Primary biliary cholangitis

What is PBC (Primary biliary cholangitis)?

PBC is a chronic autoimmune liver disease in which the body’s own immune system mistakenly attacks the cells of the bile ducts, causing inflammation. As a result, bile drainage becomes impaired, leading to bile stasis (cholestasis). The ongoing inflammation progressively scars the bile ducts—a process also known as fibrosis. If fibrosis advances, it can result in liver cirrhosis or even liver failure.1 Without treatment, more than half of patients develop liver cirrhosis within four years.2

Read more about how liver cirrhosis can develop and its consequences.

The persistent chronic inflammation leads to damaged bile duct cells and their subsequent loss.3 Early diagnosis and targeted treatment are therefore particularly important in order to slow down the progression of the disease and to improve the quality of life of those affected.

Here you can watch a video that explains PBC

Prevalence and etiology

PBC is most commonly diagnosed in people between the ages of 40 and 60. It can affect anyone, regardless of gender or ethnicity. However, it is remarkable that women are approximately four to six times more likely to develop PBC than men.4 In Germany, approximately 37 out of every 100,000 people are affected by PBC.5

The exact cause of PBC remains unclear and is the focus of ongoing research. Experts believe that a combination of genetic predisposition and environmental factors—such as smoking, existing urinary tract infections and/or a lack of diversity in the intestinal flora—plays a role in its development.6 The immune system gets out of balance and attacks the body’s own cells in the bile ducts, leading to a chronic inflammatory reaction.6 People with autoimmune diseases (e.g., Hashimoto’s thyroiditis) also have an increased risk of developing PBC. Conversely, people with PBC are also more likely to develop other autoimmune diseases.12

The symptoms of PBC vary from person to person.7 Initially, the disease is often asymptomatic, but as it progresses, many patients develop symptoms.7,8 The most common ones—severe itching and chronic exhaustion (fatigue)—can significantly impact quality of life.9,10 Learn more about how you can cope better with it in the tab “Itching and Fatigue”.

Fatty stools and deficiency symptoms

As the disease progresses, patients may experience impaired absorption of fat-soluble vitamins, which can lead to deficiencies and fatty stools.7

Symptoms associated with progressive liver damage

As liver damage progresses, jaundice may develop, along with typical symptoms of liver cirrhosis, such as internal bleeding or fluid accumulation in the abdomen (ascites).11

Other possible symptoms

Other possible symptoms may include lower abdominal pain, darker skin pigmentation and the appearance of small, yellowish or white skin nodules.11

Extrahepatic manifestations

Extrahepatic manifestations are clinical presentations that do not directly affect the liver but are associated with a liver disease such as PBC. Up to 73% of patients experience these manifestations, which commonly include Sjögren’s syndrome, thyroid dysfunction and systemic sclerosis.12

Sjögren’s syndrome

Sjögren’s syndrome is an autoimmune disease in which the immune system mistakenly attacks the lacrimal and salivary glands, resulting in dry eyes and dry mouth. Women may also experience vaginal dryness. In rarer cases, joint pain, vascular inflammation or kidney inflammation can also occur.12,13

Thyroid dysfunction

Thyroid dysfunction is a common comorbidity in PBC, typically manifesting as hypothyroidism or, less frequently, hyperthyroidism. Many PBC patients develop Hashimoto’s thyroiditis, an autoimmune condition that leads to hypothyroidism, while Graves’ disease, which causes hyperthyroidism, is less common.12

Systemic sclerosis

Systemic sclerosis is an autoimmune disease that affects the connective tissue in the skin and organs, causing hardening and scarring (fibrosis). Its symptoms vary widely and can include skin changes, digestive issues, as well as heart and kidney complications.12

Itching (pruritus)

Approximately 20–80% of PBC patients suffer from itching, typically affecting the palms of the hands and soles of the feet.6,9 Intense itching can lead to sleep disturbances and concentration problems, especially if it is more intense, and can contribute to low self-esteem.10 Using special moisturizers and soothing skincare products may help, as well as taking cool showers to counteract heat-induced itching at night. Psychological support can also be beneficial in managing compulsive scratching, and testing for possible allergies may provide additional insights.1

Chronic exhaustion (fatigue) and cognitive impairment

Many PBC patients suffer from fatigue8—a persistent physical and mental exhaustion that is not easily relieved, even with adequate rest. Fatigue is often accompanied by cognitive issues, such as concentration and memory problems. To improve or alleviate fatigue, experts recommend first identifying and addressing any underlying causes, such as anemia, hypothyroidism or sleep disorders.1 Additionally, patients can develop coping strategies, like avoiding social isolation, which can further worsen fatigue.1

Unfortunately, fatigue is a challenging symptom to manage and can also be associated with episodes of itching. In these cases, treatment of the itching can also have a positive effect on fatigue.9

In its early, asymptomatic stages, PBC is usually discovered incidentally—typically during routine blood tests that reveal elevated liver values.11 The diagnosis primarily relies on the analysis of certain laboratory parameters, complemented by a thorough medical history and, if necessary, a tissue biopsy. PBC is diagnosed when at least two of the following three criteria are met:1,14

  1. Evidence of bile stasis (cholestasis): This is indicated by an increase in specific liver values in the blood. The key marker is alkaline phosphatase (ALP), the liver enzyme most closely associated with diagnosing and monitoring PBC progression. Additionally, gamma-glutamyl transferase (GGT) and bilirubin levels may be measured—GGT primarily when PBC is suspected and bilirubin as a prognostic marker.
  2. Detection of antimitochondrial antibodies (AMA) in the blood: These antibodies target specific structures within liver cells and play a key role in the bile duct damage associated with PBC. If AMA are not detectable, other specific antibodies, such as sp100 or gp210, may also indicate the presence of PBC. The AMA test is one of the most critical diagnostic tools for confirming the disease.
  3. Liver biopsy and imaging: In some cases, a liver biopsy is performed to confirm the inflammatory changes in the tissue that are typical of PBC. Alternatively, these changes can be detected using ultrasound or magnetic resonance imaging (MRI). In addition, these imaging techniques help rule out other possible causes of cholestasis, such as fatty liver inflammation or autoimmune hepatitis, and assess the severity of PBC.

