What are the primary symptoms of PBC. How is primary biliary cholangitis diagnosed. What causes PBC and who is at risk. What are the treatment options for primary biliary cholangitis. How does PBC progress over time. What lifestyle changes can help manage PBC symptoms. What are the potential complications of untreated PBC.

Understanding Primary Biliary Cholangitis: An Overview

Primary Biliary Cholangitis (PBC), formerly known as Primary Biliary Cirrhosis, is a chronic liver disease characterized by the gradual destruction of small bile ducts within the liver. This progressive condition can lead to liver damage, cirrhosis, and potentially liver failure if left untreated. PBC primarily affects women, with approximately 90% of cases occurring in females, typically between the ages of 35 and 60.

What exactly happens in PBC? The disease causes inflammation in the bile ducts, preventing the proper flow of bile from the liver to the small intestine. As a result, bile and other harmful substances accumulate in the liver and bloodstream, leading to various symptoms and complications.

Recognizing the Symptoms of Primary Biliary Cholangitis

Identifying PBC in its early stages can be challenging, as many patients remain asymptomatic for years. However, when symptoms do manifest, they often include:

• Fatigue
• Itchy skin (pruritus)
• Discomfort or pain in the upper right abdomen
• Joint pain or arthritis
• Dry eyes and mouth (associated with Sjögren’s syndrome)

As the disease progresses, additional symptoms may emerge:

• Darkening of skin color
• Xanthomas (fatty deposits appearing as yellow bumps on the skin)
• Edema (fluid retention)
• Jaundice (yellowing of the skin and eyes)
• Unintended weight loss

What is the most common initial symptom of PBC? Fatigue and itchy skin are typically the first noticeable signs, often prompting patients to seek medical attention.

The Enigma of Primary Biliary Cholangitis: Unraveling the Causes

The exact cause of Primary Biliary Cholangitis remains a mystery to medical researchers. However, current evidence suggests that PBC is an autoimmune disorder, where the body’s immune system mistakenly attacks its own bile duct cells. Several factors are believed to contribute to the development of PBC:

Genetic Predisposition

While not directly inherited, there appears to be a genetic component to PBC. Individuals with certain genes may be more susceptible to developing the condition. How significant is the genetic factor? Studies have shown that PBC is more common among siblings and in families with a history of the disease, indicating a genetic predisposition.

Environmental Triggers

In genetically susceptible individuals, environmental factors may trigger the autoimmune response that leads to PBC. Potential triggers include:

• Infections
• Exposure to certain chemicals
• Cigarette smoking

What role do environmental factors play in PBC development? While not definitively proven, these triggers may interact with genetic susceptibility to initiate the autoimmune process that characterizes PBC.

Diagnosing Primary Biliary Cholangitis: A Multi-Faceted Approach

Diagnosing PBC often involves a combination of methods, as symptoms may not be present in the early stages. The diagnostic process typically includes:

Blood Tests

Specific blood tests can detect elevated liver enzymes and the presence of antimitochondrial antibodies (AMA), which are present in about 95% of PBC cases. What is the significance of AMA in PBC diagnosis? The presence of AMA is highly specific to PBC and is often considered a hallmark of the disease.

Liver Biopsy

In some cases, a liver biopsy may be necessary to confirm the diagnosis and assess the extent of liver damage. During this procedure, a small sample of liver tissue is examined under a microscope to look for characteristic changes associated with PBC.

Imaging Studies

Ultrasound, CT scans, or MRI may be used to visualize the liver and bile ducts, ruling out other potential causes of liver dysfunction.

How early can PBC be diagnosed? With advanced blood testing, about 60% of PBC cases are now diagnosed before symptoms appear, allowing for earlier intervention and management.

Treatment Strategies for Primary Biliary Cholangitis

While there is no cure for PBC, various treatment options can slow disease progression and manage symptoms:

Ursodeoxycholic Acid (UDCA)

UDCA is the primary medication used to treat PBC. It helps improve bile flow and reduce inflammation in the liver. How effective is UDCA in treating PBC? When started early, UDCA can significantly slow disease progression and improve liver function in many patients.

Obeticholic Acid

For patients who don’t respond adequately to UDCA, obeticholic acid may be prescribed. This medication works by reducing bile acid production and decreasing inflammation in the liver.

