Dr. James L. Boyer
Yale University School of Medicine
Dr. James L. Boyer is one of our nation’s foremost hepatologists. He has been practicing medicine since 1969 and is the founding director of the Liver Center at Yale University School of Medicine. ALF asked him to share his perspective on medical advances that have improved prospects for PBC patients, current challenges to effective treatment and how people with PBC can work with healthcare providers to overcome those challenges.
Nearly fifty years ago, when I first started my practice, treating this disease was very frustrating. We often didn’t see patients until they were in the more advanced stages of PBC. And there just wasn’t much we could do for them. We had treatments for the itching, eye drops for patients who had dry eyes, and fat-soluble vitamins. That was about it until the 1970s, when we started to offer liver transplants in select cases. Unfortunately, even though there were a lot of trials for drugs that sought to improve liver function, none were very effective.
Now we have a range of therapies that, in many cases, slow down the progression of the disease and help people live long lives. We can also do a much better job of helping PBC patients cope with their symptoms. And current clinical trials are showing a lot of promise.
I don’t want to sugarcoat this, however. There is still no cure for PBC. And the available therapies still don’t adequately address the debilitating symptoms that can accompany this disease, including fatigue and itching.
Nevertheless, I believe it’s important to appreciate how far we’ve come. I’m very optimistic that there will be even more positive developments in the near future. There are several clinical studies currently underway in the US. For example, one study is investigating whether certain genes make people more likely to develop PBC. Discovery of these proposed genes can improve our understanding of how PBC develops. This information will ultimately enable us to apply new approaches for its prevention, diagnosis and treatment. You can learn more at https://clinicaltrials.gov/ct2/show/NCT01161953.
Things have really improved. Now, PBC patients who are diagnosed and treated while in the early stages of the disease – Stages 1 or 2 – will most likely have a normal life expectancy.
Compare that to the median survival rate we saw at Yale in patients who were followed from 1955 to 1989. I was involved in this research from 1979 to 1989. Median survival was 7.5 years for people who had symptoms when their PBC was diagnosed. The life expectancy was about twice as long for people who lacked symptoms when the disease was detected. But once they started to have symptoms, their survival rate drastically diminished as well. And, as I already mentioned, there was very little we could do.
The initial discovery that led to improved treatments happened in 1985. That was when scientists noticed that ursodeoxycholic acid (UDCA or ursodiol), which had been used for years to treat gallstones, also helped people with PBC and other liver diseases. Eventually, after a series of successful trials, the FDA approved UDCA for treating PBC in 1997.
That was the first breakthrough. UDCA improves liver function in more than 50% of patients with PBC. But until very recently, we lacked options for patients who didn’t respond to it, beyond helping them cope with their symptoms.
That began to change in 2016, when the FDA approved a second PBC drug: obeticholic acid (OCA). It’s now used in combination with UDCA or on its own for people who are unable to tolerate UDCA.
Other therapies have also shown promise. They include fibric acid derivatives, also called fibrates. These are medications that lower blood triglyceride levels and have been approved in the US by the FDA to treat hyperlipidemia, or high concentrations of fats in the blood. A clinical trial evaluating Benzafibrate for the treatment of PBC was reported last year in France and published this month in the New England Journal. The results show significant improvement in liver function, symptoms of itching and liver fibrosis as measured by fibroscan. Long term effects remain to be determined.
I believe we will be able to help even more people in the future because therapy for PBC will involve combinations of these and other drugs.
There is still a lot we don’t understand. For one thing, it’s not clear why some people diagnosed with PBC have a lot of symptoms and some don’t have any. We also don’t know why some people have very severe itching or other symptoms, yet don’t have major scarring of the liver. And it’s not clear yet what causes the symptoms.
Researchers have found clues but no definitive answers to these questions. Once they do, it should be possible to make even more progress.
Other challenges have to do with gaps in the knowledge of many physicians treating PBC. Most of them aren’t specialists. This is one of the reasons that it’s important for patients to be informed. They need to be empowered to help maximize the effectiveness of available treatments.
I’ll give just a few important examples, with the understanding that this is by no means a comprehensive list:
We couldn’t agree more that patients have an important role to play in shaping health care. We invite our blog readers to stay tuned for our upcoming blogpost on ALF’s legislative advocacy program. Thank you Dr. Boyer for your time.
Last updated on August 3rd, 2022 at 01:25 pm