Q&A: This is an ‘exciting time’ for PBC treatment options
Primary biliary cholangitis is a chronic autoimmune disease that causes progressive destruction of the bile ducts. While the disease is considered rare with fewer than 200,000 cases in the U.S. per year, many physicians and patient advocacy groups have made strides toward increasing awareness about the disease, as early diagnosis and treatment can help to manage complications and prevent progression of inflammation and fibrosis.
For Primary Biliary Cholangitis Awareness Month, Healio Gastroenterology and Liver Disease spoke with Gideon M. Hirschfield, MD, from the Toronto Center for Liver Disease and the University of Toronto in Canada, about the etiology of PBC, important steps for diagnosis and follow-up, and the current and future options for therapy.
Healio: Who is most affected by PBC?
Hirschfield: Primary biliary cholangitis is a chronic disease. The predominant population we see are women, and the majority of patients are aged 50 years or older, although a significant minority — probably 20% to 30% — are diagnosed before age 50 years. Increasingly, because we are doing more laboratory testing, we are diagnosing more cases of PBC early, which is important for the patients as well as beginning therapy.
Healio: Are there any concerns with screening and diagnostics?
Hirschfield: I think the most important thing would still be awareness. The diagnosis of PBC is generally straightforward. For the most part, you can diagnose PBC without a liver biopsy using blood tests. Those blood tests focus on the serum liver test, looking for cholestasis, elevated alkaline phosphatase and gamma-glutamyl, and then there are immunology tests in which we look for antimitochondrial antibodies. We still see about 5% to 10% of patients who don’t have antimitochondrial antibodies who may need either more specific immunology testing done at a reference laboratory or sometimes liver biopsy to confirm the diagnosis.
The only other thing that we are increasingly challenged by is that as metabolic syndrome, obesity and fatty liver become more prevalent, we are seeing patients whose diagnosis can be a bit more challenging and can take longer to determine if they have PBC alone, PBC with fatty liver, or just fatty liver with an incidental antimitochondrial antibody. However, that’s not the majority. Most patients we see follow the textbook. The rate limiting step is making sure that primary and secondary care do send blood tests for antimitochondrial antibodies.
Healio: What is currently available for treatment and management?
Hirschfield: Things are quite exciting in PBC. We’ve had ursodeoxycholic acid for more than 25 years and we now have obeticholic acid [Ocaliva, Intercept] as an approved therapy for patients who are nonresponsive or have an insufficient response to UDCA or cannot tolerate UDCA therapy. Those are the two licensed therapies. There is also a phase 3 clinical trial of seladelpar [CymaBay Therapeutics] and there will be another late-stage trial of elafibranor [Genfit] for PBC. In some parts of the world, there is an appetite to use unapproved therapies such as fenofibrate or bezafibrate, although this is not really the case in North America where the consensus remains that patients are ideally treated with approved therapies first.
Healio: What should treating physicians know about P B C?
Hirschfield: For one, hepatologists are more concerned with risk than with stage. By that I mean that we still see some patients presenting with late-stage disease, but predominantly we are identifying patients early in their stage of disease, so we want to determine early on in their treatment whether UDCA alone, UDCA plus obeticholic acid, or other therapies available in the future are right for that patient. We’re very tuned into looking at risks for patients, which we examine through measuring biochemistry and looking for improvements in alkaline phosphatase.
The second thing is that, if we’re going to get the best for our patients, the treatment targets are going to have to be more strident than they were in the past. We will be heading for eventual treatment targets that suggest normalizing the alkaline phosphatase at least along with bilirubin, ideally. This will put the onus on physicians looking after patients with PBC to be very much aware that when they see a patient, they should initiate treatment according to the guidelines and carefully follow the patient to see if they are achieving the adequate response. If a patient doesn’t have adequate response to treatment, that is the time they want to consider how else they can optimize care. As I’ve mentioned, for a patient diagnosed with PBC in 2019, what’s exciting is that we have two approved options, two more in late-stage trials, and investigative work initiated for repurposed therapy.
Disclosure: Hirschfield reports advisory committee or review panel roles with GlaxoSmithKline and Intercept; consulting roles with CymaBay and Novartis; and grant or research support from BioTie, Falk and Takeda.