Symptom Management

Various medications and treatments may be used to address specific symptoms:

• Antihistamines or bile acid sequestrants for itching
• Supplements for fat-soluble vitamin deficiencies
• Treatments for associated conditions like osteoporosis or Sjögren’s syndrome

Liver Transplantation

In advanced cases where liver function is severely compromised, a liver transplant may be necessary. What is the success rate of liver transplantation for PBC? Liver transplants for PBC generally have excellent outcomes, with survival rates comparable to or better than those for other liver diseases.

Living with Primary Biliary Cholangitis: Lifestyle Modifications and Self-Care

Managing PBC often involves lifestyle changes to support overall health and minimize complications:

• Maintaining a balanced, nutritious diet
• Avoiding alcohol and tobacco
• Exercising regularly, as tolerated
• Managing stress through relaxation techniques or counseling
• Getting adequate rest to combat fatigue

How can diet impact PBC management? A well-balanced diet can help maintain overall health, support liver function, and potentially reduce the risk of complications associated with PBC.

Monitoring and Long-Term Outlook for Primary Biliary Cholangitis

Regular medical follow-ups are crucial for individuals with PBC to monitor disease progression and adjust treatment as needed. These check-ups typically involve:

• Periodic blood tests to assess liver function
• Imaging studies to evaluate liver structure
• Bone density scans to check for osteoporosis
• Screening for associated autoimmune conditions

What is the long-term prognosis for PBC patients? With early diagnosis and appropriate treatment, many individuals with PBC can lead normal lives with a good quality of life. However, the disease course can vary significantly between individuals, emphasizing the importance of personalized care and regular monitoring.

Emerging Research and Future Directions in PBC Treatment

The field of PBC research is dynamic, with ongoing studies exploring new treatment options and improved understanding of the disease mechanisms. Some areas of current research include:

• Novel immunomodulatory therapies
• Antifibrotic agents to slow liver scarring
• Combination therapies to enhance treatment efficacy
• Genetic studies to identify risk factors and potential therapeutic targets

What promising developments are on the horizon for PBC treatment? While it’s difficult to predict specific breakthroughs, the growing understanding of PBC’s underlying mechanisms is paving the way for more targeted and effective treatments in the future.

Primary Biliary Cholangitis is a complex autoimmune liver disease that requires ongoing management and monitoring. While it presents challenges, advances in diagnosis and treatment have significantly improved outcomes for many patients. By working closely with healthcare providers, adhering to treatment plans, and making appropriate lifestyle modifications, individuals with PBC can often maintain a good quality of life and manage their condition effectively. As research continues to uncover new insights into PBC, there is hope for even better treatment options and outcomes in the years to come.

Symptoms & Causes of Primary Biliary Cholangitis (Primary Biliary Cirrhosis)

What are the symptoms of primary biliary cholangitis?

The most common symptoms of primary biliary cholangitis are

• feeling tired
• itchy skin

Other symptoms may include

• discomfort or pain in the upper-right side of your abdomen
• joint pain or arthritis
• symptoms of other health problems that may occur along with primary biliary cholangitis, such as dry eyes and dry mouth due to Sjögren’s syndrome

As the disease gets worse, symptoms may include

• darkening of skin color
• fatty deposits that appear as yellow bumps on the skin, called xanthomas
• symptoms of cirrhosis, such as edema, jaundice, and weight loss

Many people have no symptoms when they are first diagnosed with primary biliary cholangitis. Doctors diagnose about 60% of people with primary biliary cholangitis before symptoms begin. ³ 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 most common symptoms of primary biliary cholangitis are feeling tired and having itchy skin.

What causes primary biliary cholangitis?

Experts aren’t sure what causes primary biliary cholangitis. Studies suggest that certain genes make some people more likely to develop the disease. In people with these genes, factors in the environment may trigger an autoimmune reaction that causes their immune system to attack the small bile ducts in the liver, causing primary biliary cholangitis.

Possible environmental triggers include

• infections
• cigarette smoking
• exposure to certain chemicals

References

Last Reviewed March 2021

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This content is provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), part of the National Institutes of Health. The NIDDK translates and disseminates research findings to increase knowledge and understanding about health and disease among patients, health professionals, and the public. Content produced by the NIDDK is carefully reviewed by NIDDK scientists and other experts.

Primary Biliary Cholangitis Signs and Treatment

Primary Billiary Cirrhosis, or PBC, is a chronic, or long-term, a disease that very gradually damages and eventually destroys the medium-sized bile ducts within the liver. Bile is a digestive liquid that is made in the liver and, through the bile ducts, travels to the small intestine to help in digestion and absorption of fats and fat-soluble vitamins (Vitamins A, D, E, and K).

