Industry Insight

How is primary biliary cholangitis (PBC) currently affecting patients; and, more importantly, what hopes does PBC awareness month bring for new treatment options?

By Palak Trivedi, University of Birmingham, UK.

As we enter September, which is primary biliary cholangitis (PBC) Awareness Month, many experts who work in the field are raising awareness of the impact of PBC. By championing awareness (or simply reading this article), a wider audience can be part of the solution to some of the challenges facing people living with PBC.

PBC is a chronic liver disease in which the body’s immune system attacks the bile ducts. 1 Left untreated, this can lead to cirrhosis, liver failure and cancer. 1 Whilst considered a rare disease, PBC can affect one in 1,000 women above the age of 40 years old. 2 At this time, there is no cure for PBC, however, there are treatments that seek to slow disease progression.

The onset of PBC can be subtle, present without symptoms, or with non-specific features such as fatigue, brain fog and itching. 3 This issue is reflective of a broader challenge: the need for improved awareness and innovative approaches to enhance care for people living with PBC.

Whilst most people do not have symptoms when diagnosed, these may develop over time and have a profound impact on health-related quality of life, even when liver blood tests improve. Some treatment approaches fall short of addressing symptoms in PBC, underscoring the need for a more holistic approach to care delivery.

Positive lifestyle changes, including physical therapy, alongside traditional medical support, can make all the difference to the holistic care of someone living with PBC (and many other chronic conditions for that matter). For instance, dietary changes (such as minimising ultraprocessed foods), aerobic and resistance exercises, alongside mind-body wellness programmes may help alleviate fatigue and enhance overall well-being. 4 Additionally, incorporating mental health services into routine care can be incredibly valued as people living with PBC often experience anxiety, depression and feelings of isolation, which exacerbate symptoms and lower health quality of life. 5 This includes access to counselling, support groups, and interventions designed to address the emotional and psychological challenges associated with the disease. Empowering people with knowledge about their condition and its management can also reduce anxiety and enhance self-efficacy, leading to improved health outcomes.

Many people living with PBC are diagnosed incidentally through abnormal liver biochemistry, and less commonly with features of advanced diseases, such as jaundice and ascites. The current diagnostic paradigm relies heavily on the detection of disease specific autoantibodies, namely anti-mitochondrial antibodies (AMAs) and certain types of antinuclear antibodies (ANAs), which are part of the body’s natural defence mechanisms to perceived threats. 6

However, increasing awareness of PBC among healthcare professionals is the key to optimise an early path to care and management. Ultimately, there is a need to be attuned to the possibility of PBC in people presenting with unexplained cholestasis or persistent fatigue that can affect their health quality of life. Dedicated training and educational programmes could help bridge this gap in awareness, ensuring that PBC is considered as a differential diagnosis more routinely. Additionally, there is a compelling need for the development of new, more specific diagnostic tools, particularly for patients who present atypically; for instance, those with predominantly elevated transaminase values (serum ALT and AST), often of younger age (eg, below 40 years).7,8

Furthermore, it is important for people to understand the impact of the condition, when to visit their healthcare provider for an assessment and how often those who are diagnosed should be monitored and in what way.9 Improved health literacy has been shown to give people a greater sense of control over their health, improving treatment outcomes in the longer-term.9 While awareness of PBC is not as widespread as common conditions like diabetes and hypertension, it is important to acknowledge the number of people affected worldwide – and to empower them in their journey by ensuring information on PBC is made widely available. One step could be to recommend routine liver biochemistry assessment for people who have a relative with PBC, those with unexplained itching without a rash and in people who have other autoimmune diseases that commonly coexist with PBC (such as Sjogren’s syndrome and coeliac disease).2

While PBC primarily affects women, more men are now being diagnosed.10 Preventing or slowing the progression of PBC to cirrhosis and liver failure remains a significant concern, especially for the 30% to 40% of people who do not normalise liver tests with first-line treatment, or those who struggle with symptoms such as increased itching, brain fog and fatigue.11

For people living with PBC, current treatment goals are evolving to include normalising liver biochemistry (alkaline phosphatase and alanine transaminase) and sub-normalisation in serum bilirubin, to ensure that liver disease severity (fibrosis) does not worsen, overall reducing the experience of pruritus and fatigue.12, 13, 14 Atreatment plan that helps sustain normal liver biochemistry, and which effectively manages symptoms, may help people living with PBC improve mental health and increase self-advocacy.9,15

Advances in personalised medicine hold promise for addressing these needs. By tailoring treatments to the genetic and molecular profiles of individuals, healthcare providers could potentially enhance treatment efficacy and minimise adverse events. Personalised approaches could involve a combination of novel drug candidates, targeted therapies, and a deeper understanding of the molecular mechanisms underlying PBC.3 Collaboration between researchers, pharmaceutical companies, and clinicians will be crucial in driving these advancements forward.

