What is primary biliary cholangitis

Primary biliary cholangitis is used to be called primary biliary cirrhosis, is a chronic, progressive liver disease in which the bile ducts in your liver become inflamed and are slowly destroyed ¹. Bile is a fluid made in your liver. Bile aids with digestion and helps your body get rid of cholesterol, toxins and worn-out red blood cells. When the bile ducts are damaged, bile can back up in your liver and sometimes lead to poor liver function and irreversible scarring of liver tissue (cirrhosis) and eventual liver failure ¹.

Primary biliary cholangitis is more common in women ². Many people do not have symptoms when they are first diagnosed and may not develop symptoms for several years ³. Early symptoms may include fatigue (the most common symptom), itchy skin (pruritus), and abdominal pain. As the disease progresses, people with primary biliary cholangitis may develop weakness, nausea, diarrhea, swelling in the legs and feet (edema), bone and joint pain, jaundice, dark urine, and xanthomas. The symptoms of primary biliary cholangitis can significantly impair quality of life ³.

The diagnosis of primary biliary cholangitis may involve blood tests, imaging studies (such as X-ray or ultrasound), and sometimes, a liver biopsy. Blood tests may include tests for anti-mitochondrial antibodies (which may confirm the diagnosis), liver function tests, and cholesterol tests. Abnormal blood test results commonly lead to the diagnosis in people with primary biliary cholangitis who do not have symptoms.

Primary biliary cholangitis is considered an autoimmune disease in which the immune system malfunctions and mistakenly attacks a person’s healthy bile duct cells, causing the inflammation and damage. It is thought to be caused by a combination of genetic susceptibility and environmental triggers (multifactorial inheritance) ³.

Medication can slow liver damage, especially if treatment begins early. The first treatment recommended for people with primary biliary cholangitis is ursodiol, also called ursodeoxycholic acid (UDCA), which has been shown to slow disease progression and reduce the need for a liver transplant ³. Obeticholic acid (OCA) is available as a second-line treatment either in combination with UDCA (in those with an inadequate response to UDCA), or by itself (in those who are not able to tolerate UDCA) ³. The symptoms of primary biliary cholangitis typically do not improve with UDCA or OCA, so individual symptoms are treated separately ³. A liver transplant may be needed when primary biliary cholangitis leads to liver failure ¹.

The rate of progression varies greatly among people with primary biliary cholangitis, and the disease may progress over many decades before resulting in end-stage liver disease and its complications ³.

Primary biliary cholangitis causes

The exact cause of primary biliary cholangitis is unknown. Many experts think that a person’s tendency to have an overactive immune system (an autoimmune disease) in which the body turns against its own cells, which may be genetic and unknown environmental triggers play a role in causing primary biliary cholangitis. Possible environmental triggers include:

• infections
• cigarette smoking
• exposure to certain chemicals

The liver inflammation seen in primary biliary cholangitis starts when certain types of white blood cells called T cells (T lymphocytes) start to collect in the liver. Normally, these immune cells detect and help defend against germs, such as bacteria. But in primary biliary cholangitis, they mistakenly destroy the healthy cells lining the small bile ducts in the liver.

Inflammation in the smallest ducts spreads and eventually damages other cells in the liver. As the cells die, they’re replaced by scar tissue (fibrosis) that can lead to cirrhosis. Cirrhosis is scarring of liver tissue that makes it difficult for your liver to work properly.

Risk factors for primary biliary cholangitis

The following factors may increase your risk of primary biliary cholangitis:

• Sex. Most people with primary biliary cholangitis are women.
• Age. It’s most likely to occur in people 30 to 60 years old.
• Genetic factors. You’re more likely to get the condition if you have a family member who has or had it.
• Geography. It’s most common in northern Europe and North America.

Researchers think that genetic factors combined with certain environmental factors trigger primary biliary cholangitis. These environmental factors may include:

• Infections caused by bacteria, fungi or parasites
• Smoking
• Toxic chemicals

Primary biliary cholangitis prevention

Working together, you and your doctor can help prevent these specific complications:

• Increased pressure in the portal vein (portal hypertension). Your doctor is likely to screen and monitor you for portal hypertension and enlarged veins if you have liver disease.
• Weak bones (osteoporosis). Exercise most days of the week can help increase your bone density. If you have osteoporosis, your treatment may include calcium and vitamin D supplements.
• Vitamin deficiencies. Your doctor may recommend supplements of vitamins A, D, E and K to improve vitamin levels. Avoid taking herbs or nutritional supplements without talking to your doctor first.

