be perhaps easier on oncologists.

Ghassan K. Abou-Alfa, MD: Fair enough. It’s totally understandable, and I know we go through that challenge. If anything, the Child-Pugh is actually quite intriguing to start with, because in 1973, what was developed initially by Professor Pugh back in the UK, this study was to look at patients who had esophageal varices and were at risk of bleeding from esophageal varices. None of them had HCC. And you just wonder, how can we look at the prognostics while there’s not a single parameter that’s related to the cancer itself? And that’s why we came up with so many of the different scoring systems, as you mentioned, the ALBI, the CLIP—which is Cancer of the Liver Italian Program—the CUPI—Chinese University Prognostic Index, etc. And, of course, the BCLC as well that’s used rather more of a roadmap in regard to the assessment of patients in a clinical setting. Riccardo, how do you assess patients from their cirrhosis component to decide if you’re going to be able to intervene with a local therapy or not? What do you use, or what are your thoughts on that?

Riccardo Lencioni, MD: Of course, interventional radiology options are ideal for this patient population, because clearly we can deliver therapy with a minimally invasive approach. So, we can use ablation in place of resection. We can use different forms of transcatheter therapies. Clearly, patients with compromised liver function are indeed eligible for local regional interventional therapy, provided that they do not reach a certain level of decomposition. I would say that in clinical practice, the Child-Pugh class is still a key factor, and the big difference that I think has to be clearly made is between patients in Child classes A or B and patients in Child class C. Those who are in Child class C should probably not receive any form of anti-cancer therapy because they are very unlikely to have any benefit from the anti-cancer therapy. Of course, this does not apply to liver transplantation.

Ghassan K. Abou-Alfa, MD: Fair enough. If anything, I may add here that a lot of the therapies that we apply are based on clinical trials that were really based on the Child-Pugh score. To begin with, the sorafenib study, which is a phase III clinical trial which accrued patients only with Child-Pugh score A, is a good attestation to that. And, obviously, practices are going to be influenced one way or the other by those kinds of clinical trials that are either reported or are ongoing, which we’re going to talk quite a bit about as well.

Transcript Edited for Clarity
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Transcript:

Ghassan K. Abou-Alfa, MD:
There are probably what I would call the bulk risk factors, or the key risk factors, for HCC being hepatitis C, hepatitis B, alcoholic cirrhosis, and also nonalcoholic steatohepatitis (NASH). Tell us a little bit more about why you are that concerned nowadays about nonalcoholic steatohepatitis.

Amit G. Singal, MD: I think what we are going to see is a shift in the epidemiology of HCC, and I think that’s what you’re getting at. Let’s remember, worldwide, chronic hepatitis B is actually the most common risk factor for HCC, and that’s really outside the US. That’s in East Asia and Africa. In the United States currently, chronic hepatitis C is the most common cause for HCC, and this accounts for anywhere from 50%, in some centers even up to 65% to 70%, of HCCs that are being seen. As you know, there’s new effective agents for hepatitis C, and so we’re going to see cures being offered to many of the patients who currently have hepatitis C. And this should hopefully reduce the future burden of HCV-related HCC.

Unfortunately, as we continue to solve one problem, another one arises. So, we have increasing rates of obesity and increasing rates of diabetes, and patients who have underlying metabolic syndrome are at high risk for developing nonalcoholic steatohepatitis. It’s currently estimated that 30% of Americans actually have nonalcoholic steatohepatitis with approximately 2% to3% of the population actually having the form that can progress to cirrhosis and HCC. When you look at this from a population-attributable fraction, nonalcoholic fatty liver disease is actually one of the most common reasons that we’re going to be seeing HCC. So, I think that this is really the future of HCC.

Ghassan K. Abou-Alfa, MD: That’s, if anything, quite concerning because what we thought is hepatitis C—we’re going to talk a little bit more about the treatment—is a problem that will be resolved, and this is definitely great news in medicine. But, at the same time, the nonalcoholic steatohepatitis and the risk of obesity and diabetes are on the rise. As we heard, 30% of the population has some form of NASH. That’s quite concerning. Richard, do you attest to that? Are you seeing a shift in your clinic in regard to the patients with HCC? Are you seeing it?

