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Primary Biliary Cirrhosis

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Description: Primary biliary cirrhosis (PBC) is a chronic autoimmune disease that gradually destroys the bile ducts in the liver, leading to liver cirrhosis and potential liver failure.
Type: Primary biliary cirrhosis, now commonly referred to as primary biliary cholangitis (PBC), is an autoimmune disease. It does not follow a specific pattern of Mendelian genetic transmission, but genetic predisposition plays a role, and it is influenced by both genetic and environmental factors.
Signs And Symptoms: People with PBC experience fatigue (80%); this is a nonspecific symptom and can be debilitating, with a huge impact on quality of life. Its pathogenesis is still unknown, and is quite challenging to explore its specificity and to treat. Comorbidities that could contribute to or worsen fatigue, such as depression, hypothyroidism, anaemia, obesity, or medication side effects, should be promptly identified and treated. Dry skin and dry eyes are also common. Itching (pruritus) occurs in 20–70% of cases, and can develop at any stage of the disease. Textbooks tend to describe itching in the feet and hands, but patients may also experience itching of the scalp, face, back, or other areas. The itching is typically mild-to-moderate in intensity. It may manifest as a tingling, crawling or burning sensation, and can develop even with normal liver function tests. It does not correlate with progression of liver disease, and may even improve or disappear as the disease advances. Given the impact on quality of life and night sleep, pruritus is also correlated with fatigue. It can rarely be severe, non-responsive to medical therapy, and requiring liver transplant. Pruritus is characteristically intermittent, worse at night, and improves during summer.
People with more severe PBC may have jaundice (yellowing of the eyes and skin). PBC impairs bone density and the risk of fracture increases. Xanthelasma (skin lesions around the eyes) or other xanthoma may be present as a result of increased cholesterol levels.PBC can eventually progress to cirrhosis of the liver. This, in turn, may lead to a number of symptoms or complications, including:

Fluid retention in the abdomen (ascites) in more advanced disease
Enlarged spleen in more advanced disease
Oesophageal varices in more advanced disease
Hepatic encephalopathy, including coma in extreme cases in more advanced disease.People with PBC may also sometimes have the findings of an associated extrahepatic autoimmune disorder such as thyroid disease or rheumatoid arthritis or Sjögren's syndrome (in up to 80% of cases).
Prognosis: The introduction of UDCA has dramatically changed the pattern and the course of the disease. Numerous trials and observational studies have demonstrated its efficacy on liver biochemistry, histological progression, and transplant-free survival.Among the UDCA-treated patients, the degree of the liver biochemistry improvement, i.e. the UDCA-response, identifies patients with different long-term prognosis. In the absence of cirrhosis, people who experience an improvement of liver enzymes to the normal range on treatment with UDCA have excellent survival, which may be similar to the general population. Survival is significantly reduced though, in those with abnormal liver biochemistry on treatment.
The two most important parameters in evaluating response to UDCA are alkaline phosphatase and total bilirubin. Qualitative and quantitative definitions of UDCA-response have been developed, based on changes of bilirubin, transaminases and ALP, after a period of 6 to 24 months of treatment with UDCA at 13–15 mg/kg/day.Patients at diagnosis can be risk-stratified based on the probability of UDCA-response. This is relevant to identify patients who would be eligible for second-line therapies before waiting for the treatment failure under UDCA, with potential impact on disease course.Hepatocellular carcinoma (HCC) is infrequent in PBC. Recent large-scale cohort studies highlighted that the lack of UDCA-response after 12 months of therapy and male sex are associated with increased future risk of developing HCC in PBC.
After liver transplant, the recurrence of disease may be as high as 18% at five years, and up to 30% at 10 years. No consensus exists on risk factors for recurrence of the disease.
Onset: Primary biliary cirrhosis, also known as primary biliary cholangitis (PBC), typically has an insidious onset. It most commonly presents in middle-aged women, often between the ages of 40 and 60. The disease may be asymptomatic initially and be discovered through abnormal liver function tests during routine check-ups. Early symptoms, when they do occur, can include fatigue, pruritus (itching), and dry eyes or mouth. As the disease progresses, symptoms may become more severe, including jaundice, hepatomegaly (enlarged liver), and signs of cirrhosis and liver failure.
Prevalence: The prevalence of primary biliary cirrhosis (now more commonly referred to as primary biliary cholangitis, or PBC) varies by region but is estimated to be approximately 1 in 1,000 to 1 in 4,000 adults, with higher prevalence noted in Northern Europe and North America. The condition predominantly affects middle-aged women.
Epidemiology: Epidemiologic studies report heterogeneous incidence rates of 0.33 to 5.8 per 100,000 inhabitants per year, and prevalence rates of 1.9 to 40.2 per 100,000 inhabitants. Such figures, in particular the prevalence, have shown some increase in the last decades. Improvement of diagnostic tools, increasing disease awareness, and digitised patient registration with facilitation of case-findings, along with improved survival, likely contributed to the rising prevalence rates.
The disease has been described worldwide, though North America and Northern Europe have shown the highest incidence and prevalence rates. Whether a true variation in disease prevalence exists among populations of different geographical areas and of different ethnicity or if this is a consequence of a difference in study quality is unknown. PBC is more common in women, with a female:male ratio of at least 9:1. The peak incidence of PBC is in the fifth decade of life. In some areas of the US and UK, the prevalence is estimated to be as high as one in 4,000. This is much more common than in South America or Africa, which may be due to better recognition in the US and UK. First-degree relatives may have as much as a 500 times increase in prevalence, but if this risk is greater in the same-generation relatives or the one that follows is debated.
PBC is considered a prime example of the female preponderance in autoimmunity with a female to male ratio of up to 9:1, confirmed by large cohort studies, although some recent data, using administrative registries, suggest an increasing male prevalence. Major defects of sex chromosomes, i.e. enhanced monosomy X in female patients and an enhanced Y chromosome loss in male patients, have been described and might well explain the greater female predisposition to develop PBC.An association of a greater incidence of PBC at latitudes more distant from the Equator is similar to the pattern seen in multiple sclerosis.Typical disease onset is between 30 and 60 years, though cases have been reported of patients diagnosed at the ages of 15 and 93. Prevalence of PBC in women over the age of 45 years could exceed one in an estimated 800 individuals.
Intractability: Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is generally considered a chronic and progressive disease. While it is not curable, it is not entirely intractable. Treatments such as ursodeoxycholic acid (UDCA) and obeticholic acid can slow disease progression, improve liver function, and alleviate symptoms. Early diagnosis and treatment are crucial for better outcomes. However, in advanced cases, liver transplantation may be necessary.
Disease Severity: The severity of primary biliary cirrhosis (now more commonly referred to as primary biliary cholangitis, or PBC) can vary widely among affected individuals. Disease progression typically goes through stages, from asymptomatic to more severe forms:

1. **Early Stage (Asymptomatic or Mild)**: Many patients may have minimal or no symptoms early on. If symptoms occur, they may include fatigue and itching (pruritus).

2. **Moderate Stage**: As the disease progresses, symptoms become more apparent. This stage includes more pronounced fatigue, jaundice (yellowing of the skin and eyes), xanthomas (cholesterol deposits under the skin), and hepatomegaly (enlarged liver).

3. **Advanced Stage**: Severe progression can lead to significant liver damage and cirrhosis. Complications might include portal hypertension, variceal bleeding, ascites, hepatic encephalopathy, and ultimately liver failure.

The disease progression rate can vary, and not all patients will experience all stages. Regular monitoring and appropriate treatment can manage symptoms and slow disease progression.
Healthcare Professionals: Disease Ontology ID - DOID:12236
Pathophysiology: Pathophysiology of Primary Biliary Cirrhosis (PBC):

Primary Biliary Cirrhosis, now more commonly referred to as Primary Biliary Cholangitis, is a chronic, progressive liver disease characterized by the autoimmune destruction of the small intrahepatic bile ducts. This destruction leads to cholestasis, or the impairment of bile flow.

1. **Autoimmune Mechanism**: The exact cause remains unclear, but it's believed to be an autoimmune response. Autoantibodies, particularly anti-mitochondrial antibodies (AMAs), target the pyruvate dehydrogenase complex within mitochondria of bile duct epithelial cells.

2. **Bile Duct Damage**: The autoimmune attack leads to chronic inflammation and progressive destruction of the small bile ducts within the liver.

3. **Cholestasis**: With bile ducts damaged or obliterated, bile accumulates in the liver, causing cholestasis. The presence of bile acids within the liver cells can be toxic, leading to further hepatocyte damage and apoptosis.

4. **Fibrosis and Cirrhosis**: Chronic bile accumulation promotes fibrosis, eventually resulting in cirrhosis, which compromises liver function. This fibrosis effectively reorganizes the liver architecture leading to nodular regeneration.

5. **Systemic Implications**: Bile acid retention affects multiple body systems, leading to complications such as malabsorption of fat-soluble vitamins, hyperlipidemia, and pruritus (severe itching).