Primary biliary cholangitis symptoms

More than half the people with primary biliary cholangitis do not have any noticeable symptoms when first diagnosed with primary biliary cholangitis. Doctors diagnose up to 6 in 10 people with primary biliary cholangitis before symptoms begin ⁴. People with primary biliary cholangitis and no symptoms are identified through blood tests. Some people do not have symptoms for years after they have been diagnosed with primary biliary cholangitis.

The disease may be diagnosed when blood tests are done for other reasons. Symptoms eventually develop over the next five to 20 years. Those who do have symptoms at diagnosis typically have poorer outcomes.

Common early symptoms of primary biliary cholangitis include:

• Fatigue (feeling tired)
• Itchy skin
• Dry eyes and mouth

Other common early symptoms may include:

• abdominal pain
• nausea
• poor appetite
• weight loss
• arthritis

As primary biliary cholangitis gets worse, symptoms may include:

• Pain in the upper right abdomen
• Swelling of the spleen
• Bone, muscle or joint (musculoskeletal) pain
• Swollen feet and ankles (edema)
• Buildup of fluid in the abdomen due to liver failure (ascites)
• Fatty deposits (xanthomas) on the skin around the eyes, eyelids or in the creases of the palms, soles, elbows or knees
• Yellowing of the skin and eyes (jaundice)
• Darkening of the skin that’s not related to sun exposure (hyperpigmentation)
• Weak and brittle bones (osteoporosis), which can lead to fractures
• High cholesterol
• Diarrhea, which may include greasy stools (steatorrhea)
• Underactive thyroid (hypothyroidism)
• Weight loss
• Weakness
• Dark urine

Primary biliary cholangitis complications

As liver damage worsens, primary biliary cholangitis can cause serious health problems, including:

• Liver scarring (cirrhosis). Cirrhosis makes it difficult for your liver to work and may lead to liver failure. It indicates the later stage of primary biliary cholangitis. People with primary biliary cholangitis and cirrhosis have a poor prognosis and higher risk of other complications.
• Increased pressure in the portal vein (portal hypertension). Blood from your intestine, spleen and pancreas enters your liver through a large blood vessel called the portal vein. When scar tissue from cirrhosis blocks normal blood flow through your liver, blood backs up. This causes increased pressure inside the vein. Also, because blood doesn’t flow normally through your liver, drugs and other toxins aren’t filtered properly from your bloodstream.
• Enlarged spleen (splenomegaly). Your spleen can become swollen with white blood cells and platelets because your body no longer filters toxins out of the bloodstream as it should.
• Gallstones and bile duct stones. If bile cannot flow through the bile ducts, it may harden into stones, causing pain and infection.
• Enlarged veins (varices). When blood flow through the portal vein is slowed or blocked, blood may back up into other — usually those in your stomach and esophagus. Increased pressure may cause delicate veins to break open and bleed. Bleeding in the upper stomach or esophagus is a life-threatening emergency that requires immediate medical care.
• Liver cancer. Liver scarring (cirrhosis) increases your risk of liver cancer.
• Weak bones (osteoporosis). People with primary biliary cholangitis have an increased risk of weak, brittle bones that may break more easily.
• Vitamin deficiencies. A lack of bile affects your digestive system’s ability to absorb fats and the fat-soluble vitamins, A, D, E and K. Because of this, some people with advanced primary biliary may have low levels of these vitamins.
• Decreased mental function (hepatic encephalopathy). Some people with primary biliary cholangitis with liver failure have personality changes and problems with memory and concentration.
• Increased risk of other disease. Primary biliary cholangitis is associated with metabolic or immune system disorders, including thyroid problems, limited scleroderma (CREST syndrome) and rheumatoid arthritis.