Access to care for PBC varies across regions and populations due to disparities based on geographic location, socio-economic status, and healthcare system differences. This can lead to delays in diagnosis and treatment, resulting in poorer outcomes for people living with PBC.15

Global health initiatives can help address disparities in PBC care on an international scale.16 Collaborative efforts between countries, companies and healthcare systems can help ensure that advancements in PBC treatment are accessible to all people living with PBC. Addressing these disparities can ultimately improve outcomes and ensure equitable access to care for all individuals with PBC.

As we kick off PBC Awareness Month, it is important to remember that addressing the unmet needs in PBC requires a comprehensive and multifaceted approach. Enhancing early diagnosis through increased awareness, developing innovative therapeutic options, and adopting a holistic approach to symptom management are essential steps in improving patient outcomes. Additionally, integrating mental health support into standard care and addressing the unique needs of each individual affected by PBC will provide more effective care.

Continued research and collaboration among healthcare providers, researchers, companies and people living with PBC are vital to overcoming these challenges and improving the quality of life and outcomes for individuals living with PBC.

As our understanding of the disease deepens, there is hope that these unmet needs will be increasingly addressed, leading to better care and outcomes for all people living with PBC. The journey ahead involves not only advancing medical knowledge and treatment but also fostering a more inclusive and supportive environment for those affected by this challenging condition.

References

1. European Association for the study of the Liver (2017), ‘EASL clinical practice guidelines: The diagnosis and management of patients with primary biliary cholangitis’, Journal of Hepatology, 67(1), pp145–172
2. Trivedi PJ et al (2021), ‘Recent advances in clinical practice: epidemiology of autoimmune liver diseases’, Gut, 70(10), pp1989–2003
3. Hirschfield GM, et al (2018), ‘The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines’, Gut, 67(9), pp1568–1594
4. Visit: www.liverfoundation.org/liver-diseases/autoimmune-liver-diseases/primary-biliarycholangitis-pbc/
5. Sivakumar T, et al (2021), ‘Anxiety and depression in patients with primary biliary cholangitis: Current insights and impact on quality of life’, Hepatic Medicine: Evidence and Research, Volume 13, pp83–92
6. Huang YQ, (2016), ‘Recent advances in the diagnosis and treatment of primary biliary cholangitis’, World Journal of Hepatology, 8(33), p1419.
7. Lleo A, et al (2020), ‘Primary biliary cholangitis’, The Lancet, 396(10266), pp1915–1926
8. Trivedi PJ, et al (2015), ‘Risk stratification in autoimmune cholestatic liver diseases: Opportunities for clinicians and trialists’, Hepatology, 63(2), pp644–659
9. Leighton, J, et al (2020), ‘Patient ownership of primary biliary cholangitis long-term management’, Frontline Gastroenterology, 12(5), pp370–373
10. Shaker M, et al (2022), ‘Primary Biliary Cholangitis in Males: Pathogenesis, Clinical Presentation, and Prognosis’, Clinics in Liver Disease, 26(4), pp643–655
11. Zhang Y, et al (2024), ‘Noninvasive prediction of insufficient biochemical response after ursodeoxycholic acid treatment in patients with primary biliary cholangitis based on pretreatment nonenhanced MRI’, European Radiology, 34(2), pp1268–1279
12. Murillo Perez CF, et al (2020), ‘Goals of Treatment for Improved Survival in Primary Biliary Cholangitis: Treatment Target Should Be Bilirubin Within the Normal Range and Normalization of Alkaline Phosphatase’, American Journal of Gastroenterology, 115(7), pp1066–1074
13. Corpechot C, et al (2024), ‘Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain?’, Hepatology (Baltimore, Md.), 79(1), pp39–48
14. Rice S, et al (2021), ‘Effects of Primary Biliary Cholangitis on Quality of Life and Health Care Costs in the United Kingdom’, Clinical Gastroenterology and Hepatology, 19(4), pp768-776
15. Rabiee A, et al (2020), ‘Hispanic patients with primary biliary cholangitis have decreased access to care compared to Non-Hispanics’, Journal of Clinical and Translational Hepatology, 8(4), pp1–6
16. Carbone, M, et al (2018), ‘Clinical application of the Globe and United Kingdom – primary biliary cholangitis risk scores in a trial cohort of patients with primary biliary cholangitis’, Hepatology Communications, 2(6), pp 683–692