In patients with PBC, the bile ducts are damaged by inflammation. This causes bile and other harmful substances to remain in the liver and build up levels in the blood, which may lead to irreversible scarring of liver tissue, called cirrhosis. As cirrhosis progresses, the liver may lose its ability to function.

PBC advances gradually and progression can be slowed with medication. However, it is a chronic illness and in some cases may lead to life-threatening complications, especially after cirrhosis develops. This means that regular medical checkups by a specialist are very important to monitor the condition.

Causes

Recent studies consider PBC an autoimmune disease, a condition where the body turns against its own cells. In PBC, the body develops active inflammation with an unknown trigger, and the inflammation process injures bile duct cells and eventually, over decades of time, may cause cirrhosis.

Although PBC is technically not a heritable disease, meaning a disease caused by a specific gene or genetic defect that is passed from parent to child, there appears to be some family link. PBC is more common among siblings and in families where one member has been affected.

Risk Factors

Women account for about 90 percent of PBC cases. It is most commonly diagnosed in patients between the age of 35 and 60.

Signs and Symptoms

Most people with PBC do not have symptoms, especially in the early stages of the disease. When symptoms do occur, the most common is pruritus, or severe itching of the skin, often in the arms, legs, and back.

Other symptoms may include fatigue, fluid build-up in the ankles and abdomen, and darkening of the skin. A collection of fatty deposits in the skin around the eye (Xanthelasmas) or over joints and tendons (Xanthomas) can also be seen. Jaundice, or yellowing of the skin and whites of the eye, can also be present in patients with the advanced disease. Several other disorders often occur with PBC. The most common is problems with tear and salivary glands, causing dry eyes or mouth (called Sjogren’s syndrome). Arthritis and thyroid problems may also be present. Renal (kidney) stones and gallstones may develop. Bone softening and fragility (osteoporosis), which causes bones to fracture more easily, can occur in late stages of the disease if vitamin and calcium needs are not being met.

If I’ve been diagnosed with PBC, what questions should I ask my doctor about PBC?

• How severe is the liver damage?
• What treatment do you recommend? Will this slow down the progression of the disease?
• Will any medication be prescribed? What are the side effects?
• Should I change my diet?
• Are there any supplements you would suggest that I take? (or avoid!)
• What can be done to relieve my symptoms?
• If cirrhosis develops, is transplantation my only option?

Screenings and Diagnostic Tests

Often, patients are diagnosed with PBC after a routine blood test screening result shows elevated Alkaline Phosphatase, one of the several enzyme chemicals present in blood that help us judge if liver inflammation or damage is present. Doctors need to do several tests to confirm a diagnosis of PBC. One test looks for the presence of anti-mitochondrial antibodies (AMA) in the blood. This test is positive in nearly all PBC patients, and seldom in other conditions. An Ultrasound exam is usually done and sometimes other kinds of scans (CAT or MR) may be needed to support the diagnosis. A Liver biopsy, in which a small sample of liver tissue is removed for testing, may be done to further confirm the diagnosis. It is very important to distinguish PBC from a more serious disease called Autoimmune Chronic Hepatitis. About 10% of PBC cases have features of this condition and these diseases overlap. Since treatment and outlook differ considerably, a reliable diagnosis is very important.

Treatment

Patients most often take a daily dose of a drug known as Ursodiol. This drug is a naturally occurring bile acid, which improves the liver’s ability to function in PBC patients and may delay the need for a liver transplant.

The recommended dose is 15 mg per kilogram of body weight (about 300 mg two to three times daily for an average weight person), and the medication must be taken every day for life, or until a liver transplant. Side effects are limited to none, with no long-term dangers.

Other drugs are effective at relieving the symptoms of PBC, including itching. Proper vitamin intake and calcium are very important to avoid complications caused by the limited absorption of these substances due to low levels of bile in the small intestine.

A new highly expensive medication (obeticholic acid, brand name Ocaliva™) is available and being tested for those individuals who do not improve their blood tests taking ursodiol.

Treatment For Itching

Antihistamines such as diphenhydramine (Benadryl, others) and loratadine (Alavert, Claritin, others) are commonly used to reduce itching from insect bites,dry eyes and dry mouth. On the other hand, antihistamines can help with sleep if itching keeps you awake.

