Editorial: When and What to Ask—Capturing the Symptoms Experienced by Patients With PSC. Authors' Reply

We thank Professor Bowlus and Dr. Evon for their interest in our publication [1]. We agree that the development and validation of primary sclerosing cholangitis (PSC) specific patient reported outcome (PRO) measures are crucial as part of composite trial endpoints [2]. We are pleased that patient support organisations and academics are uniting to develop other PSC-specific PRO measures [3, 4], with further validation required to determine the best instrument for use in population-based studies and clinical trials [5].

We took the opportunity to use the first validated PSC-PRO instrument by Younossi et al. [6] to describe PRO in an Australian cohort of participants with PSC, and as highlighted, participants overall reported low symptom scores in contrast with other studies [1]. This reflects the limitations of PSC-PRO, with only a 24-h recall period for PSC symptoms, which results in intermittent symptoms not being captured and contrasting findings between study cohorts [5]. The discrepancy in recall period with PSC and inflammatory bowel disease (IBD) symptoms using different PRO instruments might make interpretation challenging, and consideration needs to be made towards interrogating both PSC and IBD symptoms with one PRO instrument to determine if there is truly a correlation between bowel and cholestatic symptoms.

The novel finding of a history of cholangitis being associated with reduced health-related quality of life is important, and emphasises the impact of intermittent symptoms that may not be captured in symptom-based questionnaires such as the simple cholestatic complaints score [7]. Our study only captured PSC and IBD symptoms at one timepoint, whereas repeated administration of PRO instruments with longitudinal follow-up may be more effective at capturing the frequency of recurrent cholangitis and other symptoms that fluctuate as seen in other population-based cohorts [8, 9]. The potential association between previous episodes of cholangitis and development of chronic mental stress, physical fatigue, or emotional distress due to recurrent hospitalisations, side effects of antibiotic use, invasive procedures, and loss of work and social productivity is underappreciated in the literature. As discussed by Prof Bowlus and Dr. Evon [5], the significant emotional burden of PSC is not a unique finding of our study [8, 10]. This publication should serve as a reminder to clinicians to screen for psychological distress, fatigue, and provide appropriate support when looking after individuals with PSC.

We look forward to the further PSC-specific PRO instruments that are being developed and refined with patient input, as this is crucial in deciding what types of questions reflect the true effects of this disease on individual well-being. We hope that our publication has shone light on the impact of this disease on patients with PSC in Australia. Future collaboration with international patient cohorts to assess HRQOL longitudinally in different ethnic groups, with or without IBD, is warranted for us to enhance our understanding of this complex disease and how it affects individuals across the globe. By having a greater understanding of when symptoms occur and what questions to ask to capture these symptoms systematically, we can then apply these tools to measure outcomes in clinical trials, which hopefully translates to better therapeutics for individuals with PSC.