Primary biliary cholangitis: symptoms, treatment, prognosis

What is primary biliary cholangitis?

Primary biliary cholangitis (abbr. PBH, formerly called primary biliarycirrhosis) Is a chronic (long-term) progressive liver disease that mainly affects women and usually manifests itself in middle age. About 25% of patients with PBC are women under 40, and about 10% of patients are men.

Primary biliary cholangitis causes inflammation and scarring of the small bile ducts (the "plumbing" system of the liver that transports bile, a substance that helps digest fat). When PBC is very severe, it can lead to yellowing of the skin (jaundice), which occurs when the level of bilirubin rises above 2–3 mg / dL or from 34 to 51 µmol / L.

If PBC is left untreated or there is no complete response to drug treatment, the disease can lead to cirrhosis (scarring of the entire liver), which can cause liver failure. PBC is divided into four stages from stage 1 (early stage, without significant liver scarring) to stage 4 (cirrhosis). Although the exact cause of PBC is unknown, it is believed that the disease is likely due to a combination of factors such as autoimmune (when a person's own immune system attacks his body), genetic and environmental factors Wednesday.

Signs and symptoms

The most common symptoms of primary biliary cholangitis are:

• fatigue;
• itching and irritation of the skin;
• jaundice.

The cause of PBC fatigue is unknown and can be very debilitating. Unfortunately, there are no generally accepted cures for fatigue in PBC, although research on drugs that may help treat fatigue is ongoing. Since fatigue is very common, it is important to rule out other causes of fatigue. Fatigue with PBC is not related to severity liver disease. Patients may have early disease but remain severely fatigued while while other patients with more advanced stages of the disease may not have fatigue at all. Fatigue is also not related to how quickly the disease progresses.

Like fatigue, the cause of PBC pruritus is unknown and is not always related to the severity of liver disease. It is likely that itching and irritation is caused by substances in the blood and not in the skin, as opposed to itching caused by allergy. Fortunately, unlike fatigue, there are a number of itch medications that work for most people. (See Standard Treatments below).

As mentioned above, jaundice occurs when PBC is very severe. Sometimes jaundice can be treated with PBC treatment, but sometimes patients with jaundice require liver transplants. Jaundice usually occurs when the liver is so damaged that normal liver function is impaired.

Complications of primary biliary cholangitis:

• portal hypertension (ascites, varicose veins, hepatic encephalopathy);
• violation of fat absorption;
• fat deposits;
• osteoporosis/остеомаляция.

Portal hypertension usually occurs after a patient develops cirrhosis. This can lead to fluid accumulation in the abdominal cavity (abdominal ascites) or the formation of large veins (similar to varicose veins) in the esophagus (the structure through which food enters when swallowed). It can also lead to brain problems (due to the build-up of toxins that are not excreted by the liver).

Fat malabsorption occurs only when PBC is severe and is very rare. If this does happen, it will cause diarrhea, fatty stools and weight loss. Fat deposits under the skin (xanthomas) are more common because people with PBC have more cholesterol in their blood. These fatty deposits appear as yellow bumps under the skin, usually under the eyes or above the joints. High cholesterol in PBC is not associated with increased risk heart attack, stroke or other complications.

Osteoporosis is the most common complication of PBC, although it is also very common in people without PBC. This leads to thinning of the bones and is treated with osteoporosis medications.

Other diseases are more common in patients with PBC:

• thyroid disease;
• Sjogren's syndrome: a condition causing dry eyes and mouth;
• celiac disease: a disease that affects the small intestine and causes an allergy to gluten (proteins in foods with wheat, rye, bran).

Causes and risk factors

The exact cause of primary biliary cholangitis is unknown. Possible immunological, autoimmune, genetic and / or environmental factors are investigated as potential causes.

Immunological abnormalities can be an important factor in the development of PBC. The immune system is divided into several components, the combined action of which is responsible for protecting against various infections. The T-cell system (cell-mediated immune response) is responsible for fighting off fungi, some viruses and bacteria. The B cell system (humoral immune response) fights infection with 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 secretions from the body (such as saliva). People with PBC have an inadequate, decreased number of circulating T cells in the blood, dysfunction and dysregulation of T cells (helper and suppressor T cells).