• • Cholestyramine (Questran, Prevalite) is a powder that must be mixed with food or liquids. Though cholestyramine works for most people, the taste is unpleasant.
  • Rifampin (Rifadin, Rimactane, others) is an antibacterial drug, which is taken in pill form. Exactly how rifampin reduces itching is unknown, but it may block the brain’s response to itch-inducing chemicals in your circulation.
  • Opioid antagonists such as 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 are available over-the-counter.
• Pilocarpine (Isopto Carpine, Salagen) and Cevimeline (Evoxac) are prescription medicines that may be used if over-the-counter medications do not help.

Lifestyle and Home Remedies

Diet Restrictions are seldom needed and no specific diet is known to help PBC. Our main concern is to maintain a healthy diet and avoid other liver conditions related to overweight (fatty liver) or excess alcohol. Sufficient vitamins, particularly A, D, E and K are important since they aren’t absorbed efficiently; but always get guidance from your clinician about the correct amounts of vitamins. Maintaining a healthy lifestyle will help patients feel better and may relieve or prevent some of the secondary symptoms of PBC. Your doctor may recommend:

• A reduced sodium diet (if there is fluid retention)
• Calcium and Vitamin D supplements (to maintain appropriate body levels)
• Periodic screening of bone mineral density by a test called DEXA scan (If osteoporosis is present)—
• Avoid or reduce the consumption of alcohol
• Proper skin care For dry skin
• Artificial tears for dry eyes

Diagnosis and treatment of primary biliary cirrhosis in St. Petersburg in a specialized center for the treatment of the liver. Detailed description of PBC on the website.

What is primary biliary cirrhosis?

Primary biliary cirrhosis (PBC) is a chronic liver disease that destroys the bile ducts. Primary biliary cirrhosis refers to autoimmune liver diseases – a group of diseases when, for unknown reasons, the body’s immune system fails and begins to “attack” the cells of its own body. In the case of PBC, the bile ducts that are inside the liver (interlobular and septal) are “under attack”. The lack of timely diagnosis and treatment of primary biliary cirrhosis can lead to the development of cholestasis (insufficient secretion and stagnation of bile in the liver, which is expressed in yellowing of the skin).

Symptoms of primary biliary cirrhosis (PBC)

Many patients with primary biliary cirrhosis are asymptomatic. If symptoms do occur, they may include:

• Itching
• Fatigue
• Yellowing of the skin and whites of the eyes
• Discomfort in the upper right side of the abdomen
• Dry eyes and mouth
• Vagina dryness

Further damage cirrhosis-related complications such as:

• Accumulation of fluid in the abdominal cavity (ascites, abdominal dropsy)
• Bleeding from dilated veins in the esophagus, stomach and rectum (variceal bleeding)
• Early thinning of the bones (osteoporosis)

How it manifests itself clinically primary biliary cirrhosis?

Like most liver diseases, biliary cirrhosis can proceed without any symptoms at all, develop slowly, or, conversely, progress rapidly. According to morbidity statistics 90% of the “victims” of this disease are women, the average age at which the disease was detected ranges from 35 to 60 years … It is believed that asymptomatic primary PBC occurs in 25% of patients, but there may be an error in the last figure, since it is not surprising that in the absence of symptoms, people rarely go to the doctor … Often, when examining the blood of these individuals, an increased activity of such enzymes in the blood as: alkaline phosphatase, gamma-glutamyl transferase is detected, an increase in cholesterol is observed, immunological markers are detected – antimitochondrial antibodies with normal liver function tests.

PBC most often begins suddenly and manifests itself with symptoms that can be characteristic of a host of other diseases: fatigue, constant fatigue and skin itching, which is why many patients first turn to a dermatologist. Yellowing of the skin is absent in this case, and manifests itself, in the absence of timely diagnosis and treatment, as a rule, in the period from 6 months to 2 years from the moment the above symptoms appear. But in 25% of cases, with the rapid progression of the disease, jaundice and itching of the skin can appear almost simultaneously. Yellowing of the skin before itching is extremely rare. Many patients complain of pain in the right hypochondrium.

Clinical manifestations of PBC (Ulrich Leischner, 2005) specific for PBC:

• fatigue (70-90%)
• osteoporosis
• pruritus (20-70%)
• xanthelasma, xanthomas (20%)
• urinary infection pathways (20%)
• deficiency of vitamins A, D, E, K
• malignant tumors
• portal hypertension

How is PBC diagnosed?

