Evolving Treatment Paradigms for Metastatic Liver Cancer - Episode 1

NASH and Cirrhosis in HCC


Ghassan K. Abou-Alfa, MD, MBA: We continue to make progress in improving outcomes for metastatic hepatocellular carcinoma [HCC] as therapeutic options are ever increasing. However, with increased options comes increased complexity in making treatment decisions for a given patient.

In this OncLive® Peer Exchange® discussion, “Evolving Treatment Paradigms for Metastatic Liver Cancer,” I’m joined by a panel of experts in gastrointestinal oncology. Today we will sort out through the most recent data and will provide a practical perspective on current approaches for treatment.

I am Ghassan Abou-Alfa, an attending physician at Memorial Sloan Kettering Cancer Center and a professor of medicine at Weill Cornell Medical College in New York, New York.

Joining me today are Dr Anthony El-Khoueiry, an associate professor of clinical medicine at the University of Southern California Norris Comprehensive Cancer Center and phase I program director in Los Angeles, California; Dr Catherine Frenette, the director of the liver and hepatocellular carcinoma program at the Scripps MD Anderson Cancer Center in La Jolla, California; Dr Pierre Gholam, a professor of medicine at Case Western Reserve University School of Medicine and the director of the hepatobiliary tumor multidisciplinary team at the University Hospitals Seidman Cancer Center in Cleveland, Ohio; and Dr Ahmed Kaseb, a professor in the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, at the University of Texas MD Anderson Cancer Center in Houston, Texas.

Thank you. Let’s begin.

Catherine, you and I have this discussion all the time. We understand that for HCC, the standard that all our colleagues would be cognizant of is hepatitis-B—related liver cancer, hepatitis-C liver cancer, and alcoholic liver cancer, and then we bring in nonalcoholic steatohepatitis. What’s NASH [nonalcoholic steatohepatitis]?

Catherine T. Frenette, MD: NASH is becoming a very common cause of liver cancer in the United States. There are actually areas in the country where it has become the most common cause. NASH is a nonalcoholic steatohepatitis. Patients with the metabolic syndrome and metabolic dysregulation with insulin resistance, hyperlipidemia, and central obesity, they develop steatosis in the liver that then stimulates inflammation and fibrosis development that can then result in cirrhosis, end-stage liver disease, and liver cancer, and is really becoming a huge problem in the United States.

Ghassan K. Abou-Alfa, MD, MBA: Understandably so. Anthony, are you seeing those patients?

Anthony B. El-Khoueiry, MD: Absolutely. More and more in our clinic we are seeing patients who are potentially middle-aged but with metabolic syndrome and no other predisposing risk factors, sometimes even without cirrhosis, who are presenting with hepatocellular carcinoma.

Ghassan K. Abou-Alfa, MD, MBA: Incredible. Ahmed, in your practice you see a lot of HCC patients—if you were to give percentages, how many people who come, of 100, would be naturally related HCC?

Ahmed Kaseb, MD: Lots. Fifteen, 20 years ago, the percentage was really focusing on hepatitis C and hepatitis B alcohol related. I would say in the last decade we’ve seen a major shift—at least 50% of patients are nonhepatitis related nowadays in our clinic. There are about 30% hepatitis C, 10% to 15% hepatitis B.

Ghassan K. Abou-Alfa, MD, MBA: We’re seeing more and more of this, which is quite amazing. Now, Peter, the important complexity of liver cancer is that truly it’s 2 diseases in 1. And you as a hepatologist, what can you teach us as oncologists regarding that cerotic component? What is it, and what do we do about it?

Pierre Gholam, MD: As you pointed out, there are competing risks in patients who have cirrhosis and HCC. In a sense, sometimes the underlying liver disease may be the predominant risk factor for morbidity and mortality. I think the astute training physician needs to be aware of this and understand that in the setting of very advanced liver disease, the focus should be on trying to improve both quantity and quality of life on that component as opposed to focusing as much on cancer. I know this is primarily a discussion about cancer, but having the full picture is very important in those patients.

Ghassan K. Abou-Alfa, MD, MBA: Catherine, of course 1 thing I can do that is easy—there’s a good answer on the board—is consult the hepatologist. But we have to play a hepatologist a little ourselves too. In a patient with “liver cancer/cirrhosis,” let’s say hepatitis C patients with cirrhosis, how do I assess how bad that cirrhosis is? Is there any specific metric I use? What do we do?

Catherine T. Frenette, MD: There are several metrics we can use. We’re all very comfortable and are used to using the Child-Pugh score. It’s been around for 40 or 50 years and looks at both symptoms with ascites and encephalopathy as well as lab values with albumin, bilirubin, and INR [international normalized ratio].

The performance status is still very applicable in patients with cirrhosis. We also look at the MELD score, models for end-stage liver disease. Then more and more in cancer treatments, we’re looking at the ALBI [albumin-bilirubin] score. These are all various things that we can use to really evaluate the underlying liver disease. In my mind 1 of the critical things when you’re starting the evaluation of a patient with cancer is also to evaluate the cirrhosis and see what you can do to maintain the liver function as long as possible to then allow the patient to get the benefit of further therapies for their cancer.

Transcript Edited for Clarity