Understanding the pathophysiology aids in the diagnosis and management of PBC, focusing on managing cholestasis, preventing fibrosis progression, and addressing autoimmune components.
Carrier Status: Primary biliary cirrhosis (PBC) is not a condition associated with a carrier status, as it is an autoimmune disease rather than a genetic disorder passed through carriers. It predominantly affects the small bile ducts in the liver, leading to liver damage over time.
Mechanism: Primary biliary cirrhosis, now more commonly referred to as primary biliary cholangitis (PBC), involves chronic autoimmune destruction of the small bile ducts in the liver. Here's a concise overview of its mechanisms, particularly focusing on molecular mechanisms:

1. **Immune System Dysfunction**:
- The immune system mistakenly targets the epithelial cells lining the small intrahepatic bile ducts.
- Autoantibodies, particularly antimitochondrial antibodies (AMAs), play a key role. These antibodies are predominantly directed against the E2 component of the pyruvate dehydrogenase complex (PDC-E2), an enzyme complex found in the mitochondria.

2. **T Cell-Mediated Damage**:
- T lymphocytes, particularly CD4+ and CD8+ T cells, infiltrate the small bile ducts and contribute to the inflammation and destruction of these ducts.
- Cytokines released by these immune cells, such as TNF-α, IL-12, and IFN-γ, further promote inflammation and tissue damage.

3. **Genetic Susceptibility**:
- Certain genetic factors, such as variations in the HLA (human leukocyte antigen) region, increase susceptibility to PBC.
- Other genetic regions, including IL12A and IL12RB2, have also been implicated in enhancing risk.

4. **Environmental Triggers**:
- Environmental factors, such as infections and exposure to toxic agents, may act as triggers in genetically predisposed individuals.
- Molecular mimicry might play a role, where environmental antigens share structural similarities with mitochondrial antigens, triggering an autoimmune response.

5. **Bile Duct Damage & Fibrosis**:
- Persistent autoimmune attack leads to chronic cholestasis, where bile flow is impaired.
- This results in bile acid retention, which can be toxic to liver cells, promoting inflammation, and fibrosis (scar tissue formation).
- Over time, fibrosis can progress to cirrhosis, severely impairing liver function.

Understanding these mechanisms helps in diagnosing, managing, and developing targeted treatments for primary biliary cholangitis.
Treatment: Primary biliary cirrhosis (PBC), now more commonly known as primary biliary cholangitis, is a chronic liver disease. The main treatment options include:

1. **Ursodeoxycholic Acid (UDCA)**: This is the first-line treatment and can help slow the progression of the disease and improve liver function.
2. **Obeticholic Acid**: Often used in patients who do not respond adequately to UDCA, it can further help in managing the disease.
3. **Fibrates**: These may be used in some cases to reduce cholesterol levels and relieve itching associated with PBC.
4. **Immunosuppressants**: In certain cases, drugs like methotrexate or colchicine may be used.
5. **Symptomatic Treatments**: These include cholestyramine for itching, vitamin supplements for deficiencies, and managing fatigue.
6. **Liver Transplantation**: In advanced cases where liver function is severely compromised, a transplant may be necessary.

It's important for patients to follow regular monitoring and work closely with their healthcare provider to manage the disease effectively.
Compassionate Use Treatment: For primary biliary cirrhosis (PBC), now more accurately called primary biliary cholangitis, compassionate use treatments, and off-label or experimental approaches may be considered in severe or unresponsive cases. These could include:

1. **Obeticholic Acid**: This medication is approved but may be used off-label at different dosages or stages of the disease.

2. **Fibrates (Fenofibrate or Bezafibrate)**: Although primarily used to treat high cholesterol, they have shown some effectiveness in treating PBC symptoms.

3. **Rituximab**: A monoclonal antibody that targets B cells, used off-label in some cases due to its immunomodulatory effects.

4. **Immune Modulators (e.g., Mycophenolate Mofetil)**: Sometimes used off-label to help manage symptoms in PBC patients who do not respond to standard treatments.

Experimental treatments can include:

1. **Biliary Therapies**: Drugs like nor-ursodeoxycholic acid are being researched for their potential benefits.

2. **Stem Cell Therapy**: Investigated for its ability to regenerate damaged liver tissue.

3. **Antifibrotic Agents**: New drugs aimed at reducing liver fibrosis are in various stages of clinical trials.

For all treatments, it is crucial for patients to consult with their healthcare provider to weigh the potential benefits and risks.
Lifestyle Recommendations: Primary biliary cirrhosis (now more commonly referred to as primary biliary cholangitis or PBC) is a chronic liver disease. Lifestyle recommendations for managing PBC include:

1. **Healthy Diet**: Eat a balanced diet rich in fruits, vegetables, whole grains, and lean proteins. Avoid high-fat, high-sugar, and highly processed foods.

2. **Limit Alcohol**: Alcohol can further damage the liver; it's generally recommended to avoid it entirely or consume it in very limited quantities.

3. **Regular Exercise**: Engage in regular physical activity to maintain a healthy weight and overall well-being.

4. **Avoid Smoking**: Smoking can exacerbate liver damage and other health issues. Quitting smoking is strongly advised.

5. **Manage Cholesterol**: High cholesterol can be an issue in PBC patients, so monitoring and managing cholesterol levels through diet and medication, if necessary, is important.

6. **Vitamin Supplements**: Since PBC can interfere with the absorption of certain vitamins (like vitamins A, D, E, and K), supplementing under the guidance of a healthcare provider may be beneficial.

7. **Regular Medical Follow-ups**: Regular check-ups with a healthcare provider to monitor liver function and manage any complications are essential.

8. **Medications Compliance**: Adhere to prescribed medications like ursodeoxycholic acid (UDCA) to help slow disease progression.

9. **Bone Health**: Because PBC can affect bone density, maintaining bone health through adequate calcium and vitamin D intake, as well as weight-bearing exercises, is important.

10. **Mental Health**: Seek support for emotional well-being, as chronic illness can affect mental health. Support groups or counseling may be beneficial.
Medication: Primary biliary cirrhosis (PBC), now more accurately referred to as primary biliary cholangitis, is commonly managed with medications such as ursodeoxycholic acid (UDCA) and obeticholic acid. UDCA is the first-line treatment that helps improve liver function tests and may slow disease progression. Obeticholic acid is used if there is an inadequate response to UDCA. Other supportive treatments may address symptoms and complications, such as antipruritics for itching and vitamin supplements for deficiencies.
Repurposable Drugs: Primary biliary cirrhosis (PBC) is now more commonly referred to as primary biliary cholangitis. Repurposable drugs for this condition include:

1. **Fibrates (e.g., bezafibrate)**: Fibrates may improve liver function tests and symptoms in PBC patients.
2. **Obeticholic acid**: This drug, originally used for other liver conditions, is now used to treat PBC, especially for patients not responding adequately to ursodeoxycholic acid (UDCA).

Further research and consultation with a healthcare provider are necessary to determine the best treatment plan.
Metabolites: Primary biliary cirrhosis (now more commonly known as primary biliary cholangitis, PBC) can influence several metabolites, often leading to abnormalities in liver function tests. Key metabolites and relevant changes include:

- **Bilirubin**: Often elevated due to impaired bile excretion.
- **Alkaline Phosphatase (ALP)**: Typically significantly elevated as a marker of cholestasis.
- **Gamma-glutamyl transferase (GGT)**: Usually elevated, another marker indicative of cholangiocyte damage.
- **Aminotransferases (AST and ALT)**: Mild to moderate elevation.
- **Cholesterol**: Elevated, particularly in the early stages of the disease.
- **IgM levels**: Frequently elevated.

These changes in metabolites are crucial for diagnosis and monitoring the progression of PBC.
Nutraceuticals: Primary biliary cirrhosis (PBC), now more commonly referred to as primary biliary cholangitis, is a chronic autoimmune disease that primarily affects the bile ducts of the liver. While nutraceuticals are not a primary treatment for PBC, some may provide supportive benefits:

1. **Milk Thistle (Silymarin):** May help improve liver function and reduce liver damage.
2. **Vitamin D:** Often recommended to PBC patients because they may have deficiencies due to impaired bile production.
3. **Omega-3 Fatty Acids:** May help in reducing liver inflammation.
4. **Calcium:** To counteract bone density loss often seen in PBC patients.

Always consult a healthcare provider for personalized advice.
Peptides: Primary biliary cirrhosis (PBC), now typically referred to as primary biliary cholangitis, is an autoimmune disease that leads to the progressive destruction of the bile ducts in the liver. The term "peptides" in the context of PBC may refer to those involved in diagnostic or therapeutic approaches. For instance, various peptides are being researched as potential biomarkers for early diagnosis or as targets for treatment.

If "nan" is intended to refer to nano-based approaches, nanotechnology is being explored in the context of PBC for enhancing drug delivery systems and creating more efficient diagnostic tools. Nanoparticles can potentially improve the delivery of drugs to specific liver cells, minimizing side effects and enhancing therapeutic efficacy. Researchers are also investigating the use of nanotechnology to develop more sensitive diagnostic assays for early detection of PBC.