Tanios S. Bekaii-Saab, MD, FACP: Anjana, one of the most confusing elements, but one that has been ingrained so heavily into how we select patients for therapies is how we score liver function, and we still rely on a system from the 1970s. Give an overview about the different scoring systems and your view. I know you use multiple scoring systems, but how do we make sense out of all these scoring systems when we’re selecting patients for the appropriate therapy?

Anjana Pillai, MD: Of course. As you mentioned, I think it’s really important to obviously assess liver function when we’re considering any of this. Some of the more common scoring systems, Child-Pugh A, it was from the late ’60s and uses 5 components: total bilirubin, albumin, INR [international normalized ratio], ascites, and hepatic encephalopathy [HE]. We classify patients based on the number of points and severity based on that. Then ALBI [albumin-bilirubin] uses total bilirubin albumin in a logarithmic patient and categorizes to grade 1, 2, and 3 versus A, B, and C in Child-Pugh and kind of takes out the subjectivity of HE and ascites. I don’t tend to use ALBI as much, although of course, I always think about total bilirubin and albumin in the sense of treatments. I tend to use Child-Pugh and MELD [model for end-stage liver disease] more. The underlying thing is, you should look at function as a whole and not rely on 1 or 2 things. What we’re really looking at is, does this person have portal hypertension, what is their ECOG function, what is the extent of their liver cancer? In that sense, using that BCLC [Barcelona-Clinic Liver Cancer] staging system is how you should approach treatment modalities. As long as they have preserved liver function, and Child-Pugh is old, but it still holds true. Those parameters are very important, portal hypertension…it is quite subjective, but it speaks to increased portal hypertension and worsening synthetic function in these patients. As we’re talking about newer treatments, as long as they have preserved liver function, we really have now the option of regression, BCLC stage regression, which is really important. That’s my approach to underlying liver function.

Tanios S. Bekaii-Saab, MD, FACP: Amit, go ahead, please.

Amit Singal, MD: I agree with Anjana. The Child-Pugh, while old, doesn’t mean that we should just throw it away because it’s old. It has stood the test of time. I agree with Anjana that I don’t necessarily calculate ALBI in all my patients. These newer scoring systems like ALBI allow us to identify Child-Pugh A patients who are closer to transforming to a Child-Pugh B. We’ve seen this with some of the studies that have come out in terms of degradation of liver function with different therapies and that degradation of liver function can differ between different treatment modalities. Considering something like ALBI and whether it’s the calculated ALBI, or taking a look at the individual albumin or bilirubin levels, may identify a patient with Child-Pugh A, who if you “choose the wrong therapy,” could quickly become Child-Pugh B. Therefore, they would no longer be eligible for further therapies, and this becomes particularly important as we have more and more treatment modalities on the table and we’re trying to maximize sequential therapy. The Child-Pugh is a nice base; we’re now developing infrastructure built off of the Child-Pugh that allows us to be more nuanced in terms of our understanding of liver function, particularly longitudinally.

Anjana Pillai, MD: I agree with your point on that. That is important.

Arndt Vogel, MD: The only point to add here, unfortunately, it’s really difficult to calculate. With all the scores Philip Johnson, MD, FRCP, has developed, you can hardly use them the clinic. On the other hand, if you look at the difference in survival for ALBI in the Child-Pugh A population, as he published in his initial paper for ALBI 1 and 2, it’s a 10-month survival difference. When you look at the efficacy we are seeing in most clinical trials at the moment, we’re talking about 3, 4, or 6 months at the best. The difference that might come from the liver function is severe, and therefore even if I agree, I do not calculate it in the clinic in every patient there. For clinical trials, it’s very important to be a stratification factor because it has such a strong prognostic and a predictive impact on treatment efficacy.

Amit Singal, MD: I agree.

Mark Yarchoan, MD: Remember that the Child-Pugh score was never designed to assess liver function in patients with cancer. Patients with a lot of cancer, they often have low albumin levels because of their tumor, and if the tumor is taking over a large portion of their liver, they often have high bilirubin because of their tumor. We’ve all seen these patients who are technically Child-Pugh B because of their tumor burden, but their underlying synthetic function is actually OK. It’s something important to keep in mind, and there are patients who are Child-Pugh B who I really think about as being Child-Pugh A with a lot of bad disease. And I treat them more aggressively than I would my standard patients with Child-Pugh B.

Amit Singal, MD: Mark, that’s also important when Child-Pugh B is not a Child-Pugh B. It depends on how you got there. Not only at that one time point, Child-Pugh B7 is very different than a Child-Pugh B9. To your point, what’s causing that Child-Pugh B status? Is it the tumor, is it the cirrhosis, which is super easy for us to talk about, but can be somewhat difficult at times, particularly if they’re newly presenting to you. It’s easier if you’ve been following that patient over time and they’re like, “We’re doing well,” and then all of a sudden developed HCC [hepatocellular carcinoma] and fell off a cliff. You’re thinking, likely cancer. For that patient who had bad liver function coming in, and then developed HCC, that clearly wasn’t the cancer. But it’s sort of the value of video versus a single picture in time.

Tanios S. Bekaii-Saab, MD, FACP: Go ahead, Anjana. I’m going to give you the final word on this.

Anjana Pillai, MD: Longitudinal assessment, that is really important rather than just looking at that 1 point in time, and we all see it where patients all of a sudden decompensate quickly, and it may have nothing to do with their cancer. We also see those who are Child-Pugh B who hold on quite a long time and can get multiple treatments and actually regress to Child-Pugh A. I think that longitudinal component’s also important.

Tanios S. Bekaii-Saab, MD, FACP: Absolutely. Arndt, go ahead, please.

Arndt Vogel, MD: I just saw a publication on the outcome of patients according to ALBI score in newly diagnosed glioma. When we talk about that Child-Pugh was not developed to predict outcome in cancer, ALBI is now widely used to predict whatever. Maybe this is also something we should keep in mind, that maybe there’s even something outside of this liver field and liver cirrhosis that is also related to the ALBI score. We should be cautious with all these scores; sometimes they are helpful and sometimes not.

Tanios S. Bekaii-Saab, MD, FACP: Overall, that continues to overemphasize the importance of a multidisciplinary approach to this disease. This is a disease that’s incredibly complex that relates to the tumor, to the health of the liver, and to the host. It’s very important as we see all these modalities coming together from the systemic, to the locoregional, to optimizing liver function, one cannot but overemphasize the importance of multidisciplinary care.

Transcript Edited for Clarity