Richard Finn, MD: Yes, I think, obviously, regionally across the country, we see differences in liver cancer etiology. Certainly, I think in the US, as you commented, hepatitis C dominates. I think probably in places like New York and Los Angeles, there’s a little more hepatitis B. In Los Angeles, we have a large demographic from Mexico, and there’s an increased risk of diabetes; probably in Dallas, as well. And we are seeing more nonalcoholic steatohepatitis–related liver cancer.

Ghassan K. Abou-Alfa, MD: That’s great. Going back to the story of the cirrhosis, and again let’s imagine that physician calling for an opinion to Richard or to Riccardo. You might ask like, or I need to know, how the liver is doing. So, the Child-Pugh score has been something we kind of carry on, but, at the same time, we protest sometimes and say it’s not necessarily the appropriate measure. Talk to us a little bit in regard to what Child-Pugh is.

Amit G. Singal, MD: So, Child-Pugh is a scoring system that’s based on five variables; the presence of ascites, the presence of hepatic encephalopathy, bilirubin, albumen, and INR. Using these five variables, you can get a score that goes anywhere from 5 to 15. And this has been used traditionally as a good marker of the degree of liver dysfunction. When you look at treatment algorithms for HCC, the Child-Pugh is actually what’s traditionally been built into there. Now, this has also been protested, as you said, by some people because the assessment of ascites and the assessment of hepatic encephalopathy can be quite subjective. And so there have been new scoring systems that have come up in terms of prognostic variables for patients with HCC, such as the ALBI score, which is based more so on albumen and bilirubin getting rid of the subjective ascites and encephalopathy assessments—which can be perhaps easier on oncologists.

Ghassan K. Abou-Alfa, MD: Fair enough. It’s totally understandable, and I know we go through that challenge. If anything, the Child-Pugh is actually quite intriguing to start with, because in 1973, what was developed initially by Professor Pugh back in the UK, this study was to look at patients who had esophageal varices and were at risk of bleeding from esophageal varices. None of them had HCC. And you just wonder, how can we look at the prognostics while there’s not a single parameter that’s related to the cancer itself? And that’s why we came up with so many of the different scoring systems, as you mentioned, the ALBI, the CLIP—which is Cancer of the Liver Italian Program—the CUPI—Chinese University Prognostic Index, etc. And, of course, the BCLC as well that’s used rather more of a roadmap in regard to the assessment of patients in a clinical setting. Riccardo, how do you assess patients from their cirrhosis component to decide if you’re going to be able to intervene with a local therapy or not? What do you use, or what are your thoughts on that?

Riccardo Lencioni, MD: Of course, interventional radiology options are ideal for this patient population, because clearly we can deliver therapy with a minimally invasive approach. So, we can use ablation in place of resection. We can use different forms of transcatheter therapies. Clearly, patients with compromised liver function are indeed eligible for local regional interventional therapy, provided that they do not reach a certain level of decomposition. I would say that in clinical practice, the Child-Pugh class is still a key factor, and the big difference that I think has to be clearly made is between patients in Child classes A or B and patients in Child class C. Those who are in Child class C should probably not receive any form of anti-cancer therapy because they are very unlikely to have any benefit from the anti-cancer therapy. Of course, this does not apply to liver transplantation.

Ghassan K. Abou-Alfa, MD: Fair enough. If anything, I may add here that a lot of the therapies that we apply are based on clinical trials that were really based on the Child-Pugh score. To begin with, the sorafenib study, which is a phase III clinical trial which accrued patients only with Child-Pugh score A, is a good attestation to that. And, obviously, practices are going to be influenced one way or the other by those kinds of clinical trials that are either reported or are ongoing, which we’re going to talk quite a bit about as well.

Transcript Edited for Clarity
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