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

Abstract

Despite advances throughout the field of hepatology, primary sclerosing cholangitis (PSC) remains one of the few liver diseases without an effective treatment other than liver transplantation to improve survival, symptoms or health-related quality of life (HRQOL). A major challenge for PSC clinical trials is the low frequency of events in non-cirrhotic patients. However, patients with PSC often experience symptoms including fatigue, pruritus, abdominal pain and sleep disturbances [1]. Valid PSC-specific patient-reported outcome (PRO) measures for use as trial endpoints would be a major advancement toward developing therapies that improve how patients feel and function.

Tan et al. [2] present the first publication using the PSC-PRO instrument since its development in 2018 [3]. The PSC-PRO consists of two modules: Module 1, a 24-h recall of 12 PSC symptoms to produce a total symptom score, and Module 2, a 7-day recall of the impact of symptoms on seven HRQOL domains. The PSC-PRO was administered at one timepoint along with an IBD-specific PRO measure (SIBDQ) in those with IBD. Overall, participants reported low total symptom scores, contrasting other studies suggesting greater symptom prevalence [1, 4, 5]. For example, our recent study of 200 patients from seven academic medical centres found that 21% reported moderate to severe itch in the past 24 h on a numeric rating scale [5]. Like the Tan et al. study, IBD symptoms were strongly correlated with PSC symptoms, including itch. However, a closer examination of individual symptoms shown Tan et al.'s figure 1 reveals that about half of patients experienced physical and mental tiredness, difficulty concentrating, dark urine and itch. These findings suggest that summing of individual chronic and acute PSC symptoms into one total score may obfuscate symptom experiences and treatment impacts.

Tan et al. also reported that cholangitis-related symptoms were rare during the 24-h recall period, implying that frequent administration of the PSC-PRO may be needed to capture episodic symptoms.

Additionally, the association between a history of cholangitis and reduced HRQOL in six of seven domains is novel and warrants further understanding. Future research should elucidate whether recurrent cholangitis progressively worsens symptoms and HRQOL. Finally, the results from Module 2 suggest a significant toll on emotional health, underscoring the importance of psychological distress screening and referral to PSC support groups when indicated [6].

Fortunately, several PSC-specific PRO measures are under development to provide a comprehensive assessment of PSC symptoms and HRQOL. Along with the PSC-PRO [3], the Simple Cholestatic Complaints Score (SCCS) [7] and the CLDQ-PSC [8] have been published. The PSC Partners Seeking A Cure organisation is partnering with US academicians to develop three symptom-specific measures [9] and a group in the United Kingdom is developing a PSC HRQOL measure [10]. These PRO instruments differ in their development, domains, number of items and recall period. Some may be used to evaluate multiple HRQOL domains in population-based studies, while symptom-specific measures could be fit for clinical trial endpoints. By refining these tools, we can better evaluate treatment benefits and ultimately improve the lives of individuals with PSC.