What is Primary Biliary Cholangitis (PBC)?
Primary biliary cholangitis (PBC), previously referred to as primary biliary cirrhosis, is a disease where the body’s immune system incorrectly attacks the bile ducts in the liver, causing them to slowly degrade. This results in inflammation around the liver’s edges and a condition known as cholestasis, where the flow of bile is reduced or halted. Over time, this can lead to cirrhosis, a severe scarring of the liver, and increased blood pressure in the liver’s portal vein. This condition is the most frequently diagnosed bile flow-blocking disease amongst middle-aged women in the United States.
What Causes Primary Biliary Cholangitis (PBC)?
Primary biliary cholangitis (PBC) is a condition where the body’s immune system attacks its own cells. Scientists believe that this condition happens when someone who is already genetically more likely to get it, comes into contact with certain environmental factors. This belief is strengthened by the fact that people who have a close family member with this disease are 100 times more likely to get it themselves, suggesting a genetic link.
Researchers have linked various environmental factors to this disease in animal studies. These factors include urinary tract infections, use of reproductive hormones, exposure to nail polish, cigarette smoking, harmful substances known as xenobiotics, and waste from industry. The idea is that when these environmental factors or toxins harm the body, it triggers inflammation.
Risk Factors and Frequency for Primary Biliary Cholangitis (PBC)
There’s been an increase in the number of cases of primary biliary cholangitis, a liver disease, as more health screenings are being performed these days. This illness is particularly common in middle-aged women around the globe. In fact, the ratio of women to men with this disease is 9:1, and it’s typically diagnosed in women between the ages of 30 and 60. Primary biliary cholangitis is a disease that’s commonly associated with Europe and North America, but the number of cases can greatly vary from country to country.
- The increase in primary biliary cholangitis cases is due to more health screenings being done.
- This disease is common in middle-aged women globally.
- The ratio of women to men suffering from this disease is 9:1.
- The typical age of diagnosis is between 30 and 60.
- Though the disease is associated with Europe and North America, the number of cases varies across different countries.
- In the United States, per 1 million person-years, the incidence rate is 45 for women and 7 for men, while the prevalence rate is 654 for women and 121 for men.
Signs and Symptoms of Primary Biliary Cholangitis (PBC)
Primary Biliary Cholangitis (PBC) is a liver condition that may or may not cause symptoms. People without symptoms often find out they have PBC when they undergo tests for other medical reasons. For those with symptoms, common ones include yellowing of the skin or eyes (jaundice), itchiness, and tiredness. The itchiness usually worsens at night, in hot and humid weather or when the skin is dry. Around 20% to 70% of patients suffer from itchiness, believed to be a result of excess bile salts. Another theory suggests that high levels of a compound called lysophosphatidic acid caused by bile blockage could also be responsible for the itchiness. Some patients may also have a vague pain in the right upper part of their abdomen or mild cognitive problems. Issues with absorbing nutrients, leading to nutrient deficiencies and fat in the stool, have also been reported in PBC patients.
During a physical examination, doctors may notice several changes in patients with PBC. These changes typically depend on the stage of the disease. About 40% of patients have skin problems, such as dry skin, dark patches, yellow fat deposits under the skin, jaundice, skin writing, and foot fungal infection. Scratching marks due to dry skin and itchiness are common. Patients might also have an enlarged liver, especially those without symptoms or in the later stages of the disease. When the disease is more advanced, the spleen can become enlarged too. As the liver disease progresses, more serious signs could occur such as spider-like blood vessels, fluid build-up in the abdomen, swelling, and muscle wasting. PBC can also coexist with other autoimmune conditions like Hashimoto thyroiditis, CREST syndrome, Sjogren syndrome, rheumatoid arthritis, tiny widened blood vessels, and celiac disease. Bone loss, kidney acidosis, and various skin conditions (like lichen planus, discoid lupus, and pemphigoid) are also commonly associated with PBC.
Symptom list:
- Jaundice
- Itchiness
- Tiredness
- Vague pain in the right upper abdomen
- Mild cognitive problems
Physical examination findings:
- Dry skin
- Dark patches on the skin
- Yellow fat deposits under the skin
- Jaundice
- Skin writing
- Foot fungal infection
- Enlarged liver
- Enlarged spleen
- Spider-like blood vessels
- Fluid build-up in the abdomen
- Swelling
- Muscle wasting
Testing for Primary Biliary Cholangitis (PBC)
If your doctor suspects that you have a condition called primary biliary cholangitis, a liver disease, they will need to rule out any other liver diseases, and show no signs of extrahepatic biliary obstruction–which is a blockage of biliary ducts outside your liver–in any imaging tests. Then, you must meet at least 2 out of 3 specific criteria:
1. Your alkaline phosphatase (an enzyme found in your liver) levels are at least 1.5 times higher than normal.
2. Your blood tests show the presence of antimitochondrial antibodies (indicative of an immune response) at a particular level.
3. Your tissue sample (biopsy) shows evidence of primary biliary cirrhosis (an advanced form of this disease), characterized by certain abnormal features.
While getting a liver biopsy isn’t necessary for the diagnosis, it can help predict how the disease will progress and determine its stage.
People who don’t show symptoms but have abnormal liver chemistry results, particularly regarding alkaline phosphatase, should be evaluated for this disease. If you have vague pain in the upper right portion of your abdomen, unexplained skin itching, fatigue, yellowing of the skin and eyes, darkened skin, or unexplained weight loss, you might have primary biliary cirrhosis.
