Dr Amit Singal on Unmet Needs in HCC, Shifts in At-Risk Populations


While there have been advances in screening technology, it is crucial to continue investing in emerging modalities and to ensure these advancements translate to clinical practice.

Unmet needs in hepatocellular carcinoma (HCC) span from screening implementation to treatment, Amit Singal, MD, medical director of the Liver Tumor Program and chief of hepatology at UT Southwestern Medical Center, explained. While there have been advances in screening technology, it is crucial to continue investing in emerging modalities and to ensure these advancements translate to clinical practice.

In previous videos, Singal discussed choosing the best therapies for patients, recent advances in HCC therapy, and the populations at the highest risk for HCC.


What unmet needs remain in HCC, and how might these be addressed going forward?

I think one of the main things that we have to work on is implementing some of the proven therapies that we have. We know, for example, that screening can improve early detection. It's associated with improved downstream survival because of increased curative therapy receipt. However, it's underused in clinical practice. Several studies have suggested that only 1 in 4 patients with HCC have prior screening, and that explains a lot of the late-stage presentation and a lot of the poor survival that we see that continues in clinical practice. I would argue that one of the things that we really need for screening right now is better implementation of our current therapies.

In parallel, we see a lot of advances in terms of different emerging modalities, whether those be emerging imaging modalities, like abbreviated MRI, or emerging blood-based biomarkers, where we see a lot of enthusiasm because of preserved high sensitivity for early-stage disease, but also possibly increased ease of use, depending on your clinical setting. I think in parallel with using what we know works, we should continue investing in these emerging modalities to better improve screening efficacy and effectiveness, and early detection in in the world.

In parallel, we see also underuse of curative therapies, even those patients who are found at an early stage. Unfortunately, we see underuse of curative therapies in clinical practice. So, likewise, we need to make sure that patients are going to see multidisciplinary care groups where they have access to all of the different treatment regimens, not just a single therapy. By doing that, we can once again improve survival by making sure as many patients as possible are undergoing curative therapies.

Finally, I think we've seen a lot of advances in the palliative care setting, whether that's locoregional therapies or systemic therapies. But I think we're just at the cusp of that. I think that we have a lot of other trials that are ongoing where there are newer agents in first-line settings, combination therapies like we've talked about—for example, combination of immune checkpoint inhibitors with local therapies are used in the neoadjuvant setting. I think those are important trials that are ongoing, and then also the discovery of more efficacious systemic therapies in the future.

Have there been any changes in at-risk populations over time?

One of the things that we have seen with the introduction of effective antiviral therapies is a shift from having patients with viral hepatitis and viral liver disease to more and more patients having nonviral liver disease. So we've seen many patients in the Western world now have cure for their hepatitis C and have a reduced risk of HCC; we've done a better job of vaccinating for hepatitis B and treating patients with chronic hepatitis B. So, we've seen improvements in hepatitis B–related HCC. But in parallel, we've seen more alcohol use and misuse, particularly after the COVID-19 pandemic. And we see more metabolic dysfunction associated with liver disease, particularly as we've seen increasing proportions of the world have obesity and diabetes.

As one would envision, we see more and more HCC occurring in these latter etiologies, whether alcohol or metabolic dysfunction. And this can have important implications when we think through screening as well as treatment. From a screening perspective, not only are these patients harder to identify because we don't have a blood test that identifies some of these patients, but also some of our screening tools, such as ultrasound, perform worse in these newer populations than they did in viral hepatitis. From a treatment perspective, we have to think through comorbidities, underlying liver dysfunction. And so, the competing risk of these other etiologies can be higher, and sometimes the risk of overdiagnosis or the effectiveness of our HCC therapies can be mitigated when we think of this shift from viral to nonviral liver disease.

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