Guidelines and Risk Stratification of PBC

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: Let's now talk a little bit about management. We talked about screening and diagnosis. I think the key takeaways for clinicians taking care of patients is in terms of diagnosis and risk stratification. Steve, I'll ask you to comment. There are all these different prognostic scoring systems: Paris 1, Paris 2, Toronto, Barcelona, GLOBE, or UK PBC. It can get a little bit mind-numbing. What do you do and what do you teach your fellows and residents about how do you prognosticate risk stratifying PBC?

Steven Flamm, MD, FAASLD, FACG: Well, interestingly, Kris, a lot of the patients are doing this now because of the internet. They look this up and see the GLOBE score on the internet and start plugging in the numbers and figuring out their own prognosis. I do the GLOBE score on occasion with patients. For me, I mostly use it for prognostication of the fibrosis score for the patient, which I'm very careful with and I assess it on an annual basis with a fibro scan or an MRE, if necessary. I use that as my prognostic strategy in addition to looking at the liver panel mainly. If you want to do a scoring system either for clinical practice or because patients are in studies, the GLOBE score or the UK score are the ones that I use the most. How about you?

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: Well, I'm obviously partial to the GLOBE score because I'm a longstanding member of the Global PBC Study Group.

Steven Flamm, MD, FAASLD, FACG: But do you use it on every single patient?

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: Absolutely. I think it's important because we'll talk a little bit about how changes in the GLOBE score can actually change and represent changes in prognostic classification for patients, so I think that's really useful. In terms of blood tests and imaging-based tests, one of the things that we updated in this recent guidance document for review is to really include categories for liver stiffness using elastography. We know that if it's less than 6 versus less than 8 versus less than 10 versus more than 10, that really classifies patients into higher categories regarding stage of disease. Then, any score that you choose to use, pick one so that you're comfortable with it. Most of these are free. You can calculate them online, you can bookmark it, and go from there. Sonal, is that pretty much what you do? A GLOBE score and elastography with every visit?

Sonal Kumar, MD, MPH: I definitely do an elastography annually in these patients. The more time I've spent with you, I've started using the GLOBE score a little bit more. I can't say that I used it in the past that much, but you've changed me a little bit. That's pretty much what I do.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: The thing to know about these newer scoring systems is that they're way more useful and sensitive than the older systems, which were really geared toward identifying patients towards transplantation. For example, we know alkaline phosphatase and bilirubin, if they're elevated, are going to predict 15-year outcomes as opposed to Mayo score, which is predicting outcomes in 5 years or immediate need for liver transplantation. I think it's important to recognize that these new scoring systems have value and to pick one and just sort of go by that. David, any comments from you on this topic?

David Victor III, MD: I like the scoring systems as a motivational tool for my patients taking medicine every day for a disease that is largely virtual. Their perception of their liver is not there for many of them. Showing them that their score remains stable, that the prognosis is good as long as you maintain therapy, is one of the ways that I find the scoring systems to be helpful. With the elastography, the one thing I do caution any provider using elastography is absolute numbers. The progression toward fibrosis is not a straight line, so you'll see perhaps changes and you must mitigate that with the patient's understanding and expectations so it's not absolute numbers, it's categories. I try to educate patients for those as well, but really what you're trying to do is continue motivation for a disease that has to be treated ad nauseum for life.

Steven Flamm, MD, FAASLD, FACG: Even when you have advanced liver disease on these imaging procedures, again, the scores are all great, but the cheating way is to watch that bilirubin. When the bilirubin level starts to rise, no matter how well the patient feels when they have advanced liver disease, you should start to be very worried about that patient and their prognosis.

David Victor III, MD: I will say in my younger years of practice, I did start at 1, but what I've learned now is that the bilirubin is an increase from their baseline. So, if their bilirubin has been 0.5 and it increases to 1, that can be a real concern for progression of disease. That was something that I didn't appreciate, that subtlety, for quite a few years.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: That's right. One of the things that we have increasingly recognized is that alkaline phosphatase is a dynamic number. Bilirubin is much more important than what we previously thought. Some recent work from the Global PBC Study Group shows that a bilirubin of 0.6 or higher is associated with long-term adverse outcomes and any elevation of alkaline phosphatase is associated with adverse outcomes. So, we have treatment goals, and I'm reflecting on my personal bias, which we're going to get into treatment options here in a minute, are really focused on trying to ideally get the bilirubin and alkaline phosphatase as low as possible.

Transcript edited for clarity