Liver Function as a Critical Consideration in HCC Outcomes

This discussion highlights the critical role of liver function in the management of hepatocellular carcinoma (HCC), emphasizing that most patients face the dual challenge of cancer and underlying liver disease. Dr Pierre Gholam reviews key tools used to assess liver dysfunction, including Child-Pugh and ALBI scoring, and explains how liver function directly influences prognosis, treatment selection, and the ability to tolerate therapy, particularly among the diverse population of patients with Child-Pugh B disease.

Speaker:

Pierre Gholam, MD, is a professor of medicine at Case Western Reserve University School of Medicine and a distinguished attending physician at University Hospitals Cleveland Medical Center. He directs the National Cancer Institute (NCI)-designated Case Comprehensive Cancer Center multidisciplinary hepatobiliary tumor team, where cases of benign and malignant liver lesions including HCC and cholangiocarcinoma are discussed in a collaborative manner and consensus recommendations for a plan of care or referral to appropriate clinical trials are made.

To examine the challenges of applying available clinical evidence to patients with Child-Pugh B HCC, including emerging data and key treatment considerations, see Video 2. 

To learn how experts integrate liver function, comorbidities, disease characteristics, and patient goals into individualized treatment decision-making for Child-Pugh B HCC, see Video 3. 

Transcript

Dr Gholam: Hello, everyone. My name is Dr Pierre Gholam. I am a professor of medicine at Case Western Reserve University School of Medicine, and I lead our hepatobiliary tumor team at University Hospital Seidman Cancer Center. It's my pleasure to join you today to talk about many critical aspects of HCC management, workup, and treatment, and critical among them, certainly one part of this, that I, as a hepatologist, play an important role in, as part of the team, is discussing liver function.

As you know, HCC does not typically happen in a vacuum with rare exceptions such as hepatitis B infection and fibrolamellar, which is a very specific type of HCC. The vast majority of patients with HCC actually have underlying liver disease, typically cirrhosis. And so, for the 80% or so patients who happen to fall in that category, you are not dealing with just one disease, but rather two diseases in one. And this, in turn, poses very significant issues, not the least of which is how to co-manage these two diseases together. It's important to understand that when the patient develops liver dysfunction, which typically reflects itself in symptoms such as ascites, cognitive impairment, which we call hepatic encephalopathy, or when they develop abnormalities in their blood tests, most notably, increase in their total bilirubin, this in turn very dramatically curtails their options, so it makes them less eligible to undergo local regional therapies, such as transarterial chemoembolization and transarterial radioembolization, but it also makes them less able to tolerate systemic therapies, whether these come in the form of immunotherapy or in the form of tyrosine kinase inhibitors. So preserving liver function is critically important, not only in terms of improving liver health, maintaining that, and preventing the patient from developing complications of liver disease, but also enabling the patient to receive systemic therapy or local regional therapy as appropriate.

It's also important to understand that while liver disease is not always very advanced in the setting of HCC. Many patients don't actually die from their cancer. They die from hepatic decompensation, usually from complications of portal hypertension. These include, as I mentioned before, ascites, esophageal gastric variceal bleeding, hepatic encephalopathy, and a variety of other complications of portal hypertension, which can be fatal, such as acute kidney injury related to hepatorenal syndrome and infection in the peritoneal fluid, which we call SBP. It's also important that this can affect patients who have relatively mild tumor burdens. So someone could have a small solitary tumor, which would otherwise be treated for cure, but in the setting of advanced liver disease, this may not in turn be amenable to anything else because liver function prevents it from happening. So to sum up, liver function, or dysfunction one should say, is not just a comorbidity. It's critically important in assessing the trajectory of the patient, and it can affect what treatment options they may be offered for their cancer.

The other important point to talk about is how one might assess so-called liver function. I think we use that term a little bit loosely in the sense that this is not always a patient who has a straightforward calculus in terms of where they stand in their liver disease journey. We have two time-honored systems that we broadly use, both on the hepatology and medical oncology side. One is the Child-Pugh-Turcotte score, or CPT score. This is a score that factors in three objective measures. These would be bilirubin, albumin, and PT INR, and two subjective measures, which are the presence of ascites and hepatic encephalopathy. So inherently, there is some subjectivity to this because you're grading two symptoms or signs as opposed to just picking up a number from a set of labs. And this categorizes the patient into three sets: Child-Pugh A, which is someone who has a total score up to 6; Child-Pugh B, which goes from 7 to 9; and Child-Pugh C, the most severe form of liver dysfunction, which goes from 10 to 15. The Child-Pugh score system initially was designed to see if the patient tolerates surgery. It was later adopted as a way to allocate priority for liver transplantation, and it has since become widely used for a variety of assessments, including likelihood of dying from liver dysfunction in the following year after the test is calculated.

A more recent addition to this, which tries to get around the subjective nature of assessing signs as opposed to just blood values, is the ALBI score. The ALBI score is a logarithmic formula that only plugs in albumin and bilirubin. This gives you three categories in turn: ALBI Grade 1, ALBI Grade 2, and ALBI Grade 3. One typically indicates relatively mild or no liver dysfunction, two is more severe, and three is very severe. This has gained quite a bit of popularity on the medical oncology side. I will be very candid and say that on the liver side, we don't use this very often, but it has served as an entry point for including or excluding patients in clinical trials. It's used often to monitor patients on therapy, and it is primarily lauded for being a more objective way of assessing liver dysfunction compared to the subjective nature of grading symptoms and signs.

Perhaps the single most important flaw with the Child-Pugh B score is that unlike Child-Pugh A, where it is fairly straightforward that the patient has good liver function and will tolerate treatment well, and Child-Pugh C score, where it is also equally clear that the patient has very advanced liver disease and that liver disease will likely determine their survival, their quality of life, and other factors, there's a category in the middle called Child-Pugh B, and that category is problematic in that it is a very heterogeneous group of patients. Some have barely decompensated, as we like to use it. They may have a little bit of ascites, but their liver function is otherwise fine. And some are on the verge of very, very advanced or terminal liver disease or decompensation. These patients are all lumped in the same category. One way to get around that is to actually break Child-Pugh B categories into subsets. For example, Child-Pugh B7, where a patient only gets seven points, so just one point above A, typically from ascites or a minor lab abnormality is what allocates them that extra point. These patients may, in fact, behave more or less for all intents and purposes, including treatment, like Child-Pugh A patients, and many would actually feel quite comfortable treating these patients. Compare and contrast that with Child-Pugh B8 and B9 patients, which have significant complications of portal hypertension and may be more frail and less likely to tolerate treatment. This is not a minor issue because many studies estimate that up to 40%, and in my practice and in my interactions with colleagues, sometimes people say up to 60% of patients who have HCC at presentation may actually be Child-Pugh B. So this is not a minor issue. It is an issue that's germane to many, many patients.

So to sum up, Child-Pugh scoring and ALBI are valid and reasonable ways to assess liver function. Child-Pugh B is a very heterogeneous group, and so Child-Pugh B7 perhaps may be more amenable to therapy versus Child-Pugh B8 and B9, which may be more problematic. These assessments are critical in that they impact prognosis, treatment selection, and expected tolerance.