If you have symptoms that suggest you might have primary biliary cirrhosis, your doctor will need to do a right abdominal ultrasound, a particular MRI of the liver (MRCP), or an endoscopy procedure (ERCP) to rule out any blockage outside of the liver. After eliminating the possibility of blockage, the presence of antimitochondrial antibodies in your body should be confirmed. In some cases, an elevated level of a type of antibody called IgM is also noted.
For cases where the disease presents differently, with an increase in alkaline phosphatase but normal antimitochondrial antibodies, your doctor might consider other possible diagnoses and consider doing a liver biopsy.
People with primary biliary cholangitis might also have an abnormal lipid (various fats in the body) profile due to cholestasis, a condition where bile cannot flow from the liver to the small intestine. Half of these patients have high cholesterol, which can lead to the formation of fatty deposits on the skin. Patients might also have iron deficiency anemia due to chronic blood loss, often caused by a complication of liver disease known as portal hypertensive gastropathy. If you’ve already developed cirrhosis (late stage scarring) because of primary biliary cholangitis, your blood’s ability to clot (coagulopathy, measured by prothrombin time), platelet count, and white blood cell count may be abnormally low in addition to anemia.
Treatment Options for Primary Biliary Cholangitis (PBC)
The main task when treating Primary Biliary Cholangitis (PBC) is slowing down the disease’s progress while also managing any symptoms and related complications.
One of the key treatments for this condition is a medication called Ursodeoxycholic acid (UDCA), a type of bile salt recognized and approved by the Food and Drug Administration (FDA). This drug aims to protect liver cells and prevent them from damaging effects of toxic bile salts. It also helps prevent the development of scar tissue in the liver. Patients tend to see the best outcomes when this medication is started before the disease has progressed too much. UDCA can help keep the disease from getting worse and prevent liver scarring and cirrhosis.
If UDCA isn’t effective for a patient, another medication called Obeticholic acid (OBCA) can be used alongside it. While it doesn’t improve survival rates or symptoms, OBCA can help lower specific liver enzymes due to its ability to help bile flow and slow the development of scar tissue in the liver.
There are also complications related to this condition, including bone diseases, deficiencies in certain vitamins, cholesterol issues, itchiness, and malabsorption of fats.
For bone diseases such as Osteoporosis and fractures, regular assessments are recommended, as are daily vitamin D and calcium supplements, exercise, and in some cases, estrogen therapy.
Diminished levels of vitamins A, D, E, and K may occur in patients due to malabsorption associated with bile salt deficiency and need to be monitored and supplemented.
PBC can alter cholesterol levels with high-density cholesterol levels dropping and low-density cholesterol levels rising as the disease advances. Medication to manage cholesterol, such as statins, is recommended, but do not worsen liver function.
Itchiness is a common symptom, managed with a range of agents, including cholestyramine, rifampin UDCA, naltrexone, and antihistamines.
Absorption issues can create fatty stools due to decreased levels of bile acids in the small intestine. Depending on the underlying cause, treatments might include dietary changes or broad-spectrum antibiotics.
In severe cases, a liver transplant might be needed. PBC patients with complications stemming from cirrhosis, or those who have symptoms such as severe itchiness, extreme tiredness, or drastically escalated bilirubin levels without the presence of liver cancer, should be evaluated for this procedure.
What else can Primary Biliary Cholangitis (PBC) be?
When diagnosing a condition called primary biliary cholangitis, doctors have to rule out some other medical conditions that produce similar symptoms. These symptoms might include jaundice (a condition that causes yellow skin and eyes), itchiness, and abnormal liver test results.
This diagnosis will commonly be considered for middle-aged women who present with these symptoms. Here are some other conditions that often look similar to primary biliary cholangitis:
- Blockage or narrowing of the bile ducts
- A condition that causes inflammation and damage to the bile ducts, known as primary sclerosing cholangitis
- Hepatitis (inflammation of the liver)
- Liver disease caused by certain medications
These conditions need to be considered and possibly ruled out before a firm diagnosis of primary biliary cholangitis can be made.
What to expect with Primary Biliary Cholangitis (PBC)
The prognosis, or outcome, of a patient with primary biliary cholangitis, a liver disease, can be predicted using two major indicators: the increase in serum bilirubin level and the Mayo risk score. Serum bilirubin is a substance found in the blood, and its levels can help doctors estimate a patient’s survival time:
- If the bilirubin level regularly exceeds 2, the average survival time is approximately four years.
- If it regularly exceeds 6, the average time drops to around two years.
- If it regularly exceeds 10, the average time is about 1.4 years.
According to one study, fatigue levels may also be an important predictor of the outcome for people with primary biliary cholangitis.
Possible Complications When Diagnosed with Primary Biliary Cholangitis (PBC)
Primary biliary cholangitis can lead to several complications such as:
- Osteoporosis or weak and brittle bones
- Malabsorption, when your body can’t absorb necessary nutrients
- Hyperlipidemia, having high levels of fats in your blood
- Esophageal motility dysfunction, trouble swallowing or food getting stuck in the throat
- Renal tubular acidosis, an imbalance of acid in the body due to kidney failure
- Liver cancer
- Autoimmune thrombocytopenia, a condition where the immune system destroys blood platelets resulting in bleeding and bruising
- Hypoglycemia, low blood sugar
- Myelopathy, damage to the spinal cord
