The burden of fatigue in primary sclerosing cholangitis: results from the WIND-PSC prospective cohort.

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Background and aims:
Fatigue is a burdensome but poorly understood symptom of primary sclerosing cholangitis (PSC) that
significantly impacts quality of life. Data on its persistence and relationship to other symptoms is lacking.
WIND-PSC is a global prospective observational study evaluating clinical outcomes, biomarkers and
symptom burden in adults with PSC. We report an interim analysis on the incidence, severity, and
persistence of fatigue and its correlation to other symptoms.

Method:
Adult patients with large duct PSC were prospectively enrolled at 9 sites in North America and Europe. A
patient-reported categorical symptom screening tool assessing the frequency, severity and persistence of
abdominal pain, anxiety, brain fog, fatigue, insomnia, liver pain, nausea, and pruritus is administered at
baseline and every 12 weeks. Evaluation criteria required baseline and a Week 12 and/or 24 assessment.

Results:
A total of 261 patients met symptom screening criteria with patient demographics and disease
characteristics consistent with other PSC cohorts. Cirrhosis was present in 12% of patients based on a
liver stiffness measurement (LSM) >15 kPa and clinical data. Fatigue was the most prevalent symptom at
baseline (75%) with severe and frequent/constant symptoms in 18% and 29%, respectively. Other less
frequent symptoms were insomnia (62%), anxiety (58%), brain fog (46%), abdominal pain (46%), pruritus
(44%), liver pain (36%), and nausea (27%). Most patients had > 2 symptoms at baseline (69%) and only
12% reporting no symptoms. Presence and severity of fatigue at baseline was most strongly correlated
(rS) with insomnia (0.58) followed by brain fog (0.52) and abdominal pain (0.50). Fatigue was not
associated with LSM, IBD status, duration of PSC, or any patient demographics. At Week 24, fatigue
persisted for 31%, worsened for 13%, newly emerged for 12%, remained absent for 13%, improved for
14%, and resolved for 11% of patients. Change in fatigue at Week 24 was moderately associated with
directional change or persistence in brain fog (p < 0.001), anxiety (p < 0.05), insomnia (p < 0.05), and
abdominal pain (p < 0.05), and aligned with the associations at baseline.

Conclusion:
Fatigue is a frequent but poorly understood symptom in people with PSC, independent of disease stage
or demographics and linked to the presence and persistence of other symptoms. These data support
further studies to understand the factors leading to the occurrence and persistence of fatigue and its
impact on health-related quality of life.

Conflict of interest: None declared

Applied for bursary: No