With credible, practical information about primary biliary cholangitis (PBC), you’re better able to determine what you can do to make the best choices for your health. Fortunately, we had the opportunity to talk with Dr Kris Kowdley, MD, Professor at Elson S. Floyd College of Medicine, Washington State University and Director of the Liver Institute Northwest, about PBC facts and his expert insights.
More Than PBC: What is PBC?
Dr Kowdley: PBC stands for “primary biliary cholangitis.” It was originally described as “primary biliary cirrhosis” decades ago. At the time, most patients were diagnosed with advanced disease (cirrhosis refers to heavily scarred liver). PBC results from an immune attack on the small bile ducts in the liver, resulting in leakage of bile acids from bile ducts into the adjacent liver tissue. These bile acids can be toxic to liver cells and cause injury to the cells, which may then trigger an additional immune response aimed at the damaged cells, resulting in further damage to the liver.
Over the years, we’ve made a great deal of progress in our understanding of the disease and how to make an early diagnosis. Fortunately, the majority of patients are now diagnosed before the development of cirrhosis, and at a stage when the disease can be treatable and managed. Therefore, we now refer to this condition as “primary biliary cholangitis.”
More Than PBC: What causes PBC?
Dr Kowdley: First, you have a genetic predisposition to the disease. Then, you have one or more environmental triggers. Possible environmental triggers for PBC have been widely debated and include things like viruses, antibiotics, and even hairspray.
Then you have the immune response—we all have an immune response. What makes an autoimmune disease different is that immune response is directed against the self—as opposed to a foreign substance or pathogen—and continues as opposed to dying down over time.
More Than PBC: So, it’s not caused by something you did?
Dr Kowdley: No. There is a wrong perception that liver disease only develops due to patients participating in risky behavior such as drug or alcohol abuse. We now know that liver disease can also be a consequence of an autoimmune injury, or a genetic or metabolic issue. We also know that most liver diseases can be managed successfully with medications and lifestyle modification.
More Than PBC: Who gets PBC?
Dr Kowdley: Autoimmune disorders are much more common among women than men, and PBC has been thought to be a disease of white, middle-aged women. It is important to recognize that this disease can affect men and women from all ethnic and racial groups, and it is unfortunate that diagnosis is occasionally delayed in these groups. PBC may affect anyone, and so, a higher level of awareness is necessary to consider the diagnosis—even in patients who may not fit into the “typical” demographic profile.
“You know those symptoms that you think maybe are in your head? They’re not. It’s real and you need to make sure that you speak up for yourself. The symptoms of PBC may not be immediately obvious and may be dismissed by clinicians without experience caring for PBC patients.”
–Dr Kris Kowdley
More Than PBC: What are the symptoms of PBC? If people in the early stages of the disease experience symptoms, they’re most likely to be itching and fatigue, right?
Dr Kowdley: Yes, that’s true. Fatigue and pruritus—which is the medical word for itching—can really limit patients’ ability to enjoy normal life and routine activities. Although symptoms like fatigue and pruritus can sometimes be severe and disabling, they do not necessarily indicate increased disease severity or stage of disease.
Some patients may have other symptoms such as jaundice, which may be accompanied by dark urine or light stool if diagnosed at a late stage of the disease. These symptoms do suggest the presence of advanced disease and patients with these symptoms should be referred promptly for liver transplant evaluation. Fortunately, it is now uncommon for patients to be diagnosed at such a late stage of the disease.
More Than PBC: How is PBC diagnosed?
Dr Kowdley: Occasionally, patients may be diagnosed because they present with symptoms such as unexplained severe fatigue or unexplained itching. But most patients are diagnosed through routine laboratory monitoring.
Doctors usually suspect a PBC diagnosis based on elevated liver tests, which are usually done as part of a comprehensive metabolic blood panel. Patients with PBC typically have an elevated alkaline phosphatase (ALP), usually along with elevated alanine transaminase (ALT) and aspartate aminotransferase (AST)—or liver enzymes which are also called “aminotransferases” or “transaminases.” Patients with PBC often have elevated ALT and AST, but ALP is the most elevated.
So, elevation of liver biochemical blood tests (ALP, AST, and ALT) are the most common ways in which the disease is suspected. Diagnosis can then be confirmed by testing if patients have antimitochondrial antibody (AMA) in their blood. This test is positive in about 95% of patients with PBC.
If a patient has an elevated ALP out of proportion to elevation of ALT and AST and has a positive AMA, the diagnosis of PBC is confirmed without requiring any other invasive procedures or tests. Rarely, patients without a positive AMA test can be diagnosed with PBC if they have “disease-specific anti-nuclear antibodies” (ANA). The next step for a doctor is to stage the disease, evaluate the symptom burden of the patient, and comprehensively assess other conditions that may accompany PBC.
More Than PBC: What are the stages of PBC? PBC is typically considered to have 4 stages, is that correct?
Stage 1
There is ongoing inflammation in the bile ducts and some bile duct damage.
Stage 2
In this stage there is inflammation and some fibrosis (scarring).
Stage 3
This stage is characterized by an increase in scarring.
Stage 4
In this final stage there are nodules and a jigsaw scarring pattern.
Dr Kowdley: These stages of disease were based on liver biopsy findings. However, since liver biopsy is no longer needed for diagnosis, doctors often use non-invasive tests to stage PBC. These include transient elastography by FibroScan® or magnetic resonance elastography (MRE), both of which measure liver stiffness which can be used to estimate fibrosis stage. Additionally, we can now use routine clinical lab values to predict risk of liver disease complications over a 10- to 20-year time frame.
It is important for patients to know what stage they are in and to know that they are being treated correctly for that stage. In my own practice, I follow a 3-step approach to managing PBC:
- First, stage the disease because that’s what determines where the patient is now. I use a risk calculator (such as GLOBE score or UK-PBC score) to estimate the patient’s future risk for serious liver-related complications.
- Second, I assess and optimize management of the symptoms of the disease so that the patient can maximize their quality of life.
- Third, I recognize the associated medical conditions (such as other autoimmune diseases, thinning of the bones, fat-soluble deficiencies, sicca syndrome) that can accompany PBC, so they do not get ignored and can be managed appropriately.
It’s essential to maintain a close working relationship with the patient’s primary care physician to provide comprehensive care.
More Than PBC: What is the treatment for PBC?
Dr Kowdley: We have the good fortune of currently having an approved first-line and a second-line treatment for PBC in the USA, and we anticipate several new treatments are in development. Occasionally, a liver transplant may be needed for patients who develop complications of end-stage liver disease. Fortunately, with the available medical therapies, the number of liver transplants for PBC has decreased over the years. However, the average age at which patients must undergo liver transplant has not changed, emphasizing the need to closely monitor patients and implement first- and second-line therapies as appropriate to manage the disease and prevent its progression.
Patients with PBC can also sometimes develop a deficiency of fat-soluble vitamins. That’s vitamin A, vitamin D, vitamin E, and vitamin K. It’s important to eat lots of leafy green vegetables and fresh fruits to address this concern. Patients should also discuss with their doctor any use of supplements or over-the-counter products to make sure they are safe.
More Than PBC: What do you wish your patients would tell you?
Dr Kowdley: I want to hear about their quality of life. If you’re feeling more tired than you feel you should be, or if you have itching that seems like it’s more than just dry skin here and there, please be proactive in mentioning the symptoms and their impact on your everyday life—whether they are limiting your ability to work or socialize—to your doctor.
We at More Than PBC would like to remind our readers to empower themselves to speak up about their symptoms and work with their doctors to get the care they deserve.
The information provided is not meant to override your treatment plan or advice from your doctor.
