Clinically diagnosed pruritus significantly affected fatigue and antidepressant use in adults with primary sclerosing cholangitis (PSC), based on data from nearly 5000 patients presented at The Liver Meeting 2025: American Association for the Study of Liver Diseases (AASLD).

These results suggest that pruritus in PSC should not be dismissed as a minor or isolated complaint but may be a visible signal of a much deeper systemic and psychological burden, said Sheena Bhushan, MD, of the Liver Institute Northwest, Seattle.

“Although earlier studies have hinted at connections between pruritus, fatigue, and mood disorders in cholestatic liver diseases, large population-based analyses specifically focused on PSC are lacking,” said Bhushan in an interview.

In addition, the interplay between mental health and chronic liver disease, which is increasingly recognized in clinical practice, remains a strikingly understudied area, she said.

Quality of Life

PSC is a rare but chronic cholestatic liver disease in which pruritus and fatigue are among the most distressing symptoms because they can significantly impair patients’ quality of life.

In a retrospective study, the researchers identified adults with PSC from the TriNetX US Collaborative Network, which includes electronic health records from 68 healthcare organizations. The study population included 3164 patients with pruritus and 11,160 without pruritus based on the 10th revision of the International Classification of Diseases codes. The final matched cohort included 2988 patients in each category.

Primary outcomes included fatigue and antidepressant use. Overall, patients with clinically diagnosed itching had more than twice as much fatigue as those with no itching (27.1% vs 12.5%; risk ratio [RR], 2.17). Patients with itching also had an earlier onset of illness (median time to diagnosis, 1292 days vs 3522 days) and significantly higher antidepressant use (50.8% vs 30.6%; RR, 1.66) and averaged significantly more antidepressant prescriptions (25.3 vs 14.7 per patient; P < .001).

“All the comparisons between groups were statistically significant with well-balanced baseline characteristics after matching balance,” the researchers noted.

Systemic Disease Burden?

“Our findings suggest that pruritus is not merely a symptom complaint but may reflect a broader systemic disease burden,” said Bhushan, but more research is needed.

In the meantime, effective management of PSC should include a more holistic approach to history-taking, with systematic assessment of pruritus and associated psychosocial impacts.

“Itching, fatigue, and mood symptoms often travel together, and when we fail to ask about them, we risk missing important clues about a patient’s overall well-being,” Bhushan told Medscape Medical News. “These insights are essential for advocating and advancing comprehensive, patient-centered care in PSC.”

“While we anticipated that pruritus would correlate with diminished quality of life, the magnitude of its associations was striking,” she said. “Patients with pruritus faced more than double the risk of fatigue and a 66% increase in antidepressant use; these findings challenge us to reconsider what pruritus truly represents in PSC.”

They “also challenge us to rethink how we approach symptom management in PSC,” Bhushan added. Routine screening, proactive symptom-targeted therapies, and integrated mental health support should not be optional add-ons but essential components of comprehensive care.

“A multidisciplinary approach has the potential to meaningfully reshape quality of life for this patient population,” she said.

The study findings were limited by the retrospective design and the potential for inaccurate coding in medical records and residual confounding, Bhushan told Medscape Medical News. Additionally, the researchers were unable to assess symptom severity or long-term outcomes such as transplant-free survival, which remain important research areas, she noted.

The study reported receiving no outside funding. The researchers disclosed having no financial conflicts of interest.