Primary biliary cirrhosis can be suspected by carefully and carefully taking an anamnesis or history of the development of the disease, conducting an examination of the patient. Important in the diagnosis is the conduct of laboratory tests aimed at detecting elevated levels of the enzyme alkaline phosphatase and antimitochondrial antibodies (AMA) in the blood. The doctor can also work with liver ultrasound images that show the size and structure of the liver and other organs. To diagnose this disease, a biopsy can be used – taking a small piece of liver tissue. Biopsy is one of the most reliable ways to diagnose PBC.

Diagnostic criteria for PBC are:

• Intensive pruritus, extrahepatic manifestations (dry syndrome, rheumatoid arthritis, etc.)
• 2-3 times increase in the activity of cholestasis enzymes.
• Presence of AMA in titer 1-40 and above.
• No changes in the extrahepatic bile ducts.
• Increase in the level of Ig M in the blood serum.
• Diagnosis of PBC is likely in the presence of the 4th and 6th criteria or 3-4 of these signs.
• Characteristic morphological changes in liver punctate.

Primary biliary cirrhosis treatment

Primary biliary cirrhosis is difficult to treat because the immune system is usually compromised in this disease. As with other forms of cirrhosis, treatment focuses on relieving symptoms, managing the complications of the disease, and preventing other conditions that can also cause liver damage.

After the diagnosis of primary biliary cirrhosis, preparations containing bile acids are usually prescribed. They help move bile from the liver to the small intestine. The use of these drugs in the early stages of the development of the disease significantly improves the prognosis.

The drugs cholestriamin, rifampicin, or naltrexone can help reduce itching caused by PBC.

If you have increased fatigue, your hepatologist will try to find out the cause of your fatigue.

PBC can also cause dry eyes and mouth. The best way to help dry eyes is to use eye drops (artificial tears) when dryness occurs. Saliva substitutes can also be used. If this does not help, medications can be used.

People with PBC have an increased risk of osteoporosis, so you should have your bone mineral density scans periodically. Your doctor may prescribe calcium and vitamin D supplements.

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Prashnova Maria Konstantinovna

Gastroenterologist, hepatologist, Ph. D.

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Primary biliary cirrhosis, which according to modern terminology is referred to as primary biliary cholangitis, is a chronic liver disease manifested by bile stasis, fibrosis and cirrhosis. This is one of the most common causes of cholestasis in adults. At risk are middle-aged and elderly women, who make up 95% of patients. Pathology has a steadily progressive course and requires complex therapy to prolong the life of patients.

Causes of the disease

The most important role in the mechanism of development of cirrhosis is occupied by autoimmune reactions. At the same time, some of the patient’s T-lymphocytes begin to attack the cells of the bile ducts, causing inflammatory and destructive lesions. Causes of autoimmune reactions can be:
● genetic predisposition
● past viral and bacterial infections
● physiological and pathological changes in the hormonal background (pregnancy, menopause, hormone-producing tumors)

Main symptoms

More than half of the cases of the disease are asymptomatic, and clinical manifestations occur only at an advanced stage with the development of cirrhotic changes. The manifest form of the disease is manifested by the following signs:
● heaviness and discomfort in the right hypochondrium
● stool disorders
● pruritus
● dry mouth
● skin hyperpigmentation
● jaundice
● xanthelasmas

Complications of biliary cirrhosis

The disease has the same risks as other types of liver cirrhosis. Over time, patients develop varicose veins of the esophagus and anterior abdominal wall, which causes gastrointestinal bleeding. Liver failure is complicated by disorders of protein and lipid metabolism, peripheral edema and ascites. Women often develop osteoporosis and osteomalacia, especially at the onset of the disease in menopause.

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Diagnostic methods

● Advanced biochemical blood test
● analysis for antimitochondrial antibodies
● Abdominal ultrasound
● CT and MRI of the liver
● percutaneous transhepatic cholangiography
● hepatobiliary scintigraphy
● liver biopsy

Treatment of primary biliary cirrhosis

Medical therapy includes immunosuppressive, anti-inflammatory and hepatoprotective agents. Ursodeoxycholic acid preparations are used to slow down fibrotic changes. Patients are recommended a special diet with limited fat and high protein intake.
If the patient’s condition worsens, liver transplantation is prescribed. This is the only radical treatment for primary biliary cholangitis.

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