This article has been commissioned by Ipsen. Ipsen also provided editorial content for this article.
Professor David Jones
Professor of Liver Immunology, Newcastle University
Robert Mitchell-Thain
CEO, PBC Foundation
Most of us think we understand tiredness: a long day, a short night, a few too many deadlines. Yet, fatigue is different. For many people living with the rare liver disease Primary Biliary Cholangitis (PBC), the exhaustion never fades, no matter how much rest they get.
Fatigue isn’t a temporary sense of exhaustion like tiredness. It is a debilitating daily challenge that doesn’t improve with sleep and rest. It is persistent, profound and almost entirely invisible to everyone other than the person experiencing it.1,2
Fatigue limits not only what a person can do but often what they even attempt to do. While it is considered to be one of the most burdensome symptoms of PBC,3 fatigue still isn’t taken seriously enough.
The weight of the invisible
Despite being hard to see, the impact of fatigue is clear: up to 80% of people living with PBC experience fatigue,4 with 20% experiencing it as severe.5 The impact is equally undeniable; around 60% of people living with PBC report a loss in work productivity,6 and fewer than 20% of those with severe fatigue are able to maintain their careers.7
This could be an accountant struggling to keep track of numbers amidst the brain fog fatigue can bring, or a pharmacist unable to continue prescribing life-saving medication under the strain of memory loss and exhaustion – these are examples we have come across in our roles that may be familiar to those living with PBC.
The science is catching up
As our understanding of the mechanisms behind fatigue in PBC continues to evolve, it is increasingly being recognised as a direct manifestation of the underlying autoimmune process. Magnetic resonance brain scans have shown that people with PBC have changes in how certain parts of their brain work and connect with each other. These areas help control things like motivation, emotions, memory and how we process sights, sounds and other sensations.8 These changes are thought to contribute to the experience of fatigue for people living with PBC, helping to explain why it can feel so pervasive, both mentally and physically.8
While it is considered to be one of the most burdensome symptoms of PBC,3
fatigue still isn’t taken seriously enough
A call for recognition
While our understanding of the science evolves, there is still a critical need for improved recognition, routine measurement and open dialogue about fatigue, not just as a symptom but as a core part of the condition that severely impacts quality of life.
If we want to be true partners in patient care, we must recognise that fatigue is not a subjective feeling of tiredness but a distinct clinical condition that has a significant impact on quality of life,1 independent of other PBC symptoms like pruritus.9 Healthcare professionals must be supported to see and treat the whole person, going beyond treating liver biochemistry to address the symptoms that matter most to people living with PBC. PBC fatigue takes more than energy. It steals moments, independence and freedom.
Listening to the PBC community
Living with a rare disease can be isolating, particularly when symptoms such as fatigue are misunderstood or overlooked. Greater awareness is important, but so are the small things: feeling listened to, having your experiences recognised and knowing there are others who understand the challenges you face.
To find out more about PBC fatigue please visit: pbcfoundation.org.uk
DRSC-UK-001030
September 2026
[1] Fakuda et al. 1994. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Annals of internal medicine. 121.12:953-959.
[2] Lynch et al. Understanding fatigue in primary biliary cholangitis: from pathophysiology to treatment perspectives. World Journal of Hepatology. 14.6: 1111.
[3] Kaps 2020. Symptom burden and treatment response in patients with primary biliary cholangitis. Digestive Diseases and Sciences. 65(10): 3006-3013.
[4] Chalifoux SL, et al. 2017. Extrahepatic Manifestations of Primary Biliary Cholangitis. Gut. 15;11(6):771-780
[5] Jopson and Jones 2015. Fatigue in Primary Biliary Cirrhosis: Prevalence, Pathogenesis and Management. Dig Dis. Suppl 2:109-14.
[6] Levy et al. 2023. Understanding the experience of patients with primary biliary cholangitis and pruritus. Abstract presented at ISPOR; 7-11 May 2023, Boston.
[7] Khanna et al. 2018. Rituximab for the treatment of fatigue in primary biliary cholangitis (formerly primary biliary cirrhosis): a randomised controlled trial. J Hepatol. 69(5), pp. 946–953.
[8] Mosher et al. 2017. Primary biliary cholangitis alters functional connections of the brain’s deep gray matter. Clinical and translational gastroenterology. 8(7):e107.
[9] Jones et al., Elafibranor improves fatigue versus placebo in patients with primary biliary cholangitis, with limited correlation with pruritus: Analyses from the phase III ELATIVE® trial. Poster presented at the EASL Congress May 2025.
