Management of Advanced HCC Associated With NASH

Josep M. Llovet, MD, PhD: Dr Chan, how is the NASH [nonalcoholic steatohepatitis] population in Hong Kong? What’s the prevalence of NASH HCC [hepatocellular carcinoma] in your area? And how does this impact the trial design and management of the disease?

Stephen L. Chan, MD: Twenty years ago when we looked at our epidemiology, 90% were hepatitis B related, while hepatitis C, alcoholic, and NASH, or non-B, non-C related, they contributed only 5% to 8% of the remaining etiology. Today when we look at our epidemiology, 70% to 80% are hepatitis B-related, and more than 20% of patients are so-called non-B, non-C. We don’t expect that alcohol-related disease increased significantly, so I presume this increase is largely contributed to by NASH, or metabolic syndrome-related liver disease. This raises another important point about the clinical decision or the clinical trial design. If you look at the paper published in Nature, in the animal model they used NASH. This is well established with histological proof, but when you run the meta-analysis, they call it non-B, non-C. Whether those are 100% due to NASH, we don’t know.

Would this affect my decision on giving IO [immuno-oncology] to my patient? No, because if you want to influence my practice, I need a phase 3 trial with patients with stringent criteria to define the NASH background, and then randomized to PD-1, lenvatinib, or sorafenib. If there’s a difference in overall survival, I’m then convinced. I won’t tell my patients, “I won’t prescribe the PD-1 to you, atezolizumab and bevacizumab, because you are presumably NASH related.” In our locality, when we check the non-B, non-C patients, around 30% to 40% of them have the core antibody against hepatitis B, although they are surface antigen negative. This means that these patients are occult carriers, and they may still have cccDNA [covalently closed circular DNA] in their hepatocytes. Whether these cases are due to NASH or due to the occult hepatitis B, we don’t know. This is a big area we need to work on. In the past we grouped the non-B, non-C. Today we must collect more data related to patients’ metabolic background, like BMI [body mass index] and glucose. I learned from our hepatology colleagues that they have biomarkers that tell them whether a patient has NASH or not. This will be important in the clinical trials of the future.

Josep M. Llovet, MD, PhD: Thank you very much.

Transcript Edited for Clarity