The Roles of Etiology and Biopsy in Hepatocellular Carcinoma With Augusto Villanueva, MD, PhD

At the recent American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, Dr. Augusto Villanueva, an Associate Professor of Medicine at Mount Sinai Hospital, discussed the role of the four main etiologies of hepatocellular carcinoma (HCC) in the response that patients may experience to treatment with immune checkpoint inhibitors. In this interview, Dr. Villanueva delves further into the question of whether etiology should play a part in immune-based treatment selection, as well as the role of liquid biopsy for patients newly diagnosed with HCC. 

Oncology Data Advisor: Welcome to Oncology Data Advisor. Today I’m here with Dr. Augusto Villanueva. Thank you so much for joining us today.

Augusto Villanueva, MD, PhD: It’s great to be here with you.

Oncology Data Advisor: Could you tell us a little bit about what you do at Mount Sinai?

Dr. Villanueva: I’m a hepatologist by training, but I’ve been doing research in HCC for the last 15 years, focusing on biomarker development, early detection, biomarkers of treatment response, and using liquid biopsy as a main source for biomarker development. I’m pretty much interested in any development related to HCC.

Oncology Data Advisor: Based on your presentation at the ASCO GI Symposium, what are the four major etiologies of immune alterations for HCC, and how is this important for the treatment of HCC with immune checkpoint inhibitors?

Dr. Villanueva: As you know, most of the patients with HCC can have chronic liver disease, and the majority have cirrhosis. The main etiologies of the cirrhosis are hepatitis C virus infection, hepatitis B virus infection, nonalcoholic steatohepatitis, and alcohol use disorder with cirrhosis. Those are the four major causes of cirrhosis that at the end can result in the development of HCC. We know that the molecular mechanisms and the inflammatory response—the type, the quality, and the amount of inflammatory response—in these four etiologies are different. We’ve known that for many years.

Now, there has been some suggestion that immune checkpoint inhibitors may have different efficacy depending on the etiology of the disease. This comes from subanalysis of some of the clinical trials, the phase 3 randomized controlled trials that were testing immune checkpoint inhibitors alone or in combination versus the standard of care. The suggestion was that patients with NASH, meaning nonalcoholic steatohepatitis–related HCC, may have a worse response to immune checkpoint inhibitors. Now, I want to emphasize that this is based on subanalysis, and the fact that you have a lower response to immune checkpoint inhibitors in patients with this etiology does not mean that these patients still do not perform better in terms of response when compared with the standard of care.

My point is that despite this suggestion, there is no robust evidence to recommend not giving immune checkpoint inhibitors to patients with NASH-related HCC, so we need more data. Actually, the recent HIMALAYA trial does not support this notion that NASH patients do not respond to immune checkpoint inhibitors. Again, we still need more data in these early days in order to change practice in terms of whether or not to give this therapy to patients with NASH-related HCC. As soon as we have more data, we’ll be in a better position to say whether etiology needs to be a key factor when deciding immune-based therapies in patients with HCC.

Oncology Data Advisor: When diagnosing liver cancer, is it important to have a tissue diagnosis with biopsy as opposed to a radiologic diagnosis?

I wouldn’t say that is important, meaning that clinical practice guidelines all recommend the use of imaging as standard of care in patients that fulfill certain radiological criteria to diagnosis HCC. But it’s true that there have been a number of initiatives to access tissue biopsies to run biomarker studies. Despite still not being recommended—because as a matter of fact, the clinical management of the patients will not change based on any molecular studies that we may run in the tissue samples—certainly there’s a push towards using biopsies for all patients enrolled in clinical trials, and that’s also endorsed by clinical practice guidelines.

There are many centers that are pushing towards increasing the number of biopsies in patients, not so much for confirmatory diagnostic purposes, but to have access to run molecular studies in the tissue of these patients. Actually, the fact that we don’t have access to tissue samples in these patients emphasizes the role of liquid biopsy as a potential alternative to solve the problem and get molecular information from the tumors of these patients.

Oncology Data Advisor: Thank you so much for explaining all of this research to us today.

About Dr. Villanueva

Augusto Villanueva, MD, PhD, is an Associate Professor of Medicine in the Department of Liver Diseases and the Department of Hematology Oncology at the Mount Sinai Hospital Icahn School of Medicine in New York. He specializes in the treatment of patients with liver cancer, cirrhosis, hepatitis, and alcoholic liver disease. Dr. Villanueva’s research focuses on the use of biomarkers to improve the detection and treatment of liver cancers, and he has authored or coauthored numerous publications in peer-reviewed journals.

For More Information

Kudo M (2021). Impaired response to immunotherapy in non-alcoholic steatohepatitis-related hepatocellular carcinoma? Liver Cancer, 10(4):289-295. DOI:10.1159/000517841

Abou-Alfa GK, Chan SL, Kudo M, et al (2022). Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients (pts) with unresectable hepatocellular carcinoma (uHCC): HIMALAYA [oral presentation]. American Society of Clinical Oncology Gastrointestinal Cancers Symposium. Abstract 379. DOI:10.1200/JCO.2022.40.4_suppl.379

Villanueva A (2022). Immunotherapy for early-stage hepatocellular carcinoma. Presented at: American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

Transcript edited for clarity. Any views expressed above are the speaker’s own and do not necessarily reflect those of Oncology Data Advisor. 

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