How Should Liver Function and Patient Values Guide HCC Treatment?

Treatment decisions for patients with hepatocellular carcinoma (HCC) must weigh tumor response alongside underlying liver function and what matters most to each patient.

At The Liver Meeting® 2026, CancerNetwork® spoke with Andrew Moon, MD, MPH, a transplant hepatologist and assistant professor of medicine in the Division of Gastroenterology and Hepatology at the University of North Carolina at Chapel Hill (UNC), about assessing treatment response, navigating resistance, and incorporating patient preferences into HCC care. Moon practices within the UNC Multidisciplinary HCC Clinic.

Moon began by describing what a multidisciplinary team should monitor beyond imaging, including signs of hepatic decompensation, and how liver function informs decisions when HCC shows signs of resistance. He then discussed established and emerging biomarkers, from α-fetoprotein (AFP) to circulating tumor DNA (ctDNA). Moon also outlined when care teams should look beyond treatment algorithms, shared what his research has revealed about patient priorities, and highlighted how patient-reported outcome monitoring may help clinicians catch complications early.

CancerNetwork: Response assessment in HCC must account for both tumor and liver function. Beyond imaging, what should a multidisciplinary team look for to judge whether a patient is responding to systemic or locoregional therapy?

Moon: This is a great question because in oncology, we always focus on radiologic assessment, so people know what progression is when it comes to radiologic progression. In HCC, it is much more complex because we are dealing with both cirrhosis and HCC. Arguably, progression based on impaired liver function or impaired performance status can be more important in terms of prognosis.

Patients are often seeing me every 3 months, along with the oncologist or the interventional radiologist, to assess liver function. We assess their synthetic function based on laboratory tests and any signs of decompensation, such as hepatic encephalopathy [HE], ascites, and, of course, a variceal bleed. Some of the data from systemic therapy show that developing decompensation is one of the poorest prognostic markers, so it is incredibly important.

When HCC shows signs of resistance, how do you decide whether to switch systemic therapy, add locoregional treatment, or move to a clinical trial? How does liver function shape that decision?

This is a complex question, and as a result, it often goes through a multidisciplinary tumor board. I am also lucky to practice within a co-located multidisciplinary clinic. I am in clinic every week with our interventional radiologist, radiation oncologist, and medical oncologist, where we can discuss these complex decisions about when to change treatment course.

When it comes to liver function, there are some data suggesting that patients at higher risk of decompensation may be better served by earlier systemic therapy rather than locoregional therapy, so it is important for us to consider that. We do not have great prognostication tools to know who is going to decompensate after a therapy, but we think hard about that beforehand. In addition to trying to select the right patients for the right treatment, I am also considering who may be best served by referral for liver transplantation.

Which emerging tools, such as ctDNA, AFP and other serum markers, or imaging-based models, look most promising for predicting which patients will respond to immunotherapy? How close are they to routine use?

AFP has been around for a long time. It is well established for HCC surveillance, it has good data for risk stratification, and we also use it for treatment response. We know that a high AFP is a poor prognostic marker. We also know that a drop in AFP after a treatment is a good sign that the patient responded to that treatment.

Some of the newer tools are exciting. It is still early days, and many of them are not ready for broad-scale clinical adoption. Thankfully, there are a lot of smart groups working on this, looking at other protein-based biomarkers. Some of the best known are lens culinaris agglutinin-reactive AFP [AFP-L3] percentage and des-gamma-carboxy prothrombin, also called protein induced by vitamin K absence or antagonist-II [PIVKA-II]. Those are well established, and PIVKA-II is endorsed in some of the Asian guidelines. Many groups are looking at these tools for risk stratification, surveillance, and treatment response, as well as for predicting recurrence risk after liver transplantation. ctDNA and other liquid biopsy techniques are also promising. We do not have a good sense of how best to use these yet, but there is a lot of great research in that area.

Treatment algorithms such as Barcelona Clinic Liver Cancer staging guide HCC care, but patients often weigh trade-offs differently. When should a care team step outside the algorithm to reflect what matters most to the patient?

This is an area that I am interested in. I have done a lot of research—qualitative research and now survey-based research—to better understand how patient preferences and values should play a role in choosing treatments. There are a few scenarios where this can be helpful.

One is a scenario where you have an HCC that can be treated with multiple modalities that have similar efficacy. A good example is early-stage HCC. Surgical resection is the up-front treatment of choice for patients who do not have cirrhosis and for certain patients with cirrhosis without portal hypertension. For patients who are not candidates for resection, we have a number of different treatment options: thermal ablation, radiation segmentectomy, and stereotactic body radiation therapy or external beam radiation. Ablation is better established and has more data than the other 2, but the other 2 have shown excellent outcomes in terms of local control, progression-free survival, and overall survival. In those cases, we often discuss a case in tumor board, and my colleagues will say, “We have these 3 different treatment options.” That is a perfect place where patient preferences or values could play a role. Differences in posttreatment symptoms, inconvenience, and cost can play a key role.

Another place where it is important is when the patient’s goals are not necessarily tumor control, progression-free survival, or overall survival. Certain patients tell me it is important for them to maintain quality of life, to avoid being a burden to caregivers, and to maintain their functioning, so the ideal treatment option may be very different for that patient.

I mentioned liver transplantation. That is one of the best treatments we have for HCC. It cures cirrhosis, it also cures HCC, and it reduces the recurrence risk significantly. However, it is no free lunch. Liver transplant is a huge undertaking, so you have to carefully consider the trade-offs, values, and preferences, and make sure that a patient is willing to accept all the downsides of transplant to get that improvement in HCC recurrence and overall survival.

Your research focuses on patient preferences in HCC treatment. What have patients told you they value most when choosing between options like ablation, radiation, and surgery? What has surprised you?

A few things have surprised me. Before my work on preferences, I did some qualitative work looking at posttreatment symptoms, which informed the work on preferences. One thing I was surprised by is that after locoregional therapies, which we as providers often describe to patients as well tolerated, patients stated that they often had symptoms, and those symptoms often impaired their functioning. With these well-tolerated treatments, patients were saying, “I struggled more than you realize.” That informed how we should be talking about these treatments and how we should be looking at pretreatment symptom burden and how it will inform treatment choice. That launched my work on preferences.

I interviewed clinicians, patients, and caregivers. When I spoke to many experts in the field, there was a thought that our preferences are aligned—that what is important to providers is what is important to patients. For many patients, that is true. What surprised me was how often patients had goals that were not necessarily aligned with ours. It revealed to me how important it is to ask, “What is important to you? What do you value in your life when you look at this treatment? What do you want to accomplish? What do you want to avoid?” That qualitative work showed me the importance of formal elicitation of patient preferences as part of our treatment of HCC.

Many patients with HCC have cirrhosis-related symptoms or decompensation after treatment. How can nurses, pharmacists, and clinicians use patient-reported outcomes to catch problems early and support shared decisions?

This is another research area I am interested in. How do we best capture those symptoms that, as the qualitative work showed, we are often missing? I am interested in routine patient-reported outcome monitoring, including remote patient-reported outcome monitoring, to identify posttreatment symptoms so we can intervene earlier.

In addition, there are some data on monitoring for decompensation, such as monitoring weight or signs of distension and ascites, so we can capture it early and intervene with dietary modifications, diuretics, or paracentesis. We can do the same with HE. HE is common after locoregional therapies, particularly covert HE, and we often struggle with how to identify it. I always tell patients and caregivers, even if the patient is compensated at baseline before treatment, “Here are the things to look out for.” In the future, I hope that we incorporate remote monitoring for some of those complications so we can catch them early, intervene, and improve patient outcomes.