Index
There is no cure, but treatment can slow the progression of the disease and relieve symptoms.
The main functions of the liver include cleaning toxins from the blood and processing nutrients from food into protein, fat, and carbohydrates.
The liver produces bile, this bile is stored in the gallbladder and added to the digestive tract through the bile ducts, it travels through these ducts to the small intestine, where it helps in the digestion of fats and fat-soluble vitamins (A , D, E and K).
When the ducts are destroyed, bile builds up in the liver and contributes to inflammation and scarring of the tissues (known as fibrosis).
Ultimately, this can lead to cirrhosis and its associated complications, as scar tissue replaces healthy liver tissue and liver function deteriorates more and more.
Primary biliary cholangitis, formerly known as primary biliary cirrhosis, is a chronic liver disease that results from the progressive destruction of the bile ducts in the liver, called intrahepatic bile ducts.
Women are 10 times more likely to develop primary biliary cholangitis than men, for unknown reasons.
The disease is usually diagnosed later in life, between the ages of 35 and 60.
Primary biliary cholangitis appears to be associated with a number of other autoimmune diseases, including rheumatoid arthritis , scleroderma, and Sjogren’s syndrome, although the reasons for this are not very clear.
Primary biliary cholangitis is divided into four stages, with stage 1 being the early disease, where there are no significant scars, up to stage 4, which is defined by cirrhosis.
Destruction of the bile ducts
The bile drains into the digestive tract through the bile ducts. For unknown reasons, the immune system attacks the cells that line the bile ducts within the liver. This causes chronic inflammation, damage, and scarring.
Over time, the accumulated scar tissue blocks the ducts and causes a buildup of bile within the liver, which in turn becomes inflamed.
Functional liver tissue is gradually replaced with non-functioning scar tissue. Eventually, much of the liver is replaced by scar tissue that can no longer function properly (cirrhosis).
Most people with primary biliary cholangitis never experience this degree of cirrhosis.
Signs and symptoms
The symptoms of primary biliary cholangitis vary from person to person, from nonexistent or mild to severe. Symptoms tend to be progressive and can include the following:
Fatigue
The cause of fatigue in primary biliary cholangitis is unknown and can be very debilitating. Unfortunately, there are no accepted pharmacological treatments for fatigue in primary biliary cholangitis, although research for medications that can help fatigue is ongoing.
Since fatigue is very common, it is important to rule out other causes of fatigue. Fatigue in primary biliary cholangitis is not related to the severity of liver disease.
Patients may have early disease but still have profound fatigue, while others with more advanced disease may not be fatigued at all.
Pruritus (itching)
Like fatigue, the cause of pruritus in primary biliary cholangitis is unknown and is not always related to the severity of liver disease.
The itching is likely to be caused by substances in the blood rather than the skin, unlike itching caused by allergies.
Fortunately, unlike fatigue, there are several drug treatments for itching that work for most people.
Jaundice
The jaundice occurs when primary biliary cholangitis is very serious. Sometimes it can be reversed with the treatment of primary biliary cholangitis, but sometimes, patients with jaundice will require a liver transplant.
Jaundice usually occurs when the liver is so damaged that normal liver function is impaired.
Other symptoms
Other symptoms associated with complications can be:
- Unexplained weight loss
- Indigestion.
- Easy bruising.
- Aching joints.
- Inflamed abdomen due to fluid accumulation.
- Abdominal discomfort around the liver
Complications of primary biliary cholangitis
Most of the complications of primary biliary cholangitis are related to cirrhosis and begin after the primary biliary cholangitis progresses to cirrhosis.
Portal hypertension
In some cases, portal hypertension and esophageal varices can develop before cirrhosis.
The portal vein carries blood from the stomach, intestines, spleen, gallbladder, and pancreas to the liver.
In cirrhosis, scar tissue partially blocks normal blood flow, increasing pressure in the portal vein or portal hypertension.
Portal hypertension generally occurs after a patient develops cirrhosis.
Portal hypertension can cause the following diseases:
Ascitis
It can cause fluid accumulation in the abdomen, or confusion due to a build-up of toxins that the liver does not remove.
Liver failure causes fluid accumulation leading to edema and ascites.
Ascites can lead to spontaneous bacterial peritonitis, a serious infection that requires immediate medical attention.
Varices
Portal hypertension can cause enlarged blood vessels in the esophagus, stomach, or both.
These enlarged blood vessels, called esophageal or gastric varices, cause the vessel walls to thin and blood pressure to rise, making the blood vessels more likely to burst.
If they burst, serious bleeding can occur in the esophagus or upper stomach, requiring immediate medical attention.
Splenomegaly
Portal hypertension can cause the spleen to enlarge and retain white blood cells and platelets, reducing the number of these cells and platelets in the blood.
A low platelet count may be the first evidence that a person has developed cirrhosis.
Hepatic encephalopathy
A defective liver cannot remove toxins from the blood, so they eventually accumulate in the brain, called hepatic encephalopathy.
This condition can decrease mental function and cause stupor and even coma.
Stupor is an unconscious, dream-like state from which a person can only be briefly awakened by a strong stimulus, such as acute pain.
Coma is an unconscious state, like a dream, from which a person cannot wake up by himself in a certain time. Signs of decreased mental function include:
- Confusion.
- Personality changes
- Memory loss.
- Difficult to focus.
- Changes in sleeping habits
Metabolic bone diseases
Some people with cirrhosis develop metabolic bone disease, which is a bone strength disorder usually caused by abnormalities in vitamin D, bone mass, bone structure, or minerals, such as calcium and phosphorus.
Osteopenia is a condition in which bones become less dense, making them weaker. When bone loss becomes more severe, the condition is known as osteoporosis.
Osteoporosis is the most common complication in primary biliary cholangitis, although it is also very common in people without primary biliary cholangitis. It leads to thinning of the bones and can be treated with bone medications.
People with these conditions are more likely to develop bone fractures.
Bile duct stones
If cirrhosis prevents bile from flowing freely to and from the gallbladder, the bile hardens into gallstones.
Symptoms of gallstones include abdominal pain and recurrent bacterial cholangitis – irritated or infected bile ducts.
Stones can also form and block the bile ducts, causing pain, jaundice, and bacterial cholangitis.
Steatorrhea
Steatorrhea is a condition in which the body cannot absorb fat, causing a build-up of fat in the stool and loose, greasy, and smelly stools.
Steatorrhea can be caused by impaired bile supply to the small intestine or by the pancreas not producing enough digestive enzymes.
Fat malabsorption occurs only when primary biliary cholangitis is very advanced and is very rare. If it happens, it will cause diarrhea, fatty stools, and weight loss.
Liver cancer
Liver cancer is common in people with cirrhosis and has a high death rate.
Fat deposits
Fatty deposits under the skin are more common, as there is a higher amount of cholesterol in the blood of people with primary biliary cholangitis.
These fat deposits appear as yellow bumps under the skin, usually under the eyes or on the joints.
Other diseases
Autoimmune diseases are also associated (occur more commonly) with primary biliary cholangitis.
Some examples of these other diseases include:
- Thyroid disease
- Sjogren’s syndrome, a disease that causes dry eyes and a dry mouth.
- Celiac disease, a disease that affects the small intestine and causes an allergy to gluten (that is, it is contained in products with wheat, rye, bran).
Causes
The exact cause of primary biliary cholangitis is unknown. Possible immune, autoimmune, genetic, and / or environmental factors are being investigated as possible causes of the disorder.
Immune abnormalities can be a major contributing factor in the development of primary biliary cholangitis.
The immune system is divided into several components, the combined actions of which are responsible for defense against different infectious agents, that is, invasive microscopic life forms such as microorganisms.
The T-cell system (cell-mediated immune response) is responsible for fighting yeast and fungi, various viruses, and some bacteria.
The B cell system (humoral immune response) fights infection caused by other viruses and bacteria. It does this by secreting immune factors called antibodies, also known as immunoglobulins, into the liquid portion of the blood (serum) and body secretions such as saliva.
People with primary biliary cholangitis have an unusually low number of circulating T cells in the blood and abnormalities in the function and regulation of T cells (ie, T helper and suppressor cells).
The role of T cell abnormalities in the potential contribution to symptoms associated with primary biliary cholangitis is not yet known.
Autoimmune factors may also play a contributing role in causing primary biliary cholangitis.
Autoimmune disorders occur when the body’s natural defenses against invading microorganisms mistakenly attack healthy tissue.
For example, antibodies typically directly kill “invaders” such as microorganisms, toxins, and other foreign substances, or coat them so they are more easily destroyed by white blood cells.
White blood cells (leukocytes) are part of the body’s defense system, playing an essential role in protecting against infection and fighting infection once it occurs).
However, in some patients, antibodies can be formed incorrectly against certain parts of the body such as tissues, causing autoimmune disease.
In some people with primary biliary cholangitis, specialized laboratory tests performed on the liquid portion of the blood (serum) have revealed the presence of certain antibodies typically produced in response to certain viruses (i.e., retroviral antigens).
Antigens are those substances, such as microorganisms, toxins, or other foreign substances, that can trigger the production of particular antibodies as part of an immune response.
This suggests that in individuals with primary biliary cholangitis, certain antibodies may be mistakenly reacting to one or more of the body’s own proteins that are very similar to the protein fragments of certain invading viruses, that is, the immune system cannot distinguish between the “mimic” protein on the surface of certain viruses and the body’s own proteins.
On the other hand, such findings may provide evidence that primary biliary cholangitis may be due, at least in part, to an underlying viral infection, a finding that has been demonstrated in other autoimmune disorders.
Since several familial cases of primary biliary cholangitis have been reported in the medical literature, it is also suspected that certain genetic factors may play a role in the development of primary biliary cholangitis.
Environmental or other factors can trigger symptoms in those with a genetic predisposition to the disorder.
Further studies are needed to determine the possible role that immune, autoimmune, genetic, environmental, and / or other factors may play in causing primary biliary cholangitis.
Affected Populations
Primary biliary cholangitis mainly affects women, but more men are now being diagnosed.
The disorder usually becomes apparent during middle age, initially affecting most people between the ages of 45 to 65.
However, the disorder has been diagnosed in women as young as 22 and in women in their early 90s.
Primary biliary cholangitis has been estimated to be one of the most common autoimmune diseases, affecting nearly 1 in 1,000 women over the age of 40.
Related disorders
Other illnesses with similar symptoms that can be ruled out during diagnosis include the following:
Primary sclerosing cholangitis
Although the names of primary biliary cholangitis and primary sclerosing cholangitis are similar, they are very different conditions and should not be confused with each other.
While primary biliary cholangitis affects the small ducts of the liver, primary sclerosing cholangitis affects the large bile ducts of the liver.
This leads to narrowing, inflammation, and scarring of the large bile ducts, which can lead to blockage of the bile ducts with symptoms of fever, pain, and jaundice (yellow skin).
Unlike primary biliary cholangitis, jaundice in primary sclerosing cholangitis can occur even when the disease is in the early stages, due to a large bile duct blockage.
Because primary sclerosing cholangitis also presents with high alkaline phosphatase (a liver test that indicates damage to the bile ducts), it can sometimes be mistaken for primary biliary cholangitis.
If a patient with high alkaline phosphatase has a negative antimitochondrial antibody test and a biopsy that does not resemble primary biliary cholangitis, then a test called an MRI cholangiopancreaticogram should be performed.
This test is a special type of MRI that looks closely at the bile ducts to see if they are normal.
If the bile ducts look abnormal on MRI, one of the diagnoses to consider is primary sclerosing cholangitis.
Primary sclerosing cholangitis can also lead to gallstone formation in the bile ducts (not just the gallbladder), which can also cause blockages leading to fever, pain, and jaundice.
Sometimes patients need a special test called endoscopic retrograde pancreaticography to open narrow bile ducts and / or remove gallstones from the bile ducts.
Patients with primary sclerosing cholangitis may also need antibiotics to treat bile duct infection.
Unlike primary biliary cholangitis, there is currently no medical treatment that slows or stops the progression of primary sclerosing cholangitis.
However, ursodeoxycholic acid is sometimes prescribed in primary sclerosing cholangitis.
Importantly, primary sclerosing cholangitis and primary biliary cholangitis cannot occur in the same patient at the same time.
Autoimmune hepatitis
Autoimmune hepatitis is a type of autoimmune liver disease that sometimes occurs in patients with primary sclerosing cholangitis or primary biliary cholangitis.
It is a disease that generally affects the liver tissue around the bile ducts, rather than the bile ducts themselves.
The diagnosis of autoimmune hepatitis usually requires a liver biopsy.
Treatment of autoimmune hepatitis involves medications that help control an overactive immune system, such as steroids, azathioprine, 6-mercaptopurine, mycophenolate mofetil / sodium, tacrolimus, or cyclosporine.
Nonalcoholic steatohepatitis
Nonalcoholic steatohepatitis is a chronic, slowly progressive disorder characterized by fatty infiltration of the liver (hepatic steatosis), liver inflammation (hepatitis) and / or the abnormal formation of scar tissue (fibrosis) within the liver, potentially leading to cirrhosis. in some cases.
Liver inflammation can resemble that associated with alcohol-induced liver disease. Symptoms associated with the disorder may include upper abdominal pain, an enlarged liver (hepatomegaly), and / or abnormally elevated levels of certain liver enzymes.
Although the exact cause of nonalcoholic steatohepatitis is not understood, the disorder, which affects women in most cases, often appears to occur in association with obesity, diabetes, and / or the presence of abnormally high levels of fat in plasma, the liquid portion of the blood (hyperlipidemia).
In some cases, nonalcoholic steatohepatitis has also been associated with widespread poor health, malnutrition, and weakness due to cancer (cancer cachexia).
Diagnosis
The diagnosis of primary biliary cholangitis requires the presence of high alkaline phosphatase, a liver blood test, along with
positive antimitochondrial antibody.
If the antimitochondrial antibody test is negative, then a patient would need a liver biopsy to confirm the diagnosis of primary biliary cholangitis, as several diseases can cause high alkaline phosphatase.
Treatment
In the early stages of primary biliary cholangitis, the goals of treatment are to delay the progression of tissue scarring in the liver and to prevent complications.
As primary biliary cholangitis progresses, a person may need additional treatments and hospitalization to manage complications.
Medicines
The most widely used drug is ursodiol also known as ursodeoxycholic acid (Actigall, Urso) to treat primary biliary cholangitis.
Ursodiol is a non-toxic bile acid that people can take by mouth.
Ursodiol replaces bile acids normally produced by the liver, which are more toxic and can damage the liver.
Ursodiol treatment can lower the levels of bilirubin and liver enzymes in the blood.
Early treatment with this drug reduces the chance of needing a liver transplant and improves survival.
Early treatment provides the greatest benefit; however, treatment with ursodiol late in the disease may delay the progression of liver damage.
Although treatment with ursodiol improves the outcome of primary biliary cholangitis, it does not cure the disease.
Researchers are studying the effects of several other medications on the progression of primary biliary cholangitis. To date, none have shown the positive effects of ursodiol.
Treatments for symptoms
Other treatments for primary biliary cholangitis are for symptom relief.
Pruritus (itching)
Antihistamines can help with mild itching. However, antihistamines often cause drowsiness, so it is recommended that the person take the antihistamine just before bed to help with night itching.
Experts believe that high cholesterol levels allow substances that cause itching to accumulate in the tissues.
The drugs cholestyramine or colestipol hydrochloride are usually the first drug tried because it stops the itching in many people and has limited side effects. The most common side effect is constipation.
Other medications for itching include gabapentin, sertraline, naltrexone, and fibrates.
Very rarely, treatments such as UV therapy and plasmapheresis (an invasive medical procedure that filters the blood) are needed.
In rare cases, none of these treatments work and patients require a liver transplant.
Dry eyes and mouth
Doctors generally treat dry eyes and mouth with artificial tears and saliva substitutes, respectively.
These products are pilocarpine (Salagen) or cevimeline (Evoxac). People who have difficulty with dry eyes should consult an ophthalmologist. People with a dry mouth should have regular dental exams.
Malabsorción
Fat-soluble vitamin malabsorption can be treated with vitamin K 1, A, D, and calcium supplements.
Iron deficiency anemia responds to oral iron supplements. Additional folic acid can be given to people taking cholestyramine because this drug can sometimes cause a folic acid deficiency.
Folic acid and cholestyramine should be taken several hours apart, as they can react and prevent the absorption of folic acid when taken together.
Loss of fat in the stool (steatorrhea) can be treated with a low-fat diet supplemented with medium chain triglycerides to maintain a high caloric intake.
Portal hypertension
Treatments for portal hypertension depend on the severity of the complications.
Your doctor may prescribe a beta blocker or nitrate to treat portal hypertension.
Beta-blockers lower blood pressure by helping the heart beat slower and less forcefully, and nitrates relax and widen blood vessels to allow more blood to flow to the heart and reduce the workload on the heart.
Treatment for complications
Health care providers treat symptoms and complications by:
Edema, ascites.
In the treatment of mild ascites, salt restriction may be the only treatment that is needed. When ascites is severe, diuretics (water pills that make patients urinate more to decrease fluid retention in cells) may be necessary.
The doctor may remove large amounts of ascites fluid from the abdomen and look for spontaneous bacterial peritonitis. He may also prescribe bacteria-fighting drugs called antibiotics to prevent infection.
Antibiotics are oral in cases where it is mild, however, if the infection is severe, intravenous antibiotics are required.
Hepatic encephalopathy
Hepatic encephalopathy can be treated with a specific laxative called lactulose, or rifaximin, a nonabsorbable antibiotic.
The doctor will treat hepatic encephalopathy by flushing the intestine with lactulose, a laxative given by mouth or as an enema, a liquid that is put into the rectum, he can also add antibiotics to the treatment.
Hepatic encephalopathy may improve as other complications of cirrhosis are controlled.
Osteoporosis
Your doctor may prescribe bisphosphonate medications to improve bone density, as a treatment for osteoporosis.
Bile duct stones
The doctor may use surgery to remove gallstones, may use endoscopic retrograde cholangiopancreatography, which uses balloons and basket-shaped devices, to retrieve stones from the bile duct.
Liver cancer
Your doctor may recommend screening tests every 6 to 12 months to look for signs of liver cancer.
Screening tests can find cancer before a person has symptoms of the disease.
Cancer treatment is generally most effective when the doctor finds the disease early.
Doctors use blood tests, ultrasound, or both to detect liver cancer in people with cirrhosis and can treat the cancer with a combination of surgery, radiation, and chemotherapy.
Varices
Treatment of varicose veins is usually the use of beta-blockers to reduce pressure on the varicose veins and reduce the likelihood of bleeding.
Bleeding in the stomach or esophagus requires immediate upper endoscopy.
This procedure involves the use of an endoscope with the insertion of a very small camera that goes into the esophagus to look for varicose veins.
The doctor may use the endoscope to perform a band ligation, a procedure that involves placing a special elastic band around the varicose veins that causes the tissue to die and fall off.
Liver transplantation for primary biliary cholangitis
The doctor may consider a liver transplant when primary biliary cholangitis leads to liver failure or treatment of complications is ineffective.
Liver transplantation is surgery to remove a diseased or injured liver and replace it with a healthy liver or part of another person’s liver, called a donor.
Food, diet and nutrition
A healthy diet is important in all stages of primary biliary cholangitis as malnutrition is common in people with this disease.
This condition occurs when the body is not able to assimilate enough nutrients.
Primary biliary cholangitis can lead to malnutrition because it can cause
- That people eat less due to symptoms like loss of appetite.
- Changes in metabolism occur.
- That there is a reduced absorption of vitamins and minerals.
Your doctor may recommend a meal plan that is well balanced and provides your body with enough calories and protein.
To improve nutrition, the doctor may also prescribe a nutritional supplement.
If ascites develops, your doctor or dietitian may recommend a sodium-restricted diet.
Primary biliary cholangitis affects the immune system, making people with this disease more likely than healthy people to develop allergies after eating shellfish.
It is recommended the consumption in the daily diet of foods that contain calcium and vitamin D or the use of supplements to help prevent bone deficiencies such as osteoporosis.
People with primary biliary cholangitis should not drink alcohol or take substances or foods that cause further liver damage.
People with primary biliary cholangitis should avoid complementary and alternative medications, such as herbs.
People with primary biliary cholangitis should be careful when starting new medications. Even the use of any prescription, over-the-counter or vitamin medications should be consulted with the treating physician.
Many vitamins and prescription and over-the-counter medications can affect liver function.