Although PBC cannot be cured, it can be treated. In some cases, optimized therapy can normalize the liver values and thus prevent the progression of the disease. The normalization of liver values is therefore a key therapeutic goal and can be a decisive indicator for the long-term success of treatment. Alkaline phosphatase (ALP) and bilirubin levels are particularly important and should be monitored regularly.15

In many patients, standard PBC therapy is effective and leads to a significant reduction in liver values. Nevertheless, more than a third of patients do not respond adequately to the standard therapy and therefore remain undertreated.16 For these patient groups, alternative second-line therapies can be considered, which can be used either in combination with the standard therapy or as a single therapy.1 Some PBC therapies not only target the underlying disease but also effectively alleviate itching. As already mentioned, successful managing itching can potentially have a positive effect on fatigue.17

In order to check whether the treatment of PBC is effective or whether the disease is progressing, regular follow-up checks are essential. Important liver values are measured:1,18

  • ALP: An elevated value indicates a disorder of the bile ducts.
  • Bilirubin: An increase may indicate impaired liver function.

In the first year after diagnosis, these values should be checked after three, six and 12 months to determine whether the treatment is successful or needs to be adjusted. The follow-up checks should be continued beyond the first year, whereby the time intervals should be individually adapted to the patient.18

As mentioned in “Therapy”, the normalization of liver values is an important therapeutic goal.

It is therefore essential to discuss your blood values and treatment progress with your doctor regularly. If the therapy is not as effective as expected, a referral to a specialist practice or liver outpatient clinic should be considered if this has not already been made. Personalized treatment gives you the best chance to manage the disease effectively and alleviate symptoms. Don’t hesitate to ask questions and work closely with your doctor to find the most suitable treatment options.

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References

  1. EASL. Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol 2017;67(1):145-72.
  2. Laschtowitz A, de Veer RC, Van der Meer AJ, et al. Diagnosis and treatment of primary biliary cholangitis. United European Gastroenterol J 2020;8(6):667-74.
  3. Buisson EM, Jeong J, Kim HJ, et al. Regenerative medicine of the bile duct: beyond the myth. Int J Stem Cells 2019;12(2):183-94.
  4. Trivella J, John BV, Levy C. Primary biliary cholangitis: epidemiology, prognosis, and treatment. Hepatol Commun 2023;7(6) DOI: 10.1097/HC9.0000000000000179.
  5. Sebode M, Kloppenburg A, Aigner A, et al. Population-based study of autoimmune hepatitis and primary biliary cholangitis in Germany: rising prevalences based on ICD codes, yet deficits in medical treatment. Z Gastroenterol 2020;58(5):431-8.
  6. Tanaka A, Ma X, Takahashi A, et al. Primary biliary cholangitis. Lancet 2024;404(10457):1053-66.
  7. Selmi C, Bowlus CL, Gershwin ME, et al. Primary biliary cirrhosis. Lancet 2011;377(9777):1600-9.
  8. Onofrio FQ, Hirschfield GM, Gulamhusein AF. A practical review of primary biliary cholangitis for the gastroenterologist. Gastroenterol Hepatol (N Y) 2019;15(3):145-54.
  9. Khanna A, Leighton J, Lee Wong L, et al. Symptoms of PBC – pathophysiology and management. Best Pract Res Clin Gastroenterol 2018;34-35:41-7.
  10. Hirschfield G, Lleo A, Jones D, et al. Holistic patient care in primary biliary cholangitis: managing both the disease and the symptoms. Eur. Med. J. 2022. https://doi.org/10.33590/emjhepatol/10166227. Accessed October 30, 2024.
  11. ALF. Primary biliary cholangitis (PBC). 2024. https://liverfoundation.org/liver-diseases/autoimmune-liver-diseases/primary-biliary-cholangitis-pbc/. Accessed February 6, 2025.
  12. Chalifoux SL, Konyn PG, Choi G, et al. Extrahepatic manifestations of primary biliary cholangitis. Gut Liver 2017;11(6):771-80.
  13. Brito-Zerón P, Baldini C, Bootsma H, et al. Sjögren syndrome. Nature Reviews Disease Primers 2016;2(1):16047.
  14. Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology 2019;69(1):394–419.
  15. Murillo Perez CF, Harms MH, Lindor KD, et al. Goals of treatment for improved survival in primary biliary cholangitis: treatment target should be bilirubin within the normal range and normalization of alkaline phosphatase. Am J Gastroenterol 2020;115(7):1066-74.
  16. Invernizzi P, Floreani A, Carbone M, et al. Primary biliary cholangitis: advances in management and treatment of the disease. Dig Liver Dis 2017;49(8):841-6.
  17. EMA. Seladelpar Gilead. 2024. https://www.ema.europa.eu/en/medicines/human/EPAR/seladelpar-gilead. Accessed January 13, 2025.
  18. AWMF. S3-Leitlinie. „Seltene Lebererkrankungen (LeiSe LebEr) – autoimmune Lebererkrankungen von der Pädiatrie bis zum Erwachsenenalter“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS). Februar 2025. #021–027.