J Psychosom Res. 2026 Jul 17;211:112931. doi: 10.1016/j.jpsychores.2026.112931. Online ahead of print.
ABSTRACT
BACKGROUND: Fatigue is a debilitating symptom in autoimmune liver disease, but prospective research on fatigue in Primary Sclerosing Cholangitis (PSC) remains limited. This study aimed to estimate fatigue frequency in patients with PSC and explore cross-sectional and prospective biopsychosocial associations with fatigue severity.
METHODS: This prospective study included 226 patients with PSC. Fatigue severity was assessed using the PBC-40 fatigue domain at baseline and six-month follow-up. Biomedical, psychological and social variables were assessed using clinical records, blood biomarkers and self-report measures. Descriptive statistics and multivariable linear regression models were used to examine cross-sectional and prospective associations with fatigue severity.
RESULTS: At baseline, 19% of patients reported clinically significant fatigue. Patients with fatigue reported greater psychobehavioral burden and impairment across several domains. Cross-sectionally, greater fatigue severity was significantly associated with higher depressive symptom severity (p < 0.001) and greater fear-avoidance behavior (p < 0.001), whereas biomedical disease severity markers were not independently associated with fatigue severity. At six months, most patients without baseline fatigue remained below the clinical threshold (92%), while fatigue persisted in 79% of patients with baseline fatigue. Prospectively, greater fear-avoidance behavior (p < 0.001) and detectable IL-6 serum level (p = 0.02) were associated with greater fatigue persistence over time.
DISCUSSION: Fatigue represents a clinically relevant and persistent symptom burden in PSC. Findings support a multidimensional biopsychosocial conceptualization of fatigue involving psychobehavioral and inflammatory processes and may provide useful directions for future mechanistic and interventional research.
PMID:42537269 | DOI:10.1016/j.jpsychores.2026.112931