Primary biliary cholangitis life expectancy

Primary biliary cholangitis outcome can vary. If primary biliary cholangitis is not treated, most people will die without a liver transplant. About one quarter of people who have had primary biliary cholangitis for 10 years will have liver failure. Doctors can now use a statistical model to predict the best time to do the transplant. Other diseases, such as hypothyroidism and anemia, can also develop.

Primary biliary cholangitis diagnosis

Your doctor can diagnose primary biliary cholangitis based on your medical and family history, a physical exam, and the results of medical tests.

Your doctor will ask you about your symptoms. He or she will also ask:

• whether you have a history of certain autoimmune diseases
• whether one of your parents or siblings has been diagnosed with primary biliary cholangitis
• about your history of infections and exposure to certain chemicals

Your doctor will examine your body, use a stethoscope to listen to sounds in your abdomen, and tap or press on specific areas of your abdomen. He or she will:

• look for yellowing of the whites of your eyes and your skin
• check to see if your liver and spleen are larger than they should be
• check for abdominal tenderness or pain, particularly in the upper right side of your abdomen

The following tests and procedures may be used to diagnose primary biliary cholangitis.

Blood tests:

• Cholesterol test. More than half the people with primary biliary cholangitis have extreme increases in blood fats (lipids), including total cholesterol level, which may be a sign that their liver is not working properly.
• Liver tests. These blood tests check the levels of enzymes that may signal liver disease and bile duct injury. Higher-than-normal levels of the liver enzyme alkaline phosphatase (ALP) occur in people with diseases that destroy or block the bile ducts, such as primary biliary cholangitis.
• Antibody tests for signs of autoimmune disease. Blood tests may be done to check for anti-mitochondrial antibodies (AMAs). Anti-mitochondrial antibodies (AMA) are found in the blood of about 95 percent of people with primary biliary cholangitis ⁵. These substances almost never occur in people without the disease, even if they have other liver disorders. Therefore, a positive AMA test is considered a very reliable sign of the disease. However, a small number of people with primary biliary cirrhosis don’t have anti-mitochondrial antibodies (AMAs).

Your doctor may diagnose primary biliary cholangitis if you have anti-mitochondrial antibodies and higher-than-normal levels of alkaline phosphatase in your blood, even if you have no other signs or symptoms of the disease.

Imaging tests may not be needed. However, they may help your doctor confirm a diagnosis or rule out other conditions with similar signs and symptoms. Imaging tests looking at the liver and bile ducts may include:

• Ultrasound. Ultrasound uses high-frequency sound waves to produce images of structures inside your body.
• Magnetic resonance cholangiopancreatography (MRCP). This special magnetic resonance imaging (MRI) exam creates detailed images of your organs and bile ducts.
• Magnetic resonance elastography (MRE). MRI is combined with sound waves to create a visual map (elastogram) of internal organs. The test is used to detect hardening of your liver that might be a sign of cirrhosis.
• Endoscopic retrograde cholangiopancreatography (ERCP). The doctor passes a thin, flexible tube down your throat and injects dye into the area of your small intestine where your bile ducts empty. A tiny camera attached to the end of the tube provides a picture of your bile ducts. This test may be done with or instead of an MRCP. But, it’s invasive and may cause complications. With advances in MRI, it’s usually not needed for diagnosis.

If the diagnosis is still uncertain, your doctor may perform a liver biopsy. A small sample of liver tissue is removed through a small incision using a thin needle. It’s examined in a laboratory, either to confirm the diagnosis or to determine the extent (stage) of the disease.

Your doctor may perform a liver biopsy to:

• rule out other diseases that may be causing your symptoms
• confirm the diagnosis of primary biliary cholangitis
• determine whether the disease is advanced—as shown by the amount of liver scarring or cirrhosis—or very active

Primary biliary cholangitis treatment

There’s no cure for primary biliary cholangitis, but medications are available to help slow the progression of the disease and prevent complications. Options include:

• Ursodeoxycholic acid (UDCA). This medicine, also known as ursodiol (Actigall, Urso), is commonly used first. It helps move bile through your liver. UDCA (ursodiol) doesn’t cure primary biliary cholangitis, but it can slow the progression of liver damage, it seems to improve liver function and reduce liver scarring. It’s less likely to help with itching and fatigue. Side effects may include weight gain, hair loss and diarrhea. People who respond to ursodiol early in the course of primary biliary cholangitis can live longer without needing a liver transplant. If you do not respond to ursodiol, your doctor may prescribe obeticholic acid (Ocaliva).
• Obeticholic acid (Ocaliva). This is the newest medication approved by the Food and Drug Administration for primary biliary cholangitis. Studies show that when given alone or combined with ursodiol for 12 months it can help improve liver function.
• Fibrates (Tricor). Researchers aren’t exactly sure how this medicine works to help ease primary biliary cholangitis symptoms. But, when taken with UDCA, it has reduced liver inflammation and itching in some people. More studies are needed to determine long-term benefits.
• Other medications. Many other drugs have been used or studied for treating primary biliary cholangitis with mixed results. They include methotrexate (Trexall) and colchicine (Colcrys).
• Liver transplant. When medications no longer control primary biliary cholangitis and the liver begins to fail, a liver transplant may help prolong life. A liver transplant replaces your diseased liver with a healthy one from a donor. Liver transplantation is associated with very good long-term outcomes for people with primary biliary cholangitis. However, sometimes the disease comes back several years later in the transplanted liver.

Treating the symptoms

• Your doctor may recommend treatments to control the signs and symptoms of primary biliary cholangitis and make you more comfortable.

Treatment for fatigue

• Primary biliary cholangitis causes fatigue. But, your daily habits and other health conditions can affect how tired you feel. Researchers are investigating whether a medicine called modafinil (Provigil) may help reduce fatigue in people with primary biliary cholangitis. More research is needed.

Treatment for itching

• Antihistamines such as diphenhydramine (Benadryl, others) and loratadine (Claritin, others) are commonly used to reduce itching. They may help with sleep if itching keeps you awake. For mild itchy skin, your doctor may prescribe hydroxyzine (Vistaril). For more severe itchy skin, your doctor may prescribe cholestyramine (Locholest, Questran).
• Cholestyramine (Questran) is a powder that must be mixed with food or liquids. Though cholestyramine works for most people, the taste is unpleasant.
• Rifampin (Rifadin, others) is an antibiotic that may stop itching. Exactly how it does this is unknown. Researchers think it may block the brain’s response to itch-inducing chemicals in the blood.
• Opioid antagonists such as those containing naloxone (Bunavail, Evzio) and naltrexone (Vivitrol) may help itching related to liver disease. Like rifampin, these drugs seem to reduce the itching sensation by acting on your brain.

Treatment for dry eyes and mouth

• Artificial tears and saliva substitutes, available over-the-counter or by prescription, can help ease dry eyes and mouth. Chewing gum or sucking on hard candy also can help you make more saliva and relieve dry mouth.

How do doctors treat the complications of primary biliary cholangitis?

Doctors treat the complications of primary biliary cholangitis with medicines and dietary supplements. Your doctor may recommend changes in your diet and lifestyle.

High blood cholesterol levels. If you have higher-than-normal blood cholesterol levels, your doctor may prescribe medicines called statins and recommend lifestyle changes.

Osteoporosis. For osteoporosis, your doctor may prescribe medicines that slow or stop bone loss and improve bone density. Your doctor may recommend dietary supplements of calcium and vitamin D.

Fat-soluble vitamin deficiencies. For fat-soluble vitamin deficiencies, your doctor may recommend dietary supplements of vitamins A, D, E, and K. Follow your doctor’s instructions on the type and amount of vitamins you should take.

Cirrhosis. If primary biliary cholangitis leads to cirrhosis, doctors can treat the health problems related to cirrhosis with medicines, surgery, and other medical procedures. If cirrhosis leads to liver failure, you may need a liver transplant.

When do doctors consider a liver transplant for primary biliary cholangitis?

Your doctor will consider a liver transplant when your primary biliary cholangitis leads to liver failure. Doctors consider liver transplants only after they have ruled out all other treatment options. Talk with your doctor to find out whether a liver transplant is right for you.

What can I do to help prevent further liver damage?

To help prevent further liver damage, you can do the following:

• Carefully follow your doctor’s instructions, and take your medicines and dietary supplements as directed.
• Quit smoking.
• Do not drink any alcohol or use illegal drugs.
• Have regular checkups, as recommended by your doctor.
• Talk with your doctor before taking
  • prescription medicines
  • over-the-counter medicines
  • dietary supplements
  • complementary and alternative medicines
• Try to keep a healthy body weight.

Home remedies

You may feel better if you take good care of your overall health. Here are some things you can do to improve some primary biliary cholangitis symptoms and, possibly, help prevent certain complications:

• Choose reduced-sodium foods. Opt for low-sodium foods or naturally sodium-free foods, since sodium contributes to tissue swelling and to the buildup of fluid in your abdominal cavity (ascites).
• Never eat oysters or other raw shellfish. Such seafood can carry infection-causing bacteria, which can be dangerous for people with liver disease.
• Exercise most days of the week. Exercise may reduce your risk of bone loss.
• Avoid alcohol. Your liver processes the alcohol you drink, and the added stress can cause liver damage. Generally, people with primary biliary cholangitis should abstain from alcohol.
• Check with your doctor before starting new medications or dietary supplements. Because your liver isn’t working normally, you’ll likely be more sensitive to the effects of over-the-counter and prescription medications, as well as some dietary supplements, so check with your doctor before taking anything new.

Coping and support

Living with a chronic liver disease with no cure can be frustrating. Fatigue alone can have a profound impact on your quality of life. Each person finds ways to cope with the stress of a chronic disease. In time, you’ll find what works for you. Here are some ways to get started:

• Learn about your condition. The more you understand about primary biliary cholangitis, the more active you can be in your own care. In addition to talking with your doctor, look for information at your local library and on websites affiliated with reputable organizations such as the American Liver Foundation.
• Take time for yourself. Eating well, exercising and getting enough rest can help you feel better. Try to plan ahead for times when you may need more rest.
• Get help. If friends or family want to help, let them. Primary biliary cholangitis can be exhausting, so accept the help if someone wants to do your grocery shopping, wash a load of laundry or cook your dinner. Tell those who offer to help what you need.
• Seek support. Strong relationships can help you maintain a positive attitude. If friends or family have a hard time understanding your illness, you may find that a support group can be helpful.

Primary biliary cholangitis diet

You should eat a well-balanced and nutritious diet. Good nutrition is important in all stages of primary biliary cholangitis to help your liver work properly and manage complications. When primary biliary cholangitis leads to cirrhosis, you may develop malnutrition because cirrhosis can cause:

• loss of appetite, which will cause you to eat less
• changes in your metabolism
• reduced absorption of nutrients

Your doctor can recommend a healthy eating plan that is well balanced and provides enough calories and nutrients. If you have vitamin deficiencies, your doctor may recommend foods that are high in vitamins A, D, E, and K. Your doctor may recommend that you eat foods high in calcium and vitamin D to help prevent osteoporosis.

What foods should I avoid eating if I have primary biliary cholangitis?

You should avoid eating raw shellfish such as oysters, which can have bacteria that may cause severe infections in people with liver disease. Your doctor may recommend that you make healthy food choices and avoid high-salt foods and foods that are high in fat and carbohydrates, especially those with added sugars.

If you have primary biliary cholangitis, your doctor will recommend that you quit smoking and stop drinking alcohol or, at least, limit your intake to no more than one or two drinks per week. If you have primary biliary cholangitis and cirrhosis, your doctor will recommend complete avoidance of alcohol.

References

1. Primary Biliary Cholangitis (Primary Biliary Cirrhosis). https://www.niddk.nih.gov/health-information/liver-disease/primary-biliary-cholangitis/all-content
2. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. July, 2017; 67(1):145-172. https://www.ncbi.nlm.nih.gov/pubmed/28427765
3. Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology. January, 2019; 69(1):394-419. https://www.aasld.org/sites/default/files/guideline_documents/PracticeGuidelines-PBC-November2018.pdf
4. Poupon R. Clinical manifestations, diagnosis, and prognosis of primary biliary cholangitis (primary biliary cirrhosis). http://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-prognosis-of-primary-biliary-cholangitis-primary-biliary-cirrhosis
5. Prince MI, Chetwynd, Craig WL, Metcalf JV, James OFW. Asymptomatic primary biliary cirrhosis: clinical features, prognosis, and symptom progression in a large population based cohort. Gut. 2004;53(6):865‒870.