Walid Ayoub, MD, is the director of the Autoimmune and Cholestatic Liver Disease Program, associate medical director of liver transplant, and a professor of medicine at Cedars-Sinai Medical Center in Los Angeles. He is also a professor of medicine at the UCLA David Geffen School of Medicine.
Primary biliary cholangitis (PBC) is an autoimmune disease that affects the liver. Your body's own immune system attacks the bile ducts in the liver. This causes inflammation, or cholangitis. Bile ducts are thin tubes that carry bile from the liver to intestine. Over time, the bile ducts become permanently damaged or destroyed.
Bile is a fluid made by the liver that helps with digestion and breaks down fat. When bile can't travel through the bile ducts, it builds up in the liver. This can lead to scarring and cirrhosis.
There's no cure for PBC, and the disease becomes worse over time. There are treatments that can slow down the damage and improve your quality of life. Getting diagnosed and treated in an early stage of the disease is important, because it may delay or prevent some of the complications and later stages of PBC. We spoke to Walid Ayoub, MD, director of the Autoimmune and Cholestatic Liver Disease Program at Cedars-Sinai Medical Center in Los Angeles, about signs of the disease, how it's treated, and more.
Q: Who Gets PBC?
A: PBC is considered a rare disease because it's not common. Recent global research estimates that 18 out of every 100,000 people have PBC. Women are more likely to have the disease than men, and it's more common in Caucasian people. PBC can strike 18-year-olds to 80-year-olds, but it's most often diagnosed in people ages 40 to 60.
We don't know what exactly causes PBC, but it's a constellation of factors. Genes, environment, and lifestyle play a role. Studies show that smokers have a higher risk of developing PBC, and PBC is more prevalent in the U.S., Canada, and Western Europe. There's a good possibility that there are more diagnoses in these areas because there's more awareness. But it's an interesting topic for research.
Q: What Are the Symptoms of PBC? How Is It Diagnosed?
A: PBC is a silent disease, because there aren't specific symptoms. The most common ones are fatigue and itchiness. As doctors, our suspicion for PBC is raised in people who have another autoimmune disease and these symptoms. At least half of people with PBC have one or more other autoimmune diseases. These include Sjogren's syndrome, Reynaud's phenomenon, autoimmune thyroid disease, and celiac disease.
In later stages, people may develop a yellowing of the skin and eyes, called jaundice; dry eyes and mouth; swollen feet and ankles; bone, muscle, and joint pain; and fatty bumps under the skin.
Because PBC is rare, it's not something doctors look for right away. But an early diagnosis is important. It can slow the progression of the disease. Advanced PBC can cause very high blood pressure in a vein leading to the liver, called portal hypertension. We screen for portal hypertension to prevent dangerous complications, such as bleeding from the vein to the esophagus or stomach. For these patients, a PBC diagnosis is lifesaving.
To check for PBC, doctors usually look at two blood tests that measure antimitochondrial antibodies (AMA) and alkaline phosphatase (ALP) levels. A diagnosis requires two out of three things: a positive AMA, ALP, or liver biopsy. Recently, we have newer tests that screen for specific PBC antibodies, such anti-GP-210 and anti-SP-100, so biopsies are less common. I haven't done one in five years. After a diagnosis is made, we'll order imaging, such as a specialized ultrasound or MRI-based imaging, to see how much damage the disease has caused. We can use that information and other tests to predict how quickly the disease will advance to cirrhosis.
Q: What Kind of Damage and Complications Does PBC Cause?
A: PBC is a progressive disease. It gets worse over time. How fast that happens depends on each person. But, on average, it takes 15 to 20 years for the disease to reach cirrhosis.
PBC is grouped into four stages based on the damage. At stage 1, the small bile ducts in your liver start showing signs of damage. Your liver may have some inflammation, but it still works normally. At stage 2, the inflammation may spread, and scar tissue may build along the bile ducts. The liver can still move bile, so there usually aren't symptoms. But most people start having symptoms at stage 3. The scar tissue blocks bile flow, which causes a buildup in the liver. This is called cholestasis. It causes itchiness and fatigue. In stage 4, the liver has severe scarring, or cirrhosis. There's more bile in the liver. You may have a complication, such as portal hypertension, in stage 3 or 4.
Without enough bile, your body isn't able to digest as much fat. This can lead to weight loss, high cholesterol, and fatty stools. You may become deficient in fat-soluble vitamins, such as vitamins A, D, E, and K. People with PBC are more likely to have the bone disease osteoporosis because of vitamin D deficiencies.
Q. How Is PBC Treated?
A: For the past 30 years, the first treatment for PBC is ursodiol (also called ursodeoxycholic acid or UDCA). This drug helps remove bile from the liver and reduce liver damage. Ursodiol can delay the progression of PBC. It works in about 60% of patients.
For the other 40%, the disease doesn't improve and continues to get worse. The second medicine often prescribed is obeticholic acid (Ocaliva). But one of the medicine's side effects is itching, which makes a lot of patients uncomfortable. More recently, a new class of medicine called PPAR agonists – elafibranor (Iqirvo) and seladelpar (Livdelzi) – became available for PBC. They have similar benefits as obeticholic acid for people who don't respond to ursodiol. What's exciting is that trials show that PPAR agonists may reduce some of the itching caused by PBC.
For severe cases of PBC with cirrhosis where medication is no longer working, a liver transplant may be an option.
Q. How Can You Manage the Symptoms? Are There Any Lifestyle Changes That Can Help?
A: A big challenge in treating PBC is fatigue. None of the existing medications have an impact on fatigue, which can take a toll on a patient's quality of life. In certain cases, we'll use stimulants and antidepressants to treat fatigue and itching. Small studies show that regular exercise can help, so I recommend it to my patients. I have them start with just 15 minutes and work up to 30 minutes a day.
For itching, there are medications that can help, such as antihistamines, and now research shows that PPAR agonists may reduce itching, too.
There's no specific diet that benefits PBC, but I tell my patients not to overindulge with salty foods. Too much salt can raise the blood pressure in the liver. In my opinion, why add another challenge for your liver?
You may need to take a supplement or multivitamin if you have a vitamin deficiency. But always talk to your doctor before taking any supplement or alternative medicine treatment. Every year, I see about five to 10 people with liver toxicity from taking a vitamin or alternative remedy meant to improve liver health.
Q: What Does the Future Hold for People With PBC?
A: We're excited about the potential of new medications and combinations to treat PBC. For 20 to 30 years, we only had one main treatment with ursodiol, followed by obeticholic acid years later. But over the past years, two additional drugs came out within a few months of each other. Although we still don't have a cure for PBC yet, we're getting closer. The future is bright for people with PBC.
