Alan Bonder, MD, on Primary Biliary Cholangitis

Dr Bonder reviews key presentations from The Liver Meeting about primary biliary cholangitis and advances in its treatment.

Alan Bonder, MD, is medical director for liver transplantation at Beth Israel Deaconess Medical Center and an associate professor at Harvard Medical School in Boston, Massachusetts. 

TRANSCRIPT:

So good afternoon everyone. I am Dr. Alan Bonder. I am the medical director of Liver Transplantation and also the Hepatology Section Editor for Gastroenterology and Learning Network. And today, I'll be happy to talk to you about the highlights of PBC in our most recent liver meeting at Washington, DC in November. So before, it was so nice to see everyone and hopefully we can continue to encourage our networks and seeing our friends in all of our meetings.

So PBC shows a lot of new and promising treatments. So let's just start with what do I get as a message from PBC? So we know that we need to prompt and diagnose early. We need to know that we need to treat so we can prevent cirrhosis complications. But one thing that actually came up this liver meeting is actually treating patient symptoms. There is this statistic that was published that up to 70% of the physicians don't even ask about pruritus in patients with PBC, which I think is just one of the biggest symptoms, the biggest complaint that affects quality of life in this type of patients. So we need to understand, we need to ask as physicians, all of these symptoms to patients so we can treat them properly.

So let's just start with we did find that PBC also, it's an interaction between the bowels and the hepatocytes. And we can see that from the pathophysiology of the mechanism of all the new medications were like. For example, we know there is an interaction between the FXR as well as the FGF19 and the PPARs within the bowels and the hepatocytes regulating bile flow. And because of this, we know that PBC, it's a disease that actually not only has inflammation, autoimmunity, but also bile acids played a key role mediating this inflammation, which is also one of the key messages from this liver meeting. I think we know that we have made a lot of progress.

We also have seen that there are also diversities in PBC, and this was presented by Dr. Hirschfield, saying that indigenous populations from Canada have worse outcomes than someone who's White. So again, we have all this information that we didn't have in the past. So how do we assess response? I think one of the highlights also from this liver meeting is we need to make sure, and I'm going to quote again Dr. Hirschfield, we need to target normal. We need to try to aim for normal liver tests, but also we need to aim for normal quality of life. That's so important to treat all of the symptoms.

When we look at treatments data, I want to point out the treatment data that actually was presented from the obeticholic acid. Obeticholic acid has demonstrated that decreases transplant-free survival. I mean, you look at the clinical data Dr. Hirschfield presented, there's a 63% risk reduction for death, liver transplantation and liver decompensation. this is a complementary from Dr. Nevin’s study from the New England Journal of Medicine, and we have right now close to 6 to 7 years of data showing that the use of second-line therapies improve outcomes in patients with PBC.

But how about all the treatments? So they presented data from elafibranor, which all the PPAR, which is an alpha and delta agonist, that was a 12-week study of 45 patients that also showed that there's a significant reduction in alkaline phosphate as well as itching. The ENHANCED which uses seladelpar, which is a PPAR delta agonist that included 265 patients, which showed for the first time the dual effect of both decreasing liver enzymes, but also showing improvement in itching. And finally, saroglitazar, which is a PPAR gamma, which is a 37-patient clinical trial to show improvement in cholestasis.

From that FXR agonist, there was one new FXR agonist clinical trial that was actually presented, which is the tropifexor. Tropifexor in this clinical trial, 61 patients were randomized to this FXR agonist. And in this, there was evidence of improvement specifically in alkaline phosphatase, GGT, but also quality of life and patient related outcomes.

And finally, I think from a medication standpoint, we witnessed the presence of the IPAT inhibitors. So we have all this new medications to treat itching. So the GLIMMER trial, which was presented by Cynthia Libby, which is the linerixibat, shows significant improvement in the pruritus and all of those patients who were treated. And finally, we have an antifibrotic that NOX inhibitors, show significant improvement in patients who were treated compared to placebo. So based on all those medications, what can we conclude from this liver meeting?

We could conclude that we need to diagnose PBC early. We need to restratify. So people shown that patients with normalizing alkaline phosphates, normalizing fiber scan and low fiber scan scores have really good outcomes. So we as physicians need to make sure that we stratify these patients on presentations. We need to manage symptoms. We need to ask our patients about all of their symptoms. We need to make sure we address all of their symptoms so we can treat them properly. We need to offer second line therapy.

So we were, a few years ago, based on the black box warning, afraid of using obeticholic acholic acid, but with all the data showing improvement and mortality, decreasing death, liver transplant, or even mortality, we need to make sure we get our patients on second line therapy as soon as they qualify for it. We have second line therapies approved, as I just mentioned of obeticholic acid, and we have off-label use of medications, specifically the fibrates.

And finally, we have all the clinical trials going in phase three. So hopefully in the next three to five years, we will have all the results. so as physicians, we can go to the FDA, approve all those medications and we are going to have all these options for all these patients who are not responding to conventional therapy. PBC shows significantly promising data. We are very happy to see that patients with PBC will improve not only from a liver standpoint, but also from a quality of life. And hopefully, we'll have these medications to give them all to our patients. Again, I thank you so much for listening to me about this highlights of the liver meeting and hopefully we can see you soon in person again.