Autoimmunity can also contribute to PBC. Autoimmune disorders occur when the body's natural defenses against invading microorganisms mistakenly attack healthy tissue. For example, antibodies usually kill invaders (eg, microorganisms, toxins, and other foreign substances) directly or coat them so that they are more easily destroyed by leukocytes. White blood cells (leukocytes) are part of the body's defense system and play an important role in protecting against infections, as well as fighting infections if they occur. However, in some patients, antibodies may not form properly against certain of the body's own tissues, causing autoimmune diseases.

About 95 percent of people with PBC develop antibodies (known as "autoantibodies") that target specific mitochondria in the body (mitochondrial autoantigens, eg E2 component of the pyruvate dehydrogenase complex [PDC-E2], E2 component of the branched chain 2-oxo acid dehydrogenase complex [BCOADC-E2]). Mitochondria are found in hundreds of cells within the body and carry the foundations for energy production. They have their own genetic instructions (mtDNA) and are located outside the cell nucleus (cytoplasm). The role of antimitochondrial antibodies in the potential onset of symptoms associated with PBC is not fully understood.

In addition, some people with primary biliary cholangitis have specialized laboratory tests done on the liquid portion of their blood. (serum), have identified the presence of certain antibodies, usually produced in response to certain viruses (for example, retroviral antigens). Antigens are substances such as microorganisms, toxins, or other foreign substances that can trigger the production of certain antibodies as part of the immune response. This suggests that in people with PBC, certain antibodies may mistakenly react to one or more of the body's own proteins, which are very similar to fragments proteins from certain invading viruses (ie, the immune system cannot distinguish between "mimicking" proteins on the surface of certain viruses and the body's own proteins). On the other hand, such findings may indicate that PBC can be caused by at least in part, a previous bacterial or viral infection, which has been demonstrated in other autoimmune diseases.

Since a number of familial cases of PBC have been reported in the medical literature, it is also suspected that certain genetic factors may play a role in the development of PBC. Environmental factors or other triggers can cause symptoms in people with a genetic predisposition to the disease.

Further research is needed to determine the potential role that immunological, autoimmune, genetic, environmental and / or other factors may play in the onset of PBC.

Affected populations

Primary biliary cholangitis affects mainly women, but is now being diagnosed more and more in men. The disease usually manifests itself in middle age, initially affecting most people between the ages of 45 and 65. However, the disease was diagnosed in women aged 22 years and in women aged 90 years. It has been estimated that PBC is one of the most common autoimmune diseases, affecting nearly 1 in 1000 women over the age of 40.

Related disorders

Other conditions that may need to be ruled out include the following:

—​ Primary sclerosing cholangitis (PSC).

Although the names PBC and PSC are similar, they are very different diseases and should not be confused with each other. While PBC affects the small ducts of the liver, PSC 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. Unlike PBC, jaundice in PSC can occur even in the early stages of the disease due to blockage of the large bile duct. Because patients with PSC also have high levels of alkaline phosphatase (a liver test that indicates damage to the bile ducts), it can sometimes be confused with PBC. If a patient with high alkaline phosphatase levels has a negative mitochondrial antibody test and biopsy is not similar to PBC, a test called magnetic resonance cholangiopancreatography (MRCP) should be done. This test is a special type of magnetic resonance imaging (MRI) that carefully examines the bile ducts to determine if they are normal. If bile ducts appear abnormal on MRCP, one diagnosis to consider is PSC.

PSC can also lead to the formation of gallstones 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 an endoscopic retrograde pancreaticogram (ERCP) to open narrowed bile ducts and / or remove gallstones from the bile ducts. People with PSC may also need antibiotics to treat bile duct infections.

Unlike PBC, there are currently no medical treatments known to delay or stop the progression of PSC. However, ursodeoxycholic acid is sometimes prescribed for PSC. It is important to note that PSC and PBC cannot occur in the same patient at the same time.

— Autoimmune hepatitis (AIH).

Autoimmune hepatitis Is a type of autoimmune liver disease that sometimes occurs in people with PBC or PSC. This disease usually affects the liver tissue around the bile ducts, rather than the bile ducts themselves. A liver biopsy is usually required to diagnose AIH. For the treatment of AIH, drugs are used that help control an overly active immune system. system such as steroids, azathioprine, 6-mercaptopurine, mycophenolate mofetil / sodium, tacrolimus, or cyclosporine.

- Non-alcoholic steatohepatitis (NASH).

NASH is a chronic, slowly progressive disease characterized by fatty liver infiltration (hepatic steatosis), liver inflammation (hepatitis), and / or abnormal formation scar tissue (liver fibrosis), which in some cases can lead to cirrhosis. Inflammation of the liver can mimic the inflammation caused by alcohol. Symptoms associated with the disease may include upper abdominal pain, enlarged liver (hepatomegaly) and / or abnormally elevated levels of certain liver enzymes. Although the exact cause of NASH has not been clarified, the disease is often associated with obese; diabetes; and / or the presence of abnormally high levels of fat in plasma, liquid part of the blood (hyperlipidemia). In some cases, NASH has also developed due to general poor health, malnutrition, and cancer-related weakness (cancer cachexia).

Diagnostics

A diagnosis of PBC requires:

1. high alkaline phosphatase (ALP, liver blood test) together with
2. positive antimitochondrial antibodies (+ AMA).

If the AMA test is negative, the patient will need a liver biopsy to confirm the diagnosis of PBC, as a number of diseases can cause high ALP levels.

Standard treatments

There are no known cures. Treatment includes:

• Medicines to reduce the severity of symptoms, primarily itching.
• Ursodeoxycholic acid to slow the progression of liver damage.
• Obeticholic acid is a new drug for the treatment of PBC approved by the US Food and Drug Administration (FDA) in 2016. for the treatment of primary biliary cholangitis. This drug is for use in patients in whom ursodeoxycholic acid is not effective enough. It should be used with caution in patients with advanced liver disease.
• Treatment of complications.
• Ultimately liver transplant.

You shouldn't drink alcohol. Drugs that can damage the liver should be discontinued.

Itching can be relieved by cholestyramine, as well as rifampin, naltrexone (an opioid), sertraline, or ursodeoxycholic acid combined with ultraviolet light.

Ursodeoxycholic acid, especially if taken before the disease progresses, reduces liver damage, prolongs life, and also delays the need for liver transplantation. Obeticholic acid is a new FDA-approved drug that has been shown to improve test results blood related to the liver in many patients with PBC, in whom the use of ursodeoxycholic acid alone does not give the necessary effect.

Calcium supplements are needed and vitamin Dto prevent the development of osteoporosis or slow its progression. Weight-bearing exercise, bisphosphonates, or raloxifene can also help prevent or slow down osteoporosis. You may need vitamin supplements with vitamins A, D, E and K to correct vitamin deficiencies. Vitamins A, D and E can be taken orally. Vitamin K is given by injection.

If the disease is advanced, liver transplantation remains the best treatment. It can prolong life. PBC may recur after transplantation in some patients, but the disease rarely becomes severe.

Forecast

Primary biliary cholangitis usually progresses slowly, however, the rate of progression varies greatly. Symptoms may not appear for 2 years or even up to 10-15 years. After 3-5 years, the condition of some patients may deteriorate greatly. After the onset of symptoms, life expectancy is approximately 10 years. Some characteristic signs suggesting that the disease will progress rapidly:

• rapid worsening of symptoms;
• elderly age;
• fluid accumulation and other symptoms of cirrhosis;
• the presence of autoimmune diseases, such as rheumatoid arthritis;
• some liver function tests are abnormal.

If the itching disappears, the yellow bumps of fat diminish and jaundice develops, and death may